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Objective: To investigate the effects of mild hypothermia combined with hyperbaric oxygen on myocardial injury markers, oxidative stress response and neurofactors levels in patients with acute carbon monoxide poisoning (ACMP), so as to provide clinical guidance for the treatment of ACMP. Methods: A total of 96 ACMP patients admitted to our hospital from January 2022 to May 2023 were selected and divided into study group (n = 48) and control group (n = 48) by random number table method. The control group was given hyperbaric oxygen therapy, and the study group was given mild hypothermia combined hyperbaric oxygen therapy. Myocardial injury markers, oxidative stress, neurofactors, neurological function, coma degree, ability of daily living, mortality, incidence of acute carbon monoxide poisoning delayed encephalopathy (DEACMP) and adverse reactions were compared between the two groups. Results: After treatment, the levels of brain natriuretic peptide (BNP), creatine kinase isoenzyme (CK-MB) and creatine kinase isoenzyme (cTnI) in two groups were decreased (P < 0.05) and the levels in the study group were lower than those in the control group(P<0.05). After treatment, the levels of glutathione peroxidase enzyme (GSH-Px) and superoxide dismutase(SOD) in the two groups were increased (P < 0.05), while the levels of malondialdehyde (MDA) and nitric oxide (NO) were decreased (P < 0.05) The levels of GSH-Px and SOD in the study group were higher than those in the control group (P < 0.05), and the levels of MDA and NO were lower (P < 0.05) After treatment, serum neuron specific enolase (NSE), myelin basic protein (MBP) and cerebrospinal fluid central nerve specific protein (S100ß) were decreased in both groups (P < 0.05), and those in the study group were lower than those in the control group (P < 0.05) . After treatment, the score of National Institutes of Health Stroke Scale (NIHSS) decreased (P < 0.05) while the score of Glasgow Coma Scale (GCS) and Barthel (BI) of standard daily living ability increased (P < 0.05) The NIHSS score of the study group was lower than that of the control group P < 0.05 ), and the scores of GCS and BI were higher (P < 0.05) Mortality and incidence of DEACMP in the study group were 2.08% (1/48) and 16.67% (8/48), which were lower than 10.42% (5/48) and 27.08% (13/48) in the control group (P<0.05). The incidence of adverse reactions in the study group was 12.50% (6/48), which had no statistical significance compared with 18.75% (9/48) in the control group (P>0. 05). Conclusion: The application of mild hypothermia combined with hyperbaric oxygen in the treatment of ACMP patients can reduce the degree of myocardial and nerve damage and coma, relieve the oxidative stress reaction, promote the recovery of nerve function, improve the ability of daily living, reduce the mortality and the incidence of DEACMP, with high safety. [ABSTRACT FROM AUTHOR]

Abstract Purpose Our previous research has revealed that mild hypothermia leads to excessive bleeding in thoracic surgeries, while the underlying mechanism stayed unrevealed by the standard coagulation tests. The research question in this study was as follows: “How does mild hypothermia impair the hemostatic function in patients receiving thoracic surgeries?”. The purpose was to detect the disturbed coagulation processes by comparing the TEG parameters in patients receiving active vs. passive warming during thoracic surgeries. Methods Standard coagulation tests and thromboelastography (TEG) were adopted to compare the hemostatic functions in patients receiving active vs. passive warming during thoracic surgeries. Furthermore, blood samples from passive warming group were retested for TEG at actual core body temperatures. Results Sixty-four eligible patients were included in this study. TEG revealed that mild hypothermia significantly disturbed coagulation by decreasing MA (59.4 ± 4.5 mm vs. 64.2 ± 5.7 mm, p = 0.04) and α angle (70.4 ± 5.2° vs. 74.9 ± 4.4°, p = 0.05) and prolonging ACT (122.2 ± 19.3 s vs. 117.3 ± 15.2 s, p = 0.01) and K time (1.9 ± 1.0 s vs. 1.3 ± 0.4 min, p = 0.02). TEGs conducted under core body temperatures revealed more impaired coagulation than those incubated at 37 °C. Furthermore, postoperative shivering and waking time were significantly increased in mild hypothermic patients. Conclusion Mild hypothermia significantly impaired coagulation function in patients receiving thoracic surgeries, which could be detected by TEGs other than the standard coagulation tests. Temperature-adjusted TEGs may provide a preferable method of hemostatic monitoring and transfusion guidance in thoracic surgeries, which warrants further clinical investigations.

