Hypothermia for 24 hours after asphyxic cardiac arrest in piglets provides striatal neuroprotection that is sustained 10 days after rewarming

The neuroprotective effect of hypothermia instituted after resuscitation from asphyxic cardiac arrest has not been studied in immature brain, particularly in a large animal model with recovery periods greater than 4 d. Moreover, protection from severe hypoxia seen with 3 h of hypothermia was reported to be lost when hypothermic duration was extended to 24 h in unsedated piglets, in contrast to the neuroprotection reported by 72 h of intrauterine head cooling in fetal sheep. Piglets (5-7 postnatal days) were subjected to asphyxic cardiac arrest followed by 24 h of either hypothermia (34 degrees C) or normothermia (38.5-39 degrees C). Comparisons were made with normothermic and hypothermic surgical sham animals without asphyxia. All of these groups were sedated, paralyzed, and mechanically ventilated for the first 24 h to prevent shivering and possible depletion of glucose stores. Hypothermia per se did not cause remarkable structural abnormalities. Ischemic damage was evaluated in putamen at 1 d of recovery without rewarming and at 11 d (10 d +/- SD after rewarming). Ischemic cytopathology affected 60 +/- 12% of neurons in putamen of normothermic animals compared with 9 +/- 6% in hypothermic animals at 1 d of recovery without rewarming. At 11 d of recovery from hypoxia-ischemia, the density of viable neurons (neuron profiles/mm2) in putamen was markedly reduced in normothermic animals (81 +/- 40) compared with hypothermic animals (287 +/- 22), which was the same as in sham normothermic (271 +/- 21), sham hypothermic (288 +/- 46) and na?ve animals (307 +/- 51). These data demonstrate that 24 h of hypothermia at 34 degrees C with sedation and muscle relaxation after asphyxic cardiac arrest prevents necrotic striatal neuronal cell death in immature brain before rewarming, and that the effect is sustained at 11 d after injury without deleterious side effects.     

Changes in laboratory parameters indicating cell necrosis and organ dysfunction in asphyxiated neonates on moderate systemic hypothermia

AIM: Asphyxia is a major cause of morbidity and mortality in term infants. In addition to cerebral injury other organs are also distressed due to hypoxic-ischaemic insult. Systemic hypothermia has a beneficial effect on brain injury. We tested the impact of hypothermia on hypoxic damage of other internal organs. METHODS: Asphyxiated term neonates (n = 21) were randomised to groups treated with hypothermia (n = 12) and normothermia (n = 9). Hypothermia (33-34 degrees C) was initiated within 6 h of life, and maintained for 72 h. We determined serum transaminase, lactate dehydrogenase, creatine kinase, uric acid, creatinine levels and diuresis during 6, 24, 48 and 72 postnatal hours. RESULTS: Area under curve values of aspartate aminotransferase (ASAT), lactate dehydrogenase (LDH), uric acid and creatinine during the investigated period and alanine aminotransferase (ALAT) value at 72 h were lower in neonates on hypothermia than in those on normothermia. Renal failure and liver impairment affected less hypothermic than normothermic neonates (3/12 vs. 7/9, p = 0.03, 3/12 vs. 6/9 p = 0.08, respectively). Four of the 12 hypothermic and 6 of the 9 normothermic neonates developed multiorgan failure. CONCLUSIONS: These results suggest that systemic hypothermia may protect against cell necrosis and tissue dysfunction of internal organs after neonatal asphyxia.     

