Augusto Sola

Erythropoietin after focal cerebral ischemia activates the Janus kinase-signal transducer and activator of transcription signaling pathway and improves brain injury in postnatal day 7 rats.

Erythropoietin (Epo) plays a central role in erythropoiesis but also has neuroprotective properties. Recently, Epo-related neuroprotective studies used a hypoxic-ischemic neonatal model, which is different from focal stroke, a frequent cause of neonatal brain injury. We report on the effects of Epo treatment given after focal stroke and its potential neuroprotective mechanisms in postnatal day 7 rats with focal cerebral ischemia (FCI) achieved by occlusion of the middle cerebral artery. The experimental groups included sham operation, FCI plus vehicle, and FCI plus Epo. In the Epo-treated group, pups received a single intraperitoneal injection of 1000 U/kg 15 min after FCI or three injections of 100, 1000, or 5000 U/kg, starting at 15 min and repeated at 1 and 2 d after FCI. Epo treatment produced significant reductions in the mean infarct area and volume at 1 and 3 d after FCI, demonstrated by 2,3,5-triphenyltetrazolium chloride staining. Terminal deoxynucleotidyltransferase-mediated 2′-deoxyuridine 5′-triphosphate-biotin nick end labeling (TUNEL) staining showed a markedly reduced number of TUNEL-positive cells in the Epo-treated group when compared with the vehicle control 3 d after FCI (p < 0.01). The most effective dose after FCI was 1000 U/kg for 3 d. Immunoanalyses showed that Epo induced a significant increase in phosphorylated Janus kinase 2 and signal transducer and activator of transcription-5 expressions at 1 and 3 d and up-regulated Bcl-xL expression by 24 h after FCI but did not affect Epo receptor or NF-κB expression. In conclusion, Epo given after FCI in neonatal rats provides significant neuroprotection, mediated possibly by activation of the Janus kinase–signal transducer and activator of transcription–Bcl-xL signaling pathways.

Randomized multicenter trial comparing synchronized and conventional intermittent mandatory ventilation in neonates

Abstract OBJECTIVE: To compare synchronized intermittent mandatory ventilation (SIMV) and conventional intermittent mandatory ventilation (IMV) in neonates. STUDY DESIGN: Prospective, multicenter, randomized clinical trial. SETTING: Level III neonatal intensive care units at six university or childrens hospitals. PATIENTS: Three hundred twenty-seven infants receiving conventional IMV for respiratory distress syndrome, pneumonia, or meconium aspiration pneumonitis were randomly assigned at 7.5 ± 6 hours of age to either continue with IMV or change to SIMV. Infants assigned to each mode of ventilation had similar birth weight (BW), gestational age, and Apgar scores at birth, and similar oxygenation indexes at randomization. They received similar surfactant therapy and had similar incidence of sepsis, seizures, secondary pneumonia, and necrotizing enterocolitis. In the infants with BW less than 1000 gm, more infants receiving IMV had surgical ligation of their patent ductus arteriosus than did those receiving SIMV (27 vs 7%; p = 0.02). ANALYSIS: Data was analyzed overall for all infants and also separately within three BW groups: less than 1000 gm, 1000 to 2000 gm, and more than 2000 gm. The 1000 to 2000 gm BW group was further analyzed in subgroups weighing 1000 to 1499 gm and 1500 to 2000 gm. RESULTS: In all infants, at 1 hour after randomization, the infants receiving SIMV had a lower mean airway pressure than those receiving IMV (8.08 ± 2.15 vs 8.63 ± 2.59; p EDIATR 1996;128:453-63)

Pulse Oxygen Saturation Levels and Arterial Oxygen Tension Values in Newborns Receiving Oxygen Therapy in the Neonatal Intensive Care Unit: Is 85% to 93% an Acceptable Range?

OBJECTIVE. Our aim was to define the relationship of Pao2 and pulse oxygen saturation values during routine clinical practice and to evaluate whether pulse oxygen saturation values between 85% and 93% were associated with Pao2 levels of <40 mmHg. METHODS. Prospective comparison of Pao2 and pulse oxygen saturation values in 7 NICUs at sea level in 2 countries was performed. The Pao2 measurements were obtained from indwelling arterial catheters; simultaneous pulse oxygen saturation values were recorded if the pulse oxygen saturation values changed <1% before, during, and after the arterial gas sample was obtained. RESULTS. We evaluated 976 paired Pao2/pulse oxygen saturation values in 122 neonates. Of the 976 samples, 176 (18%) from infants breathing room air had a mean pulse oxygen saturation of 93.9 ± 4.3% and a median of 95.5%. The analysis of 800 samples from infants breathing supplemental oxygen revealed that, when pulse oxygen saturation values were 85% to 93%, the mean Pao2 was 56 ± 14.7 mmHg and the median 54 mmHg. At this pulse oxygen saturation level, 86.8% of the samples had Pao2 values of 40 to 80 mmHg, 8.6% had values of <40 mmHg, and 4.6% had values of >80 mmHg. When the pulse oxygen saturation values were >93%, the mean Pao2 was 107.3 ± 59.3 mmHg and the median 91 mmHg. At this pulse oxygen saturation level, 39.5% of the samples had Pao2 values of 40 to 80 mmHg and 59.5% had values of >80 mmHg. CONCLUSIONS. High Pao2 occurs very rarely in neonates breathing supplemental oxygen when their pulse oxygen saturation values are 85% to 93%. This pulse oxygen saturation range also is infrequently associated with low Pao2 values. Pulse oxygen saturation values of >93% are frequently associated with Pao2 values of >80 mmHg, which may be of risk for some newborns receiving supplemental oxygen.

