REGRESSION OF LEFT-VENTRICULAR HYPERTROPHY PREVENTS ISCHEMIA-INDUCED LETHAL ARRHYTHMIAS - BENEFICIAL EFFECT OF ANGIOTENSIN-II BLOCKADE

To evaluate the preventive effect of regression of left ventricular hy pertrophy (LVH) on sudden cardiac death (SCD), the incidence of ventri cular tachycardia or ventricular fibrillation (VT/Vf) after left coron ary artery occlusion in Langendorff preparations was studied in the fo llowing five groups: (1) spontaneously hypertensive rats (SHR) without treatment (SHR-N), (2) SHR treated with captopril (SHR-C), (3) SHR tr eated with the angiotensin II receptor antagonist TCV-116 (SHR-A), (4) SHR treated with hydralazine (SHR-H), and (5) Wistar-Kyoto (WKY) rats . Although blood pressure was equally lowered in all treated groups, S HR-C and SHR-A but not SHR-H showed regression of LVH. The incidence o f VT/Vf was 5% in WKY rats, 63% in SHR-N (P<.005 versus WKY rats), 0% in SHR-C, 10% in SHR-A, and 45% in SHR-H (P<.05 versus WKY rats). Furt her evaluation of the effect of TCV-116 revealed that SHR treated with a low dose of TCV-116 (1 mg/kg per day) showed a decrease in left ven tricular mass with only a little decrease in blood pressure and that t he incidence of VT/Vf was reduced in association with the degree of re gression of LVH. Electrophysiological study using microelectrode techn iques revealed that in the LVH groups (SHR-N and SHR-H), the action po tential duration (APD) of the left ventricular papillary muscle was mo re prolonged than in WKY rats, whereas APD shortened to a greater exte nt during superfusion with a hypoxia/no-glucose solution. APD showed n o difference in the regression groups (SHR-C and SHR-A) compared with the WKY group. Shortening of APD at 75% repolarization 30 minutes afte r exposure to the hypoxia/no-glucose solution was 34% in WKY rats, 53% in SHR-N (P<.05 versus WKY rats), 32% in SHR-C, 28% in SHR-A, and 47% in SHR-H (P<.05 versus WKY rats). These results suggest that LVH has a greater susceptibility to VT/Vf during acute myocardial ischemia bec ause of greater APD dispersion between the normal and ischemic zones. The reduction of electrical inhomogeneity in regressed LVH may prevent SCD caused by ischemia-induced lethal arrhythmias. Effective regressi on of LVH by angiotensin II blockade may play a beneficial role in the prevention of SCD.