EFFECT OF PINACIDIL ON MYOCARDIAL BLOOD-FLOW IN THE CHRONICALLY PRESSURE OVERLOADED HYPERTROPHIED LEFT-VENTRICLE

This study examined the effect of pinacidil on the transmural distribution of myocardial blood flow in the chronically pressure overloaded hypertrophied left ventricle. Studies were performed in six dogs in which banding of the ascending aorta had resulted in an 88% increase in left ventricular mass, as well as in six normal control animals. Two doses of pinacidil were administered to decrease mean arterial pressure by 10 mm Hg (low dose) and 20 mm Hg (high dose). Animals with hypertrophy required significantly smaller drug doses to achieve the desired reductions in arterial pressure. During control conditions mean myocardial blood flow was significantly higher in animals with hypertrophy (1.90 ± 0.21 ml/min/g) than in normal animals (1.12 ± 0.08 ml/min/g; p < 0.05). Subendocardial flow (endo) exceeded subepicardial flow (epi) in normal dogs during control conditions (endo/epi = 1.41 ± 0.13), but not in animals with hypertrophy (endo/epi = 1.06 ± 0.06; p < 0.05). Pinacidil caused coronary vasodilation with similar relative increases in blood flow in both normal and hypertrophied hearts, so that after pinacidil, absolute blood flow rates remained higher than normal in animals with hypertrophy. Pinacidil caused a redistribution of blood flow away from the subendocardium in normal hearts (endo/epi = 0.90 ± 0.11 during high-dose pinacidil) and in hearts with hypertrophy (endo/epi = 0.81 ± 0.13 during high-dose pinacidil). The endo/epi ratios during high-dose pinacidil were not significantly different between the two groups. This study demonstrates that pinacidil is a potent coronary vasodilator in both normal and hypertrophied hearts. Although pinacidil resulted in redistribution of blood flow away from the subendocardium, this effect was not greater in hypertrophied than in normal hearts. © 1990 Raven Press, Ltd., New York.