Objective: Bleeding is a major complication in coronary artery bypass graft (CABG) surgery. Antifibrinolytic agents like the serine protease inhibitor aprotinin can decrease postoperative bleeding and complications of CABG surgery. However, the effects of aprotinin on the vascular function of internal mammary arteries from patients undergoing CAGB surgery have not been elucidated so far.

Methods: We compared the ex vivo vascular function of left internal mammary arteries of patients undergoing CABG surgery with and without intraoperative application of aprotinin. In a second approach, human internal mammary arteries were treated with aprotinin ex vivo and tested for changes in contraction, endothelium-dependent and -independent vascular function. In an additional model, we analyzed whether long- or short-term incubation with aprotinin affects the vascular function of rat aortic rings. Finally, the impact of different concentrations of aprotinin on expression and activity of endothelial nitric oxide synthase (eNOS) was analyzed in human endothelial cells.

Results: The patients of the control group (n=12) showed no significant differences in comparison to the aprotinin group (n=12) in terms of age, gender, BMI, ejection fraction, smoking status, plasma cholesterol, LDL, HDL and triglycerides, hypertension, diabetes, dyslipidemia, and medical therapy. We found no effect of intraoperative application of aprotinin on ex vivo vascular function of internal mammary arteries from patients undergoing CABG surgery. Blockade of nitric oxide synthases with N^G-monomethyl-L-arginine (L-NMMA) did not result in differences in endothelium-dependent vasorelaxation of patients with or without aprotinin treatment. Ex vivo incubation with aprotinin did not change contraction, endothelium-dependent and -independent vasorelaxation of human internal mammary arteries. Long-term incubation with aprotinin under physiological conditions preserved the vascular function of rat aortas. Finally, in vitro application of different concentrations of aprotinin on human endothelial cells resulted in similar expression and activity of eNOS, compared to control.

Conclusion: Aprotinin is safe and does not affect vascular function of human internal mammary arteries of patients undergoing CAGB surgery and eNOS expression and activity in human endothelial cells. Furthermore, aprotinin preserves the vascular function in the rat aorta. This might have also further clinical implications, because aprotinin has been recently shown to inhibit SARS-CoV-2 replication and is discussed as potential therapeutic strategy in the COVID-19 pandemic.