Motor performance and cognitive correlates in children cooled for neonatal encephalopathy without cerebral palsy at school age.

AIM: To investigate whether motor performance in school-age children without cerebral palsy (CP), cooled for neonatal encephalopathy, is associated with perinatal factors and 18-month developmental scores and to explore relationships between school-age motor and cognitive performance. METHODS: Motor and cognitive performance was assessed in 29 previously cooled children at six to eight years using the Movement Assessment Battery for Children-2 (MABC-2) and the Wechsler Intelligence Scale for Children (WISC-IV). Associations between MABC-2 scores less than/equal (≤) 15th centile and perinatal factors, social/family background, 18-month Bayley-III scores and WISC-IV scores were explored. RESULTS: Eleven of the 29 (38%) children had MABC-2 scores ≤15th centile including 7 (24%) ≤5th centile. No significant perinatal or socio-economic risk factors were identified. Motor scores <85 at 18 months failed to identify children with MABC-2 scores ≤15th centile. MABC-2 scores ≤15th centile were associated with lower Full Scale IQ (p = 0.045), Working Memory (p = 0.03) and Perceptual Reasoning (p = 0.005) scores at six to eight years and receiving greater support in school (p = 0.01). CONCLUSION: A third of cooled children without CP had MABC-2 scores indicating motor impairment at school age that was not identified at 18 months by Bayley-III. Most children with low MABC scores needed support at school. Sub-optimal MABC-2 scores indicate need for detailed school-age cognitive evaluation.

Fish oil supplementation induces expression of genes related to cell cycle, endoplasmic reticulum stress and apoptosis in peripheral blood mononuclear cells: a transcriptomic approach.

BACKGROUND: Fish oil supplementation has been shown to alter gene expression of mononuclear cells both in vitro and in vivo. However, little is known about the total transcriptome profile in healthy subjects after intake of fish oil. We therefore investigated the gene expression profile in peripheral blood mononuclear cells (PBMCs) after intake of fish oil for 7 weeks using transcriptome analyses. DESIGN: In a 7-week, double-blinded, randomized, controlled, parallel-group study, healthy subjects received 8 g day(-1) fish oil (1.6 g day(-1) eicosapentaenoic acid + docosahexaenoic acid) (n = 17) or 8 g day(-1) high oleic sunflower oil (n = 19). Microarray analyses of RNA isolated from PBMCs were performed at baseline and after 7 weeks of intervention. RESULTS: Cell cycle, DNA packaging and chromosome organization are biological processes found to be upregulated after intake of fish oil compared to high oleic sunflower oil using a moderated t-test. In addition, gene set enrichment analysis identified several enriched gene sets after intake of fish oil. The genes contributing to the significantly different gene sets in the subjects given fish oil compared with the control group are involved in cell cycle, endoplasmic reticulum (ER) stress and apoptosis. Gene transcripts with common motifs for 35 known transcription factors including E2F, TP53 and ATF4 were upregulated after intake of fish oil. CONCLUSION: We have shown that intake of fish oil for 7 weeks modulates gene expression in PBMCs of healthy subjects. The increased expression of genes related to cell cycle, ER stress and apoptosis suggests that intake of fish oil may modulate basic cellular processes involved in normal cellular function.

Minimum alveolar concentration (MAC) for sevoflurane and xenon at normothermia and hypothermia in newborn pigs.

