• Journal of Korean Neurosurgical Society
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• v.61 no.2
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• pp.267-276
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• 2018

Objective : The beneficial effect of hypothermia after hemicraniectomy in malignant middle cerebral artery (MCA) infarction has been controversial. We aim to investigate the safety and clinical efficacy of hypothermia after hemicraniectomy in malignant MCA infarction. Methods : From October 2012 to February 2016, 20 patients underwent hypothermia (Blanketrol III, Cincinnati Sub-Zero, Cincinnati, OH, USA) at $34^{\circ}C$ after hemicraniectomy in malignant MCA infarction (hypothermia group). The indication of hypothermia included acute cerebral infarction >2/3 of MCA territory and a Glasgow coma scale (GCS) score <11 with a midline shift >10 mm or transtentorial herniation sign (a fixed and dilated pupil). We retrospectively collected 27 patients, as the control group, who had undergone hemicraniectomy alone and simultaneously met the inclusion criteria of hypothermia between January 2010 and September 2012, before hypothermia was implemented as a treatment strategy in Dong-A University Hospital. We compared the mortality rate between the two groups and investigated hypothermia-related complications, such as postoperative bleeding, pneumonia, sepsis and arrhythmia. Results : The age, preoperative infarct volume, GCS score, National institutes of Health Stroke Scale score, and degree of midline shift were not significantly different between the two groups. Of the 20 patients in the hypothermia group, 11 patients were induced with hypothermia immediately after hemicraniectomy and hypothermia was initiated in 9 patients after the decision of hypothermia during postoperative care. The duration of hypothermia was $4{\pm}2days$ (range, 1 to 7 days). The side effects of hypothermia included two patients with arrhythmia, one with sepsis, one with pneumonia, and one with hypotension. Three cases of hypothermia were discontinued due to these side effects (one sepsis, one hypotension, and one bradycardia). The mortality rate of the hypothermia group was 15.0% and that of the control group was 40.7% (p=0.056). On the basis of the logistic regression analysis, hypothermia was considered to contribute to the decrease in mortality rate (odds ratio, 6.21; 95% confidence interval, 1.04 to 37.05; p=0.045). Conclusion : This study suggests that hypothermia after hemicraniectomy is a viable option when the progression of patients with malignant MCA infarction indicate poor prognosis.

• Biomedical Science Letters
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• v.20 no.3
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• pp.168-172
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• 2014

It has recently been shown that hypothermia treatment improves brain ischemia injury and is being increasingly considered by many clinicians. However, the precise roles of hypothermia for brain ischemia are not yet clear. In the present study we demonstrated firstly that hypothermia induced beta-catenin-interacting protein 1 (CTNNBIP1) gene expression and its expression was dramatically decreased under ischemic conditions. It was also demonstrated that hypothermia activated endoplasmic reticulum (ER) stress sensors especially both, the phosphorylation of $eIF2{\alpha}$, and ATF6 proteolytic cleavage. However, the factors of apoptosis and autophagy were not associated with hypothermia. These findings suggested that hypothermia controlled CTNNBIP1 gene expression under ischemia, which may provide a clue to the development of treatments and diagnostic methods for brain ischemia.

• Journal of Chest Surgery
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• v.46 no.6
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• pp.402-412
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• 2013

Background: Moderate and severe hypothermia with cardiopulmonary bypass during aortic surgery can cause some complications such as endothelial cell dysfunction or coagulation disorders. This study found out the difference of vascular reactivity by phenylephrine in moderate and severe hypothermia. Methods: Preserved aortic endothelium by excised rat thoracic aorta was sectioned, and then down the temperature rapidly to $25^{\circ}C$ by 15 minutes at $38^{\circ}C$ and then the vascular tension was measured. The vascular tension was also measured in rewarming at $25^{\circ}C$ for temperatures up to $38^{\circ}C$. To investigate the mechanism of the changes in vascular tension on hypothermia, NG-nitro-L-arginine methyl esther (L-NAME) and indomethacin administered 30 minutes before the phenylephrine administration. And to find out the hypothermic effect can persist after rewarming, endothelium intact vessel and endothelium denuded vessel exposed to hypothermia. The bradykinin dose-response curve was obtained for ascertainment whether endothelium-dependent hyperpolarization factor involves decreasing the phenylnephrine vascular reactivity on hypothermia. Results: Fifteen minutes of the moderate hypothermia blocked the maximum contractile response of phenylephrine about 95%. The vasorelaxation induced by hypothermia was significantly reduced with L-NAME and indomethacin administration together. There was a significant decreasing in phenylephrine susceptibility and maximum contractility after 2 hours rewarming from moderate and severe hypothermia in the endothelium intact vessel compared with contrast group. Conclusion: The vasoplegic syndrome after cardiac surgery might be caused by hypothermia when considering the vascular reactivity to phenylephrine was decreased in the endothelium-dependent mechanism.

