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Ivermectin Interaction with Transmembrane Helices Reveals Widespread Rearrangements during Opening of P2X Receptor Channels
Ivermectin Interaction with Transmembrane Helices Reveals Widespread Rearrangements during Opening of P2X Receptor Channels
Neuron, Volume 54, Issue 2,
Pages 263-274,
Publication Date 19 April 2007
Copyright © 2007 Elsevier Inc. All rights reserved.
DOI: 10.1016/j.neuron.2007.03.020
Shai D. Silberberg
Mufeng Li
Kenton J. Swartz
Molecular Physiology and Biophysics Section, Porter Neuroscience Research Center, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA
Corresponding author
P2X receptors are trimeric cation channels that open in response to binding of extracellular ATP. Each subunit contains a large extracellular ligand binding domain and two flanking transmembrane (TM) helices that form the pore, but the extent of gating motions of the TM helices is unclear. We probed these motions using ivermectin (IVM), a macrocyclic lactone that stabilizes the open state of P2X4 receptor channels. We find that IVM partitions into lipid membranes and that transfer of the TM regions of P2X4 receptors is sufficient to convey sensitivity to the lactone, suggesting that IVM interacts most favorably with the open conformation of the two TM helices at the protein-lipid interface. Scanning mutagenesis of the two TMs identifies residues that change environment between closed and open states, and substitutions at a subset of these positions weaken IVM binding. The emerging patterns point to widespread rearrangements of the TM helices during opening of P2X receptor channels.


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""All About You""/""You've Got a Friend"" is the first single from British band McFly's second studio album, Wonderland. The single was the official Comic Relief charity single for 2005, with all royalties being donated to the charity.",,,,,,
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Post Tagged with: "forex"
What You Should Know Regarding Binary Options Vs CFD Trading
A trader hoping to invest in stocks or currencies should consider the differences binary options and CFD trading.
Knowing the differences that separate the two, a trader will know which trading option to go for in search of profits
Dollar hits session highs vs. euro after ECB
The dollar hit session highs against the euro on Thursday
Forex – EUR/USD dips as market braces for ECB decision
The euro fell against the dollar on Wednesday
Why should investors care about the Australian $?
Many use the Australian $ as a tool to determine if they should over/under weight risk assets
Dollar higher vs. euro before ECB, yen near 2-1/2 year lows
The dollar remained higher against the euro on Wednesday as safe haven demand was underpinned ahead of Thursday's European Central Bank meeting
RBA Expected to Leave Rate Unchanged.
This is a busy week when it comes to central banks, with several policy meetings on the calendar
Dollar lower vs. euro, yen, pound weaker
During U.S. morning trade, the dollar hit fresh two-and-a-half-year highs against the yen, with USD/JPY rallying 1.14% to
Draghi's Dance: Weekly Currency ETF Report
As the euro continues to strengthen, Mario Draghi's policy monetary draws criticism
EUR/USD hits 14-month high on U.S. jobs
Better-than-expected employment and consumer sentiment data out of the U.S. sent the euro surging to a fresh 14-month high against the dollar on Friday
Busy Day Ahead.
Last day of the week brings some very important economic news releases, likely to create volatility in currencies


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Christina Aguilera has plenty to celebrate this month!
Less than a week after announcing her engagement to longtime boyfriend Matt Rutler, Us Weekly reports that the singer is...read more
Do you miss CeeLo Green as a judge on The Voice already? Well, you can check out the musician on the season finale of Animal Planet's Treehouse Masters...read more
Those outfits! Those wigs! Those ... pets?! There are plenty of reasons why CeeLo Green (and Purrfect the cat, and Lady the bird) are irreplaceable on The Voice. But, like it or not, NBC will soon have to start searching for the next music superstar to fill Green's big red chair this coming fall on the heels of his exit from the highly rated singing competition.
CeeLo Green not returning to The Voice
So who should fill the "Forget You" singer's bedazzled, one-of-a-kind shoes? We round out six great candidates...read more
CeeLo Green stops by the recording studio treehouse to spontaneously lay down a track with Pete. Wait until you see Pete dance and sing!
He's become a staple of the singing competition show, but he revealed some big news about returning to his judge's chair to Ellen.
On NBC's hit singing competition show The Voice, judges Adam Levine and Blake Shelton have been the two stalwart cast members. While other celebrity judges like Shakira, Usher, CeeLo Green and Christina Aguilera have cycled through the show over the years, these guys keep coming back season after season. But do they get along?
CeeLo Green lays down a track in a very unique recording studio.
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CeeLo Green has turned his chair for the last time: The Voice coach won't be returning to the hit series, he announced on Wednesday's episode of Ellen.
"I'm going to continue my relationship with NBC. I have a television show development deal with them as well and hopefully some other talk show opportunities for later in the year," the singer toldEllen DeGeneres. "But yeah, I'm going to miss The Voice, too. I'm not coming back, guys."
CeeLo Green slipped ecstasy to a 33-year-old woman while the two were dining at a restaurant in downtown Los Angeles on July 13, 2012, police say. The Voice judge, 39, is charged with furnishing a controlled substance, a felony, and faces up to four years in prison.
We guess talent runs in the family!
On Monday's season premiere of The Voice, Kaley Cuoco's sister Briana learned that she scored a coveted blind audition in front of judges Christina Aguilera, CeeLo Green, Blake Shelton and Adam Levine.
NBC has announced premiere dates for its fall schedule, including long-running drama Law & Order: SVU and anticipated new series The Blacklist and The Michael J. Fox Show.
SVU fans will have to wait until ... read more
The Billboard Music Awards will air live Sunday, May 19 at 8/7c on ABC. And with Tracy Morgan hosting, it's sure to be a memorable one.As Billboard announced, the event will feature performances by Justin Bieber, Selena Gomez, Ed Sheeran and more. read more


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Clemson Tigers (22-11, 10-8 ACC) vs. #5 seed West Virginia Mountaineers (20-11, 11-7 Big East)
Time: 12:15 EST, CBS
Common Opponents: WVU faced Miami in Coral Gables in early December, and The U beat them 79-76 after putting a run on the Mountaineers to start the 2nd half, overcoming a 13 point hole. Both teams shot pretty well, but Miami hit 54.5% overall and 50% from the arc, which made up the difference. WVU outrebounded them 37-31, hit 21/24 from the FT line, and had 12 turnovers to Miami's 11, so there was no real edge here except for the shooting percentage, reflecting the defensive effort. The 79 points Miami scored is tied for the 2nd most that WV has given up this year (81 to St Johns). Daryl Bryant had 20 points and Casey Mitchell put up 18 with 7 boards, while playing 39 minutes of the game for the Mountaineers.
The other common opponent was Seton Hall, who WV beat 56-44. WV really manhandled them defensively, allowing just 38% shooting and outrebounding them 48-36 overall.
Clemson defeated both squads, sweeping The U.
How about recently? West Va struggled in the month of February when they got into the real meat of the Big East conference schedule. They lost to Pitt twice, Nova, and Syracuse. However, they did beat Notre Dame 72-58, UConn 65-56 and Lousiville 72-70 all at home within the last month. They lost their Big East Tournament opener to Marquette 67-61.
Looks to me like they had a fair month. Theyre not as talented as these teams and still won their share. Losing to Pitt twice and Syracuse is not something to be ashamed about.
WVU | Opp |
Points Per Game |
69.5 | 64.1 |
Points Per Possession (PPP) |
1.09 | 1 |
Points Per Shot (PPS) |
1.25 | 1.16 |
True Shooting % | 52.6% | 49.5% |
WVU | Opp | |
Assists/Gm | 15.1 | 11 |
Steals/Gm | 4.6 | 6.6 |
Turnovers/Gm | 12.1 | 12.1 |
Turnover Pct | 18.9 | 18.9 |
WVU | Opp | |
Offensive Rebounds/Gm | 14.4 | 12.7 |
Defensive Rebounds/Gm | 23 | 21.2 |
Off Reb Pct | 40.5 | 35.6 |
WVU | Clemson | ||
Pace | 308 |
248 | |
WVU Offense vs Clemson Defense Ranks |
WVU Offense | CU Defense | Advantage | |
Efficiency | 32 | 6 | CU |
Effective FG% | 204 | 23 | CU big |
Turnover % | 104 | 33 | CU |
Off. Reb. % | 6 | 121 | WVU big |
FTA/FGA | 99 | 96 | Push |
Clemson Offense vs WVU Defense Ranks |
CU Offense | WVU Defense | Advantage | |
Efficiency | 70 | 29 | WVU |
Effective FG% | 108 | 29 | WVU |
Turnover % | 195 | 251 | CU |
Off. Reb. % | 134 | 275 | CU |
One thing that jumps out at me from this is the turnovers vs defensive rankings. They play good defense but don't really get that many steals or turnovers.
