Does isoproterenol-induced hypertrophy alter regional action potential duration in rat left ventricular myocytes?
Cardiac hypertrophy reverses the normal endocardial/epicardial gradient in action potential duration, which may explain T-wave inversion and contribute to arrhythmogenesis.
Background In cardiac hypertrophy, ECG T-wave changes imply an abnormal sequence of ventricular repolarization. We investigated the hypothesis that this is due to changes in the normal regional differences in action potential duration. We assessed the contribution of potassium- and calcium-dependent currents to these differences. Both the altered sequence of ventricular repolarization and the underlying cellular mechanisms may contribute to the increased incidence of ventricular arrhythmias in hypertrophy. Methods and Results Rats received daily isoproterenol injections for 7 days. Myocytes were isolated from basal subendocardial (endo), basal midmyocardial (mid), and apical subepicardial (epi) regions of the left ventricular free wall. Action potentials were stimulated with patch pipettes at 37°C. The ratio of heart weight to body weight and mean cell capacitance are increased by 22% and 18%, respectively, in hypertrophy compared with controls ( P <.001). Normal regional differences in action potential duration at 25% repolarization (APD 25 ) are reduced in hypertrophy (control: endo, 11.4±0.9 ms; mid, 8.2±0.9 ms; epi, 5.1±0.4 ms; hypertrophy: endo, 11.6±0.9 ms; mid, 10.4±0.8 ms; epi, 7.8±0.6 ms). The regional differences in APD 25 are still present in 3 mmol/L 4-aminopyridine. Hypertrophy affects APD 75 differently, depending on the region of origin of myocytes (ANOVA P <.05). APD 75 is shortened in subendocardial myocytes but is prolonged in subepicardial myocytes (control: endo, 126±7 ms; epi, 96±10 ms; hypertrophy: endo, 91±6 ms; epi, 108±7 ms). These changes in APD 75 are altered by intracellular calcium buffering. Conclusions Normal regional differences in APD and the changes observed in hypertrophy are only partially explained by differences in I to1 . In hypertrophy, the normal endocardial/epicardial gradient in APD 75 appears to be reversed. This may explain the T-wave inversion observed and will have implications for arrhythmogenesis.
Shipsey et al. (Tue,) studied this question.