COMPARISON OF THE EFFECTS OF ACETYLSALICYLIC ACID AND SODIUM SALICYLATE ON PROLONGATION OF RAT CARDIAC ALLOGRAFT SURVIVAL AND ON INHIBITION OF RAT PLATELET AGGREGATION

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Abstract
Hearts taken from DA (RET1a) rats were transplanted heterotopically to PVG (RT1c) rats of the same sex (day 0). On day 1 treatment was started with aspirin (acetylsalicylic acid) 200 mg/kg per day by s.c. injection in saline every 8 h or sodium salicylate 200 mg/kg per day by s.c. injection in water every 8 h. A control group received saline alone. Cessation of palpable graft beat was taken as the endpoint of rejection. In the control group, hearts stopped between 6 and 9 days after transplantation, with a median of 7.4 days. Aspirin-treated hearts continued to beat for from 8 days to > 6 mo., with a median of 10.5 days; Wilcoxon rank-sum analysis showed graft survival to be significantly longer than in controls (P < 0.01). When sodium salicylate was used, hearts continued to beat for from 11 days to > 6 mo., with a median of 90 days. The Wilcoxon test showed this to be significantly longer than in controls (P < 0.01) and in the aspirin-treated group (P < 0.01). Other PVG (RT1c) rats bearing DA (RT1a) hearts received treatment identical to that given to the aforementioned groups, but on day 5 their blood was tested for salicylate levels and ADP-induced platelet aggregation characteristics. Stomachs were assessed for evidence of mucosal damage and histology of transplanted hearts was compared. Mean serum salicylate in the aspirin-treated group was 0.86 .+-. 0.14 mmol/l and in the sodium salicylate treated group was 1.65 .+-. 0.15 mmol/l. ADP-induced platelet aggregation was inhibited by 22 .+-. 2% in the aspirin-treated group, but was normal in the salicylate-treated groups. When aspirin or sodium salicylate was added in vitro to platelets from untreated PVG rats, 50% inhibition of ADP-induced platelet aggregation was caused by a concentration of 1.1 mmol/l aspirin or 14.5 mmol/l sodium salicylate. There was no evidence of gastric mucosal damage in any of the treated rats. Histological examination on day 5 showed marked mononuclear cell infiltration and muscle necrosis in the control group. In the aspirin-treated group on day 5 there was slightly less mononuclear cell infiltration and muscle necrosis, but in the sodium salicylate treated group mononuclear cell infiltration and muscle necrosis was much less evident than in the control group, although it was present. Sodium salicylate was more effective than aspirin in prolonging rat cardoac allograft survival, and the prolongation of graft survival is apparently not related to the effects of the drugs on platelet activity, but rather to the suppression of mononuclear cell infiltration and muscle damage.