What they do really well is crash the boards, really well (9th nationally in offensive boards). They also apparently like the drive-n-dish with 15 assists per game and such a poor shooting percentage from the arc. So this team has been taught to follow their shots really well.
Bob Huggins has coached the Mountaineers for four years now and has a 100-40 record with West Virginia (690-251 overall with stints at Kansas State, Cincinnati, Akron and Walsh). Huggins has a 26-18 NCAA Tournament record including 14-4 in opening tourney games.
Bob Huggins is the same Bob Huggins, he preaches smothering defense to no end and it shows. He even kept some of Beilein's 1-3-1 when taking over the WVU job, though its much different from his personal defensive philosophies in the past. He's been known to run a 1-1-3 (below) and man/man defense quite a bit.
Anyways, I took a little more closer look at it and the more I looked into it, the more I liked it as a defense to use to change things up. I think in many ways, it's better than the 2-3 zone because it puts more pressure on the opposing team's point guard, who is usually the best or 2nd best player on the other team at the high school level.
1-1-3 Basic Setup:
Bob Huggins teaching points for his 1-1-3 pressure defense are:
1. Always sprint to help.
2. Stopping the ball is the first priority on and off ball.
3. Put pressure on the ball as much as possible when it is held, dribbled, passed, caught, or shot.
4. The closest man will always take the ball.
5. Sprint to coverage area and break down into defensive closeout position.
6. All five players must rebound.
X1 up top will pressure the point-guard and force him one way with the dribble or to pass the ball. X2 runs the free-throw line extended from sideline to sideline, must be well conditioned. X3 and X4 cover the lane to the corner on each side and double when the ball is entered into the post. X5 should front the post.
Pass to Wing:
When the pass goes to the wing, X2 must sprint to closeout. X1 drops down to a help position in the case of either a drive, skip pass or return pass to the point.
You can also choose to trap the wing, by having X3/X4 step up, this is assuming that they offense does not have a player in the corner.
Pass to Corner:
2 ways to cover this, you can have X2 drop down while X3/X4 jumps out to cover the corner. Or, like in the diagram below, X5 and come around and 3/4 front the post from the baseline (because you have help over the top), while the weakside forward covers the middle. X1 should be at the free-throw line to closeout on either a top of the key pass or skip pass.Summary:
As mentioned, I really like the 1-1-3. Like most zones, it is vulnerable to the 3-point shot. But we weren't a good shooting team that year, so we played right into their hands. I like the pressure aspect as well. In the 2-3, you can extend the 2 guards to pressure a little bit but I think it leaves way too much room at the high-post area. With the 1-1-3, you can have 1 guard extended putting pressure beyond the 3-point line, while the other guard can still cover the high-post area.
Matchup wise, they really mirror ourselves, but they do actually have a shooter we don't. Their front court is not dominantly big but they do crash the boards. 6'8 PF Kevin Jones racks up 35 min/gm and puts up an average of 13ppg and 7.4 boards, but he has produced bigtime against good competition this season at times. He also struggled mightily in January. 6'7 F John Flowers averages 9.6ppg and 6.5 boards.
The backcourt is pretty solid. 2G Casey Mitchell brings in 14ppg and hits 38.2% from downtown. Truck Bryant and Joe Mazzula are also big guards. All are 6'2" and up. This group is the centerpiece of their offense, and account for 46% of the offense.
This is not a team that wants to run with you much, they prefer to make shots and get back and set the D. We're not a running team anymore either, but we can score on these guys in transition. Theyre mostly upperclassmen and they dont turn it over much, but also don't force many themselves. If we're sound and remember to box out and follow shots, the game should come down to the very end, and I expect its gonna be very close.


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India: Father held his daughter 14 years as sex slave
By admin on Aug 02, 2011 with Comments 0
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The Saginaw Valley State University men's basketball team opened its 2012-13 season with an exhibition basketball game at No. 5 Michigan. The Cardinals would fall to the Wolverines 76-48 in their only preseason tune-up before taking the court against Cedarville on Nov. 15 for their regular season opener.
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FINDAR - Sensors & Software - GPR FINDAR enables police to quickly locate metallic and non-metallic buried...
More webinars in the works! Please make sure to check back often.
Abalone LLC is working with the Mendocino County (Calif.) Sheriff's Office to show children how their faces would age after long-term methamphetamine use. Abalone's compact 3D imaging Face2Face System uses off-the-shelf digital cameras mounted on a stereo bar to take two identical images offset from each other by a few degrees. Combining the two offset images in the computer results in a 3-D image on the screen. Proprietary software can then manipulate the image and show kids the effects of meth on their faces. Abalone LLC donates 10 percent of all sales to the Mendocino Drug Education Program. The company says the system is simple and inexpensive enough to be deployed at airports and other points of entry for facial recognition.
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Tags: Abalone LLC, Drug Enforcement, Imaging


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Travel Security
Security Measures
Global events continue to remind us that aviation security remains a top priority for Qantas. Qantas Group Security and Facilitation is committed to maintaining the highest aviation security standards for both our customers and employees.
Due to increased security screening, check in procedures and potential traffic delays, we recommend you allow extra time to get to the airport. For further information view our Check-in Times.
During check-in and boarding you may have noticed some of Qantas' additional security measures that include:
- Random explosive trace detection of passengers and their carry-on baggage.
- Laptop computers* and aerosols are subject to enhanced inspection at screening points.
- Increased vigilance at passenger screening points and increased guarding of our aircraft and terminals.
- On flights to and from United States, some passengers will be randomly selected for additional screening at the departure gate.
X-ray equipment used at Australia airports does not damage:+
- Computer cpus or memory;
- computer storage media such as magnetic disks (hard drives, floppy disks etc)and other devices (CDs);
- cameras (including digital cameras with electronic storage media) or
- photographic film below asa 1000 (developed or undeveloped).
The Qantas Group has a strict policy of denying boarding to, or off-loading any passenger that makes inappropriate comments or behaves inappropriately inflight or on the ground. Qantas will not accept any inappropriate comments as 'jokes'. Qantas will also seek to recover all costs incurred as a result of inflight incidents, including diversions, from those involved.
Visit our conditions of carriage page for more information.
Access within the Terminals
- Domestic - No access restrictions apply to non passengers. If intending to meet or farewell passengers you are permitted in the sterile area of Australian domestic terminals subject to security screening.
- International - Non passengers are not permitted to enter the customs controlled areas of Australian international terminals.
Security Advice
- Always pack your own baggage.
- Do not carry on your person or in your checked baggage any item for another person.
- Always carry your valuables, medication and keys in your carry-on baggage.
- All knives, sharp objects or cutting and stabbing implements need to be packed in checked baggage and not placed in carry-on baggage or on your person.
- Security measures can include random frisk search after consent is obtained. Passengers can request privacy and must be searched by a screener of the same gender.
Body Scanners
Full body scanning requirements are being progressively introduced at Australia's eight international gateway airports - Adelaide, Brisbane, Cairns, Darwin, Gold Coast, Melbourne, Perth and Sydney.
The scanners are part of the Australian Government's $200 million Strengthening Aviation Security Initiative. Passengers departing Australia may be required to pass through a body scanner as part of standard screening processes.
Unlike walk through metal detectors, the scanners are capable of detecting non-metal items under clothing.
While the proposed legislation allows for exemptions such as persons suffering from a serious medical condition, infants and small children and persons in wheelchairs, the Australian government is proposing a 'no opt out' policy.
Any person directed to undergo this type of screening must undergo the process. A refusal to screen will mean a refusal to enter the sterile area or uplift on an aircraft.
Health, privacy and safety were assessed following a trial at Sydney and Melbourne International Airports including consultation with industry and privacy groups.
The body scanners will be 'millimetre wave' as opposed to x ray. One body scan is comparable to passive exposure to a mobile phone used several metres away.
The scanner cannot detect internal medical devices such as pacemakers and metal implants, and due to very low power levels there are no safety concerns in relation to devices such as pacemakers or for women who are pregnant.
The process takes approximately seven to ten seconds - two to three seconds for the scan and five to seven seconds for the image to be generated and viewed by security personnel.
To protect people's privacy the image that is generated appears as a 'stick figure' so all persons have the same outline with no defining features. Images will not be copied or stored.
Find out more about the body scanner.
Travel Tips
When Overseas
If you are in trouble contact the Australian Consulate. Consular staff are able to issue emergency passports, provide lists of local doctors and lawyers and assist during natural disaster, civil unrest or other emergencies.
Protect your personal information and make copies of your passport, credit card and prescription details. Carry a copy with you and leave a copy at home or work where someone can access them if necessary. Ensure your emergency contacts are filled out in the back of your passport.
Be aware that some medications sold over the counter in Australia may be illegal in other countries. Check this detail by contacting the consulate of your planned destination to determine which medications are legal in that country. If you are carrying prescription medicine, ensure you have a copy of the Doctors issued prescription with you. If carrying syringes please ensure you have a copy of a letter signed by your Doctor outlining the need for the syringes. Information on the carriage of prohibited items by persons suffering from bona fide medical conditions can be found on the prohibited items guidance information paper.
