B. Preckel et al., Influence of the angiotensin II AT(1) receptor antagonist irbesartan on isehemia/reperfusion injury in the dog heart, BAS R CARD, 95(5), 2000, pp. 404-412
The aim of the present study was to investigate whether the non-peptide ang
iotensin II type 1 (AT(1)) receptor antagonist irbesartan (SR 47436, EMS 18
6295, 2-n-butyl-3[2'-(1H-tetrazol-5-yl)-biphenyl-4-yl)methyl]-1,3-diaza-spi
ro[4,4]non-1-en-4-one) has myocardial protective effects during regional my
ocardial ischemia/reperfusion in vivo. Eighteen anesthetized open-chest dog
s were instrumented for measurement of left ventricular and aortic pressure
(tip manometer and pressure transducer, respectively), and coronary flow (
ultrasonic flowprobes). Regional myocardial function was assessed by Dopple
r displacement transducers as systolic wall thickening (sWT) in the antero-
apical and the postero-basal wall. The animals underwent 1 h of left anteri
or descending coronary artery (LAD) occlusion and subsequent reperfusion fo
r 3 hours. Irbesartan (10 mg kg(-1), n = 9) or the vehicle (KOH, control, n
= 9) was injected intravenously 30 min before LAD occlusion. Regional myoc
ardial blood flow (RMBF) was measured after irbesartan injection and at 30
min LAD occlusion using colored microspheres. Infarct size was determined b
y triphenyltetrazolium chloride staining after 3 h of reperfusion. There wa
s no recovery of sWT in the LAD perfused area in both groups at the end of
the experiments (systolic bulging, -15.1 +/- 6.1 % of baseline (irbesartan)
vs. -12.3 +/- 3.0 % (control), mean +/- SEM). Irbesartan led to an increas
e in RMBF in normal myocardium (2.47 +/- 0.40 vs. 1.35 +/- 0.28 ml min(-1)
g(-1), P < 0.05), and also to an increase in collateral blood flow to the i
schemic area (0.27 +/- 0.04 vs. 0.17 +/- 0.02 ml min(-1) g(-1), P = < 0.05)
. Infarct size (percent of area at risk) was 24.8 +/- 3.2 % in the treatmen
t group compared with 26.9 +/- 4.8 % in the control group (P = 0.72). These
results indicate that a blockade of angiotensin II AT(1) receptors with ir
besartan before coronary artery occlusion led to an increase in RMBF, but d
id not result in a significant reduction of myocardial infarct size.