Hemodynamic and myocardial blood flow. Profiles of pinacidil and nitroprusside in conscious dogs.
Vasodilator antihypertensive agents can induce endocardial underperfusion relative to myocardial metabolic demand in normal hearts. We studied ten conscious normotensive dogs, paced at constant heart rate, to determine the relative probabilities of inducing endocardial ischemia with intravenous sodium nitroprusside or pinacidil, a novel antihypertensive agent. On different days, pinacidil and nitroprusside were infused in each animal to achieve mean aortic pressures (MAP) of 83 +/- 0.2 mm Hg and 62 +/- 1 mm Hg, reduced from control pressures of 106 +/- 3 mm Hg (pinacidil) and 107 +/- 3 mm Hg (nitroprusside). At MAP = 62 mm Hg, pinacidil depressed the left ventricular endocardial:epicardial blood flow (0.81 +/- 0.03) more than did nitroprusside (1.00 +/- 0.06, P less than .01). However, pinacidil increased left ventricular blood flow in all transmural layers at both levels of hypotension (P less than .05); nitroprusside increased only epicardial blood flow at MAP = 62 mm Hg (P less than .05). Neither vasodilator significantly altered myocardial oxygen consumption at either level of hypotension. At MAP = 83 mm Hg, pinacidil depressed the ratio of left ventricular vascular resistance and systemic vascular resistance indices (LVVRI/SVRI) 40 +/- 6 percent (P less than .001) to a level below that existing during nitroprusside infusion (P less than .05). These data indicate that pinacidil has greater selectivity for the coronary circulation over the systemic circulation compared to nitroprusside. Although it is unlikely that either drug caused endocardial ischemia in the present study, the data suggest that pinacidil is less likely to do so than is nitroprusside in normal hearts.
Dubé
G P
GP
Department of Medicine, Duke University Medical Center, Durham, NC 27710.
Greenfield
J C
JC
D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006146:Guanidines / Q000008:administration & dosage / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007262:Infusions, Intravenous; D009599:Nitroprusside / Q000008:administration & dosage / Q000494:pharmacology*; D010210:Papillary Muscles / Q000187:drug effects / Q000502:physiology; D020110:Pinacidil; D014655:Vascular Resistance / Q000187:drug effects
D000959:Antihypertensive Agents; D006146:Guanidines; D009599:Nitroprusside; D020110:Pinacidil