Selective dopamine-1 receptor agonist augments regional myocardial blood flow: Comparison of fenoldopam and dopamine

Abstract

A new class of vasodilators exhibiting selective dopamine-1 receptor agonist activity is being introduced into clinical practice. Inasmuch as various vasodilators either augment or decrease myocardial blood flow (“coronary steal”) depending on their pharmacologic action, the goal of this study was to assess the effects of fenoldopam (selective dopamine-1 receptor agonist) and dopamine (nonselective dopamine-1 receptor agonist) on regional myocardial blood flow in the presence of coronary occlusion. Accordingly, in 16 dogs anesthetized with pentobarbital, the left anterior descending coronary artery was occluded. Cardiovascular and renal hemodynamic effects were measured before and after intravenous infusion of renal equipotent doses of either fenoldopam ( n = 9, 0.1 μg/kg/min) or dopamine ( n = 7, 1 μg/kg/min). Both fenoldopam and dopamine caused a significant and comparable increase in renal blood flow. Fenoldopam but not dopamine significantly decreased the calculated peripheral vascular resistance and subsequently increased cardiac output. Dopamine had no effect on regional myocardial blood flow. In contrast, fenoldopam augmented transmural myocardial blood flow in normal (from 114 ± 10 to 188 ± 27 ml/100 gm/min, p < 0.02) and ischemic border myocardium (from 45 ± 5 to 68 ± 11 ml/100 gm/min, p < 0.03 and p < 0.02 vs dopamine). There was a significant increase in blood flow to both the endocardial and epicardial layers of normal and ischemic border myocardium. These changes were accompanied by a significant reduction in coronary vascular resistance in the normal myocardium. In addition, with fenoldopam increments in myocardial blood flow in normal and ischemic border myocardium showed a significant correlation with changes in renal blood flow ( r = 0.76, p < 0.01 and r = 0.80, p < 0.01, respectively). No such correlation was observed after dopamine. In conclusion, low-dose infusion of selective (fenoldopam) and nonselective (dopamine) dopamine-1 receptor agonists resulted in comparable increases in renal blood flow but divergent effects on regional myocardial perfusion. Fenoldopam but not dopamine resulted in improved perfusion in normal and ischemic border myocardium. It is postulated that these findings may have important clinical implications in the treatment of patients with heart failure, renal dysfunction, and concomitant ischemic heart disease.