Personal Security Measures
- Avoid wearing items of clothing that will draw attention.
- Only carry what you can afford to lose and carry small denominations of local cash so you can hand that over if mugged.
- Take care using ATMs, particularly at night. Preferably go into a bank to increase your personal safety.
- Be wary of strangers or new acquaintances 'offering help'.
- Avoid hailing taxis off the street. In many countries it is safe to do so (for example Japan, Singapore) however in some countries, illegal, unregistered taxis are used to rob or over-charge passengers.
- If you become the victim of a robbery, don't put up a fight. Comply with the demands of the offender.
- Report unusual and dangerous incidents to local authorities.
- Always advise a friend or relative of your schedule and whereabouts.
- Never carry items that do not belong to you. You alone are responsible for the contents of your baggage.
- Be aware of the risks of HIV or other transmittable diseases - avoid ear piercing, acupuncture, tattooing or dental work.
Access to Premium Security Lanes
- Domestic - Platinum or Gold Frequent Flyers, or anyone travelling in Business, may use dedicated Premium Security lanes during peak times at Sydney T3, Perth, Melbourne and Brisbane Domestic terminals.
- International - Selected ports offer Premium Security lanes for Platinum Frequent Flyers and those travelling in Business or First. Eligible customers will be provided with an Express Path card at check-in.
Useful Links
smartraveller - The Australian Government's travel advisory and consular assistance service for Australian residents.
Australian Department of Foreign Affairs and Trade - Information on the economic and political climate in other countries.
New Zealand Ministry of Foreign Affairs and Trade - Current travel advice for international travel for New Zealand residents.
TravelSECURE - Information to assist in clearing security checks quickly and easily at Australian airports.
+ Manufacturer's advice.


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If you're thinking about getting a facial, make sure your appointment is at least a month before the day. Facials can cause serious redness and peeling. Get your eyebrows shaped the week before, so that any redness or inflammation can go down.
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Chillin~ plz view >. Manga Moods
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this took a few hours...and i finally gave up...well shes lying down...just relaxin -trying out a new SEMI-realistic manga style-
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Book Description:A fascinating account of the cross-fertilization between Jung's analytical psychology and Kohut's self-psychology by a leading figure in the Jungian world. This book should be of interest to professionals, students and teachers in analytical psychology, psychoanalysis, clinical psychology and psychotherapy.
Tags: Health, Mind & Body, Psychology & Counseling, General,
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RIGA STRADINS UNIVERSITY Eva Strīķe Evaluation of hemodynamic fluctuations by invasive and semi- invasive monitoring during off-pump myocardial revascularization surgery Summary of Thesis Anesthesiology and Intensive care Riga 2007 Introduction While being free of some adverse effects of cardiopulmonary bypass, the off-pump coronary artery bypass grafting (OPCAB) surgery still requests a thorough monitoring of a range of cardiac function and circulation parameters. Data collecting systems, both invasive and semi-invasive, allow for obtaining circulation-specific information. A 1996 Connors A.F. study demonstrated that Pulmonary Artery catheter (РАС) extends patient stay in ICU and hospital and even contrabutes to mortality increase for 39% for those patients whose treatment was guided by РАС readings. Another 5 year randomized study of Richard C., et al. 2003, denied mortality increase, though confirmed the same recovery percentage as for patients without РАС. The above, as well as РАС-induced complications, its costs and long learning curve drew our attention to minimally invasive methods. Invasive and semi-invasive methods, whose theoretical concept should be evaluated by clinical practice, could be an alternative to РАС. Each of the methods has its advantages and drawbacks, the rendered information and application techniques may vary as well. To make our judgement evidence-based, we are to answer four major questions when implementing the new method /125/: 1. Whether the new method is as good as "golden standard" (thermodilution as a replacement for Fick method /107/). 2. Whether the new method allows for gaining new information. 3. Whether the understanding of new information changes the patient management tactics. 4. Whether the above changes, if any, influence patient recovery. The methods were assessed in their interrelation, keeping in mind the goal of the study - to develop efficacious method for intraoperative assessment of hemodynamic fluctuations. We hope that the results we obtained could be helpful for ICU and Anesthesia professionals. By analyzing published data and summarizing them with our own findings I intend to develop an optimal method for monitoring cardiac function during off-pump myocardial revascularization surgery. Early diagnostics and management of circulatory system disfunction in these patients can prevent development of such life- threatening complications as hypoperfusion-induced multiorgan failure and severe ischaemic heart failure, while stable hemodynamics during surgery improves recovery prognosis and reduces treatment duration both in ICU and hospital. Aim of the Study To develop clinically safe, meaningful and scientifically validated method for monitoring patient cardiac function during off-pump myocardial revascularization surgery. Objectives 1. To measure fluctuations of specific hemodynamic pressures, as well as alterations of myocardial circulation during revascularization of relevant cardiac muscle zones (segments). 2. To evaluate and compare continuous cardiac output alterations during revascularization of different myocardial zones, by both invasive and semi- invasive monitoring of cardiac function. 3. To study fluctuations of specific hemodynamic pressures, myocardial circulation and cardiac output, as well as interrelation of those during revascularization surgery. Thesis to defend 1. Surgical manipulations during off-pump coronary artery bypass grafting (OPCAB), regardless of the revascularization zone, result in hemodynamic fluctuations, manifested mostly as right vetricle disfunction. 2. Monitoring of cardiac circulation by ECG while heart is verticalized and stabilized is not unbiassed. 3. Ischaemia-induced left ventricle systolic disfunction may be readily revealed rather by oesophageal echo-doppler than by thermodilution. 4. Monitoring of cardiac output with oesophageal echo-doppler is necessary to detect myocardial systolic disfunction during left ventricle lateral and posterior wall revascularization. Structure of the work Research work has been written in Latvian. It consist of 12 chapters (introduction, literature review, aim and objectives, contribution and impact, material and methods, statistical analysis of results, results, discussion, conclusions, practical recommendation and list with references consisting of 146 titles). Total volume of the research work covers 94 pages including 15 tables and 44 figures. Study Design The study was being performed at VAS Paula Stradina University Hospital within Latvian Cardiac surgery center (LCSC) from year 2001 till 2005. The study was approved by Paula Stradina University Ethics Committee. Involved patients, demography, anaesthesia, extent of surgery 158 patients undergoing sternotomy OPCAB in LCSC from 2002 till 2004 were involved in the evaluative study of monitoring of cardiac function and circulatory alterations with invasive and semi-invasive methods during off-pump CABG. 36 patients were withdrawn from protocol due to the adverse effects listed in exclusion criteria, or due to swithching to other type of surgery during the intervention. Exclusion criteria included conditions, able to interfere with linear blood flow in descending aorta or right heart and/or prevented establishing selected hemodynamic monitoring systems. Exclusion criteria were the following: aortic valve disfunction, history of aortic valve implantation, subvalvular stenosis, dilation of descending thoracic aorta, cardiac arrhythmias (non-sinus), postoperative mechanical circulatory support with intraaortic balloon pumping (IABP), oesophagus diseases, preoperative history of tricuspid valve insufficiency more than degree II. Hemodynamic monitoring was performed with units and devices, available at LCSC: HP, Edvards Lifescience, HemoSoniclOO. Patients demographics 122 patients were involved in the study, thereof 94 (77%) male and 28 (23%) female patients of 34 to 83 years of age. Average analyzed patient age was 61.8±9,7 years. The dominating CHF class preoperatively was CCVS class II and IV, average myocardial functional index LVEF of 54,48 % ±8,5%, with minimum LVEF of 26% and maximum LVEF of 73% (Table 1). 