Simultaneous angiotensin converting enzyme inhibition moderates ventricular dysfunction caused by doxorubicin.
OBJECTIVE
The purpose of this study was to determine that the administration of an angiotensin converting enzyme (ACE) inhibitor enalapril would confer protection against doxorubicin-induced experimental heart failure, and attenuate the development of left ventricular dysfunction.


METHODS
Seventeen dogs were chronically instrumented with an intracoronary catheter and received doxorubicin weekly for 4 weeks. Animals were assigned to two groups: group 1: untreated heart failure; and group 2: simultaneous enalapril administration (5 mg twice a week). Hemodynamic data were obtained at week 0 and 12. Echocardiography was performed weekly.


RESULTS
Survival improved with simultaneous enalapril administration (36% in group 1 vs. 100% in group 2, P=0.04). The increase in the left ventricular end-diastolic pressure was significantly reduced at week 12 (17+/-1 mmHg in group 1 vs. 9+/-1 mmHg in group 2, P=0.0042). The fall in left ventricular stroke work index was significantly prevented (52% in group 1 vs. 21% in group 2, P=0.006). The increase in right ventricular end-diastolic diameter was significantly reduced by enalapril prophylaxis.


CONCLUSIONS
Simultaneous treatment with enalapril was beneficial in the prevention of doxorubicin-induced cardiomyopathy.
Vaynblat
Mikhail
M
Division of Cardiovascular Surgery, Department of Surgery, Maimomides Medical Center, Administration Building, Rm D, Department of Surgery, 4802 10th Ave, Brooklyn, NY 11219, USA. mishavayn@aol.com
Shah
Himansu R
HR
Bhaskaran
Dinesh
D
Ramdev
Geeta
G
Davis
Wellington J
WJ
Cunningham
Joseph N
JN
Chiavarelli
Mario
M
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D004285:Dogs; D004317:Doxorubicin; D004656:Enalapril / Q000627:therapeutic use; D006333:Heart Failure / Q000139:chemically induced / Q000188:drug therapy; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D008955:Models, Cardiovascular; D013318:Stroke Volume / Q000187:drug effects; D013997:Time Factors; D016896:Treatment Outcome; D014655:Vascular Resistance / Q000187:drug effects; D018487:Ventricular Dysfunction, Left / Q000139:chemically induced* / Q000188:drug therapy*
D000806:Angiotensin-Converting Enzyme Inhibitors; D000970:Antineoplastic Agents; D004656:Enalapril; D004317:Doxorubicin