• Biomedical Science Letters
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• v.21 no.2
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• pp.126-130
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• 2015

There are several studies that show hypothermia improves cellular ischemia damages on experimental and clinical bases. However, its exact molecular mechanisms are unclear. In this study, we demonstrate that hypothermia induced insulin-like growth factor 1 (IGF1) gene expression, and its expression was dramatically decreased under ischemic insults. It was also demonstrated that hypothermia activated endoplasmic reticulum (ER) stress sensors especially both the phosphorylation of $eIF2{\alpha}$ (eukaryotic translation initiation factor 2 alpha) and ATF6 (activating transcription factor-6) proteolytic cleavage. However, the factors of apoptosis and autophagy were not associated with hypothermia. We suggest that hypothermia-treated IGF1 gene expression after ischemia may show a good possibility for the development of treatments and diagnostic methods in cerebral ischemic damages.

• Korean Journal of Veterinary Research
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• v.38 no.4
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• pp.867-881
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• 1998

The studies were carried out to investigate the phygiological changes in deep hypothermia in rabbits. Sixty rabbits were continuously cooled with femoral arterio-venous bypass circulation to rectal temperatures of $34.0{\pm}0.3^{\circ}C$(mild hypothermia), $30.0{\pm}0.3^{\circ}C$(moderate hypothermia), and $25.0{\pm}0.3^{\circ}C$(deep hypothermia). The results obtained in these experiments were summarized as follows : In mild, moderate, and deep hypothermia, MAP, HR, RR, pH, $pCO_2$, $pO_2$, $Na^+$, $K^+$, HCT, PLT, glucose, L-lactate, BUN, and creatinine were analyzed. During hypothermia, a statistically significant decrease of MAP occurred between $30^{\circ}C$ and early $25^{\circ}C$(Start) of rectal temperature while significant increases occurred between baseline($38.7^{\circ}C$) and $30^{\circ}C$. Significant decreases of HR and RR were observed in the rabbits, particularly those changes appeared to similar patterns in proportion to hypothermia. Significant decreases of pH occurred between $34^{\circ}C$ and $25^{\circ}C$, and significant increases of $pO_2$ and $pCO_2$ were observed continuously in the hypothermic rabbits. The hypothermia had no significant effect on blood $Na^+$ and serum creatinine. Blood $K^+$ significantly decreased from $3.1{\pm}0.5$(baseline) to $2.6{\pm}0.6mmol/l$($34^{\circ}C$) with the hypothermia for about 30 minutes, and significantly increased from $2.4{\pm}0.6$($25^{\circ}C$(S)) to $2.7{\pm}0.5mmol/l$($25^{\circ}C$(E)) with the hypothermia for 2 hrs. HCT significantly increased to $34^{\circ}C$, thereafter, continuously increased to $25^{\circ}C$(Start, End). PLT increased to $34^{\circ}C$, thereafter, continuously decreased to $25^{\circ}C$(Start, End). Also PLT decreased significantly from 414.3($30^{\circ}C$) to $308.8{\times}103/mm^3$($25^{\circ}C$, Start). Significant increases of blood glucose and L-lactate occurred between $30^{\circ}C$ and $25^{\circ}C$ (Start, End). Slight increase of serum BUN continuously appeared with the hypothermia. These results, such as characteristic changes of the significant decrease of pH and PLT at $34^{\circ}C$, the significant decrease of MAP at $30^{\circ}C$, and the significant increase of glucose and l-lactate at $30^{\circ}C$, suggest that homeostasis of rabbits to hypothermia rapidly decreases at $34{\sim}30^{\circ}C$ of rectal temperature. Therefore, we suggest that, during the period with the rapidly decreased homeostasis, the very carefully control and treatment need to recover hypothermic animals under the circumstances of the various hypothermic experiments and emergency medicine.

