抄録
Background: Recent studies have revealed that tachyarrhythmias cause electrical and structural remodeling of cardiomyocytes, and that apoptosis contributes to myocardial remodeling in certain arrhythmias. We suspected that tachyarrhythmias lead to arrhythmogenic substrates through the induction of apoptosis, and then may tend to initiate and perpetuate themselves. In this study, we tested the hypothesis that rapid electrical stimulation of cardiomyocytes in culture causes apoptosis. Methods and Results: The cultured H9c2 cardiac cells were subjected to rapid electrical stimulation for 72 hours at a pacing frequency of 5 Hz. To determine the degree of apoptosis, the percentage of hypodiploid cells, mitochondrial transmembrane potential (ΔΨm), and activities of caspases-3, -8, and -9 were measured quantitatively. Compared with the cells in the absence of stimulation, the cells subjected to rapid stimulation showed apoptosis in terms of the appearance of hypodiploid cells (4.7±0.5% vs 31.0±8.5%), loss of ΔΨm (5.3±0.5% vs 19.5±2.7%), and activation of all caspases tested (caspase-3, 0.050±0.015 vs 0.117±0.030; caspase-8, 0.038±0.004 vs 0.056±0.002; caspase-9, 0.029±0.003 vs 0.046±0.010) with statistically significant differences. Conclusions: Rapid electrical stimulation of H9c2 cells induced apoptosis via both the death receptor and mitochondrial pathways. The present in vitro model may be useful to elucidate mechanisms of tachycardia-induced myocardial remodeling via apoptosis, and to lead to therapies for preventing the arrhythmogenic substrate development. [J Physiol Sci. 2006;56 Suppl:S124]