BACKGROUND: Neuroprotection from therapeutic hypothermia increases when combined with the anaesthetic gas xenon in animal studies. A clinical feasibility study of the combined treatment has been successfully undertaken in asphyxiated human term newborns. It is unknown whether xenon alone would be sufficient for sedation during hypothermia eliminating or reducing the need for other sedative or analgesic infusions in ventilated sick infants. Minimum alveolar concentration (MAC) of xenon is unknown in any neonatal species. METHODS: Eight newborn pigs were anaesthetised with sevoflurane alone and then sevoflurane plus xenon at two temperatures. Pigs were randomised to start at either 38.5°C or 33.5°C. MAC for sevoflurane was determined using the claw clamp technique at the preset body temperature. For xenon MAC determination, a background of 0.5 MAC sevoflurane was used, and 60% xenon added to the gas mixture. The relationship between sevoflurane and xenon MAC is assumed to be additive. Xenon concentrations were changed in 5% steps until a positive clamp reaction was noted. Pigs' temperature was changed to the second target, and two MAC determinations for sevoflurane and 0.5 MAC sevoflurane plus xenon were repeated. RESULTS: MAC for sevoflurane was 4.1% [95% confidence interval (CI): 3.65-4.50] at 38.5°C and 3.05% (CI: 2.63-3.48) at 33.5°C, a significant reduction. MAC for xenon was 120% at 38.5°C and 116% at 33.5°C, not different. CONCLUSION: In newborn swine sevoflurane, MAC was temperature dependent, while xenon MAC was independent of temperature. There was large individual variability in xenon MAC, from 60% to 120%.

Increased somatic morbidity in the first year after leaving opioid maintenance treatment: results from a Norwegian cohort study.

BACKGROUND/AIMS: Some patients on opioid maintenance treatment (OMT) leave treatment temporarily or permanently. This study investigated whether patients interrupting their OMT differed from non-interrupters in sociodemographic and drug-use characteristics and examined acute/sub-acute somatic morbidity among the interrupters, prior to, during, and after OMT. METHODS: Cohort design. OBSERVATION PERIOD: 5 years prior to, up to first 5 years during, and up to 5 years after interruption of OMT. PARTICIPANTS: The sample (n = 200) comprised 51 OMT interrupters and 149 non-interrupters. Data on patient characteristics were obtained from interviews and OMT register information. Data on somatic morbidity were gathered from hospital records. MEASUREMENTS: Key patient characteristics among OMT interrupters and non-interrupters. Incidence rates of acute and sub-acute somatic disease incidents leading to hospital treatment (drug-related/non-drug-related/injuries) prior to/during/after OMT. RESULTS: Interrupters and non-interrupters did not differ in sociodemographic characteristics, while longer duration of amphetamine and benzodiazepine dependence predicted OMT interruption. Interrupters scored significantly higher on drug-taking and overdose during OMT but still had a significant 41% reduction in drug-related treatment, episodes. After interruption of treatment, such episodes increased markedly and were 3.6 times more frequent during the first post-OMT year compared to the pre-OMT period (p < 0.001). This increase was highest during the first months after OMT interruption. 2-5 years after interruption there was no significant increase. CONCLUSIONS: Increased somatic morbidity was found among OMT interrupters during the first year after OMT, and especially during the immediate post-treatment period.

Protein Intake and the Risk of Pre-Frailty and Frailty in Norwegian Older Adults. The Tromsø Study 1994-2016.

BACKGROUND: Protein intake is suggested as an important dietary factor in the prevention of frailty, however, the influence of lifelong intake remains unclear. OBJECTIVES: The present study investigated the relationship between daily protein intake and patterns of protein intake over 21 years and the risk of pre-frailty/frailty. DESIGN: Prospective cohort study. SETTING: The population-based Tromsø Study in Tromsø municipality, Norway. PARTICIPANTS: In total, 1,906 women and 1,820 men aged ≥45 years in 1994 who participated in both Tromsø4 (1994-95) and Tromsø7 (2015-16). MEASUREMENTS: Frailty status in Tromsø7 was measured according to Fried's phenotype, classifying participants as "robust" (frailty components present: 0), "pre-frail" (1-2) or "frail" (≥3). Daily intake of protein was estimated from self-reported habitual dietary intake using food frequency questionnaires and assessed as grams per kilogram bodyweight (g/kg BW) and per megajoule energy intake (g/MJ). The protein-frailty association was assessed via longitudinal and cross-sectional multivariable logistic regression analyses. RESULTS: The prevalence of pre-frailty and frailty in this study was 27% and 1.0%, respectively. Longitudinal analysis showed that the odds of pre-frailty/frailty decreased by 57% (odds ratio (OR) = 0.43, 95% confidence interval (CI) = 0.31;0.58, p<0.001) with the increase in intake of one additional gram of dietary protein per kg BW. The results obtained from cross-sectional analysis were similar. Tracking analysis showed that, compared to a stable high intake of protein in g/kg BW over time, other patterns of protein intake increased the risk of pre-frailty/frailty. No associations were found between intake of protein in g/MJ and pre-frailty/frailty. CONCLUSIONS: Intake of protein in g/kg BW both in mid-life and later in life was inversely associated with pre-frailty/frailty in older adults. This emphasizes the importance of an adequate protein intake to facilitate healthy ageing in Norwegian older adults.

