Jm. Walenga et al., EVALUATION OF CGP-39393 AS THE ANTICOAGULANT IN CARDIOPULMONARY BYPASS OPERATION IN A DOG-MODEL, The Annals of thoracic surgery, 58(6), 1994, pp. 1685-1689
Recombinant desulphatohirudin HV1 (CGP 39393), a specific and potent p
eptidic inhibitor of thrombin, was evaluated as the sole anticoagulant
in a dog model of cardiopulmonary bypass. CGP 39393 was administered
as a bolus plus infusion for a 1-hour pump period at doses of 1.0 mg/k
g + 0.75 mg.kg(-1).h(-1), 1.0 mg/kg + 1.50 mg.kg(-1).h(-1), 1.0 mg/kg
+ 2.25 mg.kg(-1).h(-1), or 1.0 mg/kg + 3.0 mg.kg(-1).h(-1) (n = 5 per
group). The lowest dose was ineffective, as a high degree of clot form
ation (314 +/- 160 mg) occurred as determined by quantitation of prote
in deposits in the pump line filter. The three higher doses inhibited
clot formation (35 to 44 mg) but did not reveal a dose-dependent effec
t (p = 0.308 between groups). All four doses produced the same amount
of postoperative blood loss (6.5 to 10 g/kg over 2 hours; p = 0.215 be
tween groups) and no oozing of blood from cut tissues (sternum, muscle
, skin) during or after operation. No adverse hemodynamic or hematolog
ic effects were observed. Animals were physiologically stable coming o
ff pump, requiring minimal fluid replacement or other cardiovascular s
upportive measures. The chromogenic anti-IIa assay could be used to mo
nitor CGP 39393. Some activated partial thromboplastin time and all ac
tivated clotting time values were oft: scale on pump, but they fell im
mediately after cardiopulmonary bypass, typically reaching near-normal
levels within 30 to 60 minutes. No reversal of CGP 39393 was used, as
blood levels declined rapidly after cessation of the infusion. This s
tudy in a dog model shows that CGP 39393 administered as a bolus plus
infusion (minimum dose, 1.0 mg/kg + 1.50 mg.kg(-1).h(-1)) can be used
safely and effectively during cardiopulmonary bypass for cardiac opera
tion.