• Child Health Nursing Research
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• v.24 no.4
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• pp.517-526
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• 2018

Purpose: This study compared nursing frequency, nursing time, and nursing intervention priorities depending on the method of neonatal induced hypothermia. Methods: We observed 15 neonatal subjects receiving therapeutic hypothermia for 3 days each. Forty-five nurses experienced with nursing neonatal patients under therapeutic hypothermia provided responses about nursing intervention priorities. Analyses with the chi-square, the Fisher exact test, the paired t-test, the Wilcoxon signed rank test, and the Wilcoxon rank-sum test were performed on the data using SAS version 9.4. Results: The frequency of nursing activities was higher for selective head therapeutic hypothermia (SHTH) than for systemic therapeutic hypothermia (STH), and nursing time was also significantly longer. In terms of nursing intervention priorities, there were priority differences in "risk for ineffective thermoregulation" and "risks for impaired skin integrity" for SHTH compared to STH. Conclusion: Since SHTH for neonatal therapeutic hypothermia requires more nursing time and frequent nursing activities than STH, STH is therefore recommended if the therapeutic efficacy is similar. Appropriate nursing personnel should be allocated for neonatal SHTH nursing. Nurses should be aware of nursing interventions for therapeutic hypothermia as the priorities are different for different methods of neonatal therapeutic hypothermia.

• Clinical and Experimental Pediatrics
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• v.64 no.8
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• pp.422-429
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• 2021

Background: Carnosine has antioxidative and neuroprotective properties against hypoxic-ischemic (HI) brain injury. Hypothermia is used as a therapeutic tool for HI encephalopathy in newborn infants with perinatal asphyxia. However, the combined effects of these therapies are unknown. Purpose: Here we investigated the effects of combined carnosine and hypothermia therapy on HI brain injury in neonatal rats. Methods: Postnatal day 7 (P7) rats were subjected to HI brain injury and randomly assigned to 4 groups: vehicle; carnosine alone; vehicle and hypothermia; and carnosine and hypothermia. Carnosine (250 mg/kg) was intraperitoneally administered at 3 points: immediately following HI injury, 24 hours later, and 48 hours later. Hypothermia was performed by placing the rats in a chamber maintained at 27℃ for 3 hours to induce whole-body cooling. Sham-treated rats were also included as a normal control. The rats were euthanized for experiments at P10, P14, and P35. Histological and morphological analyses, in situ zymography, terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assays, and immunofluorescence studies were conducted to investigate the neuroprotective effects of the various interventional treatments. Results: Vehicle-treated P10 rats with HI injury showed an increased infarct volume compared to sham-treated rats during the triphenyltetrazolium chloride staining study. Hematoxylin and eosin staining revealed that vehicle-treated P35 rats with HI injury had decreased brain volume in the affected hemisphere. Compared to the vehicle group, carnosine and hypothermia alone did not result in any protective effects against HI brain injury. However, a combination of carnosine and hypothermia effectively reduced the extent of brain damage. The results of in situ zymography, TUNEL assays, and immunofluorescence studies showed that neuroprotective effects were achieved with combination therapy only. Conclusion: Carnosine and hypothermia may have synergistic neuroprotective effects against brain damage following HI injury.

• Clinical and Experimental Pediatrics
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• v.61 no.8
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• pp.239-244
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• 2018

Purpose: Hypothermia at admission is associated with increased mortality and morbidity in preterm infants. We performed a quality improvement (QI) effort to determine the impact of a decrease in admission hypothermia in preterm infants. Methods: The study enrolled very low birth weight (VLBW) infants born at Gangnam Severance Hospital between January 2013 and December 2016. This multidisciplinary QI effort included the use of occlusive wraps, warm blankets, and caps; the delivery room temperature was maintained above $23.0^{\circ}C$, and a check-list was used for feedback. Results: Among 259 preterm infants, the incidence of hypothermia (defined as body temperature <$36.0^{\circ}C$) decreased significantly from 68% to 41%, and the mean body temperature on neonatal intensive care unit admission increased significantly from $35.5^{\circ}C$ to $36.0^{\circ}C$. In subgroup analysis of VLBW infants, admission hypothermia and neonatal outcomes were compared between the pre-QI (n=55) and post-QI groups (n=75). Body temperature on admission increased significantly from $35.4^{\circ}C$ to $35.9^{\circ}C$ and the number of infants with hypothermia decreased significantly from 71% to 45%. There were no cases of neonatal hyperthermia. The incidence of pulmonary hemorrhage was significantly decreased (P=0.017). Interaction analysis showed that birth weight and gestational age were not correlated with hypothermia following implementation of the protocol. Conclusion: Our study demonstrated a significant reduction in admission hypothermia following the introduction of a standardized protocol in our QI effort. This resulted in an effective reduction in the incidence of massive pulmonary hemorrhage.