55% of all of the involved patiens had a history of myocardial infarction (MI). TABLE 1 Patients breakdown N of patients Percentage (%) Sex: male 94 77% female 28 23% Age (yearas ±SD) 61,8 ±9,7 CCVS class: I-III 120 98,6% IV 2 1,6% LVEF: >40% 109 92,4% 20-40% 9 7,6% History of MI 68 55,7% All of the patients were intubated for surgery, had a 20F arterial cannula (B Braun Medic system Arteriofix art. cat. Set. 20G/ 80mm) inserted via a. radialis or a. femoralis and central venous cannula inserted via v. jugularis int. dx. The cannula- tubing lines were used to connect cannulas to monitor (Philips M3000A/M3046A), displaying both pressure curves and readings. Involved patients got combined intravenous/inhalation anaesthesia Measuring CO fluctuations during OPCAB 7,5(F) size floating balloon catheter (177F75- CCO/Sv02) was introduced via 8(F) size port, placed in v.jugularis interna preoperatively after the patient was intubated. Transoesophageal echodoppler probe (HaemoSonic 100) was inserted to Th5-6 level, then position was checked and the probe was fixed (depth of probe taken at teehline) to avoid dislocation. Measurements of relevant hemodynamic pressures, cardiac function and myocardial circulation were taken at the following time points of surgery: 1. t1 - after pericardiotomy; 2. t2 (LAD) - during LV anterior wall revascularization (1 min after heart was positioned and stabilized); 3. t3 (Cx) - during LV lateral and inferior wall revascularization (1 min after heart was positioned and stabilized); 4. t4 (RCA) - during LV posterior wall revascularization (1 min after heart was positioned and stabilized); 5. t5 - after grafting, before the chest is closed, with stabilized hemodynamics. At the same surgery timepoints (t1, t2, t3, t4, t5) the relevant hemodynamics data were analyzed, which were supposed to influence CI values, obtained by TD and ED. Arterial blood sampling for blood gas testing was done. Core temperature of the patient was continuously measured with Foley thermosensor and recorded at the beginning of the surgery, at the end of the surgery and at 6h, 12h and 24h postoperatively. Statistical methods Hemodynamic data are presented as mean plus or minus the standard deviation. The data completely registered for all events were analyzed by group mean comparison for repeated measurement differences compared with baseline and for difference compared with the previous value. Differences between CI monitoring methods were plotted as suggested by Bland and Altaian (the difference between the two measures (TD CI- ED CI) is plotted against their mean [½( TD CI + ED CI)]). The mean difference is a measure of how well the two techniques agree on average. A measure of precision or range of agreement for a given individual is expressed as the 95% limits of agreement (if 95% limits of agreement are within clinically acceptable limits the two techniques may be used interchangeably). All statistical calculations were performed with SPSS software (version 12.0). Two - sided p value < 0,05 was regarded as statistically significant result. Measurement of relevant general parameters of hemodynamics and blood chemistry sampling in ICU. At the next stage - at 1h, 6h and 12 h postoperatively (ta - 1 h, tb - 6 h, tc - 12 h)- we measured hemodynamic parameters of the patients, as well as postoperative bleeding, and made blood count and blood chemistry sampling. Also, intubation time and duration of patient stay in ICU and the hospital were recorded. Results Medical history of the 122 involved patients is shown in Table 1. For all of the patients it was the first surgery. Duration of it was 75 to 310 minutes (M = 178.5 min, SD - 53.8 min).Duration of surgery and patients' stay in OR depended on the extent of the surgery, determined by the number of grafts (r = 0,69 with p < 0,001). Patients breakdown by the number of grafts was as follows: 32,8% (40 patients) had 2 artery grafting, 32,8% (40 patients) had 3 artery grafting, 18,9% (23 patients) had 1 artery grafting, 13,9% (17 patients) had 4 artery grafting, and just 1.6% (2 patients) had five artery grafting. Average N of grafts in one patient was 2,5 ±1,0. Overall N of grafts in LV anterior wall was 107, with 48 and 68 grafts in inferior and lateral walls respectively (Table 2). TABLE 2 N of grafts depending on revascularization area Revascularization area N of grafts LAD 107 Cx 48 RCA 68 The extent of circulatory fluctuations during surgery was measured by systemic pressure, heart rate (HR) and pulmonary artery pressure alterations. Myocardial circulation was evaluated by ST segment deviation in ECG II (ST1) and V5 (ST2) leads. Descriptive statistics of vital signs depending on revascularization area is displayed in Table 3. TABLE 3 Recorded relevant circulatory values (N = 122): HR- heart rate, SAP- systolic arterial pressure, DAP - diastolic arterial pressure, PAmP - pulmonary artery mean pressure, PAdP - pulmonary artery diastolic pressure, ST - ST segmentdeviation in leads II abd V5 of ECG, mm, standard deviation of it (±). Values Units T1(baseline) t2 (LAD) t3(Cx) U (RCA) t5 (end) Beats per HR 64±11 70±11,3 72±14,7 74±11 72±10 min (BPM) ST1(I) -0,04 0,1 -0,09 0,04 0,01 ST2(II) -0,18 -0,15 -0,05 -0,07 -0,05 SAP mmHg 123±18 98±14 87±12 96 ±13 114±16 DAP mmHg 73±14 58±14 53±14 57±12 67±11 PAmP mmHg 19±4 20±5 21±6 20±9 18±3 PAdP mmHg 11±3 11±4 12±5 12±3 10±3 The most distinct changes from baseline were found during LV posterior/inferior wall revascularization (t3), with such most variable parameters as systemic pressure (SAP = 87 ± 12,0 mmHg; DAP = 53 ± 14,0 mmHg), myocardial circulation alterations (ST/ = - 0,09; ST2 = -0,05) and mild mean HR increase (HR t3=72± 14,7 and HR t4 = 74± 11). During revascularization of other coronary arteries basins SAP and DAP decreased by 21,8% (SAP) and 27,7% (DAP) from baseline. (Charts 1, 2). We are to note that bringing the heart back to its atatomical position we observed stabilization of hemodynamics, and by the end of surgery (t4) systemic pressures were decreased by just 7,2% (SAP) and 7,4% (DAP) from baseline. Chart 1. SAP mean relative value changes (%) from baseline depending on revascularization area. Chart 2. DAP mean relative value changes (%) from baseline depending on revascularization area. Two different methods were used to measure systemic vascular resistance (SVR) along with SAP and DAP measurements. Both methods' SVR curves have no significant difference. The most distinct SVR increase was seen during left circumflex coronary artery (LCX) remodelling (t3), associated with the lowest SAP and DAP values, which can be explained by the therapy of hemodynamic alterations during surgery (Chart 3). Chart 3 Systemic vascular resistance (SVR) mean value changes from basleine and standard deviations, depending on revascularization area Alterations of pulmonary artery mean and diastolic pressures were observed during the whole surgery, especially during revascularization of LV inferior (t3) and posterior walls (t4) (PAdP by +3,6% and by +6,3%; PAmP by +3,9 % and by +1% from baseline) (Charts 4 and 5). By the end of intervention relevant preload parameters were decreased by up to 8,1% (PAdP) and 7,6% (PAmP) from baseline. Chart 4. Pulmonary artery diastolic pressure mean relative value changes (%) from baseline depending on revascularization area. Chart 5. Pulmonary artery mean pressure mean relative value changes (%) from baseline depending on revascularization area. During OPCAB for LCX and RCA grafting {t3) heart is being displaced out of its anatomical position in thorax. Loss of cardiac muscle contact with pericardium and changes in heart electrical axis result in ECG voltage decrease. In 12 patients undergoing LV inferior and lateral wall revascularization we failed to register ST segments in lead II or observed R-wave voltage decrease. The above means that in these patients myocardial circulation cannot be monitored by ECG. We found no ST segment deviations exceeding ±1,0 mm (Chart 6) for all patients. Chart 6. ST segment deviations, mm, from baseline, depending on revascularization area. 13 patients developed heart rate and rhythm alterations during surgery, thereof four had impaired atrioventricular conduction and six had sinus bradycardia (below 40 bpm). The above arhythmias were controlled by temporary atrial pacing. In two patients cardioversion was necessary due to tahysystolic atrial fibrillation, while one patient underwent defibrillation due to ventricular fibrillation. The rest of the patients had no significant HR changes whatever the revascularization area was. The changes were controllable without switching to another type of surgery (Chart 7). Chart 7. Heart rate changes, depending on revascularization area. Cardiac function changes during surgery were monitored in all of 122 patients: by ED alone in 28 patients, simultaneous CO measurement by both thermodilution and ED in 88 patients, total of 326 pair measurements (Chart 8). Six patients were withdrawn from protocol, as getting stable and full ED signal failed. In these patients CO changes were measured with TD alone. Chart 8. Patient distribution by CO measurement methods. A parameter to compare under this protocol was CI, which is indexed CO value, divided by patients body surface area (BSA) in m2 (CI = CO/BSA). When testing a hypothesis of mean CI value equality for both methods we found statistically reliable difference only during LV lateral/inferior wall revascularization: t3 r = 0,34; p = 0,032 and t4 r = 0,185; p = 0,477. Lowest CI values were shown by ED method, demonstrating even dangerously low values (Chart 9) - ED CI = 1,73 1/min/m Chart 9. Descriprive statistics of ED (HemoSonic100) and TD (РАС) measured cardiac index (1/min/m2) alterations, depending on revascularization area. At the beginning and at the end of surgery for other LV walls revascularization both methods demonstrated close correlation (Table 4) between CI mean values with high reliability. TABLE 4 Descriptive statistics of cardiac index (1/min/m2) alterations and correlation, depending on revascularization area Timepoints and ED CI РАС CI r P areas M N SD SEM M N SD SEM Baseline 2,46 88 0,51 0,05 2,45 88 0,55 0,06 0,698 0,001 LAD 2,25 76 0,52 0,06 2,28 76 0,52 0,06 0,629 0,001 Dl 2,16 17 0,67 0,16 2,71 17 0,81 0,20 0,185 0,477 Cx 1,62 40 0,39 0,06 1,89 40 0,43 0,07 0,340 0,032 RCA 2,51 54 0,15 0,43 2,06 54 0,50 0,07 0,426 0,001 Endpoint 2,56 85 0,53 0,06 2,60 85 0,55 0,06 0,824 0,001 According to Bland and Altman method mean, difference and shift are the tools to find correlation between mean values /9/, obtained by the two methods. Separate fluctuations of accuracy of measurements or coincidence are supposed to lie within 95% confidence interval, which is at two standard deviation levels. Difference between baseline values, measured by ED and TD methods in involved patients is displayed in Chart 10 by linear regression line (straight), considering confidence interval to be 95%. Chart 10. Difference between ED-derived and TD-derived CI baseline values in involved patients. Chart displays linear regression line (straight) and its 95% confidence interval. Chart shows that in three patients biggest CI values were measured by ED and in five patients the ED value exceeded the TD value. Data for 8 patients are beyond the 95% confidence interval, which means that 6.6% of patients