Development of Novel Synthetic Serine-Protease Inhibitors to Reduce Postoperative Blood Loss After Cardiac Surgery
Gábor Szabó1, Gabor Veres1, Tamás Radovits1, Matthias Karck1, Andreas van de Locht2; 1Universtiy of Heidelberg, Heidelberg, Germany; 2Curacyte Discovery Ltd., Leipzig, Germany
Comment on this Abstract
Objective: The non-specific serine-protease inhibitor aprotinin is used to reduce perioperative blood loss after cardiopulmonary bypass. Because of allergic and infectious risk and clinical side effets substitutes of aprotinin would be highly preferable. We investigated the efficacy of the novel synthetic serine-protease inhibitors CJ2010 and CJ2020 on blood loss in a canine model.
Methods: 37 dogs were divided into five groups: control (n=5), aprotinin (n=8; Hammersmith scheme), CJ2010 I. (n=8, 1,6 mg/kg Hammersmith scheme) CJ2010 II. (n=8, 1,6 mg/kg continuous infusion) and CJ2020 (n=8, 8,9 mg/kg, Hammersmith scheme). All animals underwent 90-minute cardiopulmonary bypass. Endpoints were blood loss during the first two hours after application of protamin, activated clotting time (ACT), partial thromboplastin time (PTT), and prothrombin time (PT).
Results: CJ2010 and CJ2020 significantly reduced blood loss comparable to aprotinin (Figure 1, *p<0.05). While ACT and PTT normalized after protamine in the control, aprotinin and CJ2010 I. groups they remained elevated in the CJ2010 II. and CJ2020 groups. PT values did not differ beween the groups.
Conclusion: The novel serine-protease inhibitors CJ2010 and CJ2020 significantly reduce blood loss after cardiac surgery comparable to aprotinin. Furthermore, an additional anti-thrombotic protective effect is implicated by prolonged PTT and ACT values.
Figure 1. Blood loss after 20 (T120) 40 (T160) and 120 (T220) minutes after aplication of protamin, as well as cumulative total blood loss
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