AMRINONE AND THE PULMONARY VASCULAR PRESSURE-FLOW RELATIONSHIP IN CONSCIOUS CONTROL DOGS AND FOLLOWING LEFT LUNG AUTOTRANSPLANTATION

Background. 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 amrinon e as a pulmonary vasodilator, an effect that could be beneficial in th e setting of right heart failure associated with pulmonary hypertensio n. Methods. Investigated were the effects of intravenous amrinone (750 mug/kg loading dose plus 1-20 mug . kg-1 . min-1 maintenance dose) on the left pulmonary vascular pressure-flow (LPQ) relationship in chron ically instrumented, conscious dogs. The effects of amrinone on the LP Q relationship were assessed in a series of conscious control dogs wit h (n = 10) and without (n = 9) acute preconstriction with the thrombox ane analog U46619 and in a series of conscious dogs 2-4 weeks after le ft lung autotransplantation (LLA) with (n = 8) and without (n = 8) acu te U46619 preconstriction. Left pulmonary vascular pressure-flow plots were generated by continuously measuring the pulmonary vascular press ure gradient (pulmonary arterial pressure/left atrial pressure [PAP/LA P]) and left pulmonary blood flow during gradual (approximately 1 min) inflation of a hydraulic occluder implanted around the right pulmonar y artery. Results. Amrinone had no effect on the baseline LPQ relation ship in control dogs. U46619 caused acute pulmonary vasoconstriction. For example, PAP/LAP at left pulmonary blood flow of 70 ml . min-1 . k g-1 was increased (P < 0.01) from 16 +/- 2 to 37 +/- 2 mmHg during U46 619 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 ass ociated with a marked shift in the LPQ relationship, indicating a chro nic increase in pulmonary vascular resistance, i.e., PAP/LAP was incre ased (P < 0.01) from 15 +/- 2 to 32 +/- 3 mmHg. Despite the chronic in crease in pulmonary vascular resistance after LLA, amrinone had no eff ect on the baseline LPQ relationship. However, after acute preconstric tion with u46619 after LLA, amrinone caused pulmonary vasodilation, i. e., PAP/LAP was decreased (P < 0.05) from 45 +/- 4 to 39 +/- 4 mmHg. C onclusions. These results indicate that amrinone exerts a significant, although relatively modest pulmonary vasodilator influence in the set ting of acute pulmonary vasoconstriction in conscious control dogs and in conscious dogs after LLA. However, amrinone did not reverse the ch ronic increase in pulmonary vascular resistance associated with LLA.