Search

Mild therapeutic hypothermia (HT) reduces brain injury in survivors after perinatal asphyxia. Recent guidelines suggest that resuscitation of term infants should be started with air, but supplemental oxygen is still in use. It is not known whether supplemental oxygen during resuscitation affects the protection offered by subsequent HT.Wilcoxon median (95% confidence interval) hippocampal injury scores (range 0.0-4.0; 0 to ≥90% injury) were 21% O(2) normothermia (NT): 2.00 (1.25-2.50), 21% O(2) HT: 1.00 (0.50-1.50), 100% O(2) NT: 2.50 (1.50-3.25), and 100% O(2) HT: 2.00 (1.25-2.50). Although HT significantly reduced hippocampal injury (B = -0.721, SEM = 0.297, P = 0.018), reoxygenation with 100% O(2) increased injury (B = +0.647, SEM = 0.297, P = 0.033). Regression constant B = 1.896, SEM = 0.257 and normally distributed residuals.We confirm an ~50% neuroprotective effect of therapeutic HT in the neonatal rat. Reoxygenation with 100% O(2) increased injury and worsened reflex performance. HT was neuroprotective whether applied after reoxygenation with air or 100% O(2). However, HT after 100% O(2) gave no net neuroprotection.In an established neonatal rat model, hypoxia-ischemia (HI) was followed by 30-min reoxygenation in either 21% O(2) or 100% O(2) before 5 h of NT (37 °C) or HT (32 °C). The effects of HT and 100% O(2) on histopathologic injury in the hippocampus, basal ganglia, and cortex, and on postural reflex performance 7 d after the insult, were estimated by linear regression.

Systolic longitudinal myocardial function is important for cardiac ejection. Data describing hemodynamic determinants and the time course of myocardial longitudinal contraction as measured by tissue Doppler are lacking. Ten newborn pigs were used for invasive hemodynamic investigation. Tissue Doppler assessment of the lateral part of the mitral valve annulus during systole was performed during pharmacological modulation of inotropy, cardiac pacing, and modulations of loading conditions. The strongest association was found between peak systolic velocity (S') and peak systolic flow (PSF) and end-systolic pressure (ESP), respectively (β = 0.09 cm/mL, p < 0.001 and β = -0.07 cm/mL, p = 0.003). Displacement (D) was mostly influenced by stroke volume (SV) (β = 0.05 cm/mL, p < 0.001). Ejection time, SV, ESP, maximum first derivative of pressure (dP/dtmax), and PSF were all associated with S' and D under different states of hemodynamic modulation; however, the ratio between PSF and S', SV, and D were stable during hemodynamic modulations. Normalized cross correlations indicate that S' and D follow the same trajectory as flow and SV, respectively. In conclusion, this study provides validity of accounting systolic D in the long axis as the longitudinal contribution to SV and peak systolic tissue velocity as the longitudinal contribution to PSF.

Mild hypothermia can attenuate the development of brain damage after asphyxia. Supplemental oxygen during resuscitation increases generation of reactive oxygen species, compared to room air. It is unknown if supplemental oxygen affects hypothermic neuroprotection. We studied the early effects of hyperoxic reoxygenation and subsequent hypothermia on tissue oxygenation, microcirculation, inflammation and brain damage after global hypoxia. Anesthetized newborn pigs were randomized to control (n=6), or severe global hypoxia (n=46). Three pigs died during hypoxia or reoxygenation. After 20-min reoxygenation with room air (n=22) or 100% oxygen (n=21), pigs were randomized to normothermia (deep rectal temperature 39 degrees C, n=22) or total body cooling (35 degrees C, n=21) for 6.5 h before the experiment was terminated. We demonstrated a differential effect of post-hypoxic hypothermia between animals reoxygenated with 100% oxygen and with room air, with reduced damage only in hypothermic animals reoxygenated with 100% oxygen (P=0.001). Hyperoxic reoxygenation resulted in a significant overshoot in striatal oxygen tension, without affecting microcirculation. Inflammatory response after the insult did not differ between groups. The results indicate an early protective effect of hypothermia which may vary with oxygen level used during reoxygenation.

