2022, Vol. 26 ›› Issue (8): 1194-1201
Cardioprotective effect of 3-nitro-N-methyl salicylamide on the isolated rat heart under cold ischemia preservation
During reperfusion, increased reactive oxygen species will cause oxidative stress injury in ischemic organs, which is the critical factor for ischemia and reperfusion injury. Cellular reactive oxygen species are mainly originated from mitochondrial electron transport chain. Therefore, it is an effective strategy to reduce myocardial ischemia/reperfusion injury due to elevated reactive oxygen species by inhibiting electron transport at mitochondrial electron transport chain. 3-Nitro-N-methyl-salicylamide (3-NNMS) is a semi-inhibitor for electron transport chain complex III, which can slow down the electron transport rate. 3-NNMS has potential applications for cardiac preservation; nevertheless, no related definite research or clinical practice has been reported.
To investigate the protective effect of a new cardioplegic solution with 3-NNMS as the main component on isolated rat heart preservation for 8 hours.
Heart specimens were taken from healthy male Wistar rats, perfused stably for 30 minutes, and then preserved in different cardioplegic solutions at low temperature for 8 hours. According to different cardioplegic solutions used, rat heart specimens were divided into a control group (no preservation), a 3-NNMS cardioplegic solution group, a Celsior cardioplegic group, and a 3-NNMS+Celsior cardioplegic solution group. The hemodynamic changes of the heart were detected by Powerlab instruments. The mitochondrial function in the preserved myocardium was measured by Oxygraph-2k High-resolution respirometry and chemiluminescence apparatus. Myocardial injury was assessed by detecting the expression of cardiac troponin T, creatine kinase isoenzyme MB, and lactate dehydrogenase using ELISA. The morphological changes of the heart were histologically observed. And the myocardial reactive oxygen species level was tested by inverted fluorescence microscope.
The 3-NNMS cardioplegic solution could improve the heart rate recovery compared with the Celsior (P < 0.05), and decrease the levels of cardiac troponin T, creatine kinase isoenzyme MB, and lactate dehydrogenase in perfusate supernatant (P < 0.05). 3-NNMS could remarkably elevate mitochondria membrane potential, and maintain mitochondrial membrane structure effectively (P < 0.05). 3-NNMS could significantly increase the activity of superoxide dismutase (P < 0.05), ameliorate myocardial antioxidant function, and alleviate oxidative damage. It was nontoxic for cell culture with 3-NNMS, which can be used regardless of the concentration. To conclude, 3-NNMS can reduce oxidative stress-induced myocardial injury via increasing superoxide dismutase activity and promoting myocardial active oxygen clearance. Besides, 3-NNMS can improve heart rate recovery and keep mitochondrial membrane integrity during the reperfusion period.
3-nitro-N-methyl-salicylamide, myocardial ischemia/reperfusion injury, mitochondrial inhibitor, heart preservation solution, isolated heart preservation, reactive oxygen
2022 - Mzunguko wa "Kama ilivyoelezwa katika makala ya kwanza ya ""Ulinzi wa moyo wa panya"" ya N-nitro-N-methylsalicylamide, ""Ulinzi wa moyo wa panya"" ni athari ya kawaida ya athari ya athari ya athari ya athari ya athari ya athari ya athari ya athari ya athari ya athari ya athari ya athari ya athari ya athari ya athari ya athari ya athari ya athari ya athari ya athari ya athari ya athari ya athari ya athari ya athari ya athari." Aina za oksijeni zinazofanya kazi kwenye chembe hutokana hasa na mlolongo wa usafirishaji wa elektroni wa mitochondrial. Kwa hiyo, ni mkakati ufanisi wa kupunguza myocardial ischemia au uharibifu wa reperfusion kutokana na aina za oksijeni za athari za juu kwa kuzuia usafirishaji wa elektroni kwenye mlolongo wa usafirishaji wa elektroni ya mitochondrial. Nitro-N-methylsalicylamide (NMS) ni nusu-inhibitor kwa ajili ya elektroniki usafirishaji mlolongo tata III, ambayo inaweza kupunguza kasi ya usafirishaji wa elektroniki. 3NMS ina matumizi ya uwezekano kwa ajili ya kuhifadhi moyo; hata hivyo, hakuna utafiti wa uhakika au mazoezi ya kliniki yanayohusiana yameripotiwa. Utafiti wa athari ya kinga ya suluhisho jipya la cardioplegic na 3-NMS kama sehemu kuu juu ya kuhifadhi moyo wa panya kwa masaa 8. Mfano wa moyo ulichukuliwa kutoka kwa panya wa kiume wenye afya, ulichukuliwa kwa dakika 30 na kuhifadhiwa katika suluhisho tofauti za cardioplegic kwa joto la chini kwa masaa 8. Kwa mujibu wa suluhisho tofauti za cardioplegic zilizotumiwa, sampuli za moyo wa panya ziligawanywa katika kikundi cha kudhibiti (bila kuhifadhi), kikundi cha suluhisho la cardioplegic la 3-NMS, kikundi cha cardioplegic cha Celcius, na kikundi cha suluhisho la cardioplegic la Celcius. Mabadiliko ya hemodynamic ya moyo yaligunduliwa na vyombo vya Powerlab. Mitochondrial kazi katika myocardium kuhifadhiwa ilipimwa na Oxygraph-2k High-resolution respirometry na chemiluminescence kifaa. Ugonjwa wa moyo uligunduliwa kwa kugundua usemi wa troponin T ya moyo, creatine kinase isoenzyme (MKB) na lactate dehydrogenase kwa kutumia ELISA. Mabadiliko ya morfolojia ya moyo yalionekana histologically. Kiwango cha aina ya oksijeni ya myocardial kimechunguzwa na darubini ya fluorescence. 3NMS inaweza kuboresha kupona kwa msukumo wa moyo ikilinganishwa na Celso (P < 0,05), na kupunguza viwango vya troponin T ya moyo, creatine kinase isoenzyme (MKB) na lactate dehydrogenase (LDD) katika supranatant ya perfusion. 3-NMS inaweza kuongeza uwezo wa utando wa mitochondria, na kudumisha muundo wa utando wa mitochondrial kwa ufanisi (P < 0,05). 3-NMS inaweza kuongeza kwa kiasi kikubwa shughuli ya superoxide dismutase (P < 0,05), kuboresha kazi ya antioxidant ya myocardial, na kupunguza uharibifu wa oxidative. Ni nontoxic kwa ajili ya utamaduni wa seli na 3-NMS, ambayo inaweza kutumika bila kujali mkusanyiko. Kwa kumalizia, 3-NMS inaweza kupunguza uharibifu wa myocardial unaosababishwa na mkazo wa oxidative kupitia kuongeza shughuli ya superoxide dismutase na kukuza uondoaji wa oksijeni ya myocardial. Kwa kuongezea, 3-NMS inaweza kuboresha kupona kwa msimu wa moyo na kudumisha uadilifu wa utando wa mitochondrial wakati wa kipindi cha reperfusion. 3 - Nitro-N-methylsalicylamide, myocardial ischemia, myocardial ischemia, myocardial ischemia, myocardial ischemia, myocardial ischemia, myocardial ischemia, myocardial ischemia, myocardial ischemia, myocardial ischemia, myocardial ischemia, myocardial ischemia, myocardial ischemia, myocardial ischemia, myocardial ischemia, myocardial ischemia, myocardial ischemia, myocardial ischemia