头部贴敷式亚低温对HIBD新生大鼠脑组织线粒体ATP酶活性的影响

目的：研究头部贴敷式亚低温治疗对缺氧缺血脑损伤（hypoxic-ischemic brain damage, HIBD）新生大鼠的脑组织线粒体ATP酶活性的影响,以进一步探讨亚低温对缺氧缺血脑组织的保护机制。方法：将84只Wistar新生鼠随机分为4组：假手术常温对照组、假手术亚低温对照组、HIBD模型常温恢复组、HIBD模型亚低温治疗组。各组动物在HI后不同时间点（2,6,12 h）断头取脑,提取脑组织线粒体并测定其中Na+K+ATP酶和Ca2+ATP酶活性。结果①HIBD常温恢复组及亚低温治疗组在2,6,12 h时Ca2+ATP酶活性均呈下降趋势,分别为3.17±0.81,2.26±0.53,1.31±0.78 μmol/mgPr．h及5.25±0.61,4.59±0.81,4.61±0.62 μmol/mgPr．h,但亚低温治疗各组该酶活性均明显高于相应的常温组（P<0.01）。②HIBD常温及亚低温2 h组Na+K+ATP酶活性较之假手术组无明显改变,6 h、12 h组该酶活性明显低于假手术组,分别为3.76±0.78,3.12±0.53 μmol/mgPr．h及5.25±0.66、 4.74±0.80 μmol/mg Pr．h,但亚低温治疗组明显高于相应常温组（P<0.01）。结论 贴敷式局部亚低温可增加HIBD后脑线粒体ATP酶活性,保护脑组织。［中国当代儿科杂志,2007,9（4）：305-307］     

低温对新生大鼠缺氧缺血性脑损伤的保护作用及其机制

目的　探讨全身低温对缺氧缺血性脑损伤的保护作用及其机理。方法　结扎 7日龄Wistar大鼠左侧颈总动脉后吸入 7 7%氧气 6 0min制成脑缺氧缺血 (HI)模型 ,随机分成低温组(30℃ ,n =18)和常温组 (36℃ ,n =18)给予维持恒定目标温度 10h。在HI后 2 4h ,每组 8只取脑进行匀浆用于半胱天冬酶 2 ,3(caspase 2 ,3)活性测定和Western蛋白印迹检查 ,其余每组 10只在HI后 72h处死 ,取脑进行石蜡包埋 ,冠状切片 10 μm用于活性caspase 3,凋亡诱导因子 (AIF) ,发夹寡核苷酸探针原位杂交 (HPP)检测凋亡及相关因子 ,微管相关蛋白 2 (MAP 2 )免疫组化染色用于计算脑梗塞体积和海马CA1神经元丢失 ,HE染色计算脑损伤积分。结果　常温组在HI后 2 4h损伤侧大脑半球caspase 2 ,3的活性 [(2 7 7± 14 7)、(94 9± 5 3 1) pmol/(min·mg蛋白 ) ]均明显高于正常对照组 [(7 6± 0 7)、(12 9± 0 5 ) pmol/(min·mg蛋白 ) ]和低温干预组 [(7 9± 3 4 )、(2 1 1± 18 7)pmol/(min·mg蛋白 ) ],P <0 0 1;而低温组与正常对照组相比无明显差异。Western蛋白印迹结果显示低温组caspase 3的激活受到明显抑制。免疫组化显示常温组活性caspase 3及AIF的阳性细胞数(中位数 14 8 5 ;2 2 /视野 )明显高于低温组 (中位数 4 8 5 ;9/视     

Epileptiform activity during rewarming from moderate cerebral hypothermia in the near-term fetal sheep

