Beneficial effects of milrinone and enalapril on long-term survival of rats with healed myocardial infarction.
The long-term survival of rats with healed myocardial infarction and congestive heart failure treated with milrinone, enalapril and the combination of milrinone plus enalapril, was documented. Seven days after sham or coronary ligation, 200 rats (99 sham and 101 myocardial infarcted) were randomized based on electrocardiographic criteria to receive tap water, milrinone (20-40 mg/l drinking water), enalapril (17-25 mg/l) or the combination of milrinone plus enalapril (20-40 mg/17-25 mg per l). The date of spontaneous death was recorded and heart weights and myocardial infarct size (by planimetry) were determined. Long-term enalapril therapy prolonged survival with a median 50% survival (MS50) of 233 days compared to 203 days in the tap water group. Milrinone therapy also prolonged survival with a MS50 of 297 days. The combination therapy prolonged survival with a MS50 of 277 days. In general, there were three times as many rats alive in the treatment groups at the end of one year compared to untreated control groups. Cardiac hypertrophy was evident in all myocardial infarcted groups and heart weights were significantly reduced by all treatments. The average myocardial infarct sizes and the distribution of infarct sizes were not different between groups (36.8-43% of left ventricle). This study demonstrates that long-term therapy with enalapril and milrinone prolongs survival in rats with healed myocardial infarctions. The prolongation of survival was comparable in the milrinone plus enalapril groups, indicating that there was no synergy with these two agents with survival as the end point.
Sweet
C S
CS
Merck Sharp & Dohme Research Laboratories, West Point, PA 19486.
Ludden
C T
CT
Stabilito
I I
II
Emmert
S E
SE
Heyse
J F
JF
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D006332:Cardiomegaly / Q000517:prevention & control; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004562:Electrocardiography; D004656:Enalapril / Q000494:pharmacology*; D006333:Heart Failure / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D008297:Male; D020105:Milrinone; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D011728:Pyridones / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D002316:Cardiotonic Agents; D011728:Pyridones; D004656:Enalapril; D020105:Milrinone