Effects of novel synthetic serine protease inhibitors on postoperative blood loss, coagulation parameters, and vascular relaxation after cardiac surgery

G. Szabó, Gábor Veres, T. Radovits, Humaira Haider, Nelli Krieger, Susanne Bährle, Christiane Miesel-Gröschel, Silke Niklisch, Matthias Karck, Andreas van de Locht

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

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 ± 4, 43 ± 8, 52 ± 7, 61 ± 7, respectively, vs control 149 ± 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.

Original languageEnglish
Pages (from-to)181-188
Number of pages8
JournalJournal of Thoracic and Cardiovascular Surgery
Volume139
Issue number1
DOIs
Publication statusPublished - Jan 2010

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Postoperative Hemorrhage
Serine Proteinase Inhibitors
Blood Coagulation
Thoracic Surgery
Blood Vessels
Aprotinin
Partial Thromboplastin Time
Protamines
Prothrombin Time
Cardiopulmonary Bypass
Nitroprusside
CU-2010
Acetylcholine
Canidae
Dogs
Control Groups

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Surgery
  • Pulmonary and Respiratory Medicine

Cite this

Effects of novel synthetic serine protease inhibitors on postoperative blood loss, coagulation parameters, and vascular relaxation after cardiac surgery. / Szabó, G.; Veres, Gábor; Radovits, T.; Haider, Humaira; Krieger, Nelli; Bährle, Susanne; Miesel-Gröschel, Christiane; Niklisch, Silke; Karck, Matthias; van de Locht, Andreas.

In: Journal of Thoracic and Cardiovascular Surgery, Vol. 139, No. 1, 01.2010, p. 181-188.

Research output: Contribution to journalArticle

Szabó, G. ; Veres, Gábor ; Radovits, T. ; Haider, Humaira ; Krieger, Nelli ; Bährle, Susanne ; Miesel-Gröschel, Christiane ; Niklisch, Silke ; Karck, Matthias ; van de Locht, Andreas. / Effects of novel synthetic serine protease inhibitors on postoperative blood loss, coagulation parameters, and vascular relaxation after cardiac surgery. In: Journal of Thoracic and Cardiovascular Surgery. 2010 ; Vol. 139, No. 1. pp. 181-188.
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AU - Haider, Humaira

AU - Krieger, Nelli

AU - Bährle, Susanne

AU - Miesel-Gröschel, Christiane

AU - Niklisch, Silke

AU - Karck, Matthias

AU - van de Locht, Andreas

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N2 - 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 ± 4, 43 ± 8, 52 ± 7, 61 ± 7, respectively, vs control 149 ± 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.

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