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© 1995 American Heart Association, Inc.
Articles |
Regression of Left Ventricular Hypertrophy Prevents Ischemia-Induced Lethal Arrhythmias
Beneficial Effect of Angiotensin II Blockade
From the Department of Cardiovascular Medicine (T.K., H.Y., A.K.) and the First (H.S.) and Second (N.T., M.K.) Departments of Pharmacology, Hokkaido University School of Medicine, Sapporo, Japan, and the Department of Pharmacology (H.N.), Chiba (Japan) University School of Medicine.
Correspondence to T. Kohya, MD, Department of Cardiovascular Medicine, Hokkaido University School of Medicine, Kita 15, Nishi 7, Kita-ku, Sapporo 060, Japan.
Abstract To evaluate the preventive effect of regression of left ventricular hypertrophy (LVH) on sudden cardiac death (SCD), the incidence of ventricular tachycardia or ventricular fibrillation (VT/Vf) after left coronary artery occlusion in Langendorff preparations was studied in the following five groups: (1) spontaneously hypertensive rats (SHR) without treatment (SHR-N), (2) SHR treated with captopril (SHR-C), (3) SHR treated 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, SHR-C and SHR-A but not SHR-H showed regression of LVH. The incidence of 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). Further 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 ventricular mass with only a little decrease in blood pressure and that the incidence of VT/Vf was reduced in association with the degree of regression of LVH. Electrophysiological study using microelectrode techniques revealed that in the LVH groups (SHR-N and SHR-H), the action potential duration (APD) of the left ventricular papillary muscle was more prolonged than in WKY rats, whereas APD shortened to a greater extent during superfusion with a hypoxia/no-glucose solution. APD showed no difference in the regression groups (SHR-C and SHR-A) compared with the WKY group. Shortening of APD at 75% repolarization 30 minutes after 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 because 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 regression of LVH by angiotensin II blockade may play a beneficial role in the prevention of SCD.
Key Words: regression of left ventricular hypertrophy • sudden cardiac death • ischemia-induced lethal arrhythmias • dispersion of action potential durations • angiotensin II blockade
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