Objective: To determine the efficacy of mechanical thrombectomy combined with prolonged mild hypothermia compared with conventional treatment in managing acute middle cerebral artery occlusion, and to explore whether extending the duration of hypothermia can improve neurological function. Method: From 2018 to June 2023, a retrospective analysis was conducted on 45 patients with acute middle cerebral artery occlusion treated at the NICU of Suzhou Kowloon Hospital, affiliated with Shanghai Jiao Tong University School of Medicine. After thrombectomy, patients were admitted to the neurological intensive care unit (NICU) for targeted temperature management. Patients were divided into two groups: the mild hypothermia group (34.5-35.9°C) receiving 5-7 days of treatment, and the normothermia group (control group) whose body temperature was kept between 36 and 37.5°C using pharmacological and physical cooling methods. Baseline characteristics and temperature changes were compared between the two groups of patients. The primary outcome was the modified Rankin Scale (mRS) score at 3 month after surgery, and the secondary outcomes were related complications and mortality rate. Prognostic risk factors were investigated using both univariate and multivariate logistic regression analyses. Results: Among 45 patients, 21 underwent prolonged mild hypothermia, and 24 received normothermia, with no significant differences in baseline characteristics between the two groups. The duration of mild hypothermia ranged from 5 to 7 days. The incidence of chills (33.3% vs. 8.3%, p = 0.031) and constipation (57.1% vs. 20.8%, p = 0.028) was significantly higher in the mild hypothermia group compared with the control group. There was no significant difference in mortality rates between the mild hypothermia and the control group (4.76% vs. 8.33%, p = 1.000, OR = 1.75, 95% CI, 0.171-17.949). At 3 month, there was no significant difference in the modified mRS (0-3) score between the mild hypothermia and control groups (52.4% vs. 25%, p = 0.114, OR = 0.477, 95% CI, 0.214-1.066). Infarct core volume was an independent risk factor for adverse neurological outcomes. Conclusion: Prolonged mild hypothermia following mechanical thrombectomy had no severe complications and shows a trend to improve the prognosis of neurological function. The Infarct core volume on CTP was an independent risk factor for predicting neurological function. [ABSTRACT FROM AUTHOR]

Objective To investigate the protective effect of target temperature management based different durations with delayed hypothermia for traumatic brain injury(TBI) in rats. Methods 36 healthy adult male SD rats were randomly divided into NT group, HT4h group, HT24h group and HT48h group. The TBI model of rats was prepared with an electronic controllable cortical injury device. NT group was treated with normal temperature (37 ) 4 h after TBI, and the experimental groups were treated with low temperature (33.0 ± 1.0 ) 4 h after TBI for 4 h, 24 h, and 48 h. Three days after TBI, the motor function of the rats in each group was evaluated by beam walking test and inclined-grid climbing test, EB staining was used to measure the blood-brain barrier permeability, the change of hippocampal neurons was observed by Nissl staining, the expression of DCX and GFAP was detected by immunofluorescence, and the expression of Bcl-2 and Bax was measured by Western blot and immunohistochemistry. Results Compared with NT group, the experimental groups could significantly improve the motor function of TBI rats, reduce the permeability of blood-brain barrier,protect hippocampal neurons, promote DCX expression, inhibit GFAP expression, up-regulate the expression of Bcl-2 protein, and down-regulate the expression of Bax protein. However, the protective effect was more apparent in HT48h group than other experimental groups (P < 0.05). Conclusion Long-term delayed target temperature management has a significant brain protective effect. [ABSTRACT FROM AUTHOR]

Purpose: Our previous research has revealed that mild hypothermia leads to excessive bleeding in thoracic surgeries, while the underlying mechanism stayed unrevealed by the standard coagulation tests. The research question in this study was as follows: "How does mild hypothermia impair the hemostatic function in patients receiving thoracic surgeries?". The purpose was to detect the disturbed coagulation processes by comparing the TEG parameters in patients receiving active vs. passive warming during thoracic surgeries. Methods: Standard coagulation tests and thromboelastography (TEG) were adopted to compare the hemostatic functions in patients receiving active vs. passive warming during thoracic surgeries. Furthermore, blood samples from passive warming group were retested for TEG at actual core body temperatures. Results: Sixty-four eligible patients were included in this study. TEG revealed that mild hypothermia significantly disturbed coagulation by decreasing MA (59.4 ± 4.5 mm vs. 64.2 ± 5.7 mm, p = 0.04) and α angle (70.4 ± 5.2° vs. 74.9 ± 4.4°, p = 0.05) and prolonging ACT (122.2 ± 19.3 s vs. 117.3 ± 15.2 s, p = 0.01) and K time (1.9 ± 1.0 s vs. 1.3 ± 0.4 min, p = 0.02). TEGs conducted under core body temperatures revealed more impaired coagulation than those incubated at 37 °C. Furthermore, postoperative shivering and waking time were significantly increased in mild hypothermic patients. Conclusion: Mild hypothermia significantly impaired coagulation function in patients receiving thoracic surgeries, which could be detected by TEGs other than the standard coagulation tests. Temperature-adjusted TEGs may provide a preferable method of hemostatic monitoring and transfusion guidance in thoracic surgeries, which warrants further clinical investigations. [ABSTRACT FROM AUTHOR]

