title: Depletion of plasma vitamin C but not of vitamin E in response to cardiac operations. Intravenous ascorbic acid infusion improves myocardial perfusion grade during elective percutaneous coronary intervention: relationship with oxidative stress markers. Perioperative supplementation with ascorbic acid does not prevent atrial fibrillation in coronary artery bypass graft patients. Impact of Vitamin C Supplementation on Post-Cardiac Surgery ICU and Hospital Length of Stay Effect of oral vitamin C on atrial fibrillation development after isolated coronary artery bypass grafting surgery: A prospective randomized clinical trial. Reduction of resuscitation fluid volumes in severely burned patients using ascorbic acid administration: a randomized, prospective study. Ascorbate Attenuates Atrial Pacing-Induced Peroxynitrite Formation and Electrical Remodeling and Decreases the Incidence of Postoperative Atrial Fibrillation Vitamin C Pharmacokinetics: Implications for Oral and Intravenous Use The role of ascorbic acid in the prevention of atrial fibrillation after elective on-pump myocardial revascularization surgery: a single-center experience--a pilot study. Efficacy of Combination Therapy of Statin and Vitamin C in Comparison with Statin in the Prevention of Post-CABG Atrial Fibrillation. The protective effects of high-dose ascorbic acid on myocardium against reperfusion injury during and after cardiopulmonary bypass. Oral vitamin C administration reduces early recurrence rates after electrical cardioversion of persistent atrial fibrillation and attenuates associated inflammation. Influence of intravenous vitamin E supplementation in cardiac surgery on oxidative stress: a double-blinded, randomized, controlled study. The effect of intravenous vitamin C infusion on periprocedural myocardial injury for patients undergoing elective percutaneous coronary intervention. Biochemical and hemodynamic effects of ascorbic acid and alpha-tocopherol in coronary artery surgery Perioperative ascorbic acid supplementation does not reduce the incidence of postoperative atrial fibrillation in on-pump coronary artery bypass graft patients. Oral ascorbic acid in combination with beta-blockers is more effective than beta-blockers alone in the prevention of atrial fibrillation after coronary artery bypass grafting. Effect of ascorbic acid on inflammatory markers after cardiothoracic surgery.
abstract: The whole-body inflammatory response produced by cardiopulmonary bypass is an important cause of perioperative morbidity after cardiac operations . This inflammatory response produces reactive oxygen species and other cytotoxic substances , such as the cytokines . The generation of reactive oxygen species might deplete principal antioxidant micronutrients , that is , vitamins C and E and the carotenoids . Therefore , we have investigated the time course of the plasma concentrations of vitamins C and E and the carotenoids in 18 patients undergoing coronary bypass operations after r and omization for previous vitamin E supplementation ( 300 mg dl-alpha-acetyl-tocopherol 3 times daily for 4 weeks ) or placebo .  Supplementation with alpha-tocopherol doubled the lipid-st and ardized plasma vitamin E concentration to 63.7 + /- 14.5 mumol/L when compared with that of the control subjects ( 31.2 + /- 9.0 mumol/L ) before the operation . The plasma concentrations of vitamin C ( 36.0 + /- 19.0 mumol/L and 44.0 + /- 21.7 mumol/L , respectively ) and of the carotenoids were not statistically different between the two groups at baseline . The absolute plasma concentrations of both vitamin E and the carotenoids decreased during and after cardiopulmonary bypass , but after correction for hemodilution the plasma concentrations of vitamin E and the carotenoids showed no decrease . The vitamin E concentrations in the erythrocytes did not change either . In contrast , the plasma concentration of vitamin C decreased in all subjects within 24 hours after the operation by roughly 70 % . Correction for hemodilution still revealed a significant decrease in plasma vitamin C that persisted in most patients up to 2 weeks . In conclusion , the vitamin E and the carotenoid plasma concentrations are of no major concern during and after cardiac operations . In contrast , the serious depletion of vitamin C may deteriorate the defense against reactive oxygen species-induced injury during cardiac operations OBJECTIVES Our goal was to explore whether antioxidant vitamin C infusion is able to affect the microcirculation perfusion in patients undergoing elective percutaneous coronary intervention for stable angina . BACKGROUND Periprocedural myocardial injury in the setting of elective percutaneous coronary intervention is associated with increased risk of death , recurrent infa rct ion , and revascularization at follow-up . Despite excellent epicardial blood flow , impaired microcirculatory reperfusion may persist and increases the risk of vascular recurrences . Post-percutaneous coronary intervention induced-oxidative stress is one of the potential mechanisms accounting for impaired perfusion . METHODS Fifty-six patients were enrolled in a prospect i ve , single-center , r and omized study comparing 