Abstract 11563: Vasopeptidase Inhibitor, Omapatrilat, Enhances Cardiac Positive Inotropic and Lusitropic Responses to Dobutamine and Exercise in Heart Failure: Assessment by Pressure-Volume Analysis
Background: Previous studies have suggested that both angiotensin II (ANGII) and endothelin-1 (ET-1) may alter cardiac adrenergic inotropic response in heart failure (HF). The increase in natriuretic peptides opposes several neurohormonal pathways, including ANGII and ET-1. We hypothesized that omapatrilat (OMA), a new vasopeptidase inhibitor that provides concomitant inhibition of angiotensin-converting enzyme (ACE) and neutral endopeptidase, may improve adrenergic inotropic responsiveness in HF.
Methods: We studied the effect of OMA (0.04 mg/kg, IV) on left ventricular (LV) relaxation and contractile response to dobutamine (DOB, 6 μg/kg/min, IV) and exercise in 8 chronically instrumented conscious dogs after pacing-induced CHF. LV contractile performance was measured by the slope of LV end-systolic pressure-volume relations.
Results: After HF, OMA produced a significant decrease in the time constant of relaxation (τ, 19.2%, 39.5 ± 2.0 vs 48.9 ± 6.1 msec) and caused increases in the slope of LV P-V relations, EES (25%, 4.5 ± 1.2 vs 3.6 ± 1.3 mmHg/ml) and MSW (16.1%, 62.9 ± 7.0 vs 54.2 ± 5.7 mmHg). Combination of DOB and OMA produced much greater reduction in τ (22.5%, 33.7 ± 1.9 vs 43.5 ± 2.8 mmHg/ml, P<0.05) and greater increases in EES (51.1%, 6.8 ± 0.7 vs 4.5 ± 0.7, mmHg/ml) and MSW (23.7%, 83.6 ± 8.9 vs 67.6 ± 9.7 mm/Hg, P<0.05) than dobutamine alone. After OMA, dP/dtmax, stroke volume and MSW were higher during CHF exercise. LV diastolic pressures were lower during CHF exercise after OMA.
Conclusion: In pacing-induced HF, OMA improves LV systolic and diastolic function at rest and during adrenergic stimulation and exercise.
- © 2013 by American Heart Association, Inc.