Effects of novel synthetic serine protease inhibitors on postoperative blood loss, coagulation parameters, and vascular relaxation after cardiac surgery.
OBJECTIVE
Although aprotinin has been widely used to reduce perioperative blood loss after cardiopulmonary bypass, recent concerns have led to its withdrawal. This study investigated effects of the novel synthetic serine protease inhibitors CU-2010 and CU-2020 on blood loss, coagulation parameters, and coronary relaxation in a canine model.


METHODS
Thirty-seven dogs were divided into 5 groups: control (n = 5), aprotinin (n = 8, Hammersmith scheme of intravenous bolus, prime, and continuous infusion), Hammersmith CU-2010 (n = 8, 1.6 mg/kg Hammersmith scheme), continuous CU-2010 (n = 8, 1.6 mg/kg continuous infusion), and CU-2020 (n = 8, 8.9 mg/kg Hammersmith scheme). All animals underwent 90-minute cardiopulmonary bypass. End points were blood loss during first 2 hours after protamine and activated clotting, partial thromboplastin, and prothrombin times. At end of experiments, coronary rings were removed for in vitro testing of relaxation to acetylcholine and sodium nitroprusside.


RESULTS
Hammersmith and continuous CU-2010, CU-2020, and aprotinin groups all had reduced blood loss (43 + or - 4, 43 + or - 8, 52 + or - 7, 61 + or - 7, respectively, vs control 149 + or - 24 mL, P < .05). After protamine, activated clotting time and partial thromboplastin time normalized in control, aprotinin, and Hammersmith CU-2010 groups but remained elevated in continuous CU-2010 and CU-2020 groups. Prothrombin time and vascular relaxation did not differ between groups.


CONCLUSIONS
CU-2010 and CU-2020 significantly reduced blood loss after cardiac surgery, with prolonged partial thromboplastin and activated clotting times, demonstrating improved antithrombotic profile. Neither aprotinin nor the novel serine protease inhibitors influenced vascular relaxation.
Szabó
Gábor
G
Department of Cardiac Surgery, University of Heidelberg, Heidelberg, Germany. gabor.szabo@urz.uni-heidelberg.de
Veres
Gábor
G
Radovits
Tamás
T
Haider
Humaira
H
Krieger
Nelli
N
Bährle
Susanne
S
Miesel-Gröschel
Christiane
C
Niklisch
Silke
S
Karck
Matthias
M
van de Locht
Andreas
A
D000818:Animals; D007611:Aprotinin / Q000008:administration & dosage / Q000494:pharmacology; D001777:Blood Coagulation / Q000187:drug effects*; D006348:Cardiac Surgical Procedures; D002315:Cardiopulmonary Bypass; D004285:Dogs; D010314:Partial Thromboplastin Time; D019106:Postoperative Hemorrhage / Q000517:prevention & control*; D015842:Serine Proteinase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects*
D015842:Serine Proteinase Inhibitors; D007611:Aprotinin