1 g vitamin C infusion ( 16.6 mg/min , over 1 h before percutaneous coronary intervention ) versus placebo . RESULTS At the baseline , Thrombolysis In Myocardial Infa rct ion ( TIMI ) myocardial perfusion grade < 2 was observed in 89 % and in 86 % of patients r and omized to the placebo or vitamin C infusion group , respectively ( p > 0.05 ) . After percutaneous coronary intervention , these percentages decreased in the placebo group ( 32 % ) and in greater measure in the vitamin C group ( 4 % , p < 0.01 ) . Complete microcirculatory reperfusion ( TIMI myocardial perfusion grade = 3 ) was achieved in 79 % of the vitamin C-treated group compared with 39 % of the placebo group ( p < 0.01 ) ; 8-hydroxy-2-deoxyguanosine ( p < 0.002 ) and 8-iso-prostagl and in F(2alpha ) ( p < 0.02 ) plasma levels significantly increased in the placebo group while they were significantly reduced in the vitamin C-treated group ( p < 0.0001 ) . TIMI myocardial perfusion grade changes from the baseline showed significant correlation with 8-hydroxy-2-deoxyguanosine ( p < 0.006 ) or 8-iso-prostagl and in F(2alpha ) ( p < 0.01 ) plasma levels changes . CONCLUSIONS In patients undergoing elective percutaneous coronary intervention , impaired microcirculatory reperfusion is improved by vitamin C infusion suggesting that oxidative stress is implicated in such a phenomenon BACKGROUND Atrial fibrillation occurs after approximately 25 % to 45 % of coronary artery bypass graft ( CABG ) surgeries . Oxidative stress and related electrophysiological remodeling has been proposed as a potential cause of this atrial fibrillation . Perioperative supplementation of the antioxidant ascorbic acid has been evaluated as a preventive agent . The current investigation was conducted to evaluate the efficacy of ascorbic acid in reducing atrial fibrillation  in CABG patients . METHODS A prospect i ve , r and omized , placebo-controlled , triple-blind , single-institution study was conducted in nonemergency CABG patients . Subjects were monitored for episodes of arrhythmia and other complications . RESULTS Eighty-nine treatment and 96 control subjects completed the study protocol . Demographics , comorbidities , and preoperative drugs were similar between groups . Surgical characteristics and postoperative medication use also were similar . The incidence of atrial fibrillation was 30.3 % in the treatment group and 30.2 % in the control group ( P = .985 ) . No difference was found in postoperative complications or mortality . CONCLUSIONS Our data indicate that supplementation of ascorbic acid in addition to routine postoperative care does not reduce atrial fibrillation after coronary artery bypass grafting Background : Prolonged intensive care unit ( ICU ) and hospital stay after cardiac surgery is vitally important and is influenced by both intraoperative and postoperative factors . Objectives : This r and omized clinical trial study was design ed to assess whether vitamin C supplementation could reduce the length of ICU and hospital stay in post-cardiac surgery patients . Patients and Methods : Two hundred and ninety patients scheduled for adult cardiac surgery including coronary , valve and congenital operations were r and omized into two groups : an intervention group , who received 2 g of vitamin C ( ascorbic acid ) intravenously , immediately before surgery in the operating theatre , followed by 1 g daily oral doses for the first 4 postoperative days ; and a placebo group , who received an equal number of identical tablets in the same shape and size . Results : Hospital length of stay was significantly different between the two groups ( 10.17 ± 4.63 days in the intervention group vs. 12 ± 4.51 days in the placebo group ; P = 0.01 ) , while there was no significant difference in the ICU stay between the groups ( 3.42 ± 1.06 days in intervention group vs. 3.43 ± 1.09 days in the placebo group ; P = 0.88 ) . There were significant differences in the intubation time and the drainage volume in the ICU and the first 24 postoperative hours between the two groups ( P for both = 0.003 ) . Conclusions : Vitamin C can decrease the length of hospital stay , drainage volume in the ICU and in the first 24 postoperative hours , intubation time and some complications in patients after cardiac surgery ; perhaps by decreasing inflammatory factors BACKGROUND Some evidence s have shown the role of antioxidant vitamins in preventing  atrial fibrillation ( AF ) after coronary artery bypass grafting ( CABG ) surgery . We sought to determine the effect of oral vitamin C on the incidence of postoperative AF in patients undergoing elective isolated on-pump CABG surgery . METHODS One-hundred patients who underwent isolated CABG surgery  were prospect ively assigned into two groups : Group 1 - 50 patients received 2 g of oral vitamin C before and 500 mg twice daily lasting for 5 days after surgery ; Group 2 - 50 patients as the control group did not receive any . All patients were continuously monitored after surgery in the intensive careunit ( ICU ) , and then Holter monitoring was implemented for 72 h. RESULTS The mean of patients ' age was 61.31 ± 6.42 years . Postoperative AF occurred in 16 and 4 patients in