had deviation more than 2 SDs. Chart 11. Difference between ED-derived and TD-derived CI LAD values in involved patients. Chart displays linear regression line (straight) and its 95% confidence interval. Only one patient had higher ED-derived CI value during LV anterior wall revascularization (Chart 11), but in three patients this value exceeded the TD-derived one. Data for total of 4 patients were beyond the 95% confidence interval, which means that 3.3% of patients had deviation more than 2 SDs. Similar CI mean value percentage was observed during RCA revascularization, however, during revascularization of LCX we found a difference in CI values (Table 5). Dispersion analysis showed statistycally reliable dispersion (F =18,331; p = 0,001). TABLE 5. Cardiac index (I/min/m2) alterations / test results, depending on revascularization area Timepoints and areas ΔM t P Baseline 0,011 0,248 0,804 LAD -0.029 -0.557 0.579 Dl -0,554 -2,411 0,028 Cx -0,271 -3,594 0,001 RCA 0,450 1,112 0,271 Endpoint -0,038 -1,090 0,279 There is moderate correlation (r = 0,570; r2 = 0,325; p = 0,001) between ED-derived and TD-derived CI values during revascularization of LV posterior and inferior walls. Difference between ED-derived and TD-derived CI values measured when performing distal anastomosis for LCX was beyond the 95% confidence interval in 23 patients (26%) (Chart 12). Chart 12. Correlation between ED-derived and TD-derived CI values in involved patients when performing distal anastomosis. Chart displays linear regression line (straight) and its 95% confidence interval. After performing distal anastomoses the heart was brought to its anatomical position. At this stage of surgery no major alterations of hemodynamics, myocardial circulation or cardiac function were observed. The last comparative measurement of ED-C/ and TD-C/ was done at the end of surgery. Two patients had ED-derived CI value higher than TD-derived one, however, one patient had TD-derived CI value higher than ED- derived. Data for 3 patients were beyond the 95% confidence interval, which means that 2.5% of patients had deviation more than 2 SDs (Chart 13). Chart 13. Difference between ED-derived and TD-derived CI t5 values in involved patients. Chart displays linear regression line (straight) and its 95% confidence interval. When comparing values of systemic pressures to ED-derived and TD-derived CI values we found no reliable correlation between SAP and DAP and CI values, though PAdP and PamP demonstrated negative linear trend. Chart 14 presents fluctuations of systemic pressure relative values compared to baseline and depending on revascularization area and interrelation thereof with ED-derived and TD-derived CI values. Chart 14. ED CI; TD CI relative mean values and SAP relative mean values compared to baseline and depending on revascularization area. When any of the patients developed hemodynamics impairments of different extent (MAP < 60 mm/Hg; CI < 2,0 1/min/m2) during surgery, we performed Trendelenburg maneuvre to redistribute the circulating blood volume, which resulted in increased preload, as well as in right heart flow and pressures increase. 24% of patients required circulation stabilization therapy perioperatively: • rhytm control: 8% of patients had atrial pacing (ICU 1.6%), 1.64% had cardioversion due to atrial fibrillation and 0.8% had defibrillation due to ventricular fibrillation; • 23.8% of patients were administered inotropic support with catecholamines during surgery and in ICU Minutes descriptive analysis of postoperative period Duration of patient stay in OR, thoracotomy, artificial ventilation and exposed body surface (ca. 30 - 40%) resulted in hypothermia in these patients. Despite using patient warming devices, OR temperature and warming of infusion solutions 53% of the patients undergoing surgery had core temperature decrease below 36° С Patient average core temperature at the beginning of the surgery was 36.5° С with SD = 0,48 °C, but at the end of surgery - 35.8° С with higher SD = 0.78 ° С It order to prevent hemodynamics alterations, cardiac arhythmias, excessive bleeding and blood viscosity impairments it is necessary to maintain the body temperature during the surgery close to normal. Moreover, perioperative body temperature alterations interfere with TD CO measurements. Patients with lowest recorded core temperature during surgery developed shivering followed by fever of 38.3° С in ICU (14 patients). Postoperative bleeding volume (blood volume in mL in drainage system postoperatively) was compared to patient core temperature at the end of surgery; we found reliable negative correlation. One patient had to undergo resternotomy due to excessive bleeding. After the surgery all of the patients were referred to ICU with ET tube in place. 23.8% of patients required inotropic myocardial support using catecholamines (24h in ICU), 51 patient (41.8%) developed atrial fibrillation during postoperative period. Duration of ICU stay after OPCAB was within 13 to 120 hours (M = 27,9 ± 16,2 h). 25% of 122 patients stayed in ICU for over 40 hours. Duration of intubation during ICU stay was within 90 to 910 minutes (M = 315,5 min, SD = 147,6 min). Two patients had mechanical ventilation for 1050 and 2390 minutes. Patients with prolonged ICU stay demonstrated elevated creatine kinase level but had the same systemic pressures, ventilation figures, troponine, BUN and creatinine levels, as well as diuresis and postoperative blood loss figures. Duration of stay in the ICU did not correlate with method of CO monitoring during surgery Postoperative creatine kinase (CK) alterations After 1 hr postop the CK level was 187,4 ± 80,1 U/mL on average. Maximum CK elevation was observed 12 hr after the surgery, in ICU, M = 796,9 ± 916,6 U/mL. Standard deviation of the value confirms considerable data dispersion and urges to find out the reasons for CK elevation. Chart 15. Postoperative creatine kinase (CK) and troponine I (TI) alterations (6 h, 12 h, 24 h). When analyzing CK-MB and T I elevation, we found weak but reliable positive correlation (r = 0,219; p = 0,031) between troponine and CK values with reliable difference (p = 0,001 [t = 6,652]) in t-test mean value (Chart 15). Reliable CK elevation (p<0,05) is found in patients with prolonged surgery time, bigger N of grafts, postoperative CK elevation and ED-derived CI value changes during revascularization of LV inferior and posterior walls. Patients were divided into two groups by preoperative CK level. First group had CK of up to 900 U/mL, while the second had CK of over 900 U/mL. Chart 16. Descriptive statistics of ED-derived cardiac index (L/min/m2) depending on revascularization area and postop CK level. Further analysis of correlation between CK elevation and its possible causes revealed that the second group had bigger number of grafts, more distinct ED-derived CI alterations compared to the first group. Also, the second group had lower CI values during operation (Chart 16). However, we found a correlation with ED-derived CI (r = -0,37, p < 0,05). Right heart monitoring system (TD РАС) presened lower systolic function impairments at the moment (Chart 17). Chart 17. Descriptive statistics of РАС TD-derived cardiac index (1/min/m2) depending on revascularization area and postop CK level 12 hr after the surgery. No intrahospital mortality was observed in studied patient group. Duration of stay in the hospital was distributed evenly, mostly within 6 t ol4 days (M = 10.2 days, SD = 2.9 days). Discussion Altered circilation during off-pump myocardial revascularization surgery is secondary to myocardial ischaemia, reduced preload, heart compression, myocardial dysfunction, increased mitral regurgitation to the combination of the above factors. Our study demonstrated that altered circulation dirung such kind of surgery is observed at any myocardial wall revascularization (SAP -20,8% to -9,2%, DAP - 20,2% to -29,2%, PAdP +1,4% to +6,3%; PAmP -0,6% to +3,9%). Moreover, changes in right ventricle function and filling (increase of PAdP) was seen more often during revascularization of front and inferior walls, as right ventricle has thinner wall and lower circulation pressure than left one. That is why the right ventricular effect is higher even when the left ventricular wall is stabilized. This can explain our finding: an increase in pulmonary artery diastolic pressure and pulmonary artery mean pressure (+6,3% PAdP t4), which was proportionally higher than CI changes. Our findings supplement and confirm published data about increased right heart filling and left ventricular diastolic dysfunction during Dx, LAD and RCA reconstruction to be found both in humans (Do Q.B., Cartier R., 1999) and animals (Grundeman P.F., Borst C, 1999). However, results of Do Q.B. study (2002) of hemodynamic changes during OPCAB differ from our ones. Do observed more pronounced hemodynamic changes (PAmP increase for 30% and reduced CI) only during revascularization of heart front wall. We are to note that in 55 patients, involved into Do study, another (compression) type of heart stabilizer was used. We found that the major heart function and myocardial circulation alterations were observed during lateral and posterior walls revascularization (t3), associated with the most marked systemic pressure changes (SAP = 87,2 ± 12,0 mmHg; DAP = 52,9 ± 14,0 mmHg), myocardial circulation alterations (ST1 = -0,09; ST2 = -0,05) and mild mean heart rate increase (HR t3 = 71,9 x min-1 ± 14,7 min-1 and HR t4 = 73,6 min-1 ±11 min-1). At this stage of the surgery anatomical position of the heart is changed - the heart is "verticalized" and stabilized. Nierich A.P., 2000, et al., when studying heart response to verticalization, found in TEE that atrial septum is shifted left and right ventricular geometry is changed. However, he noticed that the adequate evaluation of heart filling and contractility by TEE is difficult in these circumstances, as the echo-signal is poor. Royse C.F., 2003 explains this by the changed heart position against oesophagus. The same limitations for heart verticalization apply to ST segment analysis of ECG (Nierich A.P.; Diephuis J., 2000). The phenomenon could be explained by heart electric axis shift against ECG electrodes. Moises V.A. et al., 1998, and Kotoh K. 