Neonatal rat model of intraventricular haemorrhage and post-haemorrhagic ventricular dilatation with long-term survival into adulthood.

AIMS: post-haemorrhagic ventricular dilatation (PHVD) is a significant problem in neonatal care, with sequelae extending beyond childhood. Its management is important in determining outcome. Although rodent hydrocephalus models have been developed, PHVD, as a specific entity with a distinct pathophysiology, has not been studied in a small animal model surviving to adulthood. Our objective is to evaluate survival, to adulthood, in our immature (7-day-old, P7) neonatal rat model, and to analyse early motor reflexes and fine motor and cognitive function, and neuropathology, at 8-12 weeks. METHODS: sixty-six rats underwent sequential bilateral stereotactic intraventricular haemorrhage (IVH); 36 more acted as controls. Staircase and radial maze evaluations were carried out at 7-11 weeks; animals were sacrificed at 12 weeks. Post mortem ventricular size and corpus callosum thickness were determined. RESULTS: seventy-six per cent of IVH animals developed PHVD; median (interquartile range) composite ventricular area was 3.46 mm(2) (2.32-5.24). Sixteen (24%) animals demonstrated severe ventricular dilatation (area > 5 mm(2) ). IVH animals failed to improve on the negative geotaxis test at 2 weeks. The staircase test did not identify any significant difference. On the radial maze, animals with severe PHVD made more reference errors. Histopathology confirmed PHVD, ependymal disruption and periventricular white matter injury. Median anterior corpus callosum thickness was significantly lower in IVH animals (0.35 mm) than in those not undergoing IVH (0.43 mm). CONCLUSION: our P7 neonatal rat IVH model is suitable for long-term survival and replicates many of the morphological and some of the behavioural features seen in human PHVD.

Significant head cooling can be achieved while maintaining normothermia in the newborn piglet.

BACKGROUND: Hypothermia has been shown to be neuroprotective in animal models of hypoxia-ischaemia. It is currently being evaluated as a potentially therapeutic option in the management of neonatal hypoxic-ischaemic encephalopathy. However, significant hypothermia has adverse systemic effects. It has also recently been found that the stress of being cold can abolish the neuroprotective effects of hypothermia. It is hypothesised that selective head cooling (SHC) while maintaining normal core temperature would enable local hypothermic neuroprotection while limiting the stress and side effects of hypothermia. OBJECTIVE: To determine whether it is possible to induce moderate cerebral hypothermia in the deep brain of the piglet while maintaining the body at normothermia (39 degrees C). METHODS: Six piglets (<48 hours old) were anaesthetised, and temperature probes inserted into the brain. Temperature was measured at different depths from the brain surface (21 mm (T(deep brain)) to 7 mm (T(superficial brain))). After a 45 minute global hypoxic-ischaemic insult, each piglet was head cooled for seven hours using a cap circulated with cold water (median 8.9 degrees C (interquartile range 7.5-14)) wrapped around the head. Radiant overhead heating was used to warm the body during cooling. RESULTS: During SHC it was possible to cool the brain while maintaining a normal core temperature. The mean (SD) T(deep brain) during the seven hour cooling period was 31.1 (4.9) degrees C while T(rectal) remained stable at 38.8 (0.4) degrees C. The mean T(rectal)-T(deep brain) difference throughout the cooling period was 9.8 (6.1) degrees C. The mean T(skin) required was 40.8 (1.1) degrees C. There was no evidence of skin damage secondary to these skin temperatures. During cooling only one piglet shivered. CONCLUSIONS: It is possible to maintain systemic normothermia in piglets while significantly cooling the deeper structures of the brain. This method of cooling may further limit the side effects associated with systemic hypothermia and be feasible for premature infants.

