Kappa-opioid receptor agonists (KOR) have been well-studied in protecting cardiomyocytes from ischemia-reperfusion injury. However, whether KOR agonists can protect skeletal muscle from ischemia-reperfusion injury is less known. The purpose of this study was to investigate whether presurgical KOR agonists would improve microcirculation in a rat cremaster muscle model after ischemia-reperfusion injury.
Eighteen male rats were randomly assigned to one of three groups with an equal number in each group (n = 6). In Group 1, the muscle flap received no treatment. In Group 2, U-50488 (a selective KOR agonist, 10 mg/kg) was injected intravenously 10 min before initiation of ischemia. In Group 3, both U-50488 and norbinaltorphimine (a selective KOR antagonist, 5 mg/kg) were injected intravenously before initiation of ischcemia. All cremaster muscle flaps were subjected to 4 hr of ischemia followed by 60 min of reperfusion. Microcirculatory study parameters including the numbers of rolling, sticking, and transmigrating leukocytes, functional capillary density, and swelling index of the vessel wall of the postcapillary venule were examined.
KOR agonist treatment before ischemia decreased the numbers of leukocyte adhesion by 81% compared with the control group (p < 0.001) and by 74% compared with the group treated with both KOR agonists and antagonists (p < 0.001) 60 min after reperfusion. KOR agonist treatment before ischemia decreased the numbers of leukocyte transmigration by 67% compared with the control group (p < 0.001) and by 76% compared with the group treated with both KOR agonists and antagonists (p < 0.001) 60 min after reperfusion. In addition, functional capillary density was increased by 110% (p < 0.01) in the group treated with KOR agonist compared with control and by 65% compared with the group treated with both KOR agonist and antagonist (p < 0.001).
Intravenous KOR agonists administration reduced the interaction of leukocytes with the endothelium and improved the capillary perfusion in muscle flap microcirculation during ischemia-reperfusion injury. The protective effect of KOR agonist was partially abolished by concomitant intravenous KOR antagonist administration.