Mild hypothermia (MH) is an effective measure to alleviate cerebral ischemia–reperfusion (I/R) injury. However, the underlying biological mechanisms remain unclear. This study set out to investigate dynamic changes in urinary proteome due to MH in rats with cerebral I/R injury and explore the neuroprotective mechanisms of MH. A Pulsinelli's four-vessel occlusion (4-VO) rat model was used to mimic global cerebral I/R injury. Liquid chromatography-tandem mass spectrometry (LC–MS/MS) was employed to profile the urinary proteome of rats with/without MH (32 °C) treatment after I/R injury. Representative differentially expressed proteins (DEPs) associated with MH were validated by western blotting in hippocampus. A total of 597 urinary proteins were identified, among which 119 demonstrated significant changes associated with MH. Gene Ontology (GO) annotation of the DEPs revealed that MH significantly enriched in endopeptidase activity, inflammatory response, aging, response to oxidative stress and reactive oxygen species, blood coagulation, and cell adhesion. Notably, changes in 12 DEPs were significantly reversed by MH treatment. Among them, 8 differential urinary proteins were previously reported to be closely associated with brain disease, including NP, FZD1, B2M, EPCR, ATRN, MB, CA1and VPS4A. Two representative proteins (FZD1, B2M) were further validated by western blotting in the hippocampus and the results were shown to be consistent with urinary proteomic analysis. Overall, this study strengthens the idea that urinary proteome can sensitively reflect pathophysiological changes in the brain, and appears to be the first study to explore the neuroprotective effects of MH by urinary proteomic analysis. FZD1 and B2M may be involved in the most fundamental molecular biological mechanisms of MH neuroprotection. In a 4-VO rat model, 119 urinary proteins demonstrated significant changes associated with MH. MH is enriched in endopeptidase activity, inflammatory response, oxidative stress, etc, and significantly reversed changes in 12 DEPs. FZD1 and B2M are thought to be involved in the most fundamental molecular biological mechanisms of MH neuroprotection. [ABSTRACT FROM AUTHOR]

We report the feasibility of a combined approach of very low low tidal volume (VT) and mild therapeutic hypothermia (MTH) to decrease the ventilatory load in a severe COVID-19-related acute respiratory distress syndrome (ARDS) cohort. Inclusion criteria was patients ≥18-years-old, severe COVID-19-related ARDS, driving pressure ∆P >15 cmH2O despite low-VT strategy, and extracorporeal therapies not available. MTH was induced with a surface cooling device aiming at 34°C. MTH was maintained for 72 h, followed by rewarming of 1°C per day. Data were shown in median (interquartile range, 25%–75%). Mixed effects analysis and Dunnett’s test were used for comparisons. Seven patients were reported. Ventilatory load decreased during the first 24 h, minute ventilation (VE) decreased from 173 (170–192) to 152 (137–170) mL/kg/min (P = 0.007), and mechanical power (MP) decreased from 37 (31–40) to 29 (26–34) J/min (P = 0.03). At the end of the MTH period, the VT, P, and plateau pressure remained consistently close to 3.9 mL/kg predicted body weight, 12 and 26 cmH2O, respectively. A combined strategy of MTH and ultraprotective mechanical ventilation (MV) decreased VE and MP in severe COVID-19-related ARDS. The decreasing of ventilatory load may allow maintaining MV within safety thresholds.

We report the feasibility of a combined approach of very low low tidal volume (VT) and mild therapeutic hypothermia (MTH) to decrease the ventilatory load in a severe COVID-19-related acute respiratory distress syndrome (ARDS) cohort. Inclusion criteria was patients ≥18-years-old, severe COVID-19-related ARDS, driving pressure ΔP >15 cmH2O despite low-VT strategy, and extracorporeal therapies not available. MTH was induced with a surface cooling device aiming at 34°C. MTH was maintained for 72 h, followed by rewarming of 1°C per day. Data were shown in median (interquartile range, 25%-75%). Mixed effects analysis and Dunnett's test were used for comparisons. Seven patients were reported. Ventilatory load decreased during the first 24 h, minute ventilation (VE) decreased from 173 (170-192) to 152 (137-170) mL/kg/min (P = 0.007), and mechanical power (MP) decreased from 37 (31-40) to 29 (26-34) J/min (P = 0.03). At the end of the MTH period, the VT, P, and plateau pressure remained consistently close to 3.9 mL/kg predicted body weight, 12 and 26 cmH2O, respectively. A combined strategy of MTH and ultraprotective mechanical ventilation (MV) decreased VE and MP in severe COVID-19-related ARDS. The decreasing of ventilatory load may allow maintaining MV within safety thresholds. [ABSTRACT FROM AUTHOR]