control and treatment groups , respectively ( 32 % vs. 8 % , p = 0.003 ) . The ICU stay was 1.79 ± 0.313 and 2.10 ± 0.61 days for vitamin C and control groups , respectively ( p = 0.002 ) . The hospital stay was significantly lower in vitamin C group compared with that of the control group ( 5.32 ± 0.59 vs. 5.74 ± 1.30 days , respectively , p = 0.041 ) . Baseline erythrocyte sedimentation rate ( OR 1.030 , 95 % CI 1.003 - 1.058 , p = 0.030 ) and taking vitamin C ( OR 8.068 , 95 % CI 1.783 - 36.517 , p = 0.007 ) were the independent predictors of postoperative AF . CONCLUSIONS Oral vitamin C can be safely used to decrease the incidence of postoperative AF in patients undergoing elective isolated on-pump CABG surgery HYPOTHESIS High-dose ascorbic acid ( vitamin C ) therapy ( 66 mg/kg per hour ) attenuates postburn lipid peroxidation , resuscitation fluid volume requirements , and edema generation in severely burned patients . STUDY DESIGN AND SETTING A prospect i ve , r and omized study at a university trauma and critical care center in Japan . SUBJECTS AND METHODS Thirty-seven patients with burns over more than 30 % of their total body surface area ( TBSA ) hospitalized within 2 hours after injury were r and omly divided into ascorbic acid and control groups . Fluid resuscitation was performed using Ringer lactate solution to maintain stable hemodynamic measurements and adequate urine output ( 0.5 - 1.0 ml/kg per hour ) . In the ascorbic acid group ( n = 19 ; mean burn size , 63 % + /- 26 % TBSA ; mean burn index , 57 + /- 26 ; inhalation injury , 15/ 19 ) , ascorbic acid was infused during the initial 24-hour study period . In the control group ( n = 18 ; mean burn size , 53 % + /- 17 % TBSA ; mean burn index , 47 + /- 13 ; inhalation injury , 12/18 ) , no ascorbic acid was infused . We compared hemodynamic and respiratory measurements , lipid peroxidation , and fluid balance for 96 hours after injury . Two-way analysis of variance and Tukey test were used to analyze the data . RESULTS Heart rate , mean arterial pressure , central venous pressure , arterial pH , base deficit , and urine outputs were equivalent in both groups . The 24-hour total fluid infusion volumes in the control and ascorbic acid groups were 5.5 + /- 3.1 and 3.0 + /- 1.7 mL/kg per percentage of burn area , respectively ( P<.01 ) . In the first 24 hours , the ascorbic acid group gained 9.2 % + /- 8.2 % of pretreatment weight ; controls , 17.8 % + /- 6.9 % . Burned tissue water content was 6.1 + /- 1.8 vs 2.6 + /- 1.7 mL/g of dry weight in the control and ascorbic acid groups , respectively ( P<.01 ) . Fluid retention in the second 24 hours was also significantly reduced in the ascorbic acid group . In the control group , the ratio of PaO2 to fraction of inspired oxygen at 18 , 24 , 36 , 48 , and 72 hours after injury was less than that of the ascorbic acid group ( P<.01 ) . The length of mechanical ventilation in the control and ascorbic acid groups was 21.3 + /- 15.6 and 12.1 + /- 8.8 days , respectively ( P<.05 ) . Serum malondialdehyde levels were lower in the ascorbic acid group at 18 , 24 , and 36 hours after injury ( P<.05 ) . CONCLUSIONS Adjuvant administration of high-dose ascorbic acid during the first 24 hours after thermal injury significantly reduces resuscitation fluid volume requirements , body weight gain , and wound edema . A reduction in the severity of respiratory dysfunction was also apparent in these patients Atrial fibrillation ( AF ) , the most common chronic arrhythmia , increases the risk of stroke and is an independent predictor of mortality . Available pharmacological treatments have limited efficacy . Once initiated , AF tends to self-perpetuate , owing in part to electrophysiological remodeling in the atria ; however , the fundamental mechanisms underlying this process are still unclear . We have recently demonstrated that chronic human AF is associated with increased atrial oxidative stress and peroxynitrite formation ; we have now tested the hypothesis that these events participate in both pacing-induced atrial electrophysiological remodeling and in the occurrence of AF following  cardiac surgery . In chronically instrumented dogs , we found that rapid ( 400 min−1 ) atrial pacing was associated with attenuation of the atrial effective refractory period ( ERP ) . Treatment with ascorbate , an antioxidant and peroxynitrite decomposition catalyst , did not directly modify the ERP , but attenuated the pacing-induced atrial ERP shortening following 24 to 48 hours of pacing . Biochemical studies revealed that pacing was associated with decreased tissue ascorbate levels and increased protein nitration ( a biomarker of peroxynitrite formation ) . Oral ascorbate supplementation attenuated both of these changes . To evaluate the clinical significance of these observations , supplemental ascorbate was given to 43 patients before , and for 5 days following , cardiac bypass graft surgery . Patients receiving ascorbate had a 16.3 % incidence of postoperative AF , compared with 34.9 % in control subjects . In combination , these studies suggest that oxidative stress underlies early atrial electrophysiological remodeling and offer novel insight into the etiology