Effects of Ticlopidine and Aspirin on Endotoxin-Induced Disseminated Intravascular Coagulation in Rats

Summary

The effects of ticlopidine and aspirin on endotoxin-induced experimental disseminated intravascular coagulation (DIC) were studied in rats. Experimental DIC was induced by a 4 hr sustained infusion of endotoxin at a dose of 100 mg/kg. The rats were intraperitoneally injected with ticlopidine at 2.0, 20.0, 50.0, 100.0 or 200.0 mg/kg, or aspirin at 0.03, 0.3, 3.0 or 30.0 mg/kg, followed by the continuous infusion of 100 mg/kg/4 hr of endotoxin. A preventive effect against DIC was noted in all the parameters, such as fibrinogen and fibrin degradation products (FDP), fibrinogen level, prothrombin time, partial thromboplastin time (PTT), platelet count and the number of renal glomeruli with fibrin thrombi, in the rats treated with 20.0, 50.0, 100.0 or mg/kg of ticlopidine. Although a preventive effect was also noted in FDP, PTT, platelet count and the number of glomeruli with thrombi in rats treated with 0.03 or 0.3 mg/kg of aspirin, this agent was less effective than ticlopidine.

Keywords

DIC - Endotoxin - Ticlopidine - Aspirin - Rat

• References

• 1 Minna JD, Robboy SI, Colman RW. Disseminated intravascular coagulation in man. Charles CThomas. (ed). Springfield; 1974. pp 3-18
• 2 Maffrand JP, Eloy F. Synthèse de thienopyridines et de furopyridined d’intèrêt thèrapeutique. Eur J Med Chem 1974; 9: 483-486
• 3 Thebault JJ, Blatrix CE, Blanchard JF, Panak EA. Effects of ticlopidine, a new platelet aggregation inhibitor in man. Clin Pharmacol Ther 1975; 18: 485-190
• 4 Ashida S, Abiko Y. Inhibition of platelet aggregation by a new agent, ticlopidine. Thromb Haemostas 1978; 40: 542-550
• 5 Ebihara A, Aoki N, Sano M, Suzuki T. New antithrombotic drug, ticlopidine: phase I study in Japanese. Jpn J Clin Pharmacol 1977; 8: 63-64
• 6 Wood L. Treatment of atherosclerosis and thrombosis with aspirin. Lancet 1972; 2: 532-534
• 7 Villa S, Mysliwiec M, De GaetanoG. Prostacyclin and atherosclerosis in rats. Lancet 1977; 1: 1216-1217
• 8 Villa S, Callioni A, De GaetanoG. Normal prostacyclin-like activity in vascular tissue from thrombocytopenic rats. Thromb Res 1977; 11: 701-704
• 9 Yoshikawa T, Furukawa Y, Murakami M, Takemura S, Kondo M. Experimental model of disseminated intravascular coagulation induced by sustained infusion of endotoxin. Res Exp Med 1981; 179: 223-228
• 10 Ferreira HC, Murat LG. Immunological method for demonstrating fibrin degradation products in serum and its use the diagnosis of fibrinolytic states. Br J Haematol 1963; 9: 299-310
• 11 Goodwin JF. Estimation of plasma fibrinogen using sodium sulfate fractionation. Am J Clin Pathol 1961; 35: 227-232
• 12 Quick AJ, Stanly BM, Bancroft FW. A study of the coagulation defect in hemophilic and in jaundice. Am J Med Sci 1935; 190: 501-511
• 13 Langdell RD, Wagner RH, Brinkhaus KM. Effect of antihemophilic factor on one-stage clotting time. J Lab Clin Med 1953; 47: 637-647
• 14 Brecker G, Cronkite EP. Morphology and enumeration of human blood platelets. J Appl Physiol 1950; 3: 365-377
• 15 Weigert C. Über eine neue Methode zur Färbung von Fibrin und von Mikroorganismen. Fortschr Med 1887; 5: 228-232
• 16 Tomikawa M, Ashida S, Kakihata K, Abiko Y. Anti-thrombotic action of ticlopidine, a new platelet aggregation inhibitor. Thromb Res 1978; 12: 1157-1164
• 17 Ashida S, Abiko Y. Mode of action of ticlopidine in inhibition of platelet aggregation in the rat. Thromb Haemostas 1979; 41: 436-449
• 18 Weiss HJ, Aledort LM. Impaired platelet/connective tissue reaction in man after aspirin ingestion. Lancet 1967; 2: 495-497
• 19 Packham MA, Mustard JF. Clinical pharmacology of platelets. Blood 1977; 50: 555-573
• 20 Weiss HJ. Antiplatelet drugs: a new pharmacologic approach to the prevention of thrombosis. Am Heart J 1976; 92: 86-102
• 21 Smith JB, Willis AL. Aspirin selectively inhibits prostaglandin production in human platelets. Nature (New Biol) 1971; 231: 235-237
• 22 Samuelsson B. The role of prostaglandin endoperoxides and thromboxanes in human platelets. In: Prostaglandins in hematology. Silver MJ, Smith JB, Kocsis JJ. (Eds). Spectrum; New York: 1977. pp 1-10
• 23 Roth GJ, Stanford N, Majerus PW. Acetylation of prostaglandin synthetase by aspirin. Proc Natl Acad Sci USA 1975; 72: 3073-3076
• 24 Aubert D, Pepin O. Thrombose expérimentale artérielle et veineuse chez le rat Wistar. Etude comparative du (chloro-2 benzyl)-5 tétrahydro-4, 5, 6, 7 thiéno [3, 2-c]pyridine, chlorhydrate du ticlopidine et de 1’aspirine. In: Abstracts du 4e Congrés Méditerraneen sur les Thromboembolies (Athfenes, 2-6 Mai 1976). 1976. 162. 99
• 25 Kelton JG, Hirsh J, Carter CJ, Buchanan MR. Thrombogenic effect of high dose aspirin in rabbits. Relationship to inhibition of vessel wall synthesis of prostaglandin I₂-like activity. J Clin Invest 1978; 62: 892-895
• 26 Ashida S, Abiko Y. Effect of ticlopidine and acetylsalicylic acid on generation of prostaglandin l₂-like substance in rat arterial tissue. Thromb Res 1978; 13: 901-908