Objective: Characterize the neurophysiological effects of mild hypothermia on stroke and spreading depolarizations (SDs) in gyrencephalic brains. Methods: Left middle cerebral arteries (MCAs) of six hypothermic and six normothermic pigs were permanently occluded (MCAo). Hypothermia began 1 h after MCAo and continued throughout the experiment. ECoG signals from both frontoparietal cortices were recorded. Five-minute ECoG epochs were collected 5 min before, at 5 min, 4, 8, 12, and 16 h after MCAo, and before, during, and after SDs. Power spectra were decomposed into fast (alpha, beta, and gamma) and slow (delta and theta) frequency bands. Results: In the vascular insulted hemisphere under normothermia, electrodes near the ischemic core exhibited power decay across all frequency bands at 5 min and the 4th hour after MCAo. The same pattern was registered in the two furthest electrodes at the 12th and 16th hour. When mild hypothermia was applied in the vascular insulted hemispheres, the power decay was generalized and seen even in electrodes with uncompromised blood flow. During SD analysis, hypothermia maintained increased delta and beta power during the three phases of SDs in the furthest electrode from the ischemic core, followed by the second furthest and third electrode in the beta band during preSD and postSD segments. However, in hypothermic conditions, the third electrode showed lower delta, theta, and alpha power. Conclusion: Mild hypothermia attenuates all frequency bands in the vascularly compromised hemisphere, irrespective of the cortical location. During SD formation, it preserves power spectra more significantly in electrodes further from the ischemic core. [ABSTRACT FROM AUTHOR]

Objective To explore the optimal duration of long-term mild hypothermia (MHT) for traumatic brain injury (TBI) in rats, and observe its effect on intracranial pressure (ICP) and neurological function. Methods Forty-eight healthy adult male SD rats were divided into the normal temperature treatment (NT) group, the MHT4 h group, the MHT24 h group and the MHT48 h group by random number table method, with twelve rats in each group. The TBI model of rats was prepared by electronic controllable cortical injury device, and ICP monitoring probe was implanted. After modeling, the NT group was treated with normal temperature (37 ℃), and the other groups were treated with low temperature (33.0±1.0 ) ℃ for 4 h, 24 h and 48 h, respectively. ICP was monitored and brain water content (BWC) was calculated after MHT treatment in each group. Blood-brain barrier permeability was determined by Evansland (EB) staining. The expression of 5-bromodeoxyuracil nucleoside (BrdU), neuronal nuclear antigen antibody (NeuN) and leukocyte differentiation antigen 86 (CD86) positive cells were detected by immunofluorescence staining. The expressions of B-cell lymphoma-2 (Bcl-2), Bcl-2 associated X protein (Bax), inducable nitric oxide synthase (iNOS), interleukin (IL) -10 and arginase 1 (Arg-1) were detected by Western blot assay. Results Compared with the NT group, levels of BWC, ICP, EB, and CD86 positive cells, Bax and iNOS expression levels were decreased in the MHT4 h group, the MHT24 h group and the MHT48 h group, and the number of BrdU positive cells and BrdU/NeuN double-labeled positive cells were increased in hippocampus. The expression levels of Bcl-2, IL-10 and Arg-1 were increased (P＜0.01). Compared with the MHT24 h group, levels of BWC, ICP and EB, and CD86 positive cells, Bax and iNOS expression were decreased, and the number of BrdU positive cells and BrdU/NeuN double-labeled positive cells were increased in the MHT48 h group, while levels of Bcl-2, IL-10 and Arg-1 expression were increased (P＜ 0.01). Conclusion Long-term MHT can promote the proliferation and differentiation of neurons, inhibit apoptosis and reduce inflammation by suppressing ICP rebound, further promoting neuroprotection after TBI. [ABSTRACT FROM AUTHOR]

