Carvedilol, a selective alpha(1) and non-selective
beta-adrenoceptor antagonist and
antioxidant, has been shown to provide significant cardiac protection in animal models of
myocardial ischemia. To further explore the mechanisms contributing to the efficacy of
carvedilol cardioprotection, the effects of
carvedilol on hemodynamic variables,
infarct size and
myeloperoxidase activity (an index of neutrophil accumulation) were compared with a beta(1) selective
adrenoceptor antagonist,
bisoprolol.
Carvedilol (1 mg/kg) or
bisoprolol (1 mg/kg) was given intravenously 5 min before reperfusion. In vehicle-treated rabbits,
ischemia (45 min) and reperfusion (240 min) resulted in significant increases in left ventricular end diastolic pressure, large
myocardial infarction (64.7+/-2.6% of area-at-risk) and a marked increase in
myeloperoxidase activity (64+/-14 U/
g protein in area-at-risk).
Carvedilol treatment resulted in sustained reduction of the pressure-rate-index and significantly smaller
infarcts (30+/-2.9, P<0.01 vs. vehicle) as well as decreased
myeloperoxidase activity (26+/-11 U/
g protein in area-at-risk, P<0.01 vs. vehicle). Administration of
bisoprolol at 1 mg/kg resulted in a pressure-rate-index comparable to that of
carvedilol and also decreased
infarct size (48.4+/-2.5%, P<0.001 vs. vehicle, P<0.05 vs.
carvedilol), although to a significantly lesser extent than that observed with
carvedilol. Treatment with
bisoprolol failed to reduce
myeloperoxidase activity in the ischemic myocardial tissue. In addition,
carvedilol, but not
bisoprolol, markedly decreased cardiac
membrane lipid peroxidation measured by
thiobarbituric acid formation. Taken together, this study suggests that the superior cardioprotection of
carvedilol over
bisoprolol is possibly the result of
carvedilol's
antioxidant and anti-neutrophil effects, not its hemodynamic properties.