Moderate hypothermia is consistently neuroprotective after hypoxic-ischemic insults and is the subject of ongoing clinical trials. In pilot studies, we observed rebound seizure activity in one infant during rewarming from a 72-h period of hypothermia. We therefore quantified the development of EEG-defined seizures during rewarming in an experimental paradigm of delayed cooling for cerebral ischemia. Moderate cerebral hypothermia (n=9) or sham cooling (n=13) was initiated 5.5 h after reperfusion from a 30-min period of bilateral carotid occlusion in near-term fetal sheep and continued for 72 h after the insult. During spontaneous rewarming, fetal extradural temperature rose from 32.5 +/- 0.6 degrees C to control levels (39.4 +/- 0.1 degrees C) in 47 +/- 6 min. Carotid blood flow and mean arterial blood pressure increased transiently during rewarming. The cooling group showed a significant increase in electrical seizure events 2, 3, and 5 h after rewarming, maximal at 2 h (2.9 +/- 1.2 versus 0.5 +/- 0.5 events/h; p <0.05). From 6 h after rewarming, there was no significant difference between the groups. Individual seizures were typically short (28.8 +/- 5.8 s versus 29.0 +/- 6.8 s in sham cooled; NS), and of modest amplitude (35.9 +/- 2.8 versus 38.8 +/- 3.4 microV; NS). Neuronal loss in the parasagittal cortex was significantly reduced in the cooled group (51 +/- 9% versus 91 +/- 5%; p <0.002) and was not correlated with rebound epileptiform activity. In conclusion, rapid rewarming after a prolonged interval of therapeutic hypothermia can be associated with a transient increase in epileptiform events but does not seem to have significant adverse implications for neural outcome.     

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.     

Effect of hypothermic post-treatment on hypoxic-ischemic striatal injury, and normal striatal development, in neonatal rats: a stereological study

Fundamental questions remain about the optimal temperature, duration, and mode of delivery that provide the best striatal neuroprotection from hypothermia after perinatal hypoxia-ischemia. This study used stereological methods to investigate whether a mild (i.e. 2 degrees C) or a moderate (5 degrees C) decrease in whole body temperature, for 6 h immediately postinsult, was neuroprotective for striatal medium-spiny neurons after perinatal hypoxia-ischemia in the rat. This study also investigated whether moderate hypothermia had any effect on normal striatal development. Hypoxia-ischemia or sham hypoxia-ischemia was induced on postnatal day (PN) 7. Pups were kept either normothermic, mildly hypothermic, or moderately hypothermic for 6 h immediately postinsult. The absolute number of striatal medium-spiny neurons was calculated using modern stereological methods. There was no significant difference in the absolute number of medium-spiny neurons in the right striatum after either mild hypothermia or moderate hypothermia. There was also no significant difference in the absolute number of medium-spiny neurons between the control normothermic and the control moderately hypothermic pups. The latter results suggest that moderate hypothermia for 6 h immediately postinsult may be a safe treatment for striatal medium-spiny neurons. Yet, neither mild nor moderate hypothermia alone for 6 h immediately posthypoxia-ischemia is neuroprotective for striatal medium-spiny neurons.     

亚低温对缺氧缺血新生大鼠海马星形胶质细胞增殖和凋亡的影响

目的 观察亚低温对新生大鼠海马星形胶质细胞增殖和凋亡的影响,以探讨亚低温对缺氧缺血脑损伤保护作用的机制.方法 ①体外实验:取3日龄大鼠海马脑片,培养至第4天用氧糖剥夺法制备标本,于33℃(亚低温组)和37℃培养48 h(常温组);对照组脑片不进行氧糖剥夺处理,37℃培养7 d.采用免疫荧光染色方法观察培养脑片星形胶质细...     

Early head cooling in newborn piglets is neuroprotective even in the absence of profound systemic hypothermia

BACKGROUND: Selective head cooling in the newborn infant has been proposed as a neuroprotective treatment with a lower level of systemic adverse effect than that of systemic hypothermia. However, the efficacy is not confirmed as well as that of systemic hypothermia. In order to analyze the safety and efficacy of selective head cooling, 25 newborn piglets were randomly selected for either normothermic or hypothermic treatment. METHODS: Global hypoxic insult was induced by lowering the oxygen concentration to the maximal level to maintain the background electroencephalogram (EEG) voltage under 7 microV for 45 min. The core temperature of normothermic piglets was maintained between 38.5 degrees C and 39 degrees C, while prophylactic cooling was applied to the hypothermic piglets at the same time of the insult. Very mild systemic hypothermia by 1 degrees C was induced in addition to selective head cooling with 10 degrees C coolant temperature. Animals were killed for histopathological examination seven hours after the end of the insult. RESULTS: Two normothermic piglets died while all hypothermic piglets survived. Neuropathological findings were significantly severer in the normothermic group than in the hypothermic group. Intracranial pressure was significantly lower, and EEG recovery was significantly better in the hypothermic piglets. There was no significant difference in the lowest oxygen concentration, degrees of acidosis, blood lactate, and blood pressure between the groups, although heart rate was significantly lower in the hypothermic group. CONCLUSIONS: We have demonstrated that early head cooling was effective in preventing some of the earliest brain damage due to hypoxic insult even in the absence of profound systemic hypothermia.     

