Carvedilol attenuates CPB-induced apoptosis in dog heart: regulation of Fas/FasL and caspase-3 pathw

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Objective To evaluate the effects of Carvedilol on cardiopulmonary bypass (CPB)-induced myocardiocyte apoptosis and its effect on regulation of Fas, FasL expression, caspase-3 activity and oxidative stress in the left ventricle (LV) in this setting.Methods Ten adult dogs undergoing conventional hypothermic CPB were randomly divided into control and Carvedilol treated groups (n=5, respectively). Dogs in Carvedilol treated group 3 μg*min-1*kg-1 received a bolus of Carvedilol (1 mg/kg) intravenously and a maintenance dosage of Carvedilol for 3 hours after the reperfusion of the heart. Dogs in control group received no carvediolol. LV samples were obtained before, during and 3 hours after CPB. In situ nick end-labeling (TUNEL) technique was used to detect the apoptotic cells. The expressions of Fas and FasL were detected immunohistochemically and quantified by fluorescence activated cell sorting (FACS). The activity of caspase-3 enzyme and malondialdehyde (MDA) level were measured by cleavage of Z-DEVD-AMC substrate and thiobarbituric acid reactive substances (TBARS) method, respectively. Results Before and during CPB, all the parameters were not significantly different between groups (P>0.05). After CPB, these parameters in both groups were significantly elevated compared with those of before and during CPB (P
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