再灌注早期给予5-N,N二甲基氨氯吡咪对心肌缺血再灌注损伤的保护作用机制研究

目的探讨再灌注早期给予20μmol/L5-N,N二甲基氨氯吡咪(DMA)减轻心肌缺血再灌注损伤的作用机制。方法采用Langendorff法建立离体大鼠心肌缺血再灌注模型,全心缺血45min后,再灌注30min,在再灌注初始5min期间给予药物干预空白对照;20μmol/LDMA组;低浓度(0.5mmol/L)氨氯吡咪组;高浓度(2.0mmol/L)氨氯吡咪组],其中20μmol/LDMA可以抑制Na+/H+交换,激动Na+/Ca2+交换;低浓度氨氯吡咪主要抑制Na+/H+交换;高浓度氨氯吡咪同时抑制Na+/H+交换和Na+/Ca2+交换。观察不同的药物对离体灌流心脏再灌注期间血流动力学指标(LVSP-LVDP,+dp/dtmax,-dp/dtmax)的影响,同时观察再灌注期间冠状动脉流出液中肌酸激酶(CK)的活性变化。结果与对照组相比,3个药物干预组对再灌后各项血流动力学指标的恢复均有明显的促进作用;流出液中CK的活性较对照组也明显下降。但是再灌注30min后3个给药组血流动力学指标以及流出液中CK的活性差异无统计学意义。结论20μmol/LDMA可明显减轻心肌缺血再灌注损伤,其机制主要是通过抑制Na+/H+交换来发挥其作用,与它对Na+/Ca2+交换的激动作用关系不大。

Early ase of dimethyl amiloride was associated with a protection against myocardial ischemia reperfusion injury

Objective To investigate the potential mechanism underlying protective effects of early dimethyl amiloride (DMA) (20 μmol/L) against myocardial ischemia reperfusion injury. Methods The myocardial ischemia-reperfusion model was established according to by Langendorff′s method. After 45-min ischemia, the isolated rat heart was reperfused for 30 min. During the first 5 min of reperfusion, different drug interventions were initiated using 20 μmol/L DMA (blank control group), or 0.5 mmol/L Amiloride (low-dose Amiloride group) or 2.0 mmol/L Amiloride (high-dose Amiloride group). The 20 μmol/L DMA was designed to inhibit Na+/H+ and stimulate Na+/Ca2+ current exchanges, as low-dose Amiloride to inhibit mainly Na+/H+ current exchange, and high-dose Amiloride to inhibit Na+/H+ and Na+/Ca2+ exchange current simultaneously. Effects of these agents on hemodynamics indexes (LVSP-LVDP, +dp/dtmax, -dp/dtmax) during reperfusion of ex-vivo heart were observed, as was the creatine kinase (CK) activity in coronary effluent. Results Compared with the control group, all the test groups showed improved hemodynamics indexes during reperfusion and reduced CK activity in coronary effluent, but the differences did not reach the level of statistical significance. Conclusion 20 μmol/L DMA may be protective against myocardial ischemia-reperfusion injury, largely attributable to inhibition of Na+/H+ exchange but not to stimulation of Na+/Ca2+ exchange.