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ObjectiveThis study determined neurodevelopmental outcomes of survivors of neonatal cardiac surgery for interrupted aortic arch through an interprovincial program and explored preoperative, intraoperative, and postoperative outcome predictors.MethodsChildren who underwent neonatal cardiac surgery for interrupted aortic arch at 6 weeks old or younger between 1996 and 2006 had a multidisciplinary neurodevelopmental assessment at 18 to 24 months old (mental and psychomotor developmental indices as mean ± SD and delay [score

SPIRIT 2013 checklist: recommended items to address in a clinical trial protocol and related documents. (DOC 122 kb)

To measure the time needed to achieve changes in fraction of inspired oxygen concentration (FiO2) from the oxygen blender to the facemask during simulated neonatal resuscitation.Two oxygen analyzers were placed at each end of the T-Piece. During simulated ventilation, the duration to achieve the set oxygen concentration at the facemask was measured. This was repeated at different gas flow rates (5 L/min, 8 L/min or 10 L/min) and different FiO2 changes (0.21 to 1.0 to 0.21, with stepwise increases and decreases in 0.05, 0.1 and 0.2 increments).A total of 1134 measurements (378 measurements for each flow) were recorded. Overall, the mean (± SD) time required to achieve FiO2 changes at 5 L/min, 8 L/min and 10 L/min was 36±15 s, 31±14 s and 28±14 s, respectively.There was a lag time of approximately 30 s to achieve the FiO2 at the facemask. This delay needs to be considered when making serial adjustments to FiO2 during neonatal resuscitation.Mesurer le temps nécessaire pour modifier les concentrations de la fraction d’oxygène dans l’air inspiré (FiODeux analyseurs d’oxygène ont été installés à chaque bout de l’insufflateur néonatal. Pendant la simulation de ventilation, les chercheurs ont mesuré le temps nécessaire pour parvenir à la concentration d’oxygène voulue au masque. Ils ont repris la mesure à divers débits de gaz (5 L/min, 8 L/min ou 10 L/min) et diverses modifications de la FiOAu total, les chercheurs ont enregistré 1 134 mesures (378 mesures par débit). Dans l’ensemble, le temps moyen (± ÉT) nécessaire pour parvenir à des modifications de la FiOIl y avait un décalage d’environ 30 secondes pour parvenir à une FiO

Sensorineural hearing loss (SNHL) is a significant neurologic morbidity in survivors of neonatal congenital diaphragmatic hernia (CDH), with a reported incidence of up to 60%. In a historical cohort study of 37 neonates with CDH, we investigated the use of pancuronium bromide (PB) and common ototoxic drugs during the neonatal period and their relationship to SNHL in childhood survivors. Survivors with SNHL (n = 23) had significantly higher cumulative dose of PB administered during the neonatal illness than survivors without SNHL (n = 14). The cumulative dose and duration of PB use significantly correlated ( r = 0.66-0.81) and independently predicted (adjusted r 2 = 0.42-0.64) the greatest intensity (in decibels) and the widest band (lowest frequency in hertz) loss of SNHL. No differences were identified between survivors with and without SNHL regarding demographic and neonatal characteristics (including oxygenation and ventilation variables and the cumulative dose and duration of therapy with aminoglycosides, vancomycin, and furosemide), although survivors with SNHL had received a modestly higher cumulative dose of ethacrynic acid than survivors without SNHL. Although we show that prolonged administration of PB during the neonatal period is associated with SNHL in childhood survivors of CDH, further multicenter studies are required to investigate the possible etiologies of SNHL in this high-risk population. (J Pediatr 1999;135:233-9)

