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The Novel Synthetic Serine-Protease Inhibitor CU2010 Dose-Dependently Reduces Postoperative Blood Loss and Improves Postischemic Recovery After Cardiac Surgery
Gábor Szabó, Tamás Radovits, Gábor Veres, Matthias Karck; Department of Cardiac Surgery, University of Heidelberg, Heidelberg, Germany
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Objective: Serine-protease inhibitors such as aprotinin reduce perioperative blood loss and may improve post pump cardiac performance due to their anti-inflammatory properties. After the “aprotinin era”, we investigated the efficacy of the novel synthetic serine-protease inhibitor CU2010 with improved coagulatory and anti-inflammatory profile on blood loss and reperfusion injuryin a canine model.
Methods: 36 dogs were divided into six groups: control, aprotinin (Hammersmith scheme), and CU2010 (0.5; 0.83; 1.25 and 1.66 mg/kg). All animals underwent 90-minute cardiopulmonary bypass with 60 minutes of hypothermic cardioplegic arrest. Endpoints were blood loss during the first two hours after application of protamin, as well as recovery of myocardial contractility (slope of the end-systolic pressure volume relationship, Ees), coronary blood flow and vascular reactivity.
Results: CU2010 dose-dependently reduced blood loss which was comparble to aprotinin at lower doses and even further improved at higher doses (Figure 1, *p<0.05). While aprotinin did not influence myocardial function CU2010 improved the recovery of Ees (control: 60±6 vs. aprotinin: 73±7 vs. CU2010 at 1.66 mg/kg: 102±8 %, p<0.05). The improvement of myocardial contractility in CU2010 treated animals was also doesedependent. Coronary blood flow (52±4 vs. 88±7 vs. 96±7, p<0.05) and response to acethylcholine (44±6 vs. 77±7 vs. 81±6%, p<0.05) was improved by both aprotinin and at all doses of CU2010.
Conclusion: The novel serine-protease inhibitor CU2010 significantly reduce blood loss after cardiac surgery comparable to aprotinin. Furthermore, an additionally improved anti-inflammatory profile led to a significantly improved postischemic recovery of myocardial and endothelial function.

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