Effects of an angiotensin II antagonist on ischemic and nonischemic isolated rat hearts

Background. 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. Methods. 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. Results. 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). Conclusions. 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.