Regression of left ventricular hypertrophy using captopril or TCV-116 reduced the incidence of ischemia-induced VT/Vf to 0% and 10%, respectively, compared to 63% in untreated hypertensive rats.
Does regression of left ventricular hypertrophy by antihypertensive treatment prevent ischemia-induced lethal arrhythmias in spontaneously hypertensive rats?
Regression of left ventricular hypertrophy by angiotensin II blockade reduces electrical inhomogeneity and prevents ischemia-induced lethal arrhythmias in a rat model.
Absolute Event Rate: 0% vs 63%
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.
Kohya et al. (Mon,) conducted a other in Left ventricular hypertrophy. Captopril, TCV-116, or hydralazine vs. Untreated SHR and WKY rats was evaluated on Incidence of ventricular tachycardia or ventricular fibrillation (VT/Vf) after left coronary artery occlusion. Regression of left ventricular hypertrophy using captopril or TCV-116 reduced the incidence of ischemia-induced VT/Vf to 0% and 10%, respectively, compared to 63% in untreated hypertensive rats.