Sivelestat Attenuates Lung Injury in Surgery for Congenital Heart Disease With Pulmonary Hypertension

Abstract

Pulmonary hypertension associated with congenital heart disease increases the risk of surgery using cardiopulmonary bypass. Sivelestat is a neutrophil elastase inhibitor thought to have a prophylactic effect against lung injury after surgery using bypass. We elucidated that Sivelestat had the protective effect on lung in patients with congenital heart disease and pulmonary hypertension who underwent surgery using bypass. This study was a controlled prospective randomized trial and enrolled 13 neonates or infants with ventricular septal defect and pulmonary hypertension. The patients were assigned to either sivelestat with the dose of 0.2 mg/kg per hour (sivelestat group, n= 7) or saline (placebo group, n= 6) from the start of bypass until 6 hours after bypass. Proinflammatory cytokines and adhesion molecules on leukocytes were measured at 10 time points during the above period. Pulmonary function was assessed perioperatively. Compared with the placebo group, the sivelestat group had significantly lower values of alveolar-arterial oxygen tension gradient at 24 hours (p= 0.038) and at 48 hours (p= 0.028) after bypass, and significantly better balance of hydration at 48 hours after bypass (p=0.012). The sivelestat group also showed significantly lower plasma levels of interleukin-8 immediately after bypass (p= 0.041) and interleukin-10 at 15 minutes after removal of the aortic cross-clamp (p= 0.048), and immediately after bypass (p= 0.037). Administration of sivelestat during bypass prevented pulmonary damage and activities of proinflammatory cytokines at the cardiac operation in neonates or infants. Our results show that sivelestat may be considered to protect pulmonary function against the injury by bypass.