The acute hemodynamic effects of a new agent, MDL 17,043, in the treatment of congestive heart failure.

Abstract

SUMMARY MDL 17,043 administered intravenously or orally exerts positive inotropic and vasodilator actions in experimental animal preparations. We studied its acute hemodynamic effects in 15 patients with severe congestive heart failure by right-heart catheterization. Intravenous MDL 17,043 at 10 minutes increased cardiac index (3.4 0.8 vs 1.9 0.4 1/min/m2), narrowed arteriovenous oxygen content difference (4.6 ± 0.8 vs 7.8 2.0 vol%), increased heart rate (98 ± 14 vs 89 ± 18 beats/min), and decreased systemic arterial (67 10 vs 83 ± 11 mm Hg), pulmonary capillary wedge (12 ± 5 vs 24 ± 5 mm Hg) and right atrial (6 ± 5 vs 12 ± 7 mm Hg) mean pressures significantly (p < 0.001). In 11 patients, hemodynamics were monitored hourly for 6 hours. Compared with baseline, the cardiac index and heart rate were higher and mean systemic arterial pressure was lower for 6 hours; pulmonary capillary and right atrial mean pressures were significantly lower for 5 hours. No serious arrhythmias or side effects occurred. These data suggest that MDL 17,043 may be useful for treating congestive heart failure.THE CONCEPT that contractile strength, even of the end-stage myopathic ventricle, can be increased by enhancing the inotropic state of the myocardium has led to the search for a safer, more effective agent than digitalis for treating chronic congestive heart failure. One such prospect is MDL 17,043 fig. 1), which has been shown to possess significant inotropism in animal studies using isolated cardiac muscle strips, normal intact animal preparations, and a model of propranolol-induced heart failure.'-' MDL 17,043 also causes significant peripheral arterial vasodilation in the dog' and is effective both intravenously and orally.' Moreover, acute and chronic therapy with MDL 17,043 in various animal species has shown a remarkable lack of toxicity. For all these reasons, this agent holds hope for more effective oral therapy of heart failure.In this study, we report the acute hemodynamic effects of i.v. MDL 17,043 in 15 patients. Materials and MethodsUsing a protocol approved by the Human Use Committee at our institution, we studied 15 patients with severe congestive heart failure uncontrolled by digitalis and diuretic therapy (table 1). All patients had cardiomegaly (cardiothoracic ratio > 50%) on chest x-ray. The causes of heart failure, documented by cardiac catheterization, were ischemic heart disease in five patients and corrected mitral regurgitation with residual left ventricular dysfunction in two; heart failure was idiopathic in four patients. Of the four remain- ing patients, three (nos. 9, 12 and 14) were in normal sinus rhythm, and radionuclide angiography revealed severe global hypokinesis. Patient 13 was in atrial fibrillation and the ejection fraction by radionuclide angiography was 39%.The average age of the patients was 55 years. There were 11 men and four women. Nine patients had received various vasodilators, but the results were unsatisfactory and the patients were referred for study. In the six other patients, relat...

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