Amrinone and the Pulmonary Vascular Pressure–Flow Relationship in Conscious Control Dogs and Following Left Lung Autotransplantation

Abstract

Amrinone, a bipyridine compound, is known to improve left ventricular function via its positive inotropic and afterload-reducing effects. The goal of this study was to assess the efficacy of amrinone as a pulmonary vasodilator, an effect that could be beneficial in the setting of right heart failure associated with pulmonary hypertension. Investigated were the effects of intravenous amrinone (750 micrograms/kg loading dose plus 1-20 micrograms.kg-1.min-1 maintenance dose) on the left pulmonary vascular pressure-flow (LPQ) relationship in chronically instrumented, conscious dogs. The effects of amrinone on the LPQ relationship were assessed in a series of conscious control dogs with (n = 10) and without (n = 9) acute preconstriction with the thromboxane analog U46619 and in a series of conscious dogs 2-4 weeks after left lung autotransplantation (LLA) with (n = 8) and without (n = 8) acute U46619 preconstriction. Left pulmonary vascular pressure-flow plots were generated by continuously measuring the pulmonary vascular pressure gradient (pulmonary arterial pressure/left atrial pressure [PAP/LAP]) and left pulmonary blood flow during gradual (approximately 1 min) inflation of a hydraulic occluder implanted around the right pulmonary artery. Amrinone had no effect on the baseline LPQ relationship in control dogs. U46619 caused acute pulmonary vasoconstriction. For example, PAP/LAP at left pulmonary blood flow of 70 ml.min-1.kg-1 was increased (P < 0.01) from 16 +/- 2 to 37 +/- 2 mmHg during U46619 administration. In this setting of acute preconstriction, amrinone caused pulmonary vasodilation, i.e., PAP/LAP was decreased (P < 0.05) from 37 +/- 2 to 32 +/- 2 mmHg. Left lung autotransplantation was associated with a marked shift in the LPQ relationship, indicating a chronic increase in pulmonary vascular resistance, i.e., PAP/LAP was increased (P < 0.01) from 15 +/- 2 to 32 +/- 3 mmHg. Despite the chronic increase in pulmonary vascular resistance after LLA, amrinone had no effect on the baseline LPQ relationship. However, after acute preconstriction with U46619 after LLA, amrinone caused pulmonary vasodilation, i.e., PAP/LAP was decreased (P < 0.05) from 45 +/- 4 to 39 +/- 4 mmHg. These results indicate that amrinone exerts a significant, although relatively modest pulmonary vasodilator influence in the setting of acute pulmonary vasoconstriction in conscious control dogs and in conscious dogs after LLA. However, amrinone did not reverse the chronic increase in pulmonary vascular resistance associated with LLA.