The novel synthetic serine protease inhibitor CU-2010 dose-dependently reduces postoperative blood loss and improves postischemic recovery after cardiac surgery in a canine model

• Verfasst von: Szabó, Gábor [VerfasserIn]
• Verfasst von: Veres, Gábor [VerfasserIn]
• Verfasst von: Radovits, Tamás [VerfasserIn]
• Verfasst von: Haider, Humaira [VerfasserIn]
• Verfasst von: Krieger, Nelli [VerfasserIn]
• Verfasst von: Bährle-Szabó, Susanne [VerfasserIn]
• Verfasst von: Niklisch, Silke [VerfasserIn]
• Verfasst von: Miesel-Gröschel, Christiane [VerfasserIn]
• Verfasst von: Locht, Andreas van de [VerfasserIn]
• Verfasst von: Karck, Matthias [VerfasserIn]
• Titel: The novel synthetic serine protease inhibitor CU-2010 dose-dependently reduces postoperative blood loss and improves postischemic recovery after cardiac surgery in a canine model
• Verf.angabe: Gábor Szabó, MD, PhD, Gábor Veres, MD, Tamás Radovits, MD, Humaira Haider, Nelli Krieger, Susanne Bährle, MD, Silke Niklisch, Christiane Miesel-Gröschel, Andreas van de Locht, PhD, and Matthias Karck, MD
• E-Jahr: 2010
• Jahr: 20 February 2010
• Umfang: 9 S.
• Fussnoten: Gesehen am 08.09.2023 ; Read at the Eighty-ninth Annual Meeting of The American Association for Thoracic Surgery, Boston, Massachusetts, May 9–13, 2009
• Titel Quelle: Enthalten in: The journal of thoracic and cardiovascular surgery
• Ort Quelle: Amsterdam : Elsevier, 1959
• Jahr Quelle: 2010
• Band/Heft Quelle: 139(2010), 3, Seite 732-740
• ISSN Quelle: 1097-685X
• DOI: doi:10.1016/j.jtcvs.2009.10.059
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1859126936

Abstract

Background - Serine protease inhibitors such as aprotinin reduce perioperative blood loss and may improve postpump cardiac performance owing to their anti-inflammatory properties. After the “aprotinin era,” we investigated the efficacy of the novel synthetic serine protease inhibitors CU-2010 with improved coagulatory and anti-inflammatory profile on blood loss and reperfusion injury in a canine model. - Methods - Thirty-six dogs were divided into 6 groups: control, aprotinin (n = 8; Hammersmith scheme), and CU-2010 (0.5, 0.83, 1.25, and 1.66 mg/kg). All animals underwent 90 minutes of cardiopulmonary bypass with 60 minutes of hypothermic cardioplegic arrest. End points were blood loss during the first 2 hours after application of protamine, as well as recovery of myocardial contractility (slope of the end-systolic pressure-volume relationship, coronary blood flow, and vascular reactivity. - Results - CU-2010 dose-dependently reduced blood loss to a degree comparable with that of aprotinin at lower doses and even further improved at higher doses (control/aprotinin/CU-2010 in increasing doses: 142 ± 13, 66 ± 17, 95 ± 16, 57 ± 17, 46 ± 3, and 13 ± 4 mL; P < .05). Whereas aprotinin did not influence myocardial function, CU-2010 improved the recovery of end-systolic pressure-volume relationship (control 60 ± 6 mg kg vs aprotinin 73 ± 7 mg/kg vs CU-2010 1.66 mg/kg; 102% ± 8%; P < .05). Coronary blood flow (52 ± 4 vs 88 ± 7 vs 96 ± 7; P < .05) and response to acetylcholine (44% ± 6% vs 77% ± 7% vs 81% ± 6%; P < .05) were improved by both aprotinin and CU-2010. - Conclusions - The novel serine protease inhibitor CU-2010 significantly reduced blood loss after cardiac surgery comparable with aprotinin. Furthermore, an additionally improved anti-inflammatory profile led to a significantly improved postischemic recovery of myocardial and endothelial function.