Glucose-insulin-potassium treatment in combination with dipyridamole inhibits ischaemia-reperfusion-induced damage.

Aims/hypothesis: Treatment with intravenous glucose-insulin-potassium has beneficial effects in reperfused patients, reducing mortality in patients with myocardial infarction by 28 %. We hypothesized that insulin response to glucose-insulin-potassium infusion might lead to vasodilation in ischemia/reperfusion (I/R). Hyperglycaemia and hyperinsulinaemia determine oxidative stress. We therefore investigated the microcirculatory changes following I/R after glucose-insulin-potassium or in association with glucose-insulin-potassium dipyridamole in hamster cheek pouch.

Methods: The control (I/R), glucose-insulin-potassium groups with and without dipyridamole were treated with saline, 300 g/l, 50 U/l insulin and 80 meq/l KCl infused at 0.2 ml. 100 g-1. h-1, and GIK plus dipyridamole (0.084 mg. 100 g-1 intravenously) at beginning, 30 min before ischaemia, and continuing through reperfusion. We measured microvessel diameter changes, arteriolar red blood cell velocity, permeability increase, capillary perfused length, leukocyte and platelet adhesion.

Results: Hyperglycaemia and hyperinsulinaemia did not cause vasodilation whereas in the glucose-insulin-potassium group with dipyridamole there was a marked arterial vasodilation with increased red blood cell velocity and perfused capillary length at reperfusion. Glucose-insulin-potassium infusion reversed the arterial vasoconstriction caused by I/R at reperfusion. Adhering leukocytes to venules decreased by 56 and 86 % while platelets adhering to microvessels was reduced by 52 and 72 % at reperfusion in glucose-insulin-potassium groups with and without dipyridamole, respectively. The permeability was decreased by GIK and completely suppressed by GIKD after I/R. Conclusion hypothesis: We demonstrated that GIK, when used in combination with dipyridamole, had beneficial effects on the capillary perfusion against I/R-induced injury. There was a marked reduction of leukocyte and platelet adhesion that can be explained by the antioxidant properties of dipyridamole.