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 i schemia-reperfusion injury. We evaluated the effects of losartan, an a ngiotensin II type 1 receptor blocking agent, on ischemic and nonische mic 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-H enseleit solution during phase I of the study. During phase II, hearts were exposed to a 60-minute period of global ischemia. Ischemic arres t was induced with warm cardioplegic solution (KCI, 16 mEq/L) containi ng either high-dose losartan (182.2 mmol/L) or Krebs-Henseleit solutio n only. Results. During phase I of the study, no statistically signifi cant differences were observed between the low-dose losartan group and the control group. However, hearts treated with high-dose losartan de monstrated an increase in peak systolic pressure, maximum first deriva tive of pressure, pressure-time integral, coronary flow, and oxygen co nsumption (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 < 0.00 1), higher coronary flow (p < 0.0001), and lower creatine phosphokinas e levels (41.1 +/- 1.7 versus 73.3 +/- 5.6 U/L; p < 0.001). Conclusion s. High doses of losartan have a positive inotropic effect on normally perfused hearts. Given in cardioplegic solution, the drug has a signi ficant protective effect on ischemic isolated rat hearts. (C) 1998 by The Society of Thoracic Surgeons.