Changes in superior sagittal sinus blood velocities due to postural alterations and pressure on the head of the newborn infant.

A pulsed Doppler bidirectional ultrasound system has been used to measure alterations in the blood velocities in the superior sagittal sinus of the healthy term newborn infant in response to unilateral and bilateral jugular venous occlusion. These maneuvers were performed with the baby lying in different positions: supine, prone, and on the side (both left and right), the neck flexed or extended, and with the head in the midline or turned 90 degrees to the side (both left and right). Transfontanel pressure was also measured in these positions during occlusions. Results show that turning the head effectively occludes the jugular vein on the side to which the head is turned and that occluding the other jugular vein does not force blood through this functional obstruction. The effect of different forms of external pressure to the head on the superior sagittal sinus velocities was also examined. Alterations in velocities were frequently profound although they varied considerably from baby to baby. This work shows how readily large fluctuations in cranial venous velocities and pressures can occur in the course of normal handling of babies.

Cardiovascular changes during mild therapeutic hypothermia and rewarming in infants with hypoxic-ischemic encephalopathy.

BACKGROUND: Clinical trials of mild cooling to 35 degrees C or below in infants with early hypoxic-ischemic encephalopathy are under way. The objective of this study was to systematically document cardiovascular changes associated with mild therapeutic hypothermia and rewarming in such infants. PATIENTS AND METHODS: Nine infants with gestational ages of 36 to 42 weeks, with 10-minute Apgar scores of 5 or less, clinical encephalopathy, and an abnormal electroencephalogram before 6 hours were cooled by surface cooling the trunk (n = 3) or by applying a cap perfused with cooled water (n = 6) for a median of 72 hours. The target core temperature was 34.0 degrees C to 35.0 degrees C for head-cooled infants and 33.0 degrees C to 34.0 degrees C for surface-cooled infants. Maintenance heating and rewarming were provided by an overhead heater. RESULTS: Mean arterial blood pressure increased by a median of 10 mm Hg during cooling and fell by a median of 8 mm Hg on rewarming. Heart rate decreased by a median of 34 beats/minute on cooling and increased by a median of 32 beats/minute on rewarming. A large increase in the output of the overhead heater decreased mean arterial blood pressure in 5 infants. Anticonvulsant drugs, sedatives, or intercurrent hypoxemia also produced falls in temperature. The inspired oxygen fraction had to be increased by a median of.14 to maintain oxygenation during cooling with 2 infants requiring 100% oxygen, an effect probably attributable to pulmonary hypertension, which was reversible with rewarming. CONCLUSIONS: Therapeutic cooling produces changes in heart rate and blood pressure that are not hazardous, but the combination of inadvertent overcooling and inappropriately rapid rewarming, together with sedative drugs that can impair normal thermoregulatory vasoconstriction, can cause hypotension in posthypoxic newborn infants. Infants who already require 50% oxygen should be cooled cautiously because pulmonary hypertension may develop. Knowledge of these cardiovascular changes, careful monitoring, anticipation, and correction should help to avoid potential adverse effects in the upcoming clinical trials.

Lipid treatment goals achieved in patients treated with statin drugs in Norwegian general practice.

Statin drug treatment has still not achieved complete acceptance, and titration to recommended target goals is still not used by physicians in Norway.

Plasma proatrial natriuretic factor is predictive of clinical status in patients with congestive heart failure.

