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Comparative Hemodynamic Effects of MK-422, a Converting Enzyme Inhibitor, and a Renin Inhibitor in Dogs with Acute Left Ventricular Failure

1984; Lippincott Williams & Wilkins; Volume: 6; Issue: 6 Linguagem: Inglês

10.1097/00005344-198406060-00012

1533-4023

Charles S. Sweet, Carl T. Ludden, C. M. Frederick, Larry R. Bush, Lair G.T. Ribeiro,

Cardiac Arrhythmias and Treatments

Summary: The angiotensin-converting enzyme (ACE) inhibitor MK-422 (enalaprilat) was compared with the potent renin inhibitor SCRIP for its ability to improve left ventricular function in closed-chest dogs. Acute left ventricular failure (ALVF) was induced by repeated embolization (EMB) of the left coronary arterial vasculature with 50-μm plastic microspheres. Baseline stability data were obtained in 30 dogs in which the evolution of ALVF was monitored over time. Guided by a progressive rise in left ventricular end-diastolic pressure (LVEDP), a stepwise perturbation of the coronary circulation with microspheres over 30 min caused reductions in left ventricular dP/dt and cardiac output, averaging 47 and 40%, respectively. EMB reduced heart rate (20 beats/min) and mean arterial pressure by ˜20 mm Hg which, along with other hemodynamic variables, remained stable after induction of heart failure. MK-422 (100 μg/kg i.v.) given 45 min after ALVF was induced, decreased mean arterial pressure by 20 mm Hg (p < 0.05) and reduced total peripheral resistance (TPR) from 5,453 to 4,150 dyne · s · cm-5 (p < 0.05). The decline in LVEDP (from 14 ± 1 to 11 ± 1 mm Hg) and TPR suggests that MK-422 dilates resistance and, conceivably, capacitance vessels. In dogs with sham EMB (vehicle injections into coronary circulation), MK-422 reduced arterial pressure but had no important effects on the other hemodynamic indices. The renin inhibitor SCRIP (100 μg/kg i.v. plus 10 μg/kg/min i.v.) produced effects on systemic hemodynamics and left ventricular function qualitatively and quantitatively similar to those of enalaprilat, suggesting that the latter reduces TPR owing primarily to inhibition of angiotensin II formation rather than bradykinin-induced vasodilation. Renal function and electrolyte excretion studies revealed that EMB paradoxically increased sodium excretion and glomerular filtration rate, but there was no further increase in these parameters after ACE inhibition. In summary, inhibition of angiotensin II formation with ACE or renin inhibitors improves global ventricular performance by reducing both LVEDP and afterload.