Carvedilol attenuates CPB-induced apoptosis in dog heart: regulation

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<0.028, respectively). However, the number of apoptotic cells in Carvedilol treated group was significantly decreased compared with that of the control group (P<0.021). The expressions of Fas and FasL were significantly downregulated by Carvedilol (P<0.001 and 0.003, respectively). The caspase-3 activity and the content of MDA in the Carvedilol treated group was also significantly reduced (P<0.026 and 0.005, respectively). Conclusions Carvedilol significantly reduces CPB-induced cardiomyocyte apoptosis in dog hearts and the reduction of cardiomyocyte apoptosis is associated with downregulation of Fas and FasL expression, inhibition of caspase-3 activity and oxidative stress in LV.     

Regulatory Effect of Bcl-2 Family Proteins in CPB-induced Cardiomyocyte Apoptosis in Dog Hearts

Recent studies showed that apoptosis was in-volved in the pathophysiology of various heart dis-eases including congestive heart failure,ischemia-reperfusion injury,allograft,myocarditis,hypother-mic lung preservation and other cardiac pathologies.So far,there have no reports on the myocyte apopto-sis in human hearts following conventional hypother-mic cardiopulmonary bypass,and the mechanismsunderlying myocardiocyte apoptosis are still poorlyunderstood.The aim of the present study was to in-ve…