We tested the effects of cold air (0℃) exposure on endurance capacity to different levels of cold strain ranging from skin cooling to core cooling of Δ-1.0℃. Ten males completed a randomized, crossover, control study consisting of a cycling time to exhaustion (TTE) at 70% of their peak power output following: 1) 30-min of exposure to 22℃ thermoneutral air (TN), 2) 30-min exposure to 0℃ air leading to a cold shell (CS), 3) 0℃ air exposure causing mild hypothermia of -0.5℃ from baseline rectal temperature (HYPO-0.5℃), and 4) 0℃ air exposure causing mild hypothermia of -1.0℃ from baseline rectal temperature (HYPO-1.0℃). The latter three conditions tested TTE in 0℃ air. Core temperature and seven-site mean skin temperature at the start of the TTE were: TN (37.0±0.2℃, 31.2 ±0.8℃), CS (37.1 ±0.3℃, 25.5 ± 1.4℃), HYPO-0.5℃ (36.6 ±0.4℃, 22.3 ± 2.2℃), HYPO-1.0℃ (36.4 ±0.5℃, 21.4 ± 2.7℃). There was a significant condition effect (P < 0.001) for TTE, which from TN (23.75 ± 13.75 min) to CS (16.22 ± 10.30 min, Δ-30.9 ± 21.5%, P = 0.055), HYPO-0.5℃ (8.50 ± 5.23 min, Δ-61.4 ± 19.7%, P < 0.001), and HYPO-1.0℃ (6.50± 5.60 min, Δ-71.6 ± 16.4%, P < 0.001). Furthermore, participants had a greater endurance capacity in CS compared with HYPO-0.5℃ (P = 0.046), and HYPO-1.0℃ (P = 0.007), with no differences between HYPO-0.5℃ and HYPO-1.0℃ (P = 1.00). Endurance capacity impairment at 70% peak power output occurs early in cold exposure with skin cooling, with significantly larger impairments with mild hypothermia up to Δ-1.0℃. [ABSTRACT FROM AUTHOR]

ObjectiveCharacterize the neurophysiological effects of mild hypothermia on stroke and spreading depolarizations (SDs) in gyrencephalic brains.MethodsLeft middle cerebral arteries (MCAs) of six hypothermic and six normothermic pigs were permanently occluded (MCAo). Hypothermia began 1 h after MCAo and continued throughout the experiment. ECoG signals from both frontoparietal cortices were recorded. Five-minute ECoG epochs were collected 5 min before, at 5 min, 4, 8, 12, and 16 h after MCAo, and before, during, and after SDs. Power spectra were decomposed into fast (alpha, beta, and gamma) and slow (delta and theta) frequency bands.ResultsIn the vascular insulted hemisphere under normothermia, electrodes near the ischemic core exhibited power decay across all frequency bands at 5 min and the 4th hour after MCAo. The same pattern was registered in the two furthest electrodes at the 12th and 16th hour. When mild hypothermia was applied in the vascular insulted hemispheres, the power decay was generalized and seen even in electrodes with uncompromised blood flow. During SD analysis, hypothermia maintained increased delta and beta power during the three phases of SDs in the furthest electrode from the ischemic core, followed by the second furthest and third electrode in the beta band during preSD and postSD segments. However, in hypothermic conditions, the third electrode showed lower delta, theta, and alpha power.ConclusionMild hypothermia attenuates all frequency bands in the vascularly compromised hemisphere, irrespective of the cortical location. During SD formation, it preserves power spectra more significantly in electrodes further from the ischemic core.

Abstract Objective We designed a simplified total arch reconstruction (s-TAR) technique which could be performed under mild hypothermia (30–32 °C) with distal aortic perfusion. This study aimed to compare its efficacy of organ protection with the conventional total arch reconstruction (c-TAR). Methods We reviewed the clinical data of 195 patients who had ascending aortic aneurysm with extended aortic arch dilation and underwent simultaneous ascending aorta replacement and TAR procedure between January 2018 and December 2022 in our center. 105 received c-TAR under moderate hypothermia (25–28 °C) with circulatory arrest (c-TAR group); rest 90 received s-TAR under mild hypothermia (30–32 °C) with distal aortic perfusion (s-TAR group). Results The s-TAR group demonstrated shorter CPB time, cross-clamp time and lower body circulatory arrest time compared with the c-TAR group. The 30-day mortality was 2.9% for the c-TAR group and 1.1% for the s-TAR group (P = 0.043). The mean duration of mechanical ventilation was shorter in the s-TAR group. Paraplegia was observed in 4 of 105 patients (3.8%) in the c-TAR group, while no such events were observed in the s-TAR group. The incidence of temporary neurologic dysfunction was significantly higher in the c-TAR group. The incidence of permanent neurologic dysfunction also showed a tendency to be higher in the c-TAR group, without statistical significance. Furthermore, the incidence of reoperation for bleeding were significantly lower in the s-TAR group. The rate of postoperative hepatic dysfunction and all grades of AKI was remarkably lower in the s-TAR group. The 3-year survival rate was 95.6% in the s-TAR group and 91.4% in the c-TAR group. Conclusions s-TAR under mild hypothermia (30–32℃) with distal aortic perfusion is associated with lower mortality and morbidity, offering better neurological and visceral organ protection compared with c-TAR.