and potential treatment of an enigmatic and difficult to control arrhythmia . The full text of this article is available at http://www.circresaha.org Context Clinical studies of vitamin C as a potential anticancer agent have produced inconsistent results despite in vitro evidence that high concentrations kill cancer cells . Contribution Pharmacokinetic studies in healthy persons , using a depletion-repletion design , show that intravenous administration can achieve 70-fold higher blood levels of vitamin C than the highest tolerated oral dose . Caution s Although this study provides better underst and ing of the pharmacokinetic issues involved in research on vitamin C , it provides no evidence that vitamin C has any effect on cancer cells and can not be used to support its clinical use for therapeutic purpose s. The Editors Vitamin C in gram doses is taken orally by many people and administered intravenously by complementary and alternative medicine practitioners to treat patients with advanced cancer ( 1 , 2 ) . After oral intake ,  vitamin C plasma concentrations are tightly controlled at 70 to 85 mol/L for amounts ( as much as 300 mg daily ) that can be obtained from food ( 3 , 4 ) . However , concentrations achieved by higher pharmacologic doses are uncertain . Despite poor rationale , vitamin C in gram doses was proposed as an anticancer agent decades ago ( 5 ) . Unblinded studies with retrospective or nonr and om controls reported clinical benefit from oral and intravenous vitamin C administered to patients with terminal cancer at a dosage of 10 g daily ( 1 , 6 , 7 ) . Placebo-controlled trials in patients with cancer reported no benefit from oral vitamin C at a dosage of 10 g daily ( 8 , 9 ) , and vitamin C treatment was judged ineffective ( 10 ) . However , in vitro evidence showed that vitamin C  killed cancer cells at extracellular concentrations higher than 1000 mol/L ( 11 , 12 ) , and its clinical use by some practitioners continues . We recognized that oral or intravenous routes could produce substantially different vitamin C concentrations ( 13 ) . We report here that intravenous doses can produce plasma concentrations 30- to 70-fold higher than the maximum tolerated oral doses . These data suggest that the role of vitamin C in cancer treatment should be reexamined , and insights from vitamin C pharmacokinetics can guide its clinical use . Methods Pharmacokinetic Studies in Healthy Persons The study was approved by the Institutional Review Board of the National Institute of Diabetes and Digestive and Kidney Diseases , National Institutes of Health . After we obtained written informed consent , 17 healthy volunteers ( 7 men , 10 women ; age , 19 to 27 years ) were studied as in patients by using a depletion-repletion study design ( 3 , 4 ) . Participants were hospitalized for 3 to 6 months and consumed a  vitamin C-deficient  diet containing less than 0.005 g of vitamin C per day . At plasma vitamin C concentrations less than 8 mol/L , persons were depleted without signs of scurvy . Vitamin C , 0.015 g twice daily , was then administered orally until participants achieved a steady state for this dose ( 0.03 g daily ) . Participants received successive oral daily vitamin C doses of 0.03 g , 0.06 g , 0.1 g , 0.2 g , 0.4 g , 1.0 g , and 2.5 g until a steady state was achieved for each dose . Bioavailability sampling was conducted at a steady state for vitamin C doses of 0.015 g , 0.03 g , 0.05 g , 0.1 g , 0.2 g , 0.5 g , and 1.25 g. For each bioavailability sampling , vitamin C was administered in the fasting state . After oral administration , blood sample s were collected at 0 , 15 , and 30 minutes and at 1 , 1.5 , 2 , 2.5 , 3 , 3.5 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 19 , 22 , and 24 hours ( 3 , 4 ) . After intravenous administration at 250 mg/min , blood sample s were collected at 0 , 2.5 , 5 , 10 , 15 , and 30 minutes and at 1 , 1.5 , 2 , 2.5 , 3 , 3.5 , 4 , 5 , 6 , 7 , 8 , 9 , and 10 hours . Data obtained from bioavailability samplings were used to determine peak plasma and urine vitamin C concentrations . Pharmacokinetic Modeling We used data from 7 men to construct a unique 3-compartment vitamin C pharmacokinetic model with parameters describing saturable absorption , tissue distribution , and renal excretion and reabsorption ( 14 ) . This model was used to predict peak plasma and urine vitamin C concentrations attained when pharmacologic doses of the vitamin are administered . For intravenous administration , it was assumed that vitamin C was infused at a rate of 1 g/min , and urine output was 100 mL/h . Vitamin C Assay Vitamin C was measured by using high-performance liquid chromatography with coulometric electrochemical detection ( 3 , 4 , 15 ) . Statistical Analysis We compared plasma vitamin C concentration curves ( against either dose or time ) by repeated- measures analyses of variance ( ANOVA ) . In addition to the repeating factor ( dose or time ) , other factors considered were sex and route of administration . In the comparison of routes of administration at multiple doses , in which sex not only was an important factor itself but also had an important interaction with route , separate ANOVA