Dexamethasone pretreatment provides antiinflammatory and myocardial protection in neonatal arterial switch operation

Abstract

Background: This prospective double-blinded randomized study tested the hypothesis that preoperative treatment with dexamethasone would attenuate inflammatory priming of the myocardium, reduce the systemic inflammatory reaction upon cardiac operation, and provide organ protection in neonates.

Methods: Twenty neonates (age, 8 to 21 days) with transposition of the great arteries scheduled for arterial switch operation were included. Nine received dexamethasone (1 mg/kg body weight) 4 hours before cardiopulmonary bypass, and 11 received natrium chloride. We studied intramyocardial messenger RNA expression of interleukin (IL)-6, IL-8, IL-1β, and tumor necrosis factor-α (TNF-α), as well as IL-10 and expression of TNF-α on protein level in right atrial tissue taken before institution of CPB. We measured plasma levels of IL-6, IL-10, lipopolysaccharide binding protein, and cardiac troponin T. Cytokine expression was related to postoperative outcome.

Results: Pretreatment with dexamethasone led to a significant decrease in myocardial expression of IL-6, IL-8, IL-1β, and TNF-α messenger RNA and to a decrease in protein synthesis of TNF-α. Plasma concentrations of IL-6 were significantly lower and those of IL-10 significantly higher in pretreated patients. This was associated with lower cardiac troponin T values and lower dobutamine requirement. Levels of lipopolysaccharide binding protein were significantly higher postoperatively in pretreated neonates.

Conclusions: Dexamethasone administration before arterial switch operation leads to a shift in the myocardial and systemic cytokine expression profile in neonates with transposition of the great arteries, with downregulation of proinflammatory and upregulation of antiinflammatory cytokines. Lower myocardial cell damage and lower catecholamine requirement suggest myocardial protection in treated patients.