Background: Triggered arrhythmias arise from delayed afterdepolarizations (DADs), with Ca
2+ waves playing an important role in their formation. In ventricular hypertrophy, however, it remains unclear how Ca
2+ waves change their propagation features and affect arrhythmogenesis. We addressed this important issue in a rat model of hypertrophy.
Methods and Results: Rats were given a subcutaneous injection of 60mg/kg monocrotaline (MCT-rats) or solvent (Ctr-rats). After 4 weeks, MCT-rats showed high right ventricular (RV) pressure and RV hypertrophy. Trabeculae were dissected from 36 right ventricles. The force was measured using a silicon strain gauge and regional intracellular Ca
2+ ([Ca
2+]
i) was determined using microinjected fura-2. Reproducible Ca
2+ waves were induced by stimulus trains (2Hz, 7.5s). MCT-rats showed a higher diastolic [Ca
2+]
i and faster and larger Ca
2+ waves (P<0.01). The velocity and amplitude of Ca
2+ waves were correlated with the diastolic [Ca
2+]
i both in the Ctr- and MCT-rats. The velocity of Ca
2+ waves in the MCT-rats was larger at the given amplitude of Ca
2+ waves than that in the Ctr-rats (P<0.01). The amplitude of DADs was correlated with the velocity and amplitude of Ca
2+ waves in the Ctr- and MCT-rats.
Conclusions: The results suggest that an increase in diastolic [Ca
2+]
i and an increase in Ca
2+ sensitivity of the sarcoplasmic reticulum Ca
2+ release channel accelerate Ca
2+ waves in ventricular hypertrophy, thereby causing arrhythmogenesis. (
Circ J 2011;
75: 1343-1349)
View full abstract