Dose-Dependent Effect of Aprotinin on Aggravated Pro-Inflammatory Cytokines in Patients with Pulmonary Hypertension Following Cardiopulmonary Bypass

Abstract

Background: To investigate the dose dependent effect of aprotinin on aggravated pro-inflammatory cytokines in patients with pulmonary hypertension (PH) after cardiopulmonary bypass (CPB). Methods: Thirty-two patients with pulmonary arterial pressure (PAP) above 60 mmHg were recruited. They were assigned randomly to control (Group A, n = 8), and treated groups (Group B with aprotinin = 0.5 × 105 KIU/Kg, and Group C with aprotinin = 1.0 × 105 KIU/Kg, n = 12 each group). Blood samples were collected at various intervals of time and analyzed, from "0" hour (before CPB as baseline), at the completion of CPB, 4 hours and 24 hours after CPB, to measure the concentrations of interleukin 1β (IL-1β), interleukin-8 (IL-8), interleukin-10 (IL-10) and tumor necrosis factor-α (TNF-α). Results: All the biomarkers significantly increased after CPB. There was no significant difference in cytokine levels between Group A and group B after CPB. But IL-1β, IL-8 and TNF-α of Group C were not only significantly lower than Group A (p < 0.05), but also lower than Group B at various time points after CPB (p < 0.05). IL-10 of group C was significantly higher than Group A and Group B after CPB (p < 0.05). Conclusions: High dose aprotinin can suppress the release of pro-inflammatory cytokines IL-1β, IL-8 and TNF-α, and enhance the release of IL-10 in patients with PH after CPB. For patients having PH, there exists a simple and potential way to reduce the inflammatory response by applying high dose aprotinin.