Effect of pinacidil on myocardial blood flow in the presence of a coronary artery stenosis.
This study examined the effect of pinacidil on transmural distribution of myocardial blood flow during normal conditions and in the presence of a coronary artery stenosis. Studies were performed in 11 awake dogs; blood flow was measured with radioactive microspheres. Two doses of pinacidil were administered to decrease mean arterial pressure (MAP) by approximately 10 mm Hg (low dose, 0.18 +/- 0.02 mg/kg) and 20 mm Hg (high dose, 0.32 +/- 0.03 mg/kg). Measurements were performed during unimpeded arterial inflow and with two levels of coronary stenosis that limited blood flow to approximately 60% above (moderate stenosis) and approximately 30% above basal flow (severe stenosis). With no stenosis, coronary flow increased 227 +/- 17% after low-dose and 321 +/- 31% after high-dose pinacidil (each p less than 0.01). During control conditions, subendocardial (endo) flow exceeded subepicardial (epi) flow (endo/epi ratio = 1.33). This ratio was not changed by low-dose pinacidil but decreased to 0.93 after high-dose pinacidil (p less than 0.05). During high-dose pinacidil, a coronary stenosis caused uniform reduction of blood flow across the left ventricular wall, with no further significant change in the ratio of endo/epi flow. With low-dose pinacidil, both moderate and severe degrees of stenosis caused redistribution of flow away from the subendocardium similar to that observed with high-dose pinacidil. Although a stenosis that limited the increase in mean coronary flow after pinacidil administration to 162% of the predrug control value had a 95% probability of not causing a decrease in absolute subendocardial flow, the data suggest that pinacidil could have potential for aggravating subendocardial ischemia in severe occlusive coronary artery disease.
Department of Medicine, University of Minnesota Medical School, Minneapolis.
R J
RJ
Bache
X Z
XZ
Dai
K W
KW
Baran
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects*; D003327:Coronary Disease / Q000503:physiopathology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006146:Guanidines / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D008863:Microspheres; D020110:Pinacidil; D014665:Vasodilator Agents / Q000494:pharmacology*
D000959:Antihypertensive Agents; D006146:Guanidines; D014665:Vasodilator Agents; D020110:Pinacidil