Long-term neuroprotective effects of hypothermia on neonatal hypoxic-ischemic brain injury in rats,assessed by auditory brainstem response

A method to assess long-term neurofunctional outcome of hypothermia on immature brains has not yet been clearly established. To investigate the effects of hypothermia on long-term neurofunctional outcome, we studied brainstem function using auditory brainstem response in adult rats after neonatal hypoxic-ischemic brain injury. Seven-day-old rats underwent a combination of left common carotid artery ligation and subsequent exposure to 8% O(2) for 1 h (n = 17). The rats were divided into three groups: hypothermia group (n = 6), normothermia group (n = 6), and sham control group (n = 5). During recovery from the hypoxic-ischemic insult, body temperature was reduced to 30 degrees C for 24 h in the hypothermia group, but was kept at 37 degrees C in the normothermia and sham control group. Three months later the rats were assessed by auditory brainstem response, then killed. The normothermia group showed increased III-V latencies and wave V abnormalities. Hypothermia significantly ameliorated wave V abnormalities. Injury to the ipsilateral inferior colliculus was also reduced in the hypothermia group compared with that in the normothermia group, and the degree of damage assessed histologically correlated well with auditory brainstem response findings. The current study demonstrates that postischemic hypothermia may provide effective and long-lasting neurofunctional as well as histopathologic protection to the immature brain.     

亚低温对新生鼠缺氧缺血脑损伤能量代谢的影响(英文)

目的：探讨亚低温治疗对缺氧缺血脑损伤 (HIBD)新生大鼠的脑组织葡萄糖、ATP及脑线粒体琥珀酸脱氢酶 (SDH)活性的影响及意义。方法：将HIBD模型鼠随机分为缺氧缺血常温恢复组 (IN)和亚低温干预组 (IH) ,同时设常温对照组 (NC)和亚低温对照组 (HC)。各组动物在缺氧缺血结束后不同时间点 (0 ,2 ,6 ,2 4 ,4 8,72h)断头取脑 ,测定脑匀浆葡萄糖含量、ATP含量及脑线粒体琥珀酸脱氢酶 (SDH)活性。结果：脑糖在缺氧缺血0h明显低于对照组 ,缺氧缺血 2h后即恢复正常。IN组脑ATP含量及SDH活性先行下降 ,以后逐渐恢复 ,72h达高峰 ;IH组从缺氧缺血 6h后或 2h起ATP及SDH活性均显著高于同一时间点IN组。ATP含量与SDH活性呈显著正相关 (r =0 .5 15 ,P <0 .0 1)。结论：亚低温可减轻HIBD鼠线粒体SDH活性下降 ,改善能量代谢 ,增加脑ATP合成 ,从而保护脑组织。     

Cooling and immunomodulation for treating hypoxic‐ischemic brain injury

Therapeutic hypothermia is now well established to partially reduce disability in term and near‐term infants with moderate‐severe hypoxic‐ischemic encephalopathy. Preclinical and clinical studies have confirmed that current protocols for therapeutic hypothermia are near optimal. The challenge is now to identify complementary therapies that can further improve outcomes, in combination with therapeutic hypothermia. Overall, anti‐excitatory and anti‐apoptotic agents have shown variable or even no benefit in combination with hypothermia, suggesting overlapping mechanisms of neuroprotection. Inflammation appears to play a critical role in the pathogenesis of injury in the neonatal brain, and thus, there is potential for drugs with immunomodulatory properties that target inflammation to be used as a therapy in neonates. In this review, we examine the evidence for neuroprotection with immunomodulation after hypoxia‐ischemia. For example, stem cell therapy can reduce inflammation, increase cell survival, and promote cell maturation and repair. There are also encouraging preclinical data from small animals suggesting that stem cell therapy can augment hypothermic neuroprotection. However, there is conflicting evidence, and rigorous testing in translational animal models is now needed.     

