氯通道阻断剂NPPB拮抗离体灌注大鼠心脏钙矛盾处理引起的心肌损伤

目的观察氯离子通道阻滞剂5-硝基-2-（3-苯丙胺）苯甲酸（NPPB）对钙矛盾处理造成离体灌注大鼠心脏功能障碍和心肌细胞死亡的影响。方法钙矛盾处理由3 min无钙液、30 min有钙液接替灌注完成,实验同步记录左室压,并检测心肌损伤面积的大小。结果与正常对照组相比,钙矛盾组左室舒张末压（LVEDP）显著抬高,左室发展压（LVDP）、心室变化速率（dp/dt）为0,心脏几乎不存在活性组织;于无钙液灌注前2 min、无钙液灌注期和复钙后前5 min给予20μmol/LNPPB处理后,10例心脏的心肌损伤面积均显著缩小,其中4例LVDP大于2 mm Hg,LVEDP有降低趋势、dp/dt有升高趋势;与正常对照组相比,20μmol/L NPPB处理的对照心脏于灌流结束时左室功能、心肌损伤面积没有显著改变。结论 NPPB具有减轻钙矛盾处理引起的心肌损伤,保护心功能作用,提示氯通道参与是钙矛盾处理引起的心肌损伤。

Chloride channel blocker NPPB blunted heart injury induced by calcium paradox in rat

Objective This study evaluated the effect of chloride channel blocker 5 - nitro - 2 - （ 3 - phenyl - propylamino） - benzoic acid （NPPB） on heart injury induced by calcium paradox. Methods Calcium paradox in isolated rat heart was elicited by 3 - rain calcium depletion followed by 30 - rain calcium repletion. 20 μmol/L NPPB was added 2 rain prior to calcium depletion, throughout the period of calcium depletion and the first 5 rain after calcium repletion. Cardiac function was monitored and infarct size measured. Results Comparing to control group, calcium paradox treatment produced a marked depression in cardiac function and in- duced an enlarged infarct size. In NPPB treatment group, all the 10 hearts showed a marked decrease in infarct size, and the left ven- tricular developed pressure （LVDP） rescued in 4 of 10 hearts. Meanwhile, the left ventricnlar end -diastolic pressure （LVEDP） and dp/dt were improved in NPPB treatment group, although they did not reach significant difference. NPPB at 20μmo]/L had no effect on cardiac performance and cell death at the end of peffusion under control conditions. Conclusion The results demonstrate that NPPB protects heart against calcium paradox. It also indicates that chloride channels are involved in.