were determined for men and women to assess the importance of route of administration . Analyses were performed by using Data Desk , version 5 ( 1995 ) ( Data Description , Inc. , Ithaca , New York ) . Role of the Funding Source The funding source had no role in the design , conduct , and reporting of the study or in the decision to su bmi t the manuscript for publication . Results When 1.25 g of vitamin C was given intravenously , plasma concentrations were significantly higher than when the vitamin was given orally ( P < 0.001 by repeated- measures ANOVA ) ( Figure 1 ) . In addition , plasma concentrations were significantly higher over all doses ( P < 0.001 by repeated- measures ANOVA ) with intravenous compared with oral administration ( Figure 1 , inset ) . At the highest dose of 1.25 g , mean peak values from intravenous administration were 6.6-fold higher than mean peak values from oral administration . When all doses were considered , peak plasma vitamin C concentrations increased with increasing intravenous doses , whereas peak plasma vitamin C concentrations seemed to plateau with increasing oral doses . Urine vitamin C concentrations were higher for the same dose given intravenously compared with that administered by the oral route . At the highest dose of 1.25 g , peak urine concentrations from intravenous administration were approximately 3.5 times higher than from oral administration ( data not shown ) . Figure 1 . Plasma vitamin C concentrations in healthy volunteers after intravenous or oral administration of vitamin C. Inset : The 3-compartment vitamin C pharmacokinetic model that we developed predicted that a single oral dose of 3 g , the maximum tolerated single dose , produced a peak plasma concentration of 206 mol/L ( Figure 2 , top ) . Peak predicted concentration after a single 1.25-g oral dose was slightly lower at 187 mol/L. For 200 mg , an amount obtained from vitamin C-rich foods , peak predicted concentration was approximately 90 mol/L. Plasma concentrations for all of these amounts returned to steady-state values , approximately 70 to 85 mol/L , after 24 hours . With 3 g given orally every 4 hours , the maximum tolerable ( 6 ) , peak predicted plasma concentration was approximately 220 mol/L ( Figure 2 , top ) . By contrast , after intravenous administration , predicted peak plasma vitamin C concentrations were approximately 1760 mol/L for 3 g , 2870 mol/L for 5 g , 5580 mol/L for 10 g , 13 350 mol/L for 50 g , and 15 380 mol/L for 100 g ( Figure 2 , bottom ) . Doses of 60 g given intravenously are used for cancer treatment by complementary and alternative medicine practitioners ( 2 ) . Predicted peak urine vitamin C concentrations were as much as 140-fold higher after intravenous administration compared with oral administration ( data not shown ) . Figure 2 . Predicted plasma vitamin C concentrations in healthy persons after oral ( top ) or intravenous ( IV ) ( bottom ) administration of vitamin C. Discussion Our data show that vitamin C plasma concentrations are tightly controlled when the vitamin is taken orally , even at the highest tolerated amounts . By contrast , intravenous administration bypasses tight control and results in concentrations as much as 70-fold higher than those achieved by maximum oral consumption . Both findings have clinical relevance . Vitamin C oral supplements are among the most popular sold , and gram doses are promoted for preventing and treating the common cold , managing stress , and enhancing well-being ( 1 ) . Our data show that single supplement gram doses produce transient peak plasma concentrations that at most are 2- to 3-fold higher than those from vitamin C-rich foods ( 200 to 300 mg daily ) . In either case , plasma values return to similar steady-state concentrations in 24 hours . Because differences in plasma concentrations from supplements and from food intake are not large , supplements would be expected to confer little additional benefit , a finding supported by available evidence ( 16 , 17 ) . However , consumption of fruits and vegetables , which contain vitamin C , is beneficial for unknown reasons ( 16 , 17 ) . On the basis of current knowledge and the pharmacokinetics presented here , physicians should advise their patients to consume fruits and vegetables , not vitamin C supplements , to obtain potential benefits . Just as important , our data show that intravenous administration of vitamin C produces substantially higher plasma concentrations than can be achieved with oral administration of vitamin C. This difference was previously unrecognized and may have treatment implication s. Case series published by Cameron , Campbell , and Pauling ( l , 6 , 7 ) have been controversial . In these series , several hundred patients with terminal cancer treated with 10 g of vitamin C intravenously for 10 days and then 10 g orally indefinitely were compared with more than 1000 retrospective and prospect i ve controls . Patients treated with vitamin C  survived 150 to 300 days longer than controls ( 1 , 6 , 7 ) . Other research ers reported benefit consisting of increased survival , improved well-being , and reduced pain ( 1 ) . All of these Atrial fibrillation ( AF ) is a