Early Versus Delayed Angiotensin-Converting Enzyme Inhibition in Experimental Chronic Heart Failure

Abstract

In this rat model of CHF, early and delayed ACE inhibitor treatments both increase survival and exert similar beneficial effects on cardiac hemodynamics and remodeling. Although early treatment prevents the development of ventricular dysfunction and remodeling, delayed treatment is capable of reversing cardiac hypertrophy and remodeling, as well as ventricular dysfunction. Thus, ACE inhibitors exert marked beneficial effects even when treatment is initiated late into the evolution of heart failure (ie, at a time of established ventricular dysfunction and remodeling).

Long-Term Survival and Hemodynamics After Endothelin-A Receptor Antagonism and Angiotensin-Converting Enzyme Inhibition in Rats With Chronic Heart Failure

“…As already reported with selective ET A , mixed ET A -ET B receptor blockers, 8,23,24 and ACE inhibitors, 22,25,26 LU 135252 and trandolapril decrease arterial blood pressure, improve cardiac hemodynamics, limit left ventricular remodeling, and increase both fractional shortening and posterior wall thickening. This, together with the decrease in cardiac preload and afterload, results in an increased stroke volume and cardiac output and prevents the deterioration of global LV function, without affecting LV dP/dt max .…”

Collagen content, but not the ratios of collagen type III/I mRNAs, differs among hypertensive, alcoholic, and idiopathic dilated cardiomyopathy

“…This occurred in spite of the use of high doses of angiotensin-converting enzyme inhibitors. Experimental studies show that these drugs are able to prevent and revert cardiac dysfunction and remodeling, even restoring myocardial structure to normal (10,12,(22)(23)(24). The fact that all patients were receiving optimized treatment is consistent with the idea that the renin-angiotensin-aldosterone system is not the only determinant of myocardial fibrosis, stressing the importance of other modulating factors triggered by neurohumoral activation leading to myocyte necrosis and apoptosis.…”

Long-Term Heart Rate Reduction Induced by the Selective I f Current Inhibitor Ivabradine Improves Left Ventricular Function and Intrinsic Myocardial Structure in Congestive Heart Failure

“…Indeed, the reduced blood pressure, major LV dilatation, and increased LV end-diastolic pressure, as well as diminished cardiac output, illustrate the deteriorated pathophysiological status of the untreated animals throughout the study, in agreement with previous studies. [17][18][19][20] In this context of CHF, ivabradine induces a specific dose-dependent HRR. This pharmacological effect of this selective I f inhibitor is independent of the pathophysiological status, because ivabradine induces a similar HRR in normal rats.…”