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Rivista di Chirurgia Cardiaca, Vascolare e Toracica

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The Journal of Cardiovascular Surgery 1998 October;39(5):633-9

lingua: Inglese

r-Hirudin inhib­its plate­let-depen­dent throm­bo­sis dur­ing car­di­o­pul­mo­nary ­bypass in ­baboons

Van Wyk V., Neethling W. M. L.*, Badenhorst P. N., Kotzé H. F.

From the Departments of Haematology and * Cardiothoracic Surgery, Faculty of Medicine University of the Free State, Bloemfontein, South Africa


Background. Systemic anti­co­ag­u­la­tion is ­required dur­ing car­di­o­pul­mo­nary ­bypass (CPB) to inhib­it the acti­va­tion of plate­lets, the coag­u­la­tion ­system and ulti­mate­ly throm­bus for­ma­tion. Unfractionated hep­ar­in is ­most com­mon­ly ­used, but it is nei­ther entire­ly ­safe nor com­plete­ly effec­tive. The use of pro­ta­mine sul­phate to ­reverse the anti­co­ag­u­lant ­effect fur­ther com­pli­cates the use of hep­ar­in. The clin­i­cal ­need for a hep­ar­in sub­sti­tute is there­fore obvi­ous. We eval­u­at­ed the effi­ca­cy of r-Hirudin, a ­potent and spe­cif­ic inhib­i­tor of throm­bin, as anti­co­ag­u­lant in a ­baboon mod­el of car­di­o­pul­mo­nary ­bypass.
Methods. Ten ­baboons, divid­ed ­into two ­groups of ­five ­each, ­were ­used. The one ­group ­received 0.7 mg/kg r-Hirudin as a ­bolus ­before CPB was start­ed, fol­lowed by a con­stant infu­sion of 1.4 mg/kg/hr for the 90 min of CPB. The oth­er ­group ­received a ­bolus of 2.5 mg/kg hep­ar­in ­before the ­start of CPB, fol­lowed by main­te­nance dos­ag­es to main­tain the acti­vat­ed clot­ting ­time (ACT) >400 sec.
Results. Adequate anti­co­ag­u­la­tion was ­obtained ­with ­both anti­co­ag­u­lants. Haemodilution due to prim­ing the extra­cor­po­real ­system ­with Ringer’s lac­tate and appro­pri­ate­ly anti­co­ag­u­lat­ed ­donor ­blood, was equiv­a­lent in ­both ­groups. During CPB ­with hep­ar­in, but not ­with hir­u­din, ­there was a sig­nif­i­cant ­increase in the num­ber of cir­cu­lat­ing plate­let aggre­gates, throm­bin-anti­throm­bin (TAT) com­plex­es and 111In-­labelled plate­let accu­mu­la­tion in the oxy­gen­a­tor. After the ­initial ­decrease in plate­let ­count due to hae­mod­i­lu­tion, it fur­ther ­decreased sig­nif­i­cant­ly dur­ing CPB ­with hep­ar­in but ­remained rel­a­ti­vel­y ­con­stant ­when r-Hirudin was ­used.
Conclusions. Our ­results strong­ly sug­gest ­that r-Hirudin is super­i­or to hep­ar­in espe­cial­ly ­with ­respect to its inhib­i­to­ry ­effect on plate­let depen­dent throm­bo­gen­e­sis ­caused by the bio­mem­branes of the oxy­gen­a­tor.

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