Potential for protection and repair following injury to the developing brain: a role for erythropoietin?

Perinatal brain injury is a major contributor to perinatal morbidity and mortality, and a considerable number of these children will develop long term neurodevelopmental disabilities. Despite the severe clinical and socio-economic significance and the advances in neonatal care over the past twenty years, no therapy yet exists that effectively prevents or ameliorates detrimental neurodevelopmental effects in cases of perinatal/neonatal brain injury. Our objective is to review recent evidence in relation to the pervading hypothesis for targeting time-dependent molecular and cellular repair mechanisms in the developing brain. In addition we review several potential neuroprotective strategies specific to the developing nervous system, with a focus on erythropoietin (Epo) because of its potential role in protection as well as repair.

The impact of vaginal delivery in premature infants weighing less than 1,251 grams

OBJECTIVE: To evaluate whether mode of delivery is a predictor of poor short-term outcome at different birth weight categories in very low birth weight infants. METHODS: This study examined a cohort of infants weighing less than 1,251 g born at 2 perinatal centers from January 1, 2000, to December 31, 2003. Outborn infants or those with major anomalies were excluded from the study. Outcome variables included death, severe intraventricular hemorrhage, periventricular leukomalacia (PVL), and combined poor short-term outcomes (death, severe intraventricular hemorrhage, and PVL). RESULTS: Of the 397 infants who met enrollment criteria, 44% were born vaginally and 56% by cesarean delivery. The proportion of multiparous, breech presentation and prolonged rupture of membranes was significantly different between groups. For infants weighing less than 751 g, the risks of severe intraventricular hemorrhage (41% versus 22%; odds ratio [OR] 2.79, 95% confidence interval [CI] 1.08–7.72) and combined poor short-term outcome (67% versus 41%; OR 2.95, 95% CI 1.25–6.95) were significantly higher if delivered vaginally. Among survivors weighing less than 751 g, the risk of severe intraventricular hemorrhage was higher among those delivered vaginally (24% versus 9%; OR 8.18, 95% CI 1.58–42.20). In infants less 1,251 g who survived, vaginal delivery had a strong association with PVL (5% versus 1%; OR 11.53, 95% CI 1.66–125). CONCLUSION: In infants less than 1,251 g who survived to discharge, vaginal delivery is associated with higher risk for PVL. Furthermore, in infants less than 751 g, vaginal delivery is a predictor for severe intraventricular hemorrhage and combined poor short-term outcome. The negative impact of vaginal delivery mode decreases as birth weight category increases. LEVEL OF EVIDENCE: II-2

Treatment of peripheral tissue ischemia with topical nitroglycerin ointment in neonates

Four neonates had resolution of peripheral tissue ischemia after the application of 2% nitroglycerin ointment. A dosage of 4 mm nitroglycerin ointment per kilogram of body weight was applied to two patients with ischemia caused by vasospasm from indwelling radial artery catheterization and to two patients with ischemia resulting from dopamine extravasation. No adverse effects were noted except mild episodes of decreased blood pressure in two of the patients.

Role of Nitric Oxide in the Regulation of the Cerebral Circulation in the Lamb Fetus during Normoxemia and Hypoxemia

The influence of nitric oxide (NO) blockade on resting tone and on hypoxia-induced vasodilatation of the cerebral vascular bed was examined in chronically instrumented lamb fetuses. Total (Qbrain-tot) and regional brain blood flow were measured using radioactive microspheres. NO blockade was achieved by N omega-nitro-L-arginine (NNLA) infusion into the carotid artery via a lingual artery. Fetal cerebral blood flow and cerebral vascular resistance (Rcer) were determined during normoxemia and hypoxemia and before and during infusion of L-arginine. During normoxemia, the brain blood flow decreased, and the resistance increased significantly after NNLA infusion (Qbrain-tot from 129 +/- 25 to 89 +/- 26 ml/100 g/min, p < 0.05; Rcer from 0.46 +/- 0.03 to 0.80 +/- 0.09 mm Hg/ml/100 g/min, p < 0.05). During hypoxemia before NNLA infusion, Qbrain-tot increased (from 129 +/- 25 to 187 +/- 56 ml/100 g/min, p < 0.05), and Rcer decreased (from 0.46 +/- 0.03 to 0.39 +/- 0.07 mm Hg/ml/100 g/min, p < 0.05). This vasodilatory response was largely blocked after NNLA (Qbrain-tot 143 +/- 45 ml/100 g/min; Rcer 0.58 +/- 0.07 mm Hg/ml/100 g/min). The response to hypoxemia was restored after infusion of L-arginine (Qbrain-tot 180 +/- 47 ml/100 g/min). The resting tone of the cerebral vascular bed of the lamb fetus is under NO control, and NO mediates the cerebral vasodilatory response to hypoxia in the lamb fetus.

Cost per anomaly: What does a diaphragmatic hernia cost?

The cost of medical care in the United States is under close scrutiny. Birth defects have surpassed prematurity as the leading cause of infant mortality in the United States and contribute significantly to infant morbidity. Few estimates have been made of the costs of individual birth defects. The authors sought to determine the cost of initial hospitalization for an infant with a congenital diaphragmatic hernia (CDH). They analyzed hospital bills and professional fees from all 35 cases of infants who underwent postnatal CDH repair at their institution between January 1990 and December 1993. The cost averaged

Fructose-1,6-bisphosphate after hypoxic ischemic injury is protective to the neonatal rat brain.

137,000 per patient, and ECMO dramatically increased the cost. The cost per survivor was

ZEB1 links p63 and p73 in a novel neuronal survival pathway rapidly induced in response to cortical ischemia.

98,000 in the non-ECMO group and