Effects of Amrinone on Regional Myocardial Function and Oxygen Balance in Stunned Myocardium in Dogs

Abstract

Background: Brief myocardial ischaemia has been demonstrated to result in mechanical and coronary endothelial dysfunction. We examined whether the mechanical and vascular responses to amrinone are altered in the postischaemic, reperfused myocardium. The effects of amrinone were compared with those of dobutamine. Methods: In an open-chest canine model, coronary blood flow (CBF), myocardial oxygen consumption (MVO2), and regional mechanical function in response to either amrinone (2, 5, 7.5, and 10 g/mL of CBF) or dobutamine (0.05, 0.125, 0.25, 0.375, and 10g/mL of CBF) directly infused into the left anterior descending (LAD) artery were determined before (normal) and 30 min after 15-minperiod of LAD occlusion (stunned). Percent segment shortening (%SS), peak segment lengthening rate (dL/dtmax), and percent post-systolic shortening (%PSS) in the LAD territory was determined using ultrasonic crystals and CBF using Doppler transducer. Myocardial extractions of oxygen (EO2) and lactate (Elac) were calculated. Results: Both amrinone and dobutamine in the normal myocardium caused a dose-dependent increase in mechanical functions (%SS and dL/dtmax) and MVO2 that were comparable (range, 20-40%), but they had no effects on %PSS. Amrinone caused an increase of CBF in excess of MVO2, resulting in a modest decrease in EO2, whereas dobutamine increased CBF in proportion to MVO2, resulting in no changes in EO2. The ischemia and reperfusion insult reduced %SS, dL/dtmax, and Elac, while it did not affect mechanical (%SS and dL/dtmax) and CBF responses to either agent, except for progressive reductions of %PSS. Conclusions: These results indicate that amrinone, similar to dobutamine, exert positive inotropic and lusitropic effects in normal and stunned canine myocardium. It is also indicated that amrinone causes direct coronary vasodilation, which is not affected by an ischemia and reperfusion insult.