Effect of low dose aspirin on cardiorenal function and acute hemodynamic response to enalaprilat in a canine model of severe heart failure

Abstract

Objectives: This study examined the effect of low dose aspirin on cardiorenal and neurohumoral function and on the acute hemodynamic response to enalaprilat in a canine model of heart failure.

Background: Low dose aspirin is frequently prescribed for patients with systolic dysfunction who also benefit from angiotensin-converting enzyme inhibition. Although high doses of potent cyclo-oxygenase inhibitors cause fluid retention and vaso-constriction and antagonize the effects of angiotensin-converting enzyme inhibitors, the effects of low dose aspirin in heart failure are unknown.

Methods: A model of heart failure was produced in 11 mongrel dogs by rapid ventricular pacing (250 beats/min for 12 to 14 days). Five dogs received 325 mg aspirin/day for the final 4 days of pacing before the acute experiment; six control dogs received no aspirin. Cardiorenal and neurohumoral function was measured during chloralose anesthesia. Hemodynamic and renal responses to enalaprilat were assessed.

Results: Both groups demonstrated severe heart failure with decreased cardiac output; increased atrial pressures and systemic resistance; activation of plasma renin activity, aldosterone and atrial natriuretic factor; and sodium retention. Low dose aspirin had no detrimental effect on cardiorenal or neurohumoral function. Mean arterial pressure, pulmonary capillary wedge pressure and systemic vascular resistance decreased to a similar degree with enalaprilat in both groups. There was no difference between the groups with respect to renal response to enalaprilat.

Conclusions: The present study demonstrates that low dose aspirin has no adverse effect on hemodynamic, neurohumoral or renal function in heart failure. Furthermore, aspirin has no adverse effect on the acute response to enalaprilat. These findings suggest that there is no contraindication to concomitant treatment with low dose aspirin and angiotensin-converting enzyme inhibitors in humans with heart failure.