Sugawara E, Nakayama Y, Senoo Y, Teramoto S
Second Department of Surgery, Okayama University Medical School, Japan.
Acta Med Okayama. 1991 Jun;45(3):129-34. doi: 10.18926/AMO/32210.
The cardioprotective effect of calmodulin antagonists, trifluoperazine (TFP) and N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide (W-7) was examined on the isolated rat heart exposed to hypothermic and ischemic conditions by measuring distribution of lysosomal enzymes in myocardial cells, and leakage of creatine kinase (CK) during reperfusion and postischemic recovery in myocardial systolic function. Experimental hearts were infused with 20 degrees C Krebs-Henseleit bicarbonate buffer (KHB) or KHB containing TFP or W-7 for 2min every 30min during hypothermic ischemia. After ischemia for 120min at 20 degrees C, rat hearts were reperfused at 37 degrees C for 30min. TFP and W-7 improved functional recovery and prevented CK release. In TFP treated hearts, leakage of lysosomal enzymes was reduced significantly, whereas stabilization of lysosomes by W-7 did not occur. These results suggest that calcium-calmodulin dependent enzymes may play an important role in the development of cellular damage of the myocardium during hypothermic ischemia, although levels of leakage of lysosomal enzymes may be unreliable predictors of functional recovery after hypothermic ischemia.
通过测量心肌细胞中溶酶体酶的分布以及再灌注期间肌酸激酶（CK）的泄漏和低温缺血后心肌收缩功能的恢复情况，研究了钙调蛋白拮抗剂三氟拉嗪（TFP）和N-（6-氨基己基）-5-氯-1-萘磺酰胺（W-7）对暴露于低温和缺血条件下的离体大鼠心脏的心脏保护作用。在低温缺血期间，每隔30分钟向实验心脏灌注20℃的 Krebs-Henseleit 碳酸氢盐缓冲液（KHB）或含TFP或W-7的KHB 2分钟。在20℃缺血120分钟后，将大鼠心脏在37℃再灌注30分钟。TFP和W-7改善了功能恢复并防止了CK释放。在TFP处理的心脏中，溶酶体酶的泄漏显著减少，而W-7对溶酶体的稳定作用未出现。这些结果表明，钙-钙调蛋白依赖性酶可能在低温缺血期间心肌细胞损伤的发生中起重要作用，尽管溶酶体酶的泄漏水平可能不是低温缺血后功能恢复的可靠预测指标。
