Experimental Study Of Cardiomyocyte Apoptosis And Tachycardia-induced Cardiomyopathy

Objective: Tachycardia-induced cardiomyopathy is a reversible cause of heart failure, but the mechanism and pathogenesis is poorly understood. The goal of this study is to establish experimental model of tachycardia-induced cardiomyopathy in swine, examinate the development changes of cytokines including atrial natriuretic peptide and tumour necrosis factor alpha plasma concentration by radioimmunoassay, and histopathology is used to assess cardiomyocyte apoptosis. This study evaluate relationships between cytokines levels and cardiomyocyte apoptosis index to determine whether cytokines and apoptosis participate in the pathogenesis of tachycardia-induced cardiomyopathy.Methods: Studies were performed in three groups of conscious pigs: 1) those subjected to rapid right atrial pacing for 1 week (240 beats per minute; n=5) , 2) those subjected to supraventricular tachycardia for 4 weeks (n=5) and 3) sham-operated controls (n=5) . We serially examined plasma ANP and TNF-αconcentration at base line and again at 1, 2, 3, 4 week following rapid atrial pacing. Apotosis was assessed by terminal dUTP nick-end labeling (TUNEL) in each group.Results: The experimental model of tachycardia-induced cardiomyopathy was successfully established. Plasma ANP peaked at 1 week and remained steady state thereafter. However, plasma TNF-αincreased more progressively and peaked at 4 weeks. Significant apoptosis developed after atrium tachypacing, with maximum changes in left ventricle, but faster and transient in left atrial. Apoptosis in left atrial were mostly endothelial cells while in left ventricle were myocytes. Atrial cardiomyocyte apoptosis index is positively correlated with ANP level. While ventricular cardiomyocyte apoptosis is positively correlated with both ANP and TNF-α.Conclusions: Plasma levels of ANP and TNF-αare significantly increased during the development and progression of tachycardia-induced cardiomyopathy. ANP is sharply increased at 1 week and remaines steady state thereafter, and TNF-αincreases progressively and peak at 4 weeks. Both ANP and TNF-αcan be used as indicators of clinical diagnosis and heart function and prognosis in tachycardia-induced cardiomyopathy. Cardiomyocyte apoptosis participate in the pathogenesis of tachycardia-induced cardiomyopathy. There are qualitative and quantitative differences in atrial versus ventricular remodeling in tachycardia-induced cardiomyopathy, with potentially important consequences for understanding underlying mechanisms and developing new therapeutic approaches.