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

in Annals of Thoracic Surgery (2012), 93(3), 869-76

BACKGROUND: This prospective double-blinded randomized study tested the hypothesis that preoperative treatment with dexamethasone would attenuate inflammatory priming of the myocardium, reduce the ... [more ▼]

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-1beta, and tumor necrosis factor-alpha (TNF-alpha), as well as IL-10 and expression of TNF-alpha 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-1beta, and TNF-alpha messenger RNA and to a decrease in protein synthesis of TNF-alpha. 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. [less ▲]

Pre-treatment with dexamethasone provides anti-inflammatory and myocardial protection in neonatal arterial switch operation: A prospective randomized double-blind controlled study

Poster (2012)

Myocardial remodelling in children with atrial septal defect and significant left-to-right shunt is characterized by signals inducing hypertrophy, angiogenesis, fibrosis and inhibition of apoptosis

Poster (2012)

Children undergoing cardiac surgery for complex cardiac defects show imbalance between pro- and anti-thrombotic activity.

in Critical Care: the Official Journal of the Critical Care Forum (2006), 10(6), 165

INTRODUCTION: Cardiac surgery with cardiopulmonary bypass (CPB) is associated with the activation of inflammatory mediators that possess prothrombotic activity and could cause postoperative haemostatic ... [more ▼]

INTRODUCTION: Cardiac surgery with cardiopulmonary bypass (CPB) is associated with the activation of inflammatory mediators that possess prothrombotic activity and could cause postoperative haemostatic disorders. This study was conducted to investigate the effect of cardiac surgery on prothrombotic activity in children undergoing cardiac surgery for complex cardiac defects. METHODS: Eighteen children (ages 3 to 163 months) undergoing univentricular palliation with total cavopulmonary connection (TCPC) (n = 10) or a biventricular repair (n = 8) for complex cardiac defects were studied. Prothrombotic activity was evaluated by measuring plasma levels of prothrombin fragment 1+2 (F1+2), thromboxane B2 (TxB2), and monocyte chemoattractant protein-1 (MCP-1). Anti-thrombotic activity was evaluated by measuring levels of tissue factor pathway inhibitor (TFPI) before, during, and after cardiac surgery. RESULTS: In all patients, cardiac surgery was associated with a significant but transient increase of F1+2, TxB2, TFPI, and MCP-1. Maximal values of F1+2, TxB2, and MCP-1 were found at the end of CPB. In contrast, maximal levels of TFPI were observed at the beginning of CPB. Concentrations of F1+2 at the end of CPB correlated negatively with the minimal oesophageal temperature during CPB. Markers of prothrombotic activity returned to preoperative values from the first postoperative day on. Early postoperative TFPI levels were significantly lower and TxB2 levels significantly higher in patients with TCPC than in those with biventricular repair. Thromboembolic events were not observed. CONCLUSION: Our data suggest that children with complex cardiac defects undergoing cardiac surgery show profound but transient imbalance between pro- and anti-thrombotic activity, which could lead to thromboembolic complications. These alterations are more important after TCPC than after biventricular repair but seem to be determined mainly by low antithrombin III. [less ▲]

The production of pro- and anti-inflammatory cytokines in neonates assessed by stimulated whole cord blood culture and by plasma levels at birth.

in Biology of the Neonate (1998), 73(4), 220-7

The capability of neonates to achieve cytokine balance was evaluated. Production of the pro-inflammatory cytokines TNF alpha and IL-8, of the natural anti-inflammatory cytokine IL10 and of the regulator ... [more ▼]

The capability of neonates to achieve cytokine balance was evaluated. Production of the pro-inflammatory cytokines TNF alpha and IL-8, of the natural anti-inflammatory cytokine IL10 and of the regulator of the acute phase response IL6 was assessed after whole blood stimulation by lipopolysaccharide in cord blood (n = 10), adult volunteers serving as control (n = 17). Additionally, circulating cytokines were determined in cord and in maternal blood immediately after delivery (n = 27, respectively). Significant production of TNF alpha, IL8, IL10 and IL6 was observed in cord blood after lipopolysaccharide stimulation and was similar to cytokine production in adult blood. The plasma concentrations of TNF alpha were significantly higher in cord than in maternal blood, while plasma concentrations of IL10 and IL6 were significantly lower. Our results demonstrate fully developed capability of whole cord blood to synthesize pro- and anti-inflammatory cytokines in response to a pro-inflammatory stimulation in vitro. In vivo, however, higher circulating TNF alpha and lower IL10 and IL6 levels in cord blood suggest that the inflammatory stress associated with normal delivery does not induce detectable anti-inflammatory response in neonates at birth. [less ▲]