Background: Progressive ventricular remodeling after myocardial damage is associated with a poor prognosis. Optimal prevention of the histopathological processes involved in remodeling requires a more complete understanding of the mechanisms involved in initiating and maintaining these structural changes. Since the sympathetic nervous system and the renin-angiotensin system may be involved in the remodeling process, the structural effects of pharmacological inhibitors have been evaluated in a canine model of localized myocardial injury resulting from transmyocardial DC shock. Methods and Results: The study is comprised of two protocols run in series. In protocol 1, zofenopril (Z), a converting enzyme inhibitor (CEI), prevented the increase in left ventricular mass (LVM) and end-diastolic volume (LVV) observed in the control group (C) at 16 weeks (Z: LVM, 69.8±3.4 to 65.4±2.6 g, P=NS; LVV, 45.4±2.7 to 51.6±2.7 mL, P=NS; C: LVM, 68.4±3.2 to 91.4±2.9 g, P=.0001; LVV, 56.6±3.0 to 71.9±2.4 mL, P=.0003). Terazosin, an α1- adrenoceptor antagonist, failed to prevent remodeling at 16 weeks despite continued receptor blockade. In protocol 2, the antiremodeling effect of full-dose CEI therapy with ramipril was confirmed. Low-dose ramipril that exerted no hemodynamic effect failed to prevent remodeling (LVM, 89.7±4.6 to 105.7±3.4 g, P=.01; LVV, 61.8±3.8 to 76.8±3.3 mL, P=.002). An angiotensin it subtype 1 receptor blocker also failed to prevent the increase in LVM or LVV (LVM, 89.0±4.6 to 109.7±5.3 g, P=.0001; LVV, 66.0±1.9 to 78.4±3.6 mL, P=.007). Conclusions: High-dose CEI therapy can prevent progressive structural changes resulting from localized myocardial damage induced by DC shock. The failure of α1-adrenoceptor blockade and angiotensin II subtype 1 blockade to attenuate remodeling argues against an important direct role for norepinephrine acting through α1-receptors or angiotensin II acting through the type I receptor in the remodeling process in this model.
- receptors, adrenergic, alpha
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
- Physiology (medical)