Cariporide在不同pH停搏液中心肌保护作用的比较

The cardioprotective efficacy of cariporide as an adjunct in different pH cardioplegia

目的研究特异性Na+/H+交换抑制剂卡立泊来德(cariporide)在不同pH停搏液中的心肌保护作用。方法64只SD雄性大鼠随机分成8组(每组8只),对照组4组,停搏液为pH值分别为6·2、7·0、7·4、7·8的改良St·ThomasII停搏液;实验组4组,停搏液为加入cariporide,pH值分别为6·2、7·0、7·4、7·8的改良St·ThomasII停搏液。离体鼠心在改良Langendorff灌注模型上30min预灌注,60min停搏,30min再灌注,监测心脏缺血前及复灌后血流动力学变化,心肌酶CK-MB、LDH变化,电镜观察心肌超微结构改变,评价心肌保护效果。结果再灌注后,实验组不同pH值停搏液与对照组相应pH值停搏液比较,可显著促进低温缺血心肌的功能恢复,降低心肌酶CK-MB、LDH的漏出(P<0·05或P<0·01),明显减轻心肌超微结构损伤。实验组中pH值分别为6·2、7.0、7.4的停搏液与pH值7.8的停搏液相比,低温缺血心肌功能恢复更好,心肌酶CK-MB、LDH的漏出量更低(P<0.05或P<0.01),心肌超微结构损伤更小,尤以pH值为7·0的更佳。对照组中,pH分别为6·2、7·0、7·4的停搏液比pH值7·8的停搏液更有助于低温缺血心肌的功能恢复,降低心肌酶CK-MB、LDH的漏出量(P<0·05),心肌超微结构损伤较轻。结论特异性Na+/H+交换抑制剂cariporide加入弱酸性的St·ThomasII停搏液更有助于低温缺血心肌的功能恢复,对心肌的保护作用更强。

Objective To compare the cardiopretective efficacy of Cariporide as an adjunct in different pH eardioplegia. Methods Sixty-four male Sprague-Dawley rat hearts were randomly divided into 8 groups （8 rats in each greup） ： 4 control groups and 4 treated groups with Cariporide as an adjunct to catdioplegia. After control perfusion in Langendorff mode with Krebs-Henseleit bicarbanate buffer （KHB） for 30 minutes, the isolated rat hearts were infused with different pH （pH= 6.2 or 7.0 or 7.4 or 7.8, respectively） cardioplegia （without or with Cariporide） for 2 minutes to produce cardiac arrest and subjected to 60 minutes of 15℃ arrest. In addition, during global ischemia, cardioplegia was reinfused for 2 minutes every 30 minutes, Sixty minutes after the ischemic arrest, cardioplegia was infused as terminal cardioplegia for 2 minutes, then the hearts were reperfused with Krebs-Henseleit bicarbonate buffer for 30 minutes. The hemodyanmic parameters and the level of creatine kinase-MB （ CK-MB）, lactate dehydregenase （LDH） of coronary venous sinus drainage were measured before ischemia and during reperfusion. Myocardial and mitochondrial uhrastructures were observed under electronmicroscope. Results Application of Cariporide as an adjunct to cardioplegia improved significantly recovery of cardiac function and decreased the level of ereatine kinase-MB（CK-MB）, lactate dehydrogenase （LDH） of coronary venous sinus drainage （P 〈0.05 or P 〈0.01）, the myocardial tissue had almost normal ultra.structures. Among the treated groups, the hearts arrested with a mildly acidic cardioplegia （pH = 6.2, 7.0 or 7. 4） had better recovery of cardiac function and lower release of myocardial enzyme （CK-MB, LDH） than those arrested with cardioplegia having a pH levels of 7.8 （with maximal protection observed at a pH of 7.0, P〈0.05 or P〈0.01）, with comparatively normal ultrastructures. 3） Among control groups, infusion with a mildly acidic cardioplegia （pH = 6.2, 7.0 or 7.4） yielded better recovery of cardiac function and lower release of LDH, CK-MB than infusion with cardioplegia having pH levels of 7.8 （P〈0.05） .Conclusion These results suggest that Cariporide supplement in cardioplegia alleviates the reperfusion mediated myocardial injury, the cardioprotective efficacy of Cariporide as an adjunct to a mildly acidic cardioplegia is best.