The aim of this study was to investigate if the
angiotensin II AT1 receptor antagonist
candesartan in
antihypertensive plasma concentrations improves myocardial function and limits
infarct size in anesthetized pigs. Animals were subjected to 45 min of regional
ischemia and 240 min of reperfusion. Starting 60 min before
ischemia, two groups of pigs (n = 6 in each) received either
candesartan (25 micrograms/kg bolus followed by a continuous infusion at a rate of 14 micrograms/kg/h) or the corresponding volume of vehicle throughout the study period. Left ventricular systolic segment shortening (%SS) was measured by sonomicrometry, and
infarct size was determined by triphenyl tetrazolium
chloride staining. The plasma concentration of
candesartan during the experiment was between 100 and 150 nmol/L, which was considered to be within the therapeutic range. Neither
candesartan nor vehicle affected hemodynamics or coronary blood flow prior to
ischemia. Compared to vehicle,
candesartan improved recovery of %SS in the ischemic area. At 240 min of reperfusion, the %SS was significantly higher in pigs given
candesartan than in pigs given vehicle (7.1 +/- 0.87% vs-1 +/- 1.79%; p < 0.01). In both groups the area at risk was approximately 20% of the left ventricle.
Infarct size as a percentage of the area at risk was significantly smaller in the
candesartan group than in the vehicle group (46 +/- 3.0 vs 73 +/- 3.6%; p < 0.01). The results suggest that
angiotensin II AT1 receptor blockade, obtained in
antihypertensive plasma concentrations, supports myocardial functional recovery and limits
infarct size.