Influence of mild hypothermia after hypoxia-ischemia on the pharmacokinetics of gentamicin in newborn pigs

The renal function is often affected in asphyxiated newborn infants. The pharmacokinetics of drugs like aminoglycosides eliminated through the kidneys may be impaired and require a different than usual dosage regimen. A decrease in body temperature is associated with a decrease in glomerular filtration rate and may, therefore, impair the elimination of aminoglycosides. When hypothermia is applied as neuronal rescue therapy after birth asphyxia, the pharmacokinetics of kidney-eliminated drugs may be impaired even more. We used our well-established global hypoxia-asphyxia newborn pig model to evaluate the effect of mild hypothermia after hypoxia-ischemia on gentamicin pharmacokinetics. Newborn pigs underwent global hypoxia-ischemia followed by normothermia (39 degrees C) for 72 h (n = 8) or mild hypothermia (35 degrees C) for 24 h followed by normothermia (39 degrees C) for 48 h (n = 8). Gentamicin pharmacokinetics was studied after three gentamicin doses: before hypoxia-ischemia, after hypoxia-ischemia during mild hypothermia or normothermia, and during normothermia 48 h after the first dose. The gentamicin pharmacokinetics variables were calculated using a SAAM II program. Hypoxia-ischemia altered renal function and gentamicin pharmacokinetics. The gentamicin clearance correlated with the creatinine plasma concentration (r = 0.89) and with the kidney pathology score (r = 0.55). There was no significant difference in gentamicin pharmacokinetics at 35 and 39 degrees C in newborn pigs after hypoxia-ischemia. The gentamicin pharmacokinetics variables were not different in the hypothermic or normothermic pigs after all three studied doses. Mild hypothermia for 24 h after hypoxia-ischemia does not affect gentamicin pharmacokinetics.     

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.     

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.     

Combination of systemic hypothermia and N-acetylcysteine attenuates hypoxic-ischemic brain injury in neonatal rats

Hypoxic ischemic (HI) injury in neonates may have devastating, long-term consequences. Recently completed clinical trials in HI neonates indicate that hypothermia within 6 h of birth results in modest improvement in the combined outcome of death or severe disability. The aim of this study was to investigate the effects of combining hypothermia and N-acetylcysteine (NAC) on brain injury, neonatal reflexes and myelination after neonatal HI. Seven-day-old rats were subjected to right common carotid artery ligation and hypoxia (8% oxygen) for 2 h. Systemic hypothermia (30 + 0.5 degrees C) was induced immediately after the period of HI and was maintained for 2 h. NAC (50 mg/kg) was administered by intraperitoneal injection daily until sacrifice. Brain infarct volumes were significantly reduced at 48 h post-HI in the hypothermia plus NAC group (21.5 +/- 3.84 mm3) compared with vehicle (240.85 +/- 4.08 mm3). Neonatal reflexes were also significantly improved by combination therapy at days 1 and 7. There was a significant loss of right hemispheric brain volume in the untreated group at 2 and 4 wk after HI insult. Brain volumes were preserved in hypothermia plus NAC group and were not significantly different when compared with the sham group. Similarly, increased myelin expression was seen in brain sections from hypothermia plus NAC group, when stained for Luxol Fast Blue (LFB), Myelin Basic Protein (MBP) and Proteolipid protein (PLP). These results indicate that hypothermia plus NAC combination therapy improves infarct volume, myelin expression and functional outcomes after focal HI injury.     

