ROLE OF PLATELET-ACTIVATING-FACTOR IN ISCHEMIA-REPERFUSION INJURY OF ISOLATED RABBIT HEARTS - PROTECTIVE EFFECT OF A SPECIFIC PLATELET-ACTIVATING-FACTOR ANTAGONIST, TCV-309

Objectives: The aims were to confirm that platelet activating factor is released during reperfusion after global ischaemia in isolated blood perfused rabbit hearts, and to examine the protective action of TCV-309, a platelet activating factor antagonist, against reperfusion injury of cardiac muscle. Methods: The hearts were mounted on a Langendorff apparatus and perfused with diluted blood perfusate. After cardiac arrest with St Thomas's cardioplegic solution, the hearts were subjected to global ischaemia for 120 minutes at 25-degrees-C, and then reperfused for 60 minutes at 37-degrees-C. Release of platelet activating factor into the coronary effluent was quantified by radioimmunoassay. The effect of TCV-309 on left ventricular function and release of creatine kinase was measured. Results: A pronounced release of platelet activating factor occurred after the commencement of reperfusion, although it was not detectable before induction of ischaemia. Release of platelet activating factor occurred over 60 minutes of the reperfusion period. In the control, left ventricular developed pressure after 60 minutes of reperfusion recovered to 54.3(SEM 1.7)% (n=5) of the preischaemic value. In the hearts treated with TCV-309 at concentrations above 0.3 muM, recovery of left ventricular developed pressure was significantly improved (77.6(2.0)% at 1 muM, p<0.01 v control). Leakage of creatine kinase during the initial five minutes of reperfusion was significantly less in the hearts treated with 1 muM TCV-309 than in the controls (5.2(0.4) v 12.2(1.4) IU.g-1 wet weight, p<0.01). Conclusions: Release of platelet activating factor occurred during the reperfusion period in Langendorff perfused hearts. Treatment with the platelet activating factor antagonist TCV-309 significantly improved postischaemic left ventricular function and decreased creatine kinase release. These results suggest that platelet activating factor is involved in myocardial injury during ischaemia-reperfusion.