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 -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 -60% above (moderate stenosis) and -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 < 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 < 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.