Yukito Takei

Changes in cerebral perfusion in extremely LBW infants during the first 72 h after birth.

Cerebral perfusion and its relation with systemic circulation in extremely LBW (ELBW) infants in the early neonatal period are not well understood. The cerebral tissue oxygenation index (TOI) and cerebral fractional tissue oxygen extraction (FTOE) were monitored in stable 16 ELBW infants (GA <29 wk) using near-infrared spectroscopy (NIRS) at 3–6, 12, 18, 24, 36, 48, and 72 h after birth. The left ventricular end-systolic wall stress (ESWS), left ventricular ejection fraction (LVEF), left ventricular cardiac output (LVCO), and superior vena cava (SVC) flow were also measured simultaneously using echocardiography. The ESWS increased till 18 h and then decreased; LVEF, LVCO, and SVC flow decreased till 12 h and increased thereafter. The TOI decreased till 12 h and correlated with SVC flow; FTOE increased until 12 h and then decreased. These changes in variables of NIRS and echocardiographic measurements contrasted to changes in mean arterial blood pressure (MABP), which showed trends of continuous and gradual increase after birth. We conclude that even stable ELBW infants undergo evident transitional changes in cerebral oxygenation and perfusion in the early postnatal period, which may reflect changes in cardiac function and cardiac output.

Different effects between 7-nitroindazole and L-NAME on cerebral hemodynamics and hippocampal lesions during kainic acid-induced seizures in newborn rabbits.

We examined the effects of 7-nitroindazole (7-NI) and N-omega-nitro-L-arginine methyl ester (L-NAME) on the endogenous nitric oxide (NO) production in vivo, cerebral hemodynamics, and hippocampal lesions to investigate the different roles between endothelial NOS (eNOS) and neuronal NOS (nNOS) during kainic acid (KA)-induced seizures in newborn rabbits. After a pre-treatment with 7-NI (50 mg/kg, i.p.), L-NAME (20 mg/kg, i.v.) or saline (1 ml, i.v.), KA (12 mg/kg, i.v.) was administered. NO production in the brain, regional cerebral blood flow (rCBF), cerebral oxygenation (concentrations of oxyhemoglobin (HbO2), deoxyhemoglobin (HbR), and total hemoglobin (tHb) in the brain tissue), and electroencephalography (EEG) were continuously monitored throughout the experiment lasting at least 60 min after the KA administration. There was a significant increase in NO generation in the brain during KA-induced seizures, which was inhibited by a pre-treatment with 7-NI or L-NAME. KA-induced seizures also increased rCBF significantly, which was inhibited not by 7-NI but by L-NAME. L-NAME pre-treatment caused a significant decrease in HbO2 and a significant increase in HbR during KA-induced seizures, compared with 7-NI and saline pre-treatment. EEG abnormalities and Neuronal damages in the hippocampus were significantly lower in 7-NI- and L-NAME-treated animals respectively, than in saline-treated animals. The present data demonstrated that the selective nNOS inhibitor, 7-NI, attenuated neither rCBF nor cerebral oxygenation during the seizures, while the non-selective NOS (nNOS and eNOS) inhibitor, L-NAME, attenuated both. These findings suggest that NO, probably originating from eNOS, may play an important role in the cerebral circulation. Both 7-NI and L-NAME inhibited the NO production and EEG abnormalities during the seizures that led to less damage to the hippocampus.

Effects of nitric oxide synthase inhibition on the cerebral circulation and brain damage during kainic acid-induced seizures in newborn rabbits

The nitric oxide (NO) synthase inhibitor, N-omega-nitro-L-arginine methyl ester (L-NAME), was used to investigate the effect of endogenous NO on the cerebral circulation and brain damage during kainic acid (KA)-induced seizures in newborn rabbits. The cerebral blood flow (CBF), by laser doppler flowmetry, cerebral oxygenation (concentrations of oxy-(HbO2), deoxy-(HbR) and total hemoglobin (tHb) in brain tissue), by near-infrared spectroscopy (NIRS), mean arterial blood pressure (MABP), electroencephalography (EEG), and hippocampal neuronal damage were evaluated. Pretreatment with L-NAME caused significant decreases in CBF, HbO2, and tHb, and a significant increase in HbR during KA-induced seizures, compared with pretreatment with saline (P < 0.05), without a significant difference in MABP. Our study also demonstrated that pretreatment with L-NAME reduced the seizure activity and neuronal cell death in the hippocampus elicited by the systemic administration of KA in the neonatal brain. These results suggest that NO is of major importance in the neurodestructive process in spite of its roles in maintaining both the CBF and cerebral oxygenation during KA-induced seizures in the neonatal brain.

