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2022, Vol. 26 ›› Issue (8): 1194-1201Cardioprotective effect of 3-nitro-N-methyl salicylamide on the isolated rat heart under cold ischemia preservationWang Shuo, Liu Wenying, Lü Chaofan, Li Jiacong, Geng Yi, Zhao Yungang
Abstract: BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS AND CONCLUSION: 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. Key words:3-nitro-N-methyl-salicylamide, myocardial ischemia/reperfusion injury, mitochondrial inhibitor, heart preservation solution, isolated heart preservation, reactive oxygen |