Acceleration of Ca²⁺ Waves in Monocrotaline-Induced Right Ventricular Hypertrophy in the Rat

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Background: Triggered arrhythmias arise from delayed afterdepolarizations (DADs), with Ca²⁺ waves playing an important role in their formation. In ventricular hypertrophy, however, it remains unclear how Ca²⁺ 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 Ca²⁺ ([Ca²⁺]_i) was determined using microinjected fura-2. Reproducible Ca²⁺ waves were induced by stimulus trains (2Hz, 7.5s). MCT-rats showed a higher diastolic [Ca²⁺]_i and faster and larger Ca²⁺ waves (P<0.01). The velocity and amplitude of Ca²⁺ waves were correlated with the diastolic [Ca²⁺]_i both in the Ctr- and MCT-rats. The velocity of Ca²⁺ waves in the MCT-rats was larger at the given amplitude of Ca²⁺ waves than that in the Ctr-rats (P<0.01). The amplitude of DADs was correlated with the velocity and amplitude of Ca²⁺ waves in the Ctr- and MCT-rats. Conclusions: The results suggest that an increase in diastolic [Ca²⁺]_i and an increase in Ca²⁺ sensitivity of the sarcoplasmic reticulum Ca²⁺ release channel accelerate Ca²⁺ waves in ventricular hypertrophy, thereby causing arrhythmogenesis. (Circ J 2011; 75: 1343-1349)