Atrial stretch results in myocyte release of the prohormone atrial natriuretic factor (1-126). The N-terminal (1-98) fragment, proatrial natriuretic factor (proANF) is released on an equimolar basis with the C-terminal (99-126) active hormone and may be assayed simply due to in vitro stability. This study was undertaken to evaluate the relation between proANF and routinely available measures of clinical status. ProANF was sampled from 202 patients (median age 68 years [range 15 to 85], 77% men) recruited from an active outpatient heart failure clinic. Patients were subgrouped according to New York Heart Association functional class, radionuclide ejection fraction (EF), echocardiographic left ventricular (LV) end-diastolic diameter, and Doppler-determined systolic pulmonary arterial pressure. The median proANF (pmol/L) values for patients in New York Heart Association classes I, II, III, IV were 725, 1,527, 1,750, and 5,172, respectively. The proANF value for the group with EF > 40% was 1,534 versus 1,993 for EF < or = 40% (p < 0.05). The value for the group with LV diameter < 60 mm ws 838 versus 1,751 for LV diameter > or = 60 mm (p < 0.01). The value for the group with systolic pulmonary artery pressure < 45 mm Hg was 1,241 versus 2,660 for systolic pulmonary artery pressure > or = 45 mm Hg (p < 0.01). ProANF correlated better than the other variables with New York Heart Association functional class and was more closely associated with noninvasive measurements than New York Heart Association functional class.(ABSTRACT TRUNCATED AT 250 WORDS)

Prophylactic use of tropisetron or metoclopramide during adjuvant abdominal radiotherapy of seminoma stage I: a randomised, open trial in 23 patients.

BACKGROUND AND PURPOSE: Nausea and vomiting are frequent side effects during adjuvant abdominal radiotherapy in seminoma stage I patients. This study evaluates the efficacy and side effects of prophylactically administered tropisetron in comparison to metoclopramide. MATERIALS AND METHODS: Twenty-three seminoma stage I patients who were to undergo adjuvant abdominal radiotherapy (30 Gy) were included in a prospective, randomised, open study. The patients were allocated to receive adjuvant daily tropisetron 5 mg p.o. (TROP group) (11 patients) or metoclopramide 30 mg p.o. (MET group) (12 patients), allowing an eventual dose increase to 60 mg. Evaluation was based on diary cards filled in by the patients during the treatment period. Nausea, vomiting, abdominal pain and bowel motions were assessed. RESULTS: Nausea was significantly lower in the TROP group as compared with the MET group (median: 0.14 vs. 1.32; P = 0.03). Thirty percent of all patients experienced vomiting. In the TROP group one patient had a mean number of emetic events > 0 as compared with 6 patients in the MET group (P = 0.07). Two patients in the TROP group and one in the MET group discontinued therapy due to lacking control of emesis. In two further patients the doubling of the metoclopramide resulted in acceptable control of nausea/vomiting. Both drugs were generally well tolerated. CONCLUSION: Seminoma stage I patients on tropisetron experienced less nausea and vomiting during abdominal radiotherapy than patients receiving metoclopramide. The costs of the former drug may, however, not justify its use as first choice anti-emetic since few patients in either group experienced severe nausea.

The stress of being restrained reduces brain damage after a hypoxic-ischaemic insult in the 7-day-old rat.

Experimental animals and patients are immobilized to allow continuous monitoring of physiological parameters. Restraint stress affects brain neurotransmitter levels and induces expression of immediate early genes. Whether immobilization stress affects outcomes in newborn animals which have suffered a hypoxic-ischaemic insult is unknown. Twenty 7-day-old rats subjected to unilateral carotid ligation followed by 2 h hypoxia were randomly assigned to carry a rectal probe or to move freely. The 10 restrained animals showed 50% reduction in damage in all brain regions (p < 0.0.3). Plasma lactate levels, a marker of stress, were three times higher in animals carrying a rectal probe (p < 0.0.02) than those moving freely. We conclude that the stress of being restrained reduced damage after a hypoxic-ischaemic insult in the immature rat.

Post-hypoxic hypothermia reduces cerebrocortical release of NO and excitotoxins.