• Journal of Korean Neurosurgical Society
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• v.29 no.10
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• pp.1296-1302
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• 2000

Objective : Traumatic brain injury including diffuse axonal injury has been shown to result in a decrease in brainfree magnesium concentration, an endogenous inhibitor of calcium entry into neuron, that is associated with the development of neurological motor deficits. The goal of this study is to establish the therapeutic window during which the therapy with $MgSO_4$ and/or hypothermia improve damaged neurons by TUNEL stain. Method : Moderate brain injury was induced in 64 adult Sprague-Dawley rats, weighing 350 to 450gm each, by using a simple weight-drop device(Marmarou model). The animals were randomly assigned to four groups(sixteen rats each, a control group, a group treated with $MgSO_4$, a group treated with hypothermia, and a group treated with $MgSO_4$ and hypothermia) and the rats in each group were sacrificed and studied after 12 hrs, 24 hrs, 1 wk, and 2 wks after insult. In hypothermic group, these rats were subjected to hypothermia after injury, with their rectal temperatures maintained at $32^{\circ}C$ for 1 hour. After 1-hour period of hypothermia, rewarming to normothermic level was accomplished over 30-minute period. In the groups treated $MgSO_4$, hypothermia and $MgSO_4$ were subsequently treated with $MgSO_4$($750{\mu}moles/kg$) infused intra-muscularly at 30 minutes after trauma. Result : In all treated groups, a significant reduction in TUNEL positive cells was found in comparison with the control group each time(p<0.001). Between treatment groups, No differnce was seen 12hrs, 24hrs, and 1wk. However, hypothermic group treated with or without $MgSO_4$ showed more significant reduction in apoptotic cells than group treated with $MgSO_4$ 2 weeks after trauma(p<0.05). However, hypothermic group treated with $MgSO_4$ showed no significant reduction in apoptotic cells compared with hypothermic group(p>0.05). Conclusion : These findings suggest that both hypothermia and $MgSO_4$ significantly improve pathological changes. Otherwise simultaneously $MgSO_4$ and hypothermia treatment groups is failed to provide additional neuroprotection. These results may be relevant to the design of future clinical trials of therapeutic hypothermia and $MgSO_4$ for traumatic brain injury.

• Clinical and Experimental Pediatrics
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• v.62 no.10
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• pp.386-394
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• 2019

Background: Preterm infants have difficulty maintaining body temperature after birth. However, clinical guidelines advocate that neonatal body temperature should be maintained at 36.5℃-37.5℃. Purpose: We aimed to investigate the incidence of admission hypothermia in very low birth weight (VLBW) infants and to determine the association of admission temperature with in-hospital mortality and morbidities. Methods: A cohort study using prospectively collected data involving 70 neonatal intensive care units (NICUs) that participate in the Korean Neonatal Network. From registered infants born between January 2013 and December 2015, 5,343 VLBW infants born at less than 33 weeks of gestation were reviewed. Results: The mean admission temperature was 36.1℃±0.6℃, with a range of 31.9℃ to 38.4℃. Approximately 74.1% of infants had an admission hypothermia of <36.5℃. Lower birth weight, intubation in the delivery room and Apgar score <7 at 5 minutes were significantly related to admission hypothermia. The mortality was the lowest at 36.5℃-37.5℃ and adjusted odd ratios for all deaths increased to 1.38 (95% confidence interval [CI], 1.04-1.83), 1.44 (95% CI, 1.05-1.97) and 1.86 (95% CI, 1.22-2.82) for infants with admission temperatures of 36.0℃-36.4℃, 35.0℃-35.9℃, and <35.0℃, respectively. Admission hypothermia was also associated with high likelihoods of bronchopulmonary dysplasia, pulmonary hypertension, proven sepsis, pulmonary hemorrhage, air-leak, seizure, grade 3 or higher intraventricular hemorrhage and advanced retinopathy of prematurity requiring laser therapy. Conclusion: A large portion of preterm infants in Korea had hypothermia at NICU admission, which was associated with high mortality and several important morbidities. More aggressive interventions aimed at reducing hypothermia are required in this high-risk population.