The novel synthetic serine-protease inhibitor CU2010 dose-dependently reduces postoperative blood loss and improves postischemic recovery myocardial and endothelial function

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 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 1.66mg/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 protamin, 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 comparble to aprotinin (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: 102±8%, p<0.05). 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 CU2010. Fig. 1 Conclusions: The novel serine-protease inhibitor CU2010 significantly reduce blood loss comparable to aprotinin. Furthermore, it led to a significantly improved postischemic recovery of myocardial and endothelial function.