Rah B J, Kim H O, Park Y W
Department of Histology, College of Medicine, Chung-Ang University, Seoul, South Korea.
Coron Artery Dis. 1994 May;5(5):415-23. doi: 10.1097/00019501-199405000-00008.
It has been previously demonstrated that pretreatment with diltiazem preserves mitochondrial function during postischemic reperfusion.
The purpose of this study was to perform cytochemical and hemodynamical assessment to confirm this demonstration.
Isolated Langendorff-perfused guinea-pig hearts received 10 min of diltiazem (7.5 microM) treatment, were subjected to 10 min of global ischemia and to 20 min of reperfusion. Left ventricular function was monitored by connecting a balloon to a pressure transducer. Intracellular calcium was precipitated with potassium pyroantimonate and examined with a transmission electron microscope.
Compared with the control and the ischemic hearts, the diltiazem-pretreated hearts showed a significant increase in the left ventricular developed pressure (LVDP), dP/dtmax (P < 0.01), and recovery rates of the LVDP (P < 0.01 versus ischemic hearts) and dP/dtmax (P < 0.05), and a decrease in the heart rate (P < 0.01). The left ventricular end-diastolic pressure (LVEDP) and leakage of creatine kinase were not significantly different. Calcium deposits were seen along the inner aspects of the sarcolemma and t-tubule membranes, and in the mitochondria of the control hearts. The number of these deposits was considerably reduced after ischemia. They reappeared principally in the mitochondria by reperfusion. In contrast, the calcium deposits reappeared along the sarcolemma, t-tubule membranes, and cell junctions, and in the mitochondria in the diltiazem-pretreated hearts.
These results suggest that pretreatment with diltiazem may improve cardiac function during postischemic reperfusion, probably in part by maintenance of sarcolemmal integrity rather than by mitochondrial buffering function.
先前的研究已证明，地尔硫䓬预处理可在缺血后再灌注期间保留线粒体功能。
本研究旨在进行细胞化学和血流动力学评估以证实这一发现。
对离体Langendorff灌注的豚鼠心脏给予10分钟地尔硫䓬（7.5微摩尔）处理，进行10分钟全心缺血及20分钟再灌注。通过将球囊连接至压力传感器监测左心室功能。用焦锑酸钾沉淀细胞内钙并用透射电子显微镜检查。
与对照组和缺血心脏相比，地尔硫䓬预处理的心脏左心室舒张末压（LVDP）、dP/dtmax（P<0.01）、LVDP恢复率（与缺血心脏相比，P<0.01）和dP/dtmax（P<0.05）显著增加，心率降低（P<0.01）。左心室舒张末压（LVEDP）和肌酸激酶漏出无显著差异。在对照心脏的肌膜和横管膜内侧以及线粒体中可见钙沉积。缺血后这些沉积物的数量显著减少。再灌注时它们主要重新出现在线粒体中。相比之下，在接受地尔硫䓬预处理的心脏中，钙沉积沿肌膜、横管膜和细胞连接以及线粒体重新出现。
这些结果表明，地尔硫䓬预处理可能在缺血后再灌注期间改善心脏功能，可能部分是通过维持肌膜完整性而非线粒体缓冲功能实现的。