common arrhythmia that occurs postoperatively in cardiac surgery . There is evidence for the role of oxidative stress in the etiology of AF . In our study , we examined whether antioxidant ascorbic acid ( vitamin C ) , could help in the reduction of the incidence of postoperative AF . Patients who were scheduled to undergo elective isolated on-pump coronary artery bypass grafting ( CABG ) were included in our study . One hundred and seventy patients were r and omly divided in two groups : Group A ( n=85 ) received vitamin C preoperatively and postoperatively whereas Group B ( n=85 ) did not receive any ( control group ) . The incidence of AF was 44.7 % in the vitamin C group and 61.2 % in the control group ( P=0.041 ) . The hospitalization time , the intensive care unit stay and the time interval for the conversion of AF into sinus rhythm was significantly shorter in the vitamin C group . Patients that developed AF also had longer hospital length of stay ( 9.5±2.8 days vs. 6.7±1.9 , P=0.034 ) . Supplementation of vitamin C reduces the incidence of postCABG AF , and decreases the time needed for rhythm restoration and length of hospital stay PURPOSE Atrial fibrillation ( AF ) is the most frequent arrhythmia that follows coronary artery bypass graft ( CABG ) . Patients developing postoperative AF ( POAF ) have significantly higher mortality rates . The consistent prophylactic effectiveness of statins and vitamin C are well-accepted ; however , no evaluation on combined therapy has been performed . We aim ed at assessing the efficacy of combination therapy with statin and vitamin C in comparison with statin alone in the prevention of post CABG-AF . METHODS In a r and omized double blind clinical trial , 120 c and i date s of CABG were recruited in Tabriz Madani Educational Center in a 15-month period of time . Patients were r and omized into two groups of 60 receiving oral atorvastatin ( 40 mg ) plus oral vitamin C ( 2g/d operation day and 1g/d for five consequent days ) for intervention group and oral atorvastatin ( 40 mg ) for control group . Occurrence of post CABG AF was compared between the two groups . RESULTS There were 60 patients , 43 males and 17 females with a mean age of 61.0±11.5 ( 29 - 78 ) years , in the intervention group and sixty patients , 39 males and 21 females with a mean age of 60.5±11.3 ( 39 - 81 ) years , in the control group .  The post CABG AF occurred in 6 cases ( 10 % ) in the interventional group and 15 patients ( 25 % ) in the controls ( P=0.03 , odds ratio=0.33 , 95 % confidence interval 0.12 - 0.93 ) . CONCLUSION Based on our findings , combination prophylaxis against post CABG AF with oral atorvastatin plus vitamin C is significantly more effective than single oral atorvastatin The protective effects of high-dose ascorbic acid ( 250 mg/kg ) on the myocardium were observed in 85 patients undergoing Cardiopulmonary Bypass ( CPB ) .  The changes in serum Malonyldialdehyde ( MDA ) . Creatine Phosphokinase ( CPK ) , Creatine Phosphokinase isozyme ( CPK-MB ) and Lactic Dehydrogenase ( LDH ) in group B ( n = 45 , receiving ascorbic acid ) were lower ( p < 0.05 ) than in group A ( n = 40 , no ascorbic acid ) during and after CPB . The MDA remained at a higher level two days postoperatively ; CPK and CPK-MB , the sensitive and specific reflectors of myocardial injury , recovered very slowly in the control group ( A ) after the operation . The hearts in all the patients of group B resuscitated automatically intraoperatively while five cases ( 12.5 % ) needed defibrillation in group A. The cardiac index ( CI ) measured in ICU in group B was higher than in group A ( p < 0.05 ) . The patients needed shorter ICU and hospital stays in group B than in group A. The results indicate that ascorbic acid can act as a scavenger of free radicals to decrease the peroxidation of the lipids present in the cell membrane and remove the radicals to protect the myocardium from ischemia-reperfusion injury effectively during and after open-heart operation BACKGROUND Inflammation and oxidative stress have been recently implicated in the pathophysiology of atrial fibrillation ( AF ) . The aim of this study was to examine the potential benefit of vitamin C on the early recurrence rates and on inflammatory indices after successful cardioversion of persistent AF , as well as to investigate the time course of changes in these indices post-cardioversion . METHODS We prospect ively studied 44 consecutive patients after successful electrical cardioversion of persistent AF .  