Inhibition of arterial thrombosis by polyamines in a canine coronary artery injury model.
Polyamines are polycations present in all living organisms and have been shown to play an important role in various physiological functions. Previous studies have shown that various amines including polyamines inhibit platelet activation. Among the amines tested tetra-amine, spermine is the potent inhibitor of platelet aggregation. In spite of vast literature on the anti-aggregatory effect of amines, there are no definitive studies testing their efficacy in an in vivo thrombosis model. In the present study, we investigated if polyamines could inhibit in-vivo thrombosis. A partially occlusive thrombus was generated by application of electric current in canine coronary artery. In control animals, the artery was completely in 76+/-14 min after the current was discontinued. When 40 mg/kg (1.44 mM) spermine was given immediately after stopping the current blood flow remained patent for >240 min. At equimolar concentration, triamine, spermidine and diamine putrescine are also equally effective in preventing thrombus development. The anti thrombic effect of polyamines was not associated with increased bleeding tendency, as judged by the amount of blood adsorbed by a gauge pad placed in a surgical incision extending to the muscle tissue and by a standard template bleeding. These results indicate that apart from inhibiting in-vitro platelet aggregation polyamines can also inhibit in-vivo thrombus formation.
Pakala
Rajbabu
R
Department of Internal Medicine, Division of Cardiology, University of Texas Health Science Center-Medical School, Houston, TX 77030, USA. rajbabu.pakala@medstar.net
D000007:Abdominal Injuries / Q000150:complications; D000818:Animals; D003328:Coronary Thrombosis / Q000209:etiology / Q000517:prevention & control*; D003331:Coronary Vessels / Q000293:injuries*; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D005260:Female; D005884:Gingival Hemorrhage / Q000139:chemically induced; D006470:Hemorrhage / Q000139:chemically induced; D008297:Male; D011700:Putrescine / Q000627:therapeutic use* / Q000633:toxicity; D013095:Spermidine / Q000627:therapeutic use* / Q000633:toxicity; D013096:Spermine / Q000627:therapeutic use* / Q000633:toxicity
D013096:Spermine; D013095:Spermidine; D011700:Putrescine