Beneficial hemodynamic effects of milrinone and enalapril in conscious rats with healed myocardial infarction.
Milrinone and enalapril, which inhibit PDE-III and ACE, respectively, are able to prolong survival of myocardially infarcted (MI) rats. This study sought to identify oral hemodynamic effects of these agents which could underlie such efficacy in this heart failure model. Four weeks after ligation of the left main coronary artery, basal left ventricular (LV) systolic pressure and dP/dtmax, heart rate and mean blood pressure of the MI rats were significantly less than that of sham-operated controls, and LV end-diastolic pressure (LVEDP) was markedly elevated. Milrinone, at 2.0 mg/kg, reduced LVEDP and renal blood flow of these 4-week MI rats by an average of 39 and 18%, respectively (P less than 0.05) within 1 h. At 4.0 mg/kg, it reduced LVEDP by 46% and raised heart rate by 16% (P less than 0.05). Enalapril (1.0 mg/kg) increased small intestine blood flow of these compromised rats by 16% (P less than 0.05), and tended to reduce LVEDP (-28%) within 1.5 h. Treatment with milrinone (2.0 mg/kg) plus enalapril (1.0 mg/kg) promoted LV dP/dtmax, coronary blood flow, and heart rate by 48, 40 and 13%, and reduced LVEDP by 40% (P less than 0.05 for all effects). Thus these agents can reduce LVEDP and redistribute cardiac output of MI rats. Furthermore, the combination of enalapril and milrinone can restore LVEDP and LV dP/dtmax of MI rats to near normal and promote coronary blood flow without compromising cardiac output or renal blood flow. Such effects, it timely or sustained, may prolong survival.
DeFelice
A
A
Department of Pharmacology, Sterling Research Group, Rensselaer, NY 12144.
Harris
A
A
Frering
R
R
Horan
P
P
D000284:Administration, Oral; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004656:Enalapril / Q000627:therapeutic use*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D020105:Milrinone; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000503:physiopathology; D009929:Organ Size / Q000187:drug effects; D011728:Pyridones / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains; D014655:Vascular Resistance / Q000187:drug effects
D011728:Pyridones; D004656:Enalapril; D020105:Milrinone