Abstract Background Cold agglutinin disease can lead to significant complications, especially for patients undergoing arch repair requiring hypothermic circulatory arrest. Rituximab and plasmapheresis are treatments for cold agglutinin disease. However, its use in patients with Stanford type A dissection has not been reported. Therefore, after consultation with hematologists, we used rituximab and plasmapheresis before mild hypothermic aortic arch surgery to maintain the body temperature above the thermal altitude. Case presentation This report describes an 86-year-old male patient with acute type A aortic dissection who received outpatient treatment for rheumatoid arthritis and a 55-mm thoracic aortic aneurysm. The patient was scheduled to undergo urgent surgery for a type A intramural hematoma and progressive aortic aneurysm; however, laboratory test results indicated blood clotting and cold agglutinin. Consequently, urgent surgery was rescheduled. After consulting with hematologists, rituximab was initiated 3 months before surgery, and plasmapheresis was performed 2 days before surgery for cold agglutinin disease. Under mild hypothermia conditions, total arch replacement using the frozen elephant trunk technique was performed while maintaining cerebral and lower body perfusion. The postoperative course was uneventful. On postoperative day 42, the patient was discharged without any neurological deficits. Conclusions This case involving total arch replacement with mild hypothermia for an aortic arch aneurysm with cold agglutinin disease after rituximab treatment and plasmapheresis resulted in a successful outcome.

Abstract Background Transplant candidates on the waiting list are increasingly challenged by the lack of organs. Most of the organs can only be kept viable within very limited timeframes (e.g., mere 4–6 h for heart and lungs exposed to refrigeration temperatures ex vivo). Donation after circulatory death (DCD) using extracorporeal membrane oxygenation (ECMO) can significantly enlarge the donor pool, organ yield per donor, and shelf life. Nevertheless, clinical attempts to recover organs for transplantation after uncontrolled DCD are extremely complex and hardly reproducible. Therefore, as a preliminary strategy to fulfill this task, experimental protocols using feasible animal models are highly warranted. The primary aim of the study was to develop a model of ECMO-based cadaver organ recovery in mice. Our model mimics uncontrolled organ donation after an “out-of-hospital” sudden unexpected death with subsequent “in-hospital” cadaver management post-mortem. The secondary aim was to assess blood gas parameters, cardiac activity as well as overall organ state. The study protocol included post-mortem heparin–streptokinase administration 10 min after confirmed death induced by cervical dislocation under full anesthesia. After cannulation, veno-arterial ECMO (V–A ECMO) was started 1 h after death and continued for 2 h under mild hypothermic conditions followed by organ harvest. Pressure- and flow-controlled oxygenated blood-based reperfusion of a cadaver body was accompanied by blood gas analysis (BGA), electrocardiography, and histological evaluation of ischemia–reperfusion injury. For the first time, we designed and implemented, a not yet reported, miniaturized murine hemodialysis circuit for the treatment of severe hyperkalemia and metabolic acidosis post-mortem. Results BGA parameters confirmed profound ischemia typical for cadavers and incompatible with normal physiology, including extremely low blood pH, profound negative base excess, and enormously high levels of lactate. Two hours after ECMO implantation, blood pH values of a cadaver body restored from 130 to 41.7 ± 10.5 mmHg, sO2, base excess, and HCO3 were all elevated from below detection thresholds to 99.5 ± 0.6%, − 4 ± 6.2 and 22.0 ± 6.0 mmol/L, respectively (Student T test, p 20 to 10.5 ± 1.7 mmol/L) and hyperkalemia (from > 9 to 6.9 ± 1.0 mmol/L) was observed when hemodialysis was implemented. On balance, the first signs of regained heart activity appeared on average 10 min after ECMO initiation without cardioplegia or any inotropic and vasopressor support. This was followed by restoration of myocardial contractility with a heart rate of up to 200 beats per minute (bpm) as detected by an electrocardiogram (ECG). Histological examinations revealed no evidence of heart injury 3 h post-mortem, whereas shock-specific morphological changes relevant to acute death and consequent cardiac/circulatory arrest were observed in the lungs, liver, and kidney of both control and ECMO-treated cadaver mice. Conclusions Thus, our model represents a promising approach to facilitate studying perspectives of cadaveric multiorgan recovery for transplantation. Moreover, it opens new possibilities for cadaver organ treatment to extend and potentiate donation and, hence, contribute to solving the organ shortage dilemma.

