Paz Y, Gurevitch J, Frolkis I, Matsa M, Kramer A, Locker C, Mohr R, Keren G
Department of Thoracic and Cardiovascular Surgery, Elias Sourasky-Tel-Aviv Medical Center, Israel.
Ann Thorac Surg. 1998 Feb;65(2):474-9. doi: 10.1016/s0003-4975(97)01234-4.
Increasing evidence suggests that a locally integrated or intramyocardial renin-angiotensin system plays a significant role in ischemia-reperfusion injury. We evaluated the effects of losartan, an angiotensin II type 1 receptor blocking agent, on ischemic and nonischemic isolated rat hearts.
Using the modified Langendorff model, hearts were perfused with either low or high doses of losartan (18.2 mmol/L or 182.2 mmol/L, respectively) or with saline added to Krebs-Henseleit solution during phase I of the study. During phase II, hearts were exposed to a 60-minute period of global ischemia. Ischemic arrest was induced with warm cardioplegic solution (KCl, 16 mEq/L) containing either high-dose losartan (182.2 mmol/L) or Krebs-Henseleit solution only.
During phase I of the study, no statistically significant differences were observed between the low-dose losartan group and the control group. However, hearts treated with high-dose losartan demonstrated an increase in peak systolic pressure, maximum first derivative of pressure, pressure-time integral, coronary flow, and oxygen consumption (p < 0.0001). During phase II, hearts treated with losartan showed a significantly better recovery on reperfusion, as reflected by better contractility (p < 0.001), higher oxygen consumption (p < 0.001), higher coronary flow (p < 0.0001), and lower creatine phosphokinase levels (41.1 +/- 1.7 versus 73.3 +/- 5.6 U/L; p < 0.001).
High doses of losartan have a positive inotropic effect on normally perfused hearts. Given in cardioplegic solution, the drug has a significant protective effect on ischemic isolated rat hearts.
越来越多的证据表明，局部整合或心肌内肾素 - 血管紧张素系统在缺血 - 再灌注损伤中起重要作用。我们评估了血管紧张素II 1型受体阻断剂氯沙坦对缺血和非缺血离体大鼠心脏的影响。
在研究的第一阶段，使用改良的Langendorff模型，心脏分别用低剂量或高剂量的氯沙坦（分别为18.2 mmol/L或182.2 mmol/L）或添加到克雷布斯 - 亨塞尔特溶液中的生理盐水灌注。在第二阶段，心脏暴露于60分钟的全心缺血。用含有高剂量氯沙坦（182.2 mmol/L）或仅含有克雷布斯 - 亨塞尔特溶液的温血心脏停搏液诱导缺血性停搏。
在研究的第一阶段，低剂量氯沙坦组与对照组之间未观察到统计学上的显著差异。然而，用高剂量氯沙坦治疗的心脏在收缩压峰值、压力的最大一阶导数、压力 - 时间积分、冠状动脉血流量和氧耗方面有所增加（p < 0.0001）。在第二阶段，用氯沙坦治疗的心脏在再灌注时显示出明显更好的恢复，表现为更好的收缩性（p < 0.001）、更高的氧耗（p < 0.001）、更高的冠状动脉血流量（p < 0.0001）和更低的肌酸磷酸激酶水平（41.1±1.7对73.3±5.6 U/L；p < 0.001）。
高剂量的氯沙坦对正常灌注的心脏有正性肌力作用。在心脏停搏液中给予该药物，对缺血离体大鼠心脏有显著的保护作用。