All patients received st and ard treatment and were r and omised in one to one fashion to either oral vitamin C administration or no additional therapy . We followed-up the patients for 7 days performing successive measurements of white blood cell ( WBC ) count , C-reactive protein ( CRP ) , fibrinogen , and ferritin levels . RESULTS One week after successful cardioversion , AF recurred in 4.5 % of patients in the vitamin C group and in 36.3 % of patients in the control group ( p=0.024 ) . Compared to baseline values , inflammatory indices decreased after cardioversion in patients receiving vitamin C but did not change significantly in the control group . A significant variance was found in the serial measurements of WBC counts ( F=5.86 , p=0.001 ) and of fibrinogen levels ( F=4.10 , p=0.0084 ) in the two groups . In the vitamin C group CRP levels were lower on the seventh day ( p<0.05 ) . CRP and fibrinogen levels were higher in patients who relapsed into AF compared to patients who maintained sinus rhythm ( F=2.77 , p=0.044 and F=3.51 , p=0.017 , respectively ) . CONCLUSIONS These findings suggest that vitamin C reduces the early recurrence rates after cardioversion of persistent AF and attenuates the associated low-level inflammation . These effects indicate that therapeutic approaches targeting at inflammation and oxidative stress may exert favourable effects on atrial electrical remodeling BACKGROUND I.V. infusions of vitamin E emulsion ( all-rac-alpha-tocopherol ) may reduce ischaemia-reperfusion injury after elective cardiac surgery . METHODS Forty patients participated in a prospect i ve , double-blind , placebo-controlled , r and omized trial , receiving either placebo or four doses ( 270 mg each ) of all-rac-alpha-tocopherol between 16 h before and 48 h after surgery . We determined plasma concentrations of vitamin E , vitamin C , malondialdehyde , creatine kinase , troponin I and interleukin 6 and other measures of clinical outcome . RESULTS Infusion of vitamin E caused normalization of vitamin E plasma concentrations during and after surgery , but had no effect on the early increase in malondialdehyde concentration or the decreases in antioxidative capacity and the water-soluble antioxidant vitamin C. CONCLUSIONS Normalization of plasma vitamin E concentrations with parenteral vitamin E emulsion does not affect biochemical markers of myocardial injury and does not affect clinical outcome after cardiac surgery BACKGROUND This small study has determined the effect of vitamin C on myocardial reperfusion in patients undergoing elective percutaneous coronary intervention ( PCI ) . This study was to explore whether antioxidant vitamin C infusion before the procedure is able to affect the incidence of periprocedural myocardial injury ( PMI ) in patients undergoing PCI . METHODS In this prospect i ve single-centre r and omized study , 532 patients were r and omized into 2 groups : the vitamin C group , which received a 3-g vitamin C infusion within 6 hours before PCI , and a control group , which received normal saline . The primary end point was the troponin I-defined PMI , and the second end point was the creatine kinase (CK)-MB-defined PMI . Separate analyses using both end points were performed . PMI was defined as an elevation of cardiac biomarker values ( CK-MB or troponin I ) > 5 times the upper limit of normal ( ULN ) , alone or associated with chest pain or ST-segment or T-wave changes . RESULTS After PCI , the incidence of PMI was reduced , whether defined by troponin or by CK-MB , compared with the control group ( troponin I , 10.9 % vs 18.4 % ; P = 0.016 ; CK-MB , 4.2 % vs 8.6 % ; P = 0.035 ) . Logistic multivariate analysis showed that preprocedure use of vitamin C is an independent predictor of PMI either defined by troponin I ( odds ratio [ OR ] , 0.56 ; 95 % confidence interval [ CI ] , 0.33 - 0.97 ; P = 0.037 ) or by CK-MB ( OR , 0.37 ; 95 % CI , 0.14 - 0.99 ; P = 0.048 ) . CONCLUSIONS In patients undergoing elective PCI , preprocedure intravenous treatment with vitamin C is associated with less myocardial injury This study was undertaken to evaluate the effects of alpha-tocopherol and ascorbic acid on markers of myocardial reperfusion injury and myocardial contractile function after coronary artery surgery . Forty-eight patients were divided into 4 groups ; 300 mg/day alpha-tocopherol was given orally to the patients in group I for 14 days . In groups II and III , 4 g of ascorbic acid was administered intravenously prior to induction and in the cardioplegic solution , respectively . Group IV was the control group .  Blood sample s were taken to determine the concentrations of creatine phosphokinase MB isoenzyme , malondialdehyde , uric acid , ascorbic acid and alpha-tocopherol in the perioperative period . Left ventricular functions were determined by means of MUGA scans and echocardiography preoperatively and on the 3rd and 7th days , postoperatively . The changes in serum creatine phosphokinase MB and malondialdehyde were significantly lower in study groups , when compared with the control group . We observed no significant changes in ventricular function , requirement for ( + ) inotropic agents and the incidence of ventricular arrhythmias among the groups , postoperatively . Biochemical findings are consistent with the free radical hypothesis . But we could not confirm these data with hemodynamic findings . This is probably due to the population of low-risk elective coronary surgery patients in this study BACKGROUND Atrial fibrillation is the most common arrhythmia following cardiac surgery . It is associated with increased hemodynamic instability , systemic embolization , and complications linked to anticoagulant therapy . Oxidative stress and consequent electrophysiological remodeling have been proposed as a cause of postoperative atrial fibrillation . Ascorbic acid supplementation was