Dispersion of Ventricular Repolarization in Left Ventricular Hypertrophy: Influence of Afterload and Dofetilide

Abstract

Modulators of APD Dispersion in Hypertrophy. Introduction: Increased dispersion of ventricular repolarization is observed in cardiac hypertrophy and is associated with sudden cardiac death. At present, there is little information about the effects of cardiac hemodynamics and antiarrhythmic drugs on dispersion of repolarization in disease states. We compared the effects of increasing afterload and the Class III antiarrhythmic drug, dofetilide, on dispersion of ventricular repolarization in hypertrophied rabbit hearts to normal rabbit hearts. Methods and Results: Cardiac hypertrophy was induced in rabbits by abdominal aortic banding. Isolated hearts were studied 49 ± 4 days postsurgery in the working heart mode using a blood‐buffer perfusate. The action potential duration (APD) was measured from eight sites on the epicardium of the heart at low (50 ± 7 mmHg) afterload and high afterload (97 ± 12 mmHg) at baseline and during dofetilide perfusion. APD dispersion, determined as the difference between the maximal and minimal APD, was greater in hypertrophied hearts (42 ± 8 msec) compared with control hearts (26 ± 8 msec, P < 0.05) at baseline and low afterload. Increasing afterload caused a decrease in APD dispersion in hypertrophied hearts (P < 0.05) but not in control hearts, and APD dispersion was similar in hypertrophied hearts (31 ± 9 msec) compared with control hearts (30 ± 9 msec, P= NS). During dofetilide perfusion, APD dispersion remained greater in hypertrophied hearts (60 ± 39 msec) compared with control hearts (30 ± 13 msec, P < 0.05) at low afterload but not high afterload. Increasing afterload caused shortening of the APD in most regions of the control hearts, whereas APD did not shorten significantly in hypertrophied hearts at baseline and tended to increase during dofetilide perfusion. During dofetilide perfusion, the maximal change in APD recorded from the posterior wall of the left ventricle following an increase in afterload was −18 ± 21 msec in control hearts and 7 ± 21 ms in hypertrophied hearts (P < 0.05). Conclusion: Epicardial APD dispersion decreases in hypertrophied hearts following an increase in afterload, and this response is mediated in part by the absence of afterload‐induced shortening of the APD. This effect may be due in part to aftered responses of the delayed rectifying current to cardiac loading conditions in the setting of cardiac hypertrophy.