The actions of thiols on coronary vascular tone in the intact heart are unknown. Glutathione (GSH), glutathione disulfide (GSSG), and L-cysteine (10-1,000 microM each) and GSH ethyl ester (3-300 microM) were infused into isolated rat hearts perfused with Krebs buffer at a constant pressure by the Langendorff method. GSH, GSSG, and GSH ethyl ester, but not L-cysteine, caused a concentration-dependent increase in coronary flow with the following order of potency: GSH ethyl ester > GSH = GSSG. The nitric oxide synthase inhibitor NG-monomethyl-L-arginine (300 microM), prevented the increase in coronary flow with GSH and attenuated that with GSSG (300 microM each). The vasodilation with GSH or GSSG and the associated increase in myocardial guanosine 3',5'-cyclic monophosphate were abolished by 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (a specific inhibitor of soluble guanylate cyclase) at 1 and 3 microM, respectively. The vasodilator action of GSH was abolished by superoxide dismutase (50 U/ml). Inhibition of GSH reductase abolished GSSG-induced vasodilation. Neither glibenclamide (1 microM) nor indomethacin (4 microM) affected the vasodilator action of GSH and GSSG. We conclude that GSH and GSSG cause coronary vasodilation that is mediated by a nitric oxide- and guanylate cyclase-dependent mechanism, possibly mediated by the reaction between GSH and peroxynitrite to form S-nitrosoglutathione, a nitric oxide donor.

Although inhaled nitric oxide (INO) improves oxygenation in critically ill neonates, the neurodevelopmental outcome of premature neonates with severe hypoxemic respiratory failure treated with INO has not been reported. Mortality and prospective neurodevelopmental assessment in early childhood were studied in a cohort of 24 very low birth weight neonates (/=1500 g) consecutively admitted from 1993 to 1997 and rescued with INO because of severe hypoxemic respiratory failure (oxygenation index 28 to 52) unresponsive to aggressive conventional treatment. Significant improvements in arterial oxygen tension and oxygenation index with lower inspired oxygen concentration and less ventilator support after initiating INO were observed (P.05, analysis of variance). Despite the dramatic improvement in systemic oxygenation, the mortality rate was high (14 of 24, 58%). Only 6 of 23 had normal cranial ultrasonographies. At 13 to 40 (22 +/- 10) months of adjusted age, 10 survivors had Bayley Scales mental and psychomotor developmental indexes of 81 +/- 21 and 64 +/- 22, respectively. Of the 10 children, 5 (50%) were disabled, 2 (20%) were developmentally delayed, and 3 (30%) had normal development. In view of the poor outcome in very low-birth-weight neonates rescued by INO, randomized controlled trials are required to examine the role of INO in premature neonates. Before, during, and after INO therapy, cranial ultrasonography is recommended.

Background —Matrix metalloproteinases (MMPs) contribute to collagen degradation and remodeling of the extracellular matrix after myocardial infarction; however, their role in myocardial dysfunction immediately after ischemia and reperfusion is unknown. Methods and Results —We measured the release of MMPs into the coronary effluent of isolated, perfused rat hearts during aerobic perfusion and reperfusion after ischemia. Aerobically perfused control hearts expressed pro-MMP-2 and MMP-2, as well as an unidentified 75-kDa gelatinase. These enzymes were also detected in the coronary effluent. After 20 minutes of global no-flow ischemia, there was a marked increase in pro-MMP-2 in the coronary effluent that peaked within the first minute of reperfusion. The release of pro-MMP-2 into the coronary effluent during reperfusion was enhanced with increasing duration of ischemia and correlated negatively with the recovery of mechanical function during reperfusion ( r 2 =0.99). MMP-2 antibody (1.5 to 15 μg/mL) and the inhibitors of MMPs doxycycline (10 to 100 μmol/L) and o -phenanthroline (3 to 100 μmol/L) improved whereas MMP-2 worsened the recovery of mechanical function during reperfusion. Conclusions —These results show that acute release of MMP-2 during reperfusion after ischemia contributes to cardiac mechanical dysfunction. The inhibition of MMPs may be a novel pharmacological strategy for the treatment of ischemia-reperfusion injury.