Background: Cold agglutinin disease can lead to significant complications, especially for patients undergoing arch repair requiring hypothermic circulatory arrest. Rituximab and plasmapheresis are treatments for cold agglutinin disease. However, its use in patients with Stanford type A dissection has not been reported. Therefore, after consultation with hematologists, we used rituximab and plasmapheresis before mild hypothermic aortic arch surgery to maintain the body temperature above the thermal altitude. Case presentation: This report describes an 86-year-old male patient with acute type A aortic dissection who received outpatient treatment for rheumatoid arthritis and a 55-mm thoracic aortic aneurysm. The patient was scheduled to undergo urgent surgery for a type A intramural hematoma and progressive aortic aneurysm; however, laboratory test results indicated blood clotting and cold agglutinin. Consequently, urgent surgery was rescheduled. After consulting with hematologists, rituximab was initiated 3 months before surgery, and plasmapheresis was performed 2 days before surgery for cold agglutinin disease. Under mild hypothermia conditions, total arch replacement using the frozen elephant trunk technique was performed while maintaining cerebral and lower body perfusion. The postoperative course was uneventful. On postoperative day 42, the patient was discharged without any neurological deficits. Conclusions: This case involving total arch replacement with mild hypothermia for an aortic arch aneurysm with cold agglutinin disease after rituximab treatment and plasmapheresis resulted in a successful outcome. [ABSTRACT FROM AUTHOR]

Objective: We designed a simplified total arch reconstruction (s-TAR) technique which could be performed under mild hypothermia (30–32 °C) with distal aortic perfusion. This study aimed to compare its efficacy of organ protection with the conventional total arch reconstruction (c-TAR). Methods: We reviewed the clinical data of 195 patients who had ascending aortic aneurysm with extended aortic arch dilation and underwent simultaneous ascending aorta replacement and TAR procedure between January 2018 and December 2022 in our center. 105 received c-TAR under moderate hypothermia (25–28 °C) with circulatory arrest (c-TAR group); rest 90 received s-TAR under mild hypothermia (30–32 °C) with distal aortic perfusion (s-TAR group). Results: The s-TAR group demonstrated shorter CPB time, cross-clamp time and lower body circulatory arrest time compared with the c-TAR group. The 30-day mortality was 2.9% for the c-TAR group and 1.1% for the s-TAR group (P = 0.043). The mean duration of mechanical ventilation was shorter in the s-TAR group. Paraplegia was observed in 4 of 105 patients (3.8%) in the c-TAR group, while no such events were observed in the s-TAR group. The incidence of temporary neurologic dysfunction was significantly higher in the c-TAR group. The incidence of permanent neurologic dysfunction also showed a tendency to be higher in the c-TAR group, without statistical significance. Furthermore, the incidence of reoperation for bleeding were significantly lower in the s-TAR group. The rate of postoperative hepatic dysfunction and all grades of AKI was remarkably lower in the s-TAR group. The 3-year survival rate was 95.6% in the s-TAR group and 91.4% in the c-TAR group. Conclusions: s-TAR under mild hypothermia (30–32℃) with distal aortic perfusion is associated with lower mortality and morbidity, offering better neurological and visceral organ protection compared with c-TAR. [ABSTRACT FROM AUTHOR]

Cardiopulmonary bypass (CPB) provides cerebral oxygenation and blood flow (CBF) during neonatal congenital heart surgery, but the impacts of CPB on brain oxygen supply and metabolic demands are generally unknown. To elucidate this physiology, we used diffuse correlation spectroscopy and frequency-domain diffuse optical spectroscopy to continuously measure CBF, oxygen extraction fraction (OEF), and oxygen metabolism (CMRO2) in 27 neonatal swine before, during, and up to 24 h after CPB. Concurrently, we sampled cerebral microdialysis biomarkers of metabolic distress (lactate–pyruvate ratio) and injury (glycerol). We applied a novel theoretical approach to correct for hematocrit variation during optical quantification of CBF in vivo. Without correction, a mean (95% CI) +53% (42, 63) increase in hematocrit resulted in a physiologically improbable +58% (27, 90) increase in CMRO2 relative to baseline at CPB initiation; following correction, CMRO2 did not differ from baseline at this timepoint. After CPB initiation, OEF increased but CBF and CMRO2 decreased with CPB time; these temporal trends persisted for 0–8 h following CPB and coincided with a 48% (7, 90) elevation of glycerol. The temporal trends and glycerol elevation resolved by 8–24 h. The hematocrit correction improved quantification of cerebral physiologic trends that precede and coincide with neurological injury following CPB. [ABSTRACT FROM AUTHOR]

