Amrinone has been shown to have therapeutic effects on bupivacaine-induced cardiovascular toxicity, but its exact effects on the heart are not well understood. This study evaluated the regional myocardial effect of amrinone on bupivacaine-induced cardiovascular toxicity in in situ beating hearts in 10 dogs using a selective coronary perfusion and sonomicrometry. In the control group, bupivacaine was administered into the left anterior descending coronary artery (LAD) for 15 min at four steps: baseline, step 1, step 2 and step 3, (calculated LAD plasma concentrations; 0, 5, 5 and 10 mu g center dot ml-1, respectively). In the amrinone group, amrinone (5 mu g center dot ml-1) was simultaneously infused at steps 2 and 3 in addition to bupivacaine infusions. Regional myocardial function of the LAD supplied area was evaluated by analysis of the left ventricular pressure-segment length loop. In the control group, systolic shortening decreased from the baseline (10.5 +/- 1.3%, mean +/- SEM) to step 3 (0.1 +/- 1.3%), and post-systolic shortening increased from the baseline (18.0 +/- 3.7%) to step 3 (52.3 +/- 5.5%) dose-dependently. In contrast, with amrinone infusion at steps 2 and 3, both variables returned to near baseline values. These results indicate that amrinone reverses bupivacaine-induced regional myocardial dysfunction.