gea-3162 and Reperfusion-Injury

The effect of a new nitric oxide (NO) donor, a meso-ionic 3-aryl substituted oxatriazole-5-imine derivative, GEA 3162 was studied on constant flow-perfused ischaemic Langendorff rat heart. The perfusion was kept constant at a rate of 16 mL min-1. Ischaemia was induced by a low flow rate of 0.8 mL min-1 for 30 min, and was followed by a 40-minute reperfusion. In the first set of experiments the effects of GEA 3162-infusion were examined on perfusion pressure, left ventricular pressure, heart rate and left ventricular dP/dt. GEA 3162 infusion did not affect the pre-ischaemic maximum of left ventricular pressure. During reperfusion, maximal left ventricular pressure, maximal and minimal dP/dt values in the GEA 3162-treated group significantly exceeded those of the untreated controls (by 19.3, 36.0 and 18.0%, respectively). During reperfusion, perfusion pressure increased continuously in the control group indicating an increasing coronary resistance, but it was kept at a continuous low level with GEA 3162 treatment. In a second set of experiments bradykinin was infused in order to test the endothelial function before ischaemia and during late reperfusion. Bradykinin elicited significant vasodilation in the control group during reperfusion, meanwhile it did not cause further change in coronary resistance in the GEA 3162-infused group. We suggest, that GEA 3162 may have a protective effect on isolated rat heart in ischaemia and reperfusion, that results in an improved cardiac performance compared with untreated hearts.

Topics: Animals; Biomechanical Phenomena; Bradykinin; Heart; In Vitro Techniques; Male; Myocardial Ischemia; Nitric Oxide; Platelet Aggregation Inhibitors; Rats; Rats, Wistar; Reperfusion Injury; Triazoles; Vascular Resistance; Vasodilator Agents; Ventricular Function, Left