Effect of A Kappa-opioid Receptor Agonist U50488H Given at Early Reperfusion Phase in Isolated Rat Hearts

The experiment was performed to determine the role of κ-opioid receptor (OR) agonist U50488H given at early reperfusion. Methods: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); 1μM of U50488H, and 3) U50-10 (n = 8); 10μM of U50488H.U50488 was perfused for a period of 5 min before and 30 min after reperfusion. Results: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 10μM U50488H (62.3 ± 5.5%, P = 0.007) but not by 1μM U50488H (50.0 ± 4.1%) compared to the control (44.7 ± 4.5%).U50488H significantly increased the ＋dP/dtmax (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/dtmin also improved by 10μM U50488H (64.7 ± 4.8%, P = 0.003) compared to control (47.0 ± 2.7%). Conclusions:U50488H given at early reperfusion phase reduces both infarct size and myocardial stunning in isolated rat hearts.