Effects of spiraprilat, an angiotensin-converting enzyme inhibitor, on anesthetized dogs in a new model of acute left ventricular failure.
Spiraprilat, a new angiotensin-converting enzyme (ACE) inhibitor, was compared with enalaprilat for its ability to improve left ventricular (LV) function and metabolism in anesthetized open-chest dogs with a new model of acute LV failure (ALVF) induced by embolization of the left coronary artery with 50 microns plastic microspheres followed by intravenous (i.v.) infusion of methoxamine. With this procedure, LV end-diastolic pressure (LVEDP) increased from 4.2 +/- 0.7 to 12.8 +/- 1.3 mm Hg and remained at approximately 12 mm Hg throughout the experiment. Cardiac output (CO) decreased from 1.25 +/- 0.12 to 0.79 +/- 0.06 and 0.55 +/- 0.02 L/min at 30 and 90 min after methoxamine infusion, respectively. LVdP/dtmax and dP/dt/P decreased, while total peripheral resistance (TPR) increased. These hemodynamic changes indicated establishment of stable ALVF of a moderate degree. Moreover, decreases in myocardial lactate consumption and contents of creatine phosphate in the myocardium indicated the existence of moderate ischemia. The new ACE inhibitor, spiraprilat, as well as enalaprilat (30 micrograms/kg i.v.) effectively decreased mean aortic pressure (30%), LVEDP (20%), and TPR (30%) and increased stroke volume (SV) CO, and dP/dt/P. Both agents decreased myocardial oxygen consumption (20%) and caused a significant increase in myocardial creatine phosphate contents. These data indicate that the beneficial effects of both inhibitors extended not only to LV function but also to myocardial energy metabolism in ALVF.
Nakazawa
M
M
Department of Pharmacology, Niigata University School of Medicine, Japan.
Ishihara
T
T
Takahashi
Y
Y
Okuhira
M
M
Imai
S
S
D000255:Adenosine Triphosphate / Q000378:metabolism; D000758:Anesthesia; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects; D004195:Disease Models, Animal; D004285:Dogs; D004656:Enalapril / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D008729:Methoxamine / Q000494:pharmacology; D008863:Microspheres; D009206:Myocardium / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D010725:Phosphocreatine / Q000378:metabolism; D014655:Vascular Resistance / Q000187:drug effects; D016277:Ventricular Function, Left / Q000187:drug effects*
D000806:Angiotensin-Converting Enzyme Inhibitors; D007773:Lactates; D010725:Phosphocreatine; D019344:Lactic Acid; D004656:Enalapril; D000255:Adenosine Triphosphate; D008729:Methoxamine; C076884:spiraprilat