Effects of Angiotensin Converting Enzyme Inhibitors on Acute Heart Failure Induced in the Anesthetized Dog with Microsphere Injection
Part of the
Developments in Cardiovascular Medicine
book series (DICM, volume 167)
To study the effects of angiotensin converting enzyme (ACE) inhibitors on myocardial energy metabolism together with their effects on hemodynamic parameters in acute left ventricular failure (ALVF), a new model of ALVF was developed by embolization of the left coronary artery with 50 urn plastic microspheres followed by intravenous infusion of methoxamine. With this procedure the left ventricular end-diastolic pressure (EDP) rose from 4.2 ± 0.7 mmHg to 12.8 ± 1.3mmHg and remained at around 12mmHg during the entire course of the experiment. Cardiac output (CO) decreased from 1.25 ± 0.121/min to 0.79 ± 0.061/min and 0.55 ± 0.021/min at 30 and 90 min after methoxamine, respectively. Left ventricular max dP/dt and dP/dt/P decreased, while total peripheral resistance (TPR) increased. Creatine phosphate contents in the myocardium decreased.
Spiraprilat, as well as enalaprilat (30μg/kg intravenously), effectively lowered the mean aortic pressure (30%), EDP (20%), and TPR (30%) and increased the stroke volume, CO, and dP/dt/P. Both agents decreased the myocardial oxygen consumption (20%) and produced a significant increase in myocardial creatine phosphate contents. These data indicate that the beneficial effects of both inhibitors were exerted not only on left ventricular function but also on myocardial energy metabolism in ALVF.
Angiotensin converting enzyme (ACE) inhibitors are effective vasodilators and are used as an alternative remedy for the treatment of congestive heart failure. Several studies have demonstrated the beneficial effects of ACE inhibitors on the hemodynamics and myocardial metabolism of patients with chronic heart failure [1–6].
The effectiveness of several ACE inhibitors [7-10] has been ascertained experimentally in models of embolization-induced acute left ventricular failure (ALVF). Improvement in the left ventricular end-diastolic pressure (EDP) was the most prominent feature of these agents. We attempted to examine whether the improvement in hemodynamic performance was able to cause some beneficial effects on myocardial energy metabolism. To obtain the myocardial sample, experiments were performed under the open-chest condition.
In the first part of the experiment acute left ventricular failure was induced by repeatedly injecting microspheres into the open-chest animal . However, this model showed no increase in TPR and had a high mortality. To reduce the mortality, we modified the method, the amount of microsphere injected was reduced, and ALVF was produced by additionally increasing the TPR by intravenous infusion of methoxamine, a selective (α1-adrenoceptor agonist . No mortality was observed under this condition .
In this new model of ALVF, we examined the effects of the ACE inhibitors, spiraprilat and enalaprilat, on myocardial energy metabolism together with the effects on hemodynamic parameters. Both inhibitors effectively lowered EDP and increased myocardial creatine phosphate content.
KeywordsAngiotensin Converting Enzyme Acute Heart Failure Aortic Pressure Total Peripheral Resistance Myocardial Oxygen Consumption
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