Comparison of Temporal Artery Thermometry with Axillary and Rectal Thermometry in Full Term Neonates

Objective

To assess the efficacy of temporal artery thermometer in febrile and hypothermic neonates in comparison to axillary thermometer.

Methods

It was a cross sectional observational study. Study participants included 210 neonates admitted in neonatal intensive care unit of a tertiary care teaching hospital, divided into three groups of 70 each, namely normothermic, febrile and hypothermic. Temperatures were measured using temporal artery, axillary and rectal thermometers in each patient.

Results

Mean rectal temperature was found to be comparable to mean temporal artery temperature in normothermic babies. Temporal artery thermometer had a better sensitivity to diagnose fever, than hypothermia. Also, temporal artery temperature showed a good correlation with rectal temperature in normothermic and febrile group and not in hypothermic neonates.

Conclusions

Temporal artery thermometer can accurately detect temperature in febrile and normothermic fullterm neonates but not in hypothermic neonates. Further studies are required before advocating temporal artery thermometry as a replacement of rectal thermometry among this group of population.

     

Delayed hypothermia as selective head cooling or whole body cooling does not protect brain or body in newborn pig subjected to hypoxia-ischemia

The neuroprotective efficacy of hypothermia (HT) after hypoxia-ischemia (HI) falls dramatically the longer the delay in initiating HT. Knowledge is scarce regarding protective or adverse effects of HT in organs beyond the brain. In addition, the relative effectiveness of selective head cooling (SHC) and whole body cooling (WBC) has not been studied. We aimed to examine whether 24 h HT, initiated 3 h after global HI is brain- and/or organ-protective using pathology, neurology, and biochemical markers. Fifty, 相似文献   

亚低温减轻新生大鼠缺氧缺血脑细胞凋亡的作用及机制研究

目的：细胞凋亡在新生儿缺氧缺血性脑病(HIE)的发病机制中起重要作用,亚低温治疗是HIE最有前途的治疗方法之一。通过观察缺氧缺血后凋亡通路上关键成分的变化,探讨亚低温减轻新生大鼠脑细胞凋亡的作用及机制。方法：采用7日龄SD清洁级大鼠, 建立新生大鼠HIBD标准模型。模型动物随机分为常温缺氧缺血组 (IN, 肛温=37℃)和亚低温缺氧缺血组 (IH,肛温=33℃)。采用TUNEL结合苏木素-伊红染色、神经元Nissl染色等方法检测脑细胞凋亡;Western blotting加免疫组织化学法观察线粒体及胞浆细胞色素C蛋白改变;分别用RT-PCR和显色底物法检测caspase-3 mRNA表达及其酶活性改变。结果：IN组海马CA1区TUNEL阳性锥体细胞明显增多,DNA电泳梯状条带明显;72 h亚低温治疗显著降低脑细胞凋亡发生率,与常温比较差异有显著性（6.4±1.7 vs 25.3±1.5,P<0.01）。IN组胞浆Cyt c水平6 h开始明显升高,72 h达高峰,而线粒体内Cyt c水平则出现相应的下降;亚低温治疗组胞浆Cyt c水平降低和对应线粒体Cyt c水平的升高,以24 h、48 h和72 h最为明显,与IN组比较差异有显著性（P＜0.05）。HIBD后24 h组结扎侧脑组织caspase-3 mRNA表达明显增加,亚低温治疗显著降低caspase-3 mRNA表达水平,以48 h、72 h 治疗组最明显（P＜0.05）,而caspase-3酶活性却在24 h达高峰,亚低温治疗可明显降低HIBD 后24 h 的caspase-3酶活性,与常温比较差异有显著性（2.42±0.5 RFU vs 34.7±3.2 RFU ,P＜ 0.01)。结论：亚低温治疗能够显著降低HIBD后细胞凋亡发生率,其机制可能作用于凋亡通路的多个部位：减少Cyt c释放,减轻或抑制caspase-3表达及其蛋白酶活性等。［中国当代儿科杂志,2007,9（1）：37-41］