The experiment was performed to determine the role of κ-opioid receptor (OR) agonist U50488H given at early reperfusion.

Isolated hearts were subjected to 30 minutes of regional ischemia and 120 minutes of reperfusion. Hearts were assigned randomly to one of the three groups: 1) Control (n = 9), 2) U50-1 (n = 8); 1 µM of U50488H, and 3) U50-10 (n = 8); 10 µM of U50488H. U50488 was perfused for a period of 5 min before and 30 min after reperfusion.

U50488H significantly reduced infarct size as a percentage of ischemic area (12.2 ± 1.9% in U50-1 and 7.2 ± 1.7% in U50-10, P < 0.001) compared to the control hearts (27.2 ± 1.2%). After 2 hrs of reperfusion, left ventricular developed pressure was significantly recovered by U50488H (62.6 ± 5.7% in U50-1 and 68.6 ± 4.7% in U50-10, P = 0.018 and 0.002, respectively) compared to the control (46.3 ± 4.4%). Rate-pressure product was improved by 10 µM U50488H (62.3 ± 5.5%, P = 0.007) but not by 1 µM U50488H (50.0 ± 4.1%) compared to the control (44.7 ± 4.5%). U50488H significantly increased the +dP/dt_max (77.9 ± 5.5% in U50-1 and 78.0 ± 4.3 in U50-10, P = 0.005 and 0.001 vs. control, respectively). The -dP/dt_min also improved by 10 µM U50488H (64.7 ± 4.8%, P = 0.003) compared to control (47.0 ± 2.7%).

U50488H given at early reperfusion phase reduces both infarct size and myocardial stunning in isolated rat hearts.