Effects of enalaprilat on hemodynamics and ventricular activation duration in hypertensive patients with left ventricular hypertrophy: clinical evidence of improved excitation-contraction coupling with angiotensin converting enzyme inhibition in human hypertension.
Hypertension is a major risk factor for the development of heart failure. Despite significant progress in our knowledge of the physiopathology of heart failure, the cause for decompensation in patients with left ventricular hypertrophy (LVH) is still obscure. The angiotensin converting enzyme inhibitor enalaprilat has been found to improve electromechanical coupling of heart cells in animal models. To assess the effects of enalaprilat on ventricular electromechanical coupling in humans, we studied the His bundle electrograms and hemodynamics in 22 hypertensive patients with LVH. Patients received either 2.5 mg enalaprilat or saline placebo intravenously in a double-blind protocol. There were no significant changes in heart rate, and atrioventricular and His-Purkinje conduction times. Ventricular activity duration was reduced from 110 +/- 11 msec to 88 +/- 13 msec after enalaprilat administration (P < .01). Enalaprilat decreased peak-systolic and end-diastolic left ventricular pressures, and arterial and pulmonary pressures, as well as pulmonary and systemic vascular resistances. End-systolic wall stress decreased 18% (P < .01), ejection fraction increased 11% (P < .01), and end-diastolic pressure-volume ratio decreased 50% (P < .001) after enalaprilat administration. There were no significant changes in these parameters after saline infusion. It is concluded that enalaprilat reduces ventricular activation duration and improves ventricular performance in hypertensive patients with LVH. Data suggest that enalaprilat significantly improves excitation-contraction coupling in these patients.
Department of Medicine, Puerto Rico Cardiovascular Center, University District Hospital, Río Piedras.
R A
RA
González-Fernández
P I
PI
Altieri
R
R
Jiménez
J
J
Lastra
J R
JR
Meléndez
J A
JA
Martínez-Toro
H L
HL
Banchs
D000200:Action Potentials / Q000187:drug effects; D006328:Cardiac Catheterization; D004311:Double-Blind Method; D004562:Electrocardiography; D004594:Electrophysiology; D015773:Enalaprilat / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D006329:Heart Conduction System / Q000187:drug effects; D006333:Heart Failure / Q000209:etiology; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology*; D017379:Hypertrophy, Left Ventricular / Q000150:complications; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction / Q000187:drug effects; D011446:Prospective Studies; D016277:Ventricular Function, Left / Q000187:drug effects*
D015773:Enalaprilat