suggested as a novel and effective preventive agent . The aim of this study was to evaluate the capability of ascorbic acid to reduce the incidence of postoperative atrial fibrillation in coronary artery bypass grafting ( CABG ) patients . METHODS A prospect i ve r and omized single-center trial was conducted in patients scheduled for an elective on-pump CABG surgery . Subjects in the ascorbic acid group received 2 g of ascorbic acid 24h and 2h before the surgery and 1 g twice a day for five days after the surgery . Postoperatively , the patients were monitored for atrial fibrillation and other complications . RESULTS The ascorbic acid group consisted of 52 patients and the control group included 53 patients . The groups were well matched for baseline demographics , preoperative medications , comorbidities , and had similar intraoperative characteristics . The incidence of atrial fibrillation in the ascorbic acid group was 13.5 % and 18.9 % in the control group ( p=0.314 ) . No difference was found between groups in the time of occurrence of atrial fibrillation ( 3.71±1.89 vs. 2.91±1.58 days after the surgery ; p=0.342 ) . There was also no difference in the other observed postoperative complications . CONCLUSIONS The results of this study do not support the effectiveness of ascorbic acid supplementation in reducing the incidence of postoperative atrial fibrillation in elective on-pump CABG patients Because adrenergic beta antagonists are not sufficient to prevent atrial fibrillation after coronary artery bypass grafting , this prospect i ve , r and omized trial was design ed to evaluate the effects of ascorbic acid as an adjunct to beta-blockers .  Fifty patients formed our ascorbic acid group , and another 50 patients formed our control group . All patients were older than 50 years , were scheduled to undergo coronary artery bypass grafting , and had been treated with beta-blockers for at least 1 week before surgery . The mean age of the population was 60.19+/-7.14 years ; 67 % of the patients were men . Patients in the ascorbic acid group received 2 g of ascorbic acid on the night before the surgery and 1 g twice daily for 5 days after surgery . Patients in the control group received no ascorbic acid . Patients in both groups continued to receive beta-blockers after surgery . Telemetry monitoring was performed in the intensive care unit , and Holter monitoring was performed for 4 days thereafter . The incidence of postoperative atrial fibrillation was 4 % in the ascorbic acid group and 26 % in the control group ( odds ratio , 0.119 ; 95 % confidence interval , 0.025 - 0.558 , P = 0.002 ) . We conclude that ascorbic acid is effective , in addition to being well-tolerated and relatively safe . Therefore , it can be prescribed as an adjunct to beta-blockers for the prophylaxis of post-bypass atrial fibrillation PURPOSE The effect of ascorbic acid on inflammatory markers after cardiothoracic surgery ( CTS ) was studied . METHODS In this r and omized , double-blind , placebo-controlled trial , patients undergoing cardiopulmonary bypass graft surgery or valve replacement surgery from April 2009 through March 2010 at Hartford Hospital were r and omized to receive ascorbic acid ( 2-g loading dose followed by 500 mg every 12 hours ) or matching placebo the evening before surgery and for four days postoperatively . Inflammatory mediators were measured preoperatively and on postoperative days 1 - 4 . Intergroup comparisons were performed using two-tailed t tests and Fisher 's exact test . Multiple comparisons were conducted using repeated analyses of variance with Bonferroni tests . RESULTS Of the 62 patients screened , 24 met the study inclusion criteria . Of these , 13 were assigned to receive ascorbic acid and 11 received placebo . Ascorbic acid did not affect the natural course of inflammatory marker rise for C-reactive protein ( CRP ) concentration , white blood cell ( WBC ) count , or fibrinogen concentration versus placebo at any evaluated time point ( p > 0.05 for all intergroup comparisons ) . Intragroup analyses demonstrated significant differences among baseline and postoperative measures of all inflammatory mediators ( p < 0.05 ) . No significant differences were noted in inflammatory markers between patients undergoing cardiothoracic surgery with or without cardiopulmonary bypass , regardless of treatment group . CONCLUSION Ascorbic acid did not attenuate the rise in inflammatory markers after CTS when compared with placebo . The use of off-pump surgery did not significantly change the levels of CRP and fibrinogen or the WBC count postoperatively when compared with on-pump surgery with a biocompatible polymer coating
target: Conclusions Our meta- analysis indicates that vitamin C may prevent post-operative atrial fibrillation in some countries outside of the USA , and it may also shorten the duration of hospital stay and ICU stay of cardiac surgery patients .
  Vitamin C is an essential nutrient that is safe and inexpensive .
background: Background Atrial fibrillation ( AF ) , a common arrhythmia contributing substantially to cardiac morbidity , is associated with oxidative stress and , being an antioxidant , vitamin C might influence it .