Supplementary oxygen during resuscitation of the asphyxiated newborn is associated with increased generation of reactive oxygen species and oxidative stress. It is suspected that hyperoxic reoxygenation may cause increased damage to DNA, resulting in replication errors, and cell death or potential fixation of mutations if unrepaired. Therapeutic hypothermia may attenuate the development of brain damage after asphyxia, but it is not known how post-hypoxic hyperoxia and hypothermia affect accumulation of DNA-damage and DNA repair. Anaesthetised newborn pigs were randomised to control (n=6) or severe global hypoxia (n=46). After 20min of reoxygenation with either room air or 100% O(2), followed by 6.5h of normothermia (deep rectal temperature 39°C) or total body cooling (35°C), oxidative DNA damage (8-hydroxy-2'-deoxyguanosine) in brain, liver and urine, and transcription of DNA repair glycosylases (NEIL1, NEIL3, and OGG1) in brain and liver were measured. Hypoxic pigs displayed increased urinary 8-oxodG levels: mean (SD) 8-oxodG/creatinine was 3.55 (1.46) vs. control 2.02 (0.53), p

Perinatal hypoxic-ischaemic brain damage is an important cause of neonatal death and permanent neurological impairment. Therapeutic hypothermia may reduce the development of brain damage after hypoxia. Whether to use room-air or 100% oxygen for resuscitation of the asphyxiated neonate is still debated, and there is little knowledge about the combined effects of therapeutic hypothermia and room air resuscitation. We used human NT2-N neurons to test whether oxygen level during reoxygenation would influence the protective effect of hypothermia. Oxygen-glucose deprived (OGD) human NT2-N neurons were exposed to 20 min of low (1%), medium (21%) or high (95%) oxygen concentrations immediately after hypoxia, followed by 20.5 h of hypothermia (33 degrees C) or normothermia (37 degrees C). Cell viability was determined by a methyltetrazolium assay (MTT), cellular energy failure by hypoxanthine release to supernatant, and inflammatory response by the release of IL-8 (Interleukin-8), bFGF (basic fibroblast growth factor), IP-10 (interferon-inducible protein-10) and MCP-1 (monocyte chemotactic protein-1) to supernatant. Post-hypoxic hypothermia resulted in significantly higher MTT cleavage (average 27% of control (SD 11%) vs 24% (SD 12%), p=0.005). Hypoxanthine release was increased both immediately after hypoxia and 21 h later, however less in hypothermic (median increase 2.0 mumol/L, IQR 1.2-3.2) compared to normothermic cells (2.7 mumol/L, IQR 2.1-4.1, p

Cytokines are released in response to brain injury and inflammation. By binding to receptors, they can cause, exacerbate or inhibit cellular injury and repair. We studied RNA expression of cytokine receptors and members of inflammatory pathways in human NT2-N neurons during 3 h of hypoxia and glucose deprivation followed by 21 h of reoxygenation, and the impact of acidosis. Right after acidotic hypoxia, RNA of IL-10RA and CXCR4 were significantly increased relative to acidotic control, while Bcl-2 and Bcl-xL were significantly decreased. After 21 h of neutral reoxygenation after neutral hypoxia, there was a significant increase in RNA of CXCR1 (relative quantification (RQ)=4.1, p

Transcatheter occlusion of persistent ductus arteriosus has replaced surgery as the treatment of choice. We wanted to evaluate the results of this treatment in our hospital.From September 1989 through 2001, a total of 217 patients with persistent ductus arteriosus were scheduled for transcatheter occlusion at Rikshospitalet. Six ducts were too small for treatment. In the remaining 211 patients, 224 procedures were performed. Patients' median age was 3.4 years (range 4 months-82 years), their median weight 14 kilograms (range 4-90 kilograms).The Rashkind double umbrella was implanted successfully in 61/63 cases, coils in 99/102 cases, and an Amplatzer duct occluder in 57/59 cases. Complete closure of the duct was achieved in 197/211 patients (93%) after reintervention in 11. The complete occlusion rate for first procedures were 77% for the Rashkind device, 93% for coils and 100% for the Amplatzer plug. Only coils embolised, in 2 out of 102 procedures. Removed interventionally, they were replaced by an Amplatzer occluder. One patient developed haemolytic anaemia from residual shunting through a coil; the shunt and the anaemia both disappeared after implantation of a second coil.Transcatheter occlusion of persistent ductus arteriosus is safe and efficient. The Amplatzer duct occluder seems superior to the Rashkind double umbrella and probably also to coils.