Gurevitch J, Barak J, Hochhauser E, Paz Y, Yakirevich V
Department of Thoracic and Cardiovascular Surgery, Tel-Aviv-Elias Sourasky Medical Center, Tel-Aviv University, Israel.
J Thorac Cardiovasc Surg. 1994 Jul;108(1):109-18.
The effects of aprotinin, a protease inhibitor, on the ischemic and nonischemic isolated rat heart was investigated with the use of the modified Langendorff model. During phase I of the study, hearts were perfused with either low-dose aprotinin (10(5) KIU/L), high-dose aprotinin (10(6) KIU/L), or normal saline solution added to modified Krebs-Henseleit solution. No statistically significant differences in contraction amplitude, contractility, coronary flow, and wet/dry heart weight ratio were observed among the three groups of hearts. In phase II, hearts were exposed to a 40-minute period of global ischemia at 31 degrees C. Ischemic arrest was induced by warm cardioplegia. Before ischemia and during cardioplegia, hearts were perfused with either aprotinin 10(6) KIU/L (n = 10) or normal saline solution (n = 10) for 30 minutes. On reperfusion, recovery of hearts treated with aprotinin was significantly better than that of control hearts, as reflected by better contractility (analysis of variance, p = 0.011), higher coronary flow (p < 0.025), and lower creatine kinase levels (p < 0.05). No statistically significant differences in contraction amplitude were observed between the two groups. When the effect of ischemia within each group of hearts was analyzed, the preserving effect of aprotinin was even more pronounced. In the control group, ischemia caused a decrease in contractility (p < 0.025) and a decrease in oxygen consumption (p = 0.006); by contrast, in the aprotinin group the preischemic values were maintained. Accordingly, we conclude that aprotinin at concentrations up to 10(6) KIU/L has no deleterious effect on normally perfused hearts and has a significant protective effect on the ischemic heart when used in high doses in the preischemic period.
利用改良的Langendorff模型，研究了蛋白酶抑制剂抑肽酶对离体大鼠缺血和非缺血心脏的影响。在研究的第一阶段，用低剂量抑肽酶（10⁵KIU/L）、高剂量抑肽酶（10⁶KIU/L）或添加到改良Krebs-Henseleit溶液中的生理盐水灌注心脏。三组心脏在收缩幅度、收缩性、冠状动脉血流量和心湿/干重比方面未观察到统计学上的显著差异。在第二阶段，将心脏在31℃下进行40分钟的全心缺血。通过温血心脏停搏诱导缺血性停搏。在缺血前和心脏停搏期间，用10⁶KIU/L抑肽酶（n = 10）或生理盐水（n = 10）灌注心脏30分钟。再灌注时，抑肽酶处理的心脏恢复情况明显优于对照心脏，表现为更好的收缩性（方差分析，p = 0.011）、更高的冠状动脉血流量（p < 0.025）和更低的肌酸激酶水平（p < 0.05）。两组之间在收缩幅度上未观察到统计学上的显著差异。当分析每组心脏内缺血的影响时，抑肽酶的保护作用更为明显。在对照组中，缺血导致收缩性降低（p < 0.025）和氧耗降低（p = 0.006）；相比之下，在抑肽酶组中，缺血前的值得以维持。因此，我们得出结论，浓度高达10⁶KIU/L的抑肽酶对正常灌注的心脏没有有害影响，并且在缺血前期高剂量使用时对缺血心脏有显著的保护作用。