1999, independently of one another, studied ischaemia-induced left ventricular systolic dysfunction by comparative analysis of segmental myocardial wall motion, detected by TEE, and changes of ST-segment of ECG during OPCAB revascularization. In 64% of cases TEE registered segmental wall motion abnormalities, although altered myocardial circulation was found by ECG only in 19% of the cases. We saw reduced and irregular ECG voltage mostly during posterior wall revascularization. When evaluating myocardial circulation by ST-segment alterations in ECG leads II and V5 and comparing the results to postoperative elevation of markers of myocardial damage (troponine I), we concluded that postoperative elevation of troponine is not associated with detected ST-segment changes in ECG (the same as in Moises V.A. study), but corresponds more to CI changes, detected by ED. We explain decrease of CI at this stage of the surgery by isolated segmental left ventricular systolic dysfunction, possibly caused either by heart fixation or by decreased myocardial circulation. Segmental myocardial alterations and decreased end-diastolic filling of left ventricle (diastolic dysfunction) is the cause of global alterations in cardiac output, which we saw in our study during revascularization of posterior wall with marked decrease of ED CI (CI = 1,73 1/min/m2) and mild and delayed TD CI (CI = 1,97 1/min/m2). According to published recommendations (The Annals of Thoracic Surgery, 1997; 63: S90), we used Trendeleburg maneuver to stabilize circulation during distal anastomoses visualization (after the heart was verticalized and stabilized). The "head- down" position considerably enhanced blood flow to the heart, respectively increased heart preload, thus providing for better end-diastolic LV filling and SV (Boulain T. 2002). In majority of the patients this maneuver caused no alterations of heart contractility, but in those having preoperative history of severe cardiac systolic and diastolic failure (CHF NYHA III-IV) Trendeleburg maneuver caused decreased CI, followed by necessity to administrate inotropic stimulation (in 20 patients). Nevertheless, the increase of cardiac preload is not always possible without causing global decrease of cardiac function. In patients with considerably decreased preoperative cardiac output {EF <40%) increased preload may cause severe left heart failure. We made a comparative analysis of our results. In a patient with EF of 35% the PAmP during LAD and Dx grafting was 28 mm Hg, PAdP was 19 mm Hg, SAP 75 mm to 90 mm Hg; also both CO monitoring methods showed decreased global function of both ventricles: ED CI t2 1,9 1/min/m2; TD CI t2 2,0 1/min/m2 with prolonged postoperative ventilation (780 minutes), stay in ICU (39 hours) and hospital stay (22 days). Dagenais F. and Cartier R., 1999, presented the same results in patients having severe cardiac failure. Based on their own results they proposed for difficult situations to use invasive strategy to control pulmonary artery hypertension and right ventricle failure, namely to partially occlude v.cava inferior by applying a ligature, thus decreasing the preload. Lundell D.C. and Crouch J. D., 1998, studied use of miniature right heart support mechanical system during creation of distal anastomoses in off-pump surgery and found that right heart mechanical support is enough to provide left ventricle preload and stable circulation. Several authors confirm in their studies that OPCAB is a method of choice in patients with severe heart failure (Zaugg M., 2002; Sergeant P., de Worm E., 2001; Jagaden О., 2001; Al-Ruz:eh S., 2003). Still the risk of multiorgan hypocirculatory dysfunction is present, unless sufficient circulatory stability is provided during the procedure (unless early detection of the cause of impaired circulatory equilibrium and its prevention is possible). The following ischaemia, oxidative stress and increased calcium concentration in the cell changes its energy status, i. e. elevates the level of energy enzyme creatine kinase, CK (Shlattner U., 2005, 2002). In our patients, who had decreased blood circulation volume during surgery (ED CI) saglabājās samazināts asins cirkulāciju apjoms, involving creation of several anastomoses, we saw increased concentration of both creatine kinase (CK > 900 U/l) and troponine (r = 0,32, p = 0,004). To provide for optimal myocardial oxygen supply and circulatory equilibrium Bernard F. and Denault A., 2001, after analyzed their results, proposed the following algorithm: to decrease myocardial oxygen consumption and to provide for relatively high coronary perfusion pressure (MAP > 70 mmHg) by intensive volume replacement and vasopressors, while avoiding administration of ß-agonists even at low CI values (compared to preoperative data). Administering catecholamines in patients with limited coronary circulation may increase myocardial oxygen consumption, while the delivery is impaired, and may interfere with the course of surgery (stabilization of cardiac wall). Increased heart rate and contractility makes it difficult to model distal anastomosis, thus compromising its quality. That's why the first and the most effective step during the procedure is to communicate to a surgeon and to return the stabilized heart to its anatomical position or, when changing heart position, to stabilize circulation before creating anastomosis, as in this case its quality is not influenced by a hurry, caused by unstable circulation of the patient. Recovery of MAP when the heart is in its anatomical positions allows for improved coronary circulation and prevents from acute heart failure. This is confirmed by our results - at the end of the procedure patients' CI values recovered to baseline level. Still it is to be kept in mind that decreased CI should be above the level of undisturbed tissue perfusuion (Sv02 stays above 60%) and there are no metabolic acidosis signs in blood gas test, because early diagnosis and treatment of the shock considerably improve patient recovery prognosis (Rhodes A., 2004). Global perfusion pressure MAP is the most used and the most misinterpreted value in association with CO (Hoffman G.M., 2005). MAP depends on kinetic energy of the heart as well as on interaction of blood flow, viscosity, systemic vascular tone and backflow pressure (CVP). Concerning interaction of MAP and CO there exist two wrong conclusions: good blood pressure means good cardiac output, so, increase in MAP means increases in CO. SVR trend regarding the CO is opposite - decreased MAP is followed by activation of the sympathetic nervous system, while increased MAP is followed by decrease in sympathetic activity and increase in parasympathetic activity. This physiological response equalizes MAP fluctuations, which evidences that MAP is a late indicator of insufficient circulation till the moment of global vascular spasm. Just like Colan S.D., 1998, and Hoffman G.M., 2005, we did not notice reliable correlation between systemic pressure and CO. Actually, administration of vasopressors increases just systemic resistance by increasing the tone of capacitance vessels, but does not influence the CO. It can be clearly demonstrated by blood flow velocity in descending aorta (ED), when administration of vasopressors decreased the blood flow velocity. Decreasing vascular resistance is one of the ways to improve cardiac function in patients with signs of cardiac failure (CI < 2,2). However, changes in SVR cause systemic pressure alterations, and keeping these two parameters balanced during OPCAB requires use of more sensitive systems for monitoring of tissue perfusion and cardiac functions (CI). Our study of the efficacy of less invasive CI monitoring during off-pump myocardial revascularization was associated with repeated publications, denying significance of РАС. In their multicenter study of 1996 Connors A.F., Speroff Т., Dawson N.V. found that invasive monitoring, involving РАС, extends patient stay in ICU and the hospital and even increases mortality for up to 39% in patients, whose management was guided by РАС. In 2005 JAMA published a review by Shah M.R. , dealing with the results of ESCAPE (The Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness) study, as well as of 13 other randomized clinical trials regarding use of РАС as a management guide in 5051 patients from year 1085 till 2005. Eligible studies involved those with summarized data on patients, who underwent surgery or ICU patients with progressive cardiac failure, diagnosed ARDS, sepsis; studies involved analysis of mortality, duration of stay in the hospital, use of inotropes and vasodilators. It was found that РАС does not impact patient recovery time and does not increase mortality. Neutral effect of РАС with regards to improvement of clinical situation can be explained by the absence of evidence-based effective management strategy, guided by PAC-derived data. The use of РАС itself decreases the incidence of critical situations, but has no impact on mortality and recovery time. However, РАС is an indispensable tool when it is necessary to evaluate oxygen delivery and consumption. This means that the information on cardiac output and its components is necessary in intensive care and critical condition settings. This makes it necessary to carry out extended studies on the efficacy of patient management strategy, based on noninvasive evaluation of hemodynamics. In the same ESCAPE study it was concluded that reduced volume therapy regardless of the preload monitoring type (with or without РАС) considerably improved condition of the patients with cardiac failure. The main discussion in the above studies was about the evaluation of heart filling. According to Frank-Starling law of the heart, the end-diastolic length of muscle fibers defines the force of cardiac muscle contraction. The increase in cardiac output volume induced by increased transmural filling pressure is an important adaptive mechanism of normal heart function, providing adaptation to changed venous backflow. In cardiac failure the Starling curve becomes more flat, because the ventricle becomes less sensitive to preload, i. e. equivalent cardiac output can be achieved with higher filling pressures. However, higher heart filling pressure results in altered myocardial