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

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 micrograms/kg/min) or dopamine (n = 7, 1 micrograms/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 less than 0.02) and ischemic border myocardium (from 45 +/- 5 to 68 +/- 11 ml/100 gm/min, p less than 0.03 and p less than 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.(ABSTRACT TRUNCATED AT 250 WORDS)

Myocardial protection with autoperfusion during prolonged coronary artery occlusion.

Passive transcatheter coronary arterial perfusion, i.e., autoperfusion, has been introduced for clinical use to ameliorate short episodes of myocardial ischemia during percutaneous transluminal coronary angioplasty. The primary goal of this study was to evaluate the cardioprotective effect of autoperfusion after prolonged coronary artery occlusion. Accordingly, in 24 anesthetized dogs, either the left anterior descending or left circumflex coronary artery was occluded for 6 hours. The dogs were randomized to a control group subjected to coronary artery occlusion alone (n = 13) or to a group treated with transcatheter autoperfusion (n = 11). The hypoperfused zone, i.e., risk area and infarct size, were measured by autoradiography and triphenyltetrazolium chloride staining, respectively. The hypoperfused zone was 30 +/- 2% and 29 +/- 2% in the control and treated (NS) groups, respectively. When infarct size was expressed as a percent of the hypoperfused zone, it was 84 +/- 5% in the control group and 25 +/- 9% in the group treated with transcatheter autoperfusion (p less than 0.001), showing a reduction of 70%. In addition, an in vitro study showed pressure-dependent flow during autoperfusion as reflected by close linear relationship between perfusion pressure and flow (Flow = 0.54 X Pressure + 16.16, r = 0.99, n = 16). These data suggest that although passive coronary arterial perfusion for 6 hours after coronary occlusion does not prevent myocardial necrosis, it markedly reduces myocardial infarction in the canine model.