Hypothermia applied after hypoxia offers neuroprotection in neonatal animals, but the mechanisms involved remain unknown. Hypoxia was induced in newborn piglets and changes in excitatory amino acids (EAAs) and the citrulline:arginine ratio (CAR) were followed by microdialysis for 5 h. After the 45 min hypoxic insult, the animals were randomized to receive normothermia (39 degrees C; n=7) or hypothermia (35 degrees C; n = 7). After reoxygenation, extracellular glutamate, aspartate and the excitotoxic index were significantly lower in the cerebral cortex of hypothermic animals than in normothermic animals. A progressive rise of the CAR occurred during reoxygenation in the normothermic group whereas the ratio tended to decrease in the hypothermic group. In conclusion, post-hypoxic hypothermia attenuated NO production and overflow of EAAs.

Effects of neuropeptide Y and noradrenaline on uterine artery blood pressure and blood flow velocity in the pregnant guinea-pig.

Neuropeptide Y (NPY) coexists with noradrenaline (NA) in many peripheral sympathetic nerves. Since it has been found that patients with preeclampsia have elevated myometrial levels of both NPY and NA, we have examined the effects of NPY and NA on blood pressure and blood flow velocity in the uterine artery of the term pregnant guinea-pig (n = 7). We found that NPY (10-1000 pmol) significantly increased local blood pressure, with increases ranging from 15.4% (P less than 0.05) to 46.4% (P less than 0.001) as compared to control. NA (10-1000 pmol) had similar effects, increasing local blood pressure (5%-57.5% (P less than 0.01]. NPY had no significant effect on uterine blood flow velocity as measured by pulsed Doppler ultrasound, whereas NA (10-1000 pmol) decreased local uterine blood flow velocity (5.9%-30.2% (P less than 0.05]. The effect of NPY on blood pressure was phentolamine-resistant, indicating that it is not alpha-adrenoceptor-mediated. The results indicate that NPY and NA have significant pressor effects in the local uterine circulation during pregnancy in the guinea-pig.

Antenatal steroids and the developing brain.

Randomised clinical trials show that two injections of corticosteroid into the mother before preterm delivery reduce respiratory distress syndrome, neonatal mortality, and intraventricular haemorrhage. However, repeated courses of antenatal steroid are not backed by such evidence of safety and efficacy. Animal studies have shown that maternal corticosteroid delays myelination and reduces the growth of all fetal brain areas particularly the hippocampus. Corticosteroids may reduce or enhance hypoxic-ischaemic injury to the developing brain depending on timing and dosage. Clinical trials of maternally administered corticosteroid show no evidence of increased disability on follow up but numbers are small. Postnatal trials of dexamethasone when brain maturity is still preterm show a significant increase in later disability in the dexamethasone treated groups. There is evidence from randomised trials, retrospective data, experiments on pregnant mice, and the chemical make up of the preparations that betamethasone may be safer and more protective of the immature brain than dexamethasone. Single course corticosteroid treatment before preterm delivery must still be recommended as a life saving and cost effective intervention, but clinicians may wish to change from using dexamethasone to betamethasone. In view of the animal and postnatal data, clinicians should be cautious with repeated courses of antenatal corticosteroids and repetition may be unnecessary for lung maturity.

Posthaemorrhagic ventricular dilatation.

Posthaemorrhagic ventricular dilatation is the most serious direct complication of intraventricular haemorrhage after preterm birth. It results initially from multiple small blood clots throughout the cerebrospinal fluid channels impeding circulation and reabsorption. Management is difficult and new treatment approaches are needed.

Cardiac output, pulmonary artery pressure, and patent ductus arteriosus during therapeutic cooling after global hypoxia-ischaemia.

