The effect of inhibition of the platelet release reaction on platelet behaviour in vitro and in vivo

The possibility of modifying the in vivo behaviour of platelets by drugs which inhibit the platelet ‘release reaction’ is currently a subject of considerable interest. The suppressive effect of amitriptyline and acetylsalicylic acid (ASA) on collagen induced platelet aggregation in vitro is ascribed to inhibition of the release mechanism. The effects of these materials on the platelet response to biolaser induced endothelial injury in conscious rabbits and the formation and stability of haemostatic plugs formed in transected mesenteric vessels of anaesthetised rabbits were studied. Neither ASA (200 mg/kg body weight i.v. given in THAM buffered saline) nor amitriptyline chloride (5 mg/kg b.w., i.v.) had any effect on platelet reactivity at sites of biolaser induced endothelial injury in rabbit ear chamber preparations. The same dose of amitriptyline given i.v. to urethane anaesthetised rabbits did not alter arteriolar or venular bleeding time from transected mesenteric vessels. In contrast, while ASA (200 mg/kg i.v.) did not alter the arteriolar bleeding time, the venular bleeding time was significantly decreased when compared with saline treated animals. The same result was obtained when ASA was given i.v. to pentobarbital anaesthetised animals or 2 h after oral administration of the drug. ASA had no effect on portal or central venous pressures and measurements of plasma salicylate levels after THAM-ASA gave results similar to those reported in man. The results show that, in the experimental models used, aggregation and adhesion of platelets at sites of vessel damage are not suppressed by drugs which inhibit the platelet release reaction.