DISPERSION OF VENTRICULAR REPOLARIZATION IN LEFT-VENTRICULAR HYPERTROPHY - INFLUENCE OF AFTERLOAD AND DOFETILIDE

Introduction: Increased dispersion of ventricular repolarization is ob served in cardiac hypertrophy and is associated with sudden cardiac de ath. At present, there a's little information about the effects of car diac hemodynamics and antiarrhythmic drugs on dispersion of repolariza tion in disease states, We compared the effects of increasing afterloa d and the Class III antiarrhythmic drug, dofetilide, on dispersion of ventricular repolarization in hypertrophied rabbit hearts to normal ra bbit hearts, Methods and Results: Cardiac hypertrophy was induced in r abbits by abdominal aortic banding. Isolated hearts were studied 49 +/ - 4 days postsurgery in the working beast mode using a blood-buffer pe rfusate, The action potential duration (APD) was measured from eight s ites on the epicardium of the heart at low (50 +/- 7 mmHg) afterload a nd high afterload (97 +/- 12 mmHg) at baseline and during dofetilide p erfusion. APD dispersion, determined as the difference between the max imal and minimal APD, was greater in hypertrophied hearts (42 +/- 8 ms ec) compared with control hearts (26 +/- 8 msec, P < 8.05) at baseline and low afterload, Increasing afterload caused a decrease in APD disp ersion in hypertrophied hearts (P < 0.05) brat not ha control hearts, and APD dispersion was similar in hypertrophied hearts (31 +/- 9 msec) compared with control hearts (30 +/- 9 msec, P = NS), During dofetili de perfusion, APD dispersion remained greater in hypertrophied hearts (60 +/- 39 msec) compared with control hearts (30 +/- 13 msec, P < 0.0 5) at low afterload but not high afterload, Increasing afterload cause d 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 am increase ire afterload was - 18 +/ - 21 msec in control hearts and 7 +/- 21 ms in hypertrophied hearts (P < 0.05), Conclusion: Epicardial APD dispersion decreases in hypertrop hied hearts following an increase in afterload, and this response is m ediated ha part by the absence of afterload-induced shortening of the APD, This effect may be due in part to altered responses of the delaye d rectifying current to cardiac loading conditions in the setting of c ardiac hypertrophy.