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.
Paz
Y
Y
Department of Thoracic and Cardiovascular Surgery, Elias Sourasky-Tel-Aviv Medical Center, Israel.
Gurevitch
J
J
Frolkis
I
I
Matsa
M
M
Kramer
A
A
Locker
C
C
Mohr
R
R
Keren
G
G
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
D000804:Angiotensin II; D019808:Losartan