perfusion or congestion in pulmonary circulation loop, up to pulmonary eodema in the most severe cases. The results we obtained demonstrate that the use of the most frequent indicator for preload evaluation - the CVP - is disputable; also the preload cannot be unambiguously evaluated by PAmP or PAWP, because right heart and left heart preloads are not the same. According to Harris L.M., 1997, and Maynar J., 2005, these pressures have limited clinical relevance, affected by a range of such factors, as heart and patient positioning, venous capacity, heart ventricle compliance, heart valves function, pulmonary pressure, as well as lung ventilation volume and mode. Moreover, evaluation of circulating volume should be done before administering vasopressors. Another way to evaluate heart filling is to measure the duration of systolic blood flow in descending thoracic aorta (Singer M., 1989; Vallee F., 2005; Monnet X, 2005). Randomized study of McKendry M., 2004, demonstrated that patients, in whom postoperative volume substitution was carried out according to ED-method guided protocol, had considerably shorter duration of stay in a hospital. It is difficult to prove whether static (absolute) duration of systolic blood flow in descending aorta is dependent or independent part of the volume as per Frank-Starling law of the heart. Recent Monett X., 2005, report proved the opposite, i. e. adjusted duration of flow is a poor indicator of volume deficite. In similar studies, but in different physiological settings, Leather H.A. and Wouters F.F., 2001, clearly demonstrated that epidural anesthesia-induced redistribution of circulation increased the difference between ED and TD values. Based on these studies, the authors concluded that the ED method is possibly not the right one to analyze absolute values of heart filling and cardiac function. After having reviewed the results of the aforementioned studies and compared those to our own results we concluded that contradictory results of different studies could be associated with detecting the diameter of the aorta by nomograms, not by actual measurements. In our study we used ED method with M-mode signal in addition to Doppler signal, Which allowed us to detect diameter of aorta in every systole. A range of other studies (Wakeling H.G., 2005; Tan H.L., 2005), as well as our one, proved that dynamic monitoring of heart rate adjusted duration of Doppler-flow is a good preload indicator. The other most frequently evaluated worldwide indicator in patients having unstable hemodynamics is cardiac output, which is measured in different ways (pulse contour analysis, transpulmonary, lithium dilution, thermodilution, echodoppler, transthoracic electrical bioimpedance, etc.). Each of the methods have its own advantages in different clinical situations. In order to develop clinically safe and relevant method of patient cardiac function monitoring during off-pump myocardial revascularization surgery, we used both TD and ED to measure and compare changes in cardiac function during revascularization of different myocardial zones. We found that cardiac output values were virtually the same in stable hemodynamic conditions (t1 r = 0,7; p = 0,001; t5 r = 0,82; p = 0,001), but reliably different in altered hemodynamics (r = 0,34; p = 0,032), which can be explained by peculiarities of each of the methods - different location of measurement, time to obtaining the value and concomitant factors. The same results were demonstrated in Valtier В., 1998, Singer M, 1989, and Bein В. studies in ICU patients, as well as in Hullett В., 2003, study in OPCAB patients. TD CI value is being measured automatically every 2 minutes by thermodilution catheter, placed in right ventricle. The proximal part of the thermodilution circuit imitates heat signal at a constant rate, while the distal part senses the temperature difference, influenced by right ventricular blood flow velocity and direction, as well as by blood temperature. That is why CI evaluation by TD method requires consideration of temperature of injecte dvolume, injection velocity and patient own temperature fluctuations. The above factors may influence the thermodilution curve (Lichtenthal P.R., 1983) and, correspondingly, the CI absolute value (Section 3.2.3., Table 3.3.)- Despite the use of heating devices and warming of infusions 53% of the patients, involved in our study, had bode temperature decreased below 36,0°C (mean temperature at the beginning of the surgery was 36,5 °C ± 0,48 °C, but at the end of the surgery it was 35,8 °C with SD = 0,78 °C). Decreased tissue temperature during surgery may cause hemodynamic alterations, heart arrhytmias, changed blood viscosity and excessive bleeding (Fig. 8.16). Patients with lower tissue temperature during surgery had postoperative shivering in ICU, followed (in 1.5 hours) by hyperthermia over 38,3 °C (14 patients), which causes higher oxygen demand while oxygen supply is limited. ED CO is less influenced by external factors (temperature, ventilation volume), but more influenced by cardiac function and precise location of the probe (Monnet X., 2006). ED-derived direct measurement is aortic blood flow (ABF) in descending thoracic aorta, which means that ED probe measures ABF, not the CO. ABF is always less than CO, because part of the stroke volume gets to the vessels of the aortic arch. Although this volume varies and depends on the circulatory status and concomitant diseases of the patient, ABF mostly is 70% of CO (Boulnois J.G., 2000). Blood flow velocity, acceleration and duration is being measured by ED every systole (while by TD method - every two minutes), so measurement trends (Royse A.G., 2003) may early reveal systolic dysfunction of left ventricle. Still some factors may influence the CO measurements: • It is assumed that descending aorta is a cylinder, although its actual anatomy may be different depending on the pulse pressure and aortic compliance; • Aortic blood flow is assumed to be laminar, although tachycardia, anaemia and aortic valve lesions may cause turbulent flow (Chaney J.C, 2002); • For precise measurement the Doppler ray shoud be directed transversely to blood flow or with the deviation of less than 20° (Oh J.K., 1999); • Red blood cells velocity is higher in the centre of aortic lumen than at the aortic wall; • CI deriving from aortic blood flow is done with an assumption that 30% of stroke volume is distributed to brachiocephalic and coronary arteries. However, this figure depends on patient circulation and concomitant diseases (Boulnois J.L., 2000); • It is assumed that diastolic blood flow in descending aorta is negligible. Unstable hemodynamics is associated with redistribution of circulation, primarily with decreased blood flow in abdominal organs, which blood supply is determined by blood flow in descending aorta, that is why flowmetry in decscending aorta is helpful in understanding physiological alterations of circulation. Published reports on ED and TD comparative analysis have considerably discrepant results. Correlation coefficient value varies from r - 0,52 (Schmid E. R., 1993) to r = 0,98 (Lavandier В., 1988; MarkJ.B., 1986; Perrino A.C., 1990). Schmid E.R., et al. 2003, consider the reason of the discrepant results to be non-uniform and small involved patient populations, different statistical analyses, different protocols of the studies, as well as different requirements for accuracy of both studied and reference methods, or even commercial interest. In his studies, comparing different methods, Critchley L.A.H..1999, calculated combined measurement error (20% in each of the methods) and concluded that it shoud not exceed 30%. Sure, comparative analysis of the two methods should take into account also standard deviation, which in "ideal" case is to be 0 L/min (Bland M.J., Altman D.G., 1986). In his study Dummler R. et al, 2000, found conformity of the obtained values, but calculated combined measurement error happened to be 44%. In out study this value was 36%. Several studies mark out clinical relevancy of ED method, noting improved patient recovery in case the therapy was guided according to results, derived byED method. Although the ED method cannot completely replace the TD method, it can offer instant, accurate enough and noninvasive CO evaluation during OPCAB. Conclusions 1. Revascularization of any of myocardial zones by off-pump CABG is followed by hemodynamic alterations. 2. Right ventricle disfunction prevails during revascularization of left ventricle anterior, lateral and inferior walls. 3. Cardiac output values, monitored by invasive and semi-invasive methods, do not considerably differ in stable hemodynamic status (r = 0,9; p < 0,001), but are reliably different (p < 0,005) in altered hemodynamic (LV posterior and lateral wall revascularization). 4. Our study evidences that semi-invasive cardiac output monitoring by echo- doppler during off-pump myocardial revascularization surgery is alternative, safe and informative method of detection of ischaemia-induced left ventricle systolic disfunction during left coronary artery grafting. Practical recommendations 1. Due to heart transposition and heart electrical axis displacement it is impossible to detect decrease in myocardial circulation with following systolic dysfunction neother by ECG nor by TEE and TD РАС. We may recommend in this instance to use ED method to evaluate preload and systolic function of the heart. 2. After summarizing the information on evaluation of cardiac function and circulatory alterations using invasive and semi-invasive methods during OPCAB myocardial revascularization surgery we may recommend eosophageal echo-doppler for semi-invasive cardiac output monitoring as alternative, safe and informative method of evaluation of left ventricle systolic dysfunction during left coronary artery grafting. 3. We recommend to use ED method during OPCAB revascularization surgery: • As separate method or combined with TD РАС; • To measure CO in all of the patients with left coronary artery lesion; • To measure preload; • To detect circulatory alterations; • To help select patients for invasive cardiac monitoring using РАС. 4. ED method is not applicable during OPCAB surgery in the event that oxygen supply and consumption is to be assessed.