Hypothermia during kainic acid-induced seizures reduces hippocampal lesions and cerebral nitric oxide production in immature rabbits

We investigated (1) whether cerebral hypothermia during kainic acid (KA)-induced seizures was neuroprotective; and (2) whether nitric oxide (NO) production in the brain during seizures was altered by cerebral hypothermia in immature rabbits. Twelve female rabbits, aged 2 weeks, were anesthetized, paralyzed and mechanically ventilated. We continuously measured NO production in the brain by NO-selective electrode, cortical electroencephalogram (EEG), regional cerebral blood flow (rCBF) by laser Doppler flowmetry, rectal and cerebral temperatures and mean arterial blood pressure (MABP) during KA (12 mg/kg, i.v.)-induced seizures in the hypothermic group (n = 6; rectal temperature, 33 degrees C), and in the normothermic group (n = 6; rectal temperature, 37 degrees C). The normothermic group showed a gradual increase in NO generation in the brain, which was significantly inhibited in the hypothermic group. There were no significant differences in the increases in rCBF, MABP, arterial blood gases, blood glucose, or EEG abnormalities between the two groups. Neuronal damages in the hippocampus (CA3) were significantly lower in hypothermia than in normothermia. These results suggest that hypothermia attenuates NO production during drug-induced seizures and decreases hippocampal brain lesions in the immature rabbit brain. These results may help to explain the neuroprotective effects of hypothermia.

Usefulness of Indomethacin for Patent Ductus Arteriosus in Full-Term Infants

The aim of this retrospective study was to evaluate the effectiveness of indomethacin therapy for patent ductus arteriosus (PDA) in full-term infants. The patients were 41 full-term infants with a PDA birth weight (BW) ≥2500 g and a gestational age (GA) ≥37 weeks. The echocardiographic evaluation and medical management of PDA in these infants was similar to that for PDA in low-birth-weight infants. Indomethacin (0.2–0.25 mg/kg/dose) was given intravenously at 12–24-hour intervals within 23 days of birth. Of the 41 infants, 12 showed complete closure, and 13 showed improvement of clinical symptoms. These 25 infants were classified as the responder group (61%). The other 16 infants, who did not show improvement in clinical symptoms, were classified as the nonresponder group. Statistical analysis revealed no difference between the two groups regarding GA, BW, Apgar score at 1 minute, minimum diameter of the DA before treatment, the average age at the initiation of treatment, and DA flow pattern. No severe adverse reactions were observed in any infant. Indomethacin therapy appears to be an effective medical treatment option for PDA in full-term symptomatic infants prior to considering surgical treatment.

Monitoring of cerebral oxygenation during hypoxic gas management in congenital heart disease with increased pulmonary blood flow.

In the preoperative management of congenital heart disease (CHD) with increased pulmonary blood flow, hypoxic gas management to control pulmonary blood flow is useful. However, the cerebral oxygenation state has rarely been studied, and there is concern about neurologic development. In eight infants with CHD accompanied by increased pulmonary blood flow, hypoxia was induced after a 1-h baseline period in room air (FiO2, 0.21). The infants were simultaneously monitored in both the front-temporal region and the right-brachial region for 90 min using near-infrared spectroscopy (NIRS). The minimum SaO2 (pulse oximetry) after hypoxic gas administration was 80.8 ± 2.9% when the minimum FiO2 was 16.2 ± 1.1%. With a decrease in SaO2, oxy-Hb (O2Hb) decreased and total Hb [cHb: O2Hb + deoxy-Hb (HHb)] increased in both regions in the majority of infants. HHb increased in both regions with a decrease in SaO2. The maximum change in the tissue oxygenation index (TOI: O2Hb/cHb × 100) was –8.3 ± 2.6% in the front-temporal region and –3.6 ± 2.3% in the right-brachial region. Cerebral oxygenation decreased despite an increase in cerebral blood flow during hypoxic gas management. The change in TOI was ≤10% when the SaO 2 was ≥80%. Safer control of SaO2 should be maintained over 80% for hypoxia management in CHD based on the results of the present study.

A Case of Wilson-Mikity Syndrome With High Serum KL-6 Levels

KL-6 and surfactant protein D (SP-D) serum concentrations are known to rise in adult patients with various types of interstitial pneumonia. We evaluated the time course of serum KL-6, SP-D, and lactate dehydrogenase (LDH) levels in an infant with Wilson-Mikity syndrome. In this case, serum KL-6 levels correlated with clinical symptoms better than serum SP-D and LDH levels. The findings of this case suggest that high serum levels of KL-6 show activity of interstitial lung disease of Wilson-Mikity syndrome.

Nitric oxide donor increases cerebral blood flow and oxygenation during kainic acid-induced seizures in newborn rabbits

Background : We investigated the hypothesis that sodium nitroprusside (SNP), a nitric oxide (NO) donor, increased the cerebral blood flow and oxygenation during kainic acid (KA)‐induced seizures in newborn rabbits.

Effects of rapid rewarming on cerebral nitric oxide production and cerebral hemodynamics after hypothermia therapy for kainic acid-induced seizures in immature rabbits

Abstract  Background : The aim of the present study was to investigate whether rapid rewarming after hypothermia therapy during seizures alters the endogenous nitric oxide (NO) production in and around hippocampus, cortical cerebral blood flow (cCBF), and mean arterial blood pressure (MABP) in immature rabbits.