SPIRIT 2013 checklist: recommended items to address in a clinical trial protocol and related documents. (DOC 122 kb)

To determine the systemic, pulmonary, mesenteric, and renal hemodynamic effects of short and prolonged infusions of dobutamine.Prospective randomized unblinded study.University research laboratory.Thirteen newborn (1-3 days old) piglets.Piglets were instrumented and studied 48 hrs later. Fifteen-minute infusions of dobutamine at 5, 10, 20 and 50 microg/ kg x min were randomly given with 15-min rests between the doses. After a 1-hr hiatus, a dose of 10 microg/kg x min was continuously administered for 2 hrs.Systemic and pulmonary arterial pressures, cardiac index (thermodilution), and superior mesenteric and renal artery flows were measured. Vascular resistance values were calculated.Fifteen-minute infusions: Dobutamine dose-dependently increased cardiac index with tachycardia but not stroke volume (from 187 +/- 43 to 238 +/- 51 mL/kg x min at baseline and 50 microg/ kg x min, respectively, p.05; values expressed as mean +/- SD). Systemic, but not pulmonary, vascular resistance decreased, resulting in a significant decrease in systemic to pulmonary arterial pressure ratio (from 3.8 +/- 0.8 at baseline to 3.2 +/- 1.0 at 50 microg/ kg x min). Superior mesenteric and renal flows were not affected. Two-hour infusion at 10 microg/kg x min: Cardiac index progressively increased from 173 +/- 34 to 240 +/- 58 mL/kg x min at baseline and 120 mins, respectively, (p.05). The initial tachycardia was transient, and stroke volume was significantly increased at 60 mins and thereafter. Although systemic and pulmonary vascular resistance values fell simultaneously, systemic to pulmonary arterial pressure ratio decreased significantly to 3.4 +/- 0.9 at 120 mins from 3.9 +/- 0.7 at baseline. Superior mesenteric and renal artery flows increased significantly with vasodilation after 60 mins.Short infusions of dobutamine dose-dependently increase cardiac output due to tachycardia, without significant effect on mesenteric and renal blood flows. Prolonged infusion of dobutamine at 10 microg/kg x min progressively increases cardiac output and stroke volume with transient tachycardia, and increases mesenteric and renal blood flows. Caution is required in the treatment of critically ill neonates with dobutamine, which could also reduce systemic to pulmonary arterial pressure ratio.

Although bleeding associated with thrombocytopenia often complicates extracorporeal membrane oxygenation (ECMO), the mechanisms of platelet dysfunction during ECMO remain poorly understood. We investigated the role of matrix metalloproteinase (MMP)-2, which recently has been shown to mediate a novel pathway of platelet aggregation, in the platelet dysfunction induced by ECMO.Prospective longitudinal case study.Level III neonatal intensive care unit.Ten neonates treated with ECMO.ECMO procedure.Platelet counts and collagen-induced platelet aggregation ex vivo; plasma markers of platelet (soluble P-selectin) and endothelial (soluble E-selectin and total nitrite/nitrate) activation; plasma MMP-2 and MMP-9 activities; and concentrations of tissue inhibitors of MMPs.During ECMO, time-dependent platelet activation, as evidenced by thrombocytopenia, decreased platelet aggregation, and increased plasma soluble P-selectin concentrations were found in the absence of endothelial activation, as shown by normal plasma concentrations of soluble E-selectin and nitric oxide metabolites (nitrite/nitrate). There was a time-dependent increase in plasma MMP-2 but not MMP-9 activity; tissue inhibitors of MMPs were not detected. Plasma soluble P-selectin concentrations significantly correlated with simultaneous plasma MMP-2 (r2 = .37, p.0001) but not with MMP-9 activities. Platelet dysfunction persisted despite repeated platelet transfusions to maintain platelet counts100 x 10(9)/L.ECMO resulted in the activation of platelets but not endothelial cells. During ECMO, platelet dysfunction persisted despite platelet transfusions. MMP-2 may play a role in the development of platelet dysfunction caused by ECMO.