Angiotensin II type 1 receptor blockade with candesartan protects the porcine myocardium from reperfusion-induced injury.
Angiotensin-converting enzyme (ACE) inhibitors reduce myocardial ischemia/reperfusion injury. It is unclear whether reduced formation of angiotensin II or attenuated degradation of bradykinin is responsible for the beneficial effects. We investigated the role of endogenous angiotensin II in ischemia/reperfusion injury by studying the effects of the angiotensin II type 1 receptor antagonist candesartan on myocardial function, infarct size, and perfusion after ischemia/reperfusion. Anesthetized pigs were subjected to 45 min of regional ischemia and 240 min of reperfusion. Starting 5 min before reperfusion, four groups of pigs (n = 6 in each) received coronary venous retroinfusion of candesartan (0.2, 2, or 20 microg/kg) or vehicle for 30 min. Myocardial regional blood flow was measured with radioactive microspheres in two separate groups (n = 6 in each) given 20 microg/kg candesartan or vehicle. Retroinfusion of 20 microg/kg of candesartan improved recovery of left ventricular systolic segment shortening measured by sonomicrometry in the ischemic area compared with 0.2 microg/kg of candesartan and vehicle. Infarct size, as a percentage of the area at risk, was smaller in the 2 and 20 microg/kg groups than in the vehicle group (39.1 +/- 11.6% and 34.8 +/- 10.2% vs. 78.3 +/- 8.9%, p < 0.01). There was no difference between candesartan and vehicle in their effects on regional myocardial blood flow. Angiotensin II type 1 receptor blockade supports myocardial functional recovery and reduces infarct size. This effect is not related to improved regional myocardial blood flow during reperfusion.
Department of Cardiology, Karolinska Hospital, Stockholm, Sweden.
M
M
Shimizu
Q D
QD
Wang
P O
PO
Sjöquist
L
L
Rydén
D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001562:Benzimidazoles / Q000097:blood / Q000494:pharmacology*; D001713:Biphenyl Compounds; D003326:Coronary Circulation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D009203:Myocardial Infarction / Q000503:physiopathology / Q000517:prevention & control; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D013552:Swine; D013777:Tetrazoles / Q000097:blood / Q000494:pharmacology*; D016277:Ventricular Function, Left / Q000187:drug effects
D057911:Angiotensin Receptor Antagonists; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D013777:Tetrazoles; C081643:candesartan