M. Nakazawa et al., EFFECTS OF SPIRAPRILAT, AN ANGIOTENSIN-CONVERTING ENZYME-INHIBITOR, ON ANESTHETIZED DOGS IN A NEW MODEL OF ACUTE LEFT-VENTRICULAR FAILURE, Journal of cardiovascular pharmacology, 22(4), 1993, pp. 585-593
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 ne
w model of acute LV failure (ALVF) induced by embolization of the left
coronary artery with 50 mum plastic microspheres followed by intraven
ous (i.v.) infusion of methoxamine. With this procedure, LV end-diasto
lic 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. Card
iac output (CO) decreased from 1.25 +/- 0. 12 to 0.79 +/- 0.06 and 0.5
5 +/- 0.02 L/min at 30 and 90 min after methoxamine infusion, respecti
vely. LV dP/dt(max) and dP/dt/P decreased, while total peripheral resi
stance (TPR) increased. These hemodynamic changes indicated establishm
ent of stable ALVF of a moderate degree. Moreover, decreases in myocar
dial lactate consumption and contents of creatine phosphate in the myo
cardium indicated the existence of moderate ischemia. The new ACE inhi
bitor, spiraprilat, as well as enalaprilat (30 mug/kg i.v.) effectivel
y decreased mean aortic pressure (30%), LVEDP (20%), and TPR (30%) and
increased stroke volume (SV) CO, and dP/dt/P. Both agents decreased m
yocardial oxygen consumption (20%) and caused a significant increase i
n myocardial creatine phosphate contents. These data indicate that the
beneficial effects of both inhibitors extended not only to LV functio
n but also to myocardial energy metabolism in ALVF.