Investigation of apoptosis in a canine model of chronic heart failure induced by tachycardia.

Abstract

Participation of apoptosis during the development of pacing-induced dilated cardiomyopathy is not fully understood. After 7 weeks rapid right ventricular pacing, gene expressions of Bax, Bcl-2 and Caspase-3 were measured by RTQ-PCR from interventricular septum biopsies that were taken weekly in 21 beagle dogs during the development of heart failure. We evaluated protein levels of these genes by Western blot and DNA fragmentation by TUNEL method from autopsy samples. Gene expression of Bax remained unchanged during the pacing period; Bcl-2 mRNA expression transiently decreased in moderate heart failure and their ratio (Bcl-2/Bax) was not significantly altered. Caspase-3 gene expression increased in heart failure. Compared to the control group, expression of Bax and Bcl-2 proteins and their ratio were increased in dogs only after 4 weeks of pacing. No band of activated Caspase was found in the normal nor in the paced myocardium. In the TUNEL assay there was no significant difference between numbers of apoptotic cells in any of the groups, although a few TUNEL-positive cells were detected in the paced groups. Our results are not in favour of apoptosis in the pathogenesis of heart failure in this model and may be it could be attributed to activation of other systems.