Beneficial hemodynamic and renal effects of intravenous enalaprilat following coronary artery bypass surgery complicated by left ventricular dysfunction.
OBJECTIVE
Angiotensin-converting enzyme inhibitors are an effective therapy for all stages of heart failure due to reduced systolic left ventricular function. Because sufficient data on intravenous angiotensin-converting enzyme inhibitors following coronary artery bypass surgery complicated by postoperative left ventricular dysfunction are unavailable, the efficacy and safety of intravenously administered enalaprilat were evaluated.


METHODS
A placebo-controlled, randomized, double-blind protocol.


METHODS
Postoperative intensive care unit at the German Heart Institute Berlin.


METHODS
Forty patients with a left ventricular ejection fraction <35% following coronary artery bypass surgery on the second postoperative day or after weaning from intra-aortic balloon counterpulsation.


METHODS
A loading dose of enalaprilat 0.625 mg infused over 1 hr was followed by 5 mg/24 hrs administered continuously for up to 72 hrs.


RESULTS
Systemic and pulmonary hemodynamic variables, blood gases, hormonal variables, renal function, and electrolytes were measured before and repeatedly during therapy. Acute effects were as follows: At 1 hr, enalaprilat increased the cardiac index (p <.001), stroke volume index (p <.001), and right ventricular stroke work index (p <.03) compared with placebo, whereas mean arterial pressure (p <.008) and both systemic (p <.001) and pulmonary (p <.02) vascular resistance decreased. Continuous effects were as follows: Over 72 hrs, enalaprilat decreased diastolic pulmonary artery pressure (p <.019), pulmonary artery occlusion pressure (p <.02), and central venous pressure (p <.02). The cardiac and stroke volume indexes were consistently higher in the enalaprilat group, whereas systemic and pulmonary vascular resistances were lower. The arterial blood-pressure lowering effect was blunted and heart rate remained unchanged. Mixed venous oxygenation (p <.02) was higher and arterial oxygenation was not modified. Finally, enalaprilat increased creatinine clearance (p <.002) and decreased creatinine (p <.02) and urea (p <.03).


CONCLUSIONS
Intravenous enalaprilat safely and effectively improves cardiac and renal function following coronary artery bypass surgery complicated by postoperative left ventricular dysfunction.
Wagner
Frank
F
Deutsches Herzzentrum, Berlin, Germany. Wagner@dhzb.de
Yeter
Ruhi
R
Bisson
Susanne
S
Siniawski
Henryk
H
Hetzer
Roland
R
D000328:Adult; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology; D001784:Blood Gas Analysis; D001806:Blood Urea Nitrogen; D001026:Coronary Artery Bypass / Q000009:adverse effects*; D003404:Creatinine / Q000378:metabolism; D004311:Double-Blind Method; D016903:Drug Monitoring; D015773:Enalaprilat / Q000008:administration & dosage* / Q000494:pharmacology; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007262:Infusions, Intravenous; D007668:Kidney / Q000187:drug effects*; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D008875:Middle Aged; D011182:Postoperative Care / Q000379:methods; D012449:Safety; D013997:Time Factors; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy* / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology
D000806:Angiotensin-Converting Enzyme Inhibitors; D003404:Creatinine; D015773:Enalaprilat