The role of
platelet activating factor (PAF) in acute
myocardial ischemia (MI), produced by the
ligation of the left main coronary artery, was studied in anesthetized rats. A significant loss of cardiac amino-
nitrogen concentration and
cathepsin D activity was observed 6 hr after permanent occlusion MI or 10 min of MI followed by 6 hr of reperfusion in rats. A novel, potent, PAF antagonist,
CV-6209 (160 nmol/kg or 1.6 mumol/kg) injected after the
ligation, significantly retarded the loss of amino-
nitrogen and
cathepsin D activity in a dose-related manner. In another group of rats,
CV-6209 (1.6 mumol/kg) significantly blocked the
hypotension induced by repetitive
injections of PAF (570 pmol/kg) with an apparent half-life of approximately 180 min. In isolated rat hearts perfused with
Krebs-Henseleit solution, PAF (25 nmol/l) significantly increased coronary perfusion pressure by 15 +/- 2 mmHg and induced an increase in cardiac permeability using
fluorescein isothiocyanate bovine albumin as a marker. Furthermore, the increase in cardiac permeability induced in isolated perfused rat hearts undergoing 15 min global
ischemia followed by reperfusion was significantly attenuated by
CV-6209 (250 nmol/l). These data indicate that PAF is an important mediator of ischemic damage in rat MI. Moreover, the extension of ischemic damage may be enhanced by the increase in cardiac permeability induced by PAF.