Effects of angiotensin II type 1 receptor antagonist (candesartan) in preventing fatal ventricular arrhythmias in dogs during acute myocardial ischemia and reperfusion
N. Hiura et al., Effects of angiotensin II type 1 receptor antagonist (candesartan) in preventing fatal ventricular arrhythmias in dogs during acute myocardial ischemia and reperfusion, J CARDIO PH, 38(5), 2001, pp. 729-736
Citations number
41
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
Fatal arrhythmias may be prevented by long-term oral administration of angi
otensin-converting enzyme (ACE) inhibitors or angiotensin II type 1 (AT(1))
receptor antagonists. However, there have been no studies evaluating the e
lectrophysiologic changes that occur with the acute administration of AT(1)
receptor antagonists during acute myocardial ischemia and reperfusion. Thi
s study aimed to evaluate the ability of candesartan to prevent fatal arrhy
thmias during acute myocardial ischemia and reperfusion. The left anterior
descending (LAD) coronary artery was ligated for 10 min and then reperfused
for 10 min in 45 adult mongrel dogs. Candesartan (1 mg/kg) or saline was a
dministered intravenously 10 min before ligation of the LAD coronary artery
(candesartan group [n = 20] and control group [n = 25] respectively). Chan
ges in ventricular effective refractory period (ERP) and intramyocardial co
nduction time (ICT) in the risk area were compared during LAD occlusion and
reperfusion. Ischemia-induced shortening of ERP was inhibited in the cande
sartan group compared with the control. There was a 4.7 +/- 5.8% increase i
n ERP in the candesartan group, compared with a 11.5 +/- 6.3% shortening in
the control group (p < 0.01). Prolongation of ICT was inhibited in the can
desartan group compared with the control group during both ischemia and rep
erfusion (maximal prolongation of ICT: 0.1 +/- 3.0% vs. 37.7 +/- 9.6%, resp
ectively; p < 0.01). Incidence of ventricular fibrillation was lower in the
candesartan group than in the control group (25% [5/20] vs. 72% [18/25], r
espectively; p < 0.01). Candesartan suppresses changes in ERP and ICT durin
g acute myocardial ischemia and reperfusion, suggesting that candesartan ca
n prevent the development of fatal arrhythmias.