title: Effects of an angiotensin II antagonist on ischemic and nonischemic isolated rat hearts.
abstract: 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.
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Elias Sourasky-Tel-Aviv Medical Center, Israel.
authors.forename: Y
authors.initials: Y
authors.lastname: Paz
authors.forename: J
authors.initials: J
authors.lastname: Gurevitch
authors.forename: I
authors.initials: I
authors.lastname: Frolkis
authors.forename: M
authors.initials: M
authors.lastname: Matsa
authors.forename: A
authors.initials: A
authors.lastname: Kramer
authors.forename: C
authors.initials: C
authors.lastname: Locker
authors.forename: R
authors.initials: R
authors.lastname: Mohr
authors.forename: G
authors.initials: G
authors.lastname: Keren
mesh_terms: D000804:Angiotensin II / Q000037:antagonists & inhibitors*; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D006321:Heart / Q000503:physiopathology*; D006324:Heart Arrest, Induced; D006439:Hemodynamics; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D017202:Myocardial Ischemia / Q000378:metabolism / Q000503:physiopathology*; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000804:Angiotensin II; D019808:Losartan