OBJECTIVE: To assess by Doppler echocardiography the effects of 24 hours of whole body mild hypothermia compared with normothermia on cardiac output (CO), pulmonary artery pressure (PAP), and the presence of a persistent ductus arteriosus (PDA) after a global hypoxic-ischaemic insult in unsedated newborn animals. DESIGN: Thirty five pigs (mean (SD) age 26.6 (12.1) hours and weight 1.6 (0.3) kg) were anaesthetised with halothane, mechanically ventilated, and subjected to a 45 minute global hypoxic-ischaemic insult. At the end of hypoxia, halothane was stopped; the pigs were randomised to either normathermia (39 degrees C) or hypothermia (35 degrees C) for 24 hours. Rewarming was carried out for 24-30 hours followed by 42 hours of normothermia. Unanaesthetised pigs were examined with a VingMed CFM 750 ultrasound scanner before and 3, 24, 30, and 48 hours after the hypoxic-ischaemic insult. Aortic valve diameter, forward peak flow velocities across the four valves, and the occurrence of a PDA were measured. Tricuspid regurgitation (TR) velocity was used to estimate the PAP. Stroke volume was calculated from the aortic flow. RESULTS: Twelve animals (seven normothermic, five hypothermic) had a PDA on one or more examinations, which showed no association with cooling or severity of insult. There were no differences in stroke volume or TR velocity between the hypothermic and normothermic animals at any time point after the insult. CO was, however, 45% lower at the end of cooling in the subgroup of hypothermic pigs that had received a severe insult compared with the pigs with mild and moderate insults. CO and TR velocity were transiently increased three hours after the insult: 0.38 (0.08) v 0.42 (0.08) litres/min/kg (p = 0.007) for CO; 3.0 (0.42) v 3.4 (0.43) m/s (p < 0.0001) for TR velocity (values are mean (SD)). CONCLUSIONS: The introduction of mild hypothermia while the pigs were unsedated did not affect the incidence of PDA nor did it lead to any changes in MABP or PAP. Stroke volume was also unaffected by temperature, but hypothermic piglets subjected to a severe hypoxic-ischaemic insult had reduced CO because the heart rate was lower. Global hypoxia-ischaemia leads to similar transient increases in CO and estimated PAP in unsedated normothermic and hypothermic pigs. There were no signs of metabolic compromise in any subgroup, suggesting that 24 hours of mild hypothermia had no adverse cardiovascular effect.

Posthypoxic cooling of neonatal rats provides protection against brain injury.

AIM: To determine whether moderate hypothermia, applied after a hypoxic-ischaemic insult in neonatal rats, reduces cerebral damage. METHOD: Unilateral hypoxic-ischaemic brain damage was induced in 7 day old rats by left carotid ligation, followed by 120 minutes of normothermic exposure to 8% O2, followed by random selection to three hours of hypothermia (rectal temperature, mean (SD), 32.5 (0.4) degrees C) or normothermia (38.3 (0.4) degrees C). One hundred and one animals were used for brain temperature or blood chemistry studies and 24 for survival studies (7 days) with neuropathology, including cell counting as outcome measures. RESULTS: Thirty sections from each brain were histologically examined with respect to distribution and pattern of damage and given a score from 0 to 4. Animals treated with hypothermia had significantly less damage than normothermic animals (score 0.5 (0.3) vs 1.8 (0.5)). CONCLUSIONS: Posthypoxic hypothermia reduces brain damage in awake, unrestrained 7 day old rats.

Cerebral, tympanic and colonic thermometry in the piglet.

The temperature of the brain is crucial for the outcome of hypoxic/ischaemic brain damage. In clinical medicine and in animal experiments involving survival after hypoxia/ischaemia, non-invasive measurement of cerebral temperature is needed. We have therefore compared tympanic and colonic temperature with cerebral temperature in the newborn piglet during hypothermia. Ten piglets aged 12-60 h were cooled to 35 degrees C (mild hypothermia) for 150 min and rewarmed. Thereafter, four of the piglets were again cooled to approximately 29 degrees C for less than one hour (moderate hypothermia). During stable mild hypothermia and normothermia the cerebro-tympanic temperature difference in individual piglets was less than +/- 0.4 degrees C (95% confidence intervals < or = 0.18 degrees C) and the cerebro-colonic temperature difference was -0.7 to 0.4 (95% confidence interval < or = 0.28 degrees C). The differences were larger during moderate than during mild hypothermia and largest during rapid changes in body temperature. Then the tympanic temperature correlated with the cerebral temperature significantly better than did the colonic temperature (95% confidence interval -0.3 to 0.3 versus -0.6 to 1.4 for the ten minutes with the least good correlation).