Background: Hypothermia is an effective method of reducing brain injury caused by a variety of neurological insults. It is aimed to elucidate whether a change in the expression of PERK‐mediated pathway proteins is an indicator of the neuroprotective effect of mild hypothermia after cerebral ischaemia/reperfusion. Methods: One hundred and ninety‐two male C57BL/6 mice were randomly divided into three groups: a sham group, a cerebral normothermic ischaemia/reperfusion (I/R) group and a cerebral hypothermic I/R group. A cerebral ischaemia model was established by ligating the bilateral common carotid artery for 15 min. Mice in the hypothermia group stayed in a cage that was set at 33°C, sprayed with a spray of 70% ethanol, and blown with two high‐speed fans. The state of neurons was assessed on micropreparations stained with haematoxylin–eosin and TUNEL. The expressions of GRP78, p‐perk, p‐eif2α, ATF4 and CHOP were measured by western blot analysis 6, 12, 24 and 72 h after reperfusion. Results: The number of surviving cells was significantly higher in the hypothermia group than in the group without hypothermia (p <.05). The GRP78 expression in the hypothermia group was statistically higher (p <.05) than in the ischaemia/reperfusion group. Optical densities of p‐perk, p‐eif2α and ATF4 in hippocampus CA1 neurons ischaemia were statistically significantly lower in the hypothermia group than in the ischaemia/reperfusion group (p <.05). The CHOP expression in the hypothermia group was statistically lower (p <.05) than in the ischaemia/reperfusion group. Conclusion: Mild hypothermia for 6 h promoted moderate neuroprotection by mediating the expression of GRP78, p‐PERK, p‐eIF2α, ATF4 and CHOP. [ABSTRACT FROM AUTHOR]

Simple Summary: This report describes a case of cor triatriatum dexter in which a persistent embryonic membrane within the right atrium obstructed venous blood inflow from the caudal vena cava. Several treatment options for dogs presenting with clinical signs related to cor triatriatum dexter, such as interventional approaches, cardiopulmonary bypass, or venous inflow occlusion, have been published in the veterinary literature. Each method has advantages and disadvantages; however, membranectomy via venous inflow occlusion is considered an effective and safe treatment compared with other methods, as it can be performed within a short period and reduces the risk of recurrence. To the best of our knowledge, this is the first case report documenting the surgical treatment of a cor triatriatum dexter in a dog using partial venous inflow occlusion under mild hypothermia. Cor triatriatum dexter (CTD) is an uncommon congenital cardiac anomaly in dogs. This case report describes successful membranectomy for CTD via partial venous inflow occlusion under mild hypothermia in a dog. A 7-month-old intact male mixed-breed dog weighing 20.5 kg presented with a history of abdominal distention, lethargy, and anorexia. Clinical examination, radiography, echocardiography, microbubble testing, and computed tomography revealed a remnant right atrium membrane obscuring the venous blood inflow from the vena cava. Considering the potential risk of re-stenosis following interventional treatment, curative resection involving surgical membranectomy via venous inflow occlusion was performed. By performing partial venous inflow occlusion under mild hypothermia (34.5 °C), sufficient time was obtained to explore the defect and resect the remnant membrane. The dog recovered without any complications, and the clinical signs were relieved. This case illustrates that partial venous inflow occlusion under mild hypothermia is feasible for achieving curative resection of cor triatriatum dexter in dogs. [ABSTRACT FROM AUTHOR]

Objective To investigate effects of mild hypothermia treatment on coagulation function and inflammatory factors in a swine model of extracorporeal cardiopulmonary resuscitation (ECPR) after cardiac arrest (CA). Methods Using random number table method, twelve Bama pigs were divided into the control group, the normal temperature group and the mild hypothermia group with four pigs in each group. CA model was established by right ventricular fibrillation in the normal temperature group and the mild hypothermia group, and then ECPR was performed by extracorporeal membrane oxygenation (ECMO). The target temperature of the normal temperature group was 37 ℃, and the mild hypothermia group was 34 ℃. Control group was only given conventional tube placement. Pigs were killed 24 hours later, and venous blood was taken to detect levels of prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen (FIB) and D-dimer antigen (D-D). Expression levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were detected by enzyme linked immunosorbent assay (ELISA). Results Compared with the control group, PT, APTT, TT, FIB, D-D and expression levels of TNF-α and IL-6 were significantly increased in the normal temperature group and the mild hypothermia group. Compared with the normal temperature group, the above indicators were decreased significantly in