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posted: | 3/23/2011 |
language: | English |
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text: His dad, novelist Larry McMurtry, bought him his first guitar when he was 7, and his mother, an English professor, taught him how to play it, but even so, the acorn resides close to the tree. James McMurtry's country-tinged roots rock is keyed to his facility with words, his insights into the human heart and the short-story economy with which he delivers them. Sonically, the folk-blues shuffles and bar-rock balladeering McMurtry relies on aren't particularly inventive but are redeemed largely by the dint of his storytelling gift. In fact, the nondescript style dovetails with McMurtry's deadpan, observational lyrics and speak-sung croon (reminiscent of Warren Zevon) to create the easygoing air of a grizzled storyteller sharing age-old wisdom around the campfire.


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Game Questions & Answers (Q&A) service lets you ask questions about video games for game consoles or PC games. So ask your God Eater Burst question for PSP and get answers from real gamers or answer questions and share your insights and experience with the rest of the gaming community.
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What is the next upgrade for voltaic chainsaw ii
Pls. i need help i need to upgrade my voltaic chainsaw ii coz i need to defeat 1 vajra.it says its weakness is divine and i need to upgrade it. what do i need to upgrade it?
Answer from: itachi
Equip an death scythe or hell scythe, is a better divine weapon
Answer from: prophecy
Hey, its aesy to kill juz 1 vajra... juz strike at its tail...
Answer from: ping pong
At that part you can only get a scythe with a 90 sunder plus 44 divine attack, its easy to defeat a single vajra without much heal pots used. i only do r2+triangle (works for me, i already have the tigris weapon,gun and shield by doing that dont know about how others do it and i dont dispute with results) oh and the yang shield (i think its the correct name) helps with the auto-guard and all + upgrades like spark def. and sunder+ attack. party healer helps a lot.
Answer from: LINDOW
If you have any weapon with these elements use them against the vajra fire/ice/divine
p.s. you need to obtain these items to upgrade your volcanic chainsaw ll
list of materials :
1. king armor +
2. king grease
3. mithril silver
4. vermilion
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Data on the Region and on 21 countries are compiled in Excel charts embedded within a PowerPoint PDF presentation, first by Region and then by countries (listed alphabetically, with bookmarks to each of the 22 sections). There are six slides per country (according to data available), including (1) populations at risk, (2) malaria morbidity, (3) malariometric indices (API, AFI, AVI), (4) malaria microscopy, (5) slide positivity rate (SPR), and (6) malaria mortality. (13/Sep/2008)
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In 1999, there were 818 million people living in the Region of the Americas. Of these, 299 million (36.5%) were living in areas where ecological conditions were propitious for the transmission of malaria. Of the 35 countries and territories that are members of PAHO/WHO, 21 report areas with active malaria transmission.
Click here to access to Malaria Surveillance Data.
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Train on plenty of hills before this race. There is only one small section that is even close to being flat. First two miles are uphill. Temperature changes because parts of the course are totally exposed to the wind/sun and other areas are covered by forest. Much more challenging than the Big Sur International Marathon course.
This was the most relaxed and quiet marathon, yet. I loved every pace. Not to be confused with the Big Sur International - this is a much smaller event. HINTS: CAMP! Stay close the start and you don't have to scramble for parking... and it's the coolest way to stay in Big Sur. (Andrew Molera is the starting line and is also a camp ground - it's also only a few bucks.) 1. Bring your own H2O and nutrition. You are alone on the trail. 2. Depend on getting dirty - it's muddy and I had filthy fingernails from some of the climbs. 3. Bring a small digital camera - the view from the top is the best it gets... and let youself stop to really look. Everyone does. You witness a view that only a runner can (or courageous mountain biker), as the trails are single track to the top. It's bitchin'. 4. Have dinner at the lodge at the state camp ground a couple miles down the road. It is REALLY good! The salmon is divine, and a perfect post-race meal. They also make THE BEST home-made granola and yogurt. Or, maybe I was just really hungry after the HARDEST RACE I'VE EVER RUN! PS - My dog did the first loop in 1:45! His PR. (Then he went off to sleep and wait for me. Good boy.)
This was my first marathon, and I loved it! The course was absolutely beautiful! Because it was an out-and-back course, I knew what to anticipate during the second half of the run, so I was mentally prepared for whatever showed up. The spectators are sparse, but what do you expect from trail? The water stations were staffed w/ the best volunteers ever--everyone (volunteers and runners) was so nice. Be prepared for hills, but the uphill is worth it. You'll see the most incredible views! And remember--what goes up must go down--all those uphills will be downhills when you return and vice versa. I'll definitely return next year!
No first timers on this one. Excellent planning and spectacular views, but sparse crowd support due to the isolation. No locals. All serious and very quiet runners. Although it was beautiful, it was not fun. Miles 8-12 are a 2000 ft hit with no break.
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Touring - Three Speed Touring
Bikeforums.net is a forum about nothing but bikes. Our community can help you find information about hard-to-find and localized information like bicycle tours, specialties like where in your area to have your recumbent bike serviced, or what are the best bicycle tires and seats for the activities you use your bike for.
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Three Speed Touring
Anyone here do any touring on English 3 speeds? If so, tell me what you ride, how your bike is set up (different gearing) and what type of gear you like to use.
I don't, but I have seen people who do. They did not seem at all bothered by the lack of gears. I imagine they walked up the steep hills, but so what? I have walked up more than a few inclines, and I have 27 gears.
Both were riding old bicycles that did not fit their bodies, with under-inflated tires. Gear shifting on one of the bikes was iffy. Nevertheless, riding three-speed bikes seemed to be less relevant than the fact that they were seeing and riding through beautiful countryside.
This may be of interest.
I think it's important to have the proper gearing for a three speed. If you're using a hybrid with 700 wheels, then an 18T cog and a small 35T chain ring will give you a fairly low gear for light touring.
71 inch ----- 3rd gear
53 inch ------ 2nd gear
40 inch------ 1st gear.
I've ridden several short day legs (40 kms or so) on a 3-speed step-through-frame bike with a front basket. The bikes also had ueber crappy bottle generators with halogen lights, and we really needed the lights on a couple of occasions. All in all, they were definitely NOT something I'd choose for any kind of mileage, but the rental company didn't have much offerings.
It was refreshing to be reminded that none of that really matters. We enjoyed the trip immensely and the bikes served us well as our only means of transportation. The only thing I really missed was lower gearing, we had to walk the bikes every now and then. I don't mind running out of gears in a downhill.
I haven't done any real touring on it, but I've taken my '63 Phillips on several 40-mile runs and wouldn't hesitate to do it again. I lightened it up a bit by stripping off some of the heavy steel bits, and was planning to add alloy rims, but I've since found a Raleigh Super Course that will be getting the three speed treatment and replacing the Phillips.
Define 3 speed....:innocent:
I do short tours on my Superbe and my Twenty, only modifications that I would consider a requirement would be to upgrade the brakes and to swap the rear cog out for something a bit more suitable.
My Twenty is currently running a 44/15 my Superbe a 46/22. I have done a double cog deal on the back of the Superbe in the past. IIRC you can run a 4 tooth difference and not have to lengthen or shorten the chain. You remove the spacers and put the dished cogs back to back. When you need to change gears, you stop, loosen the wheel, move the chain over, adjust the gear cable tension and go on your merry way. I have also carried different cogs and spare chain but never bothered to use them. I do walk a few hills but I look at that as a chance to give my rear a rest and use a different set of leg muscles.
By gear I assume you mean equipment for cooking and sleeping? I use a Carradice Nelson (http://www.carradice.co.uk/index.php?page_id=product&under=type&product_id=38) saddle bag with an alcohol stove, single pot and a few other necessary items. Tent and sleeping bag are strapped on the rack.
My tours are typically S24O's, mileage is around 35 or so each way. My wife and I have done one 3 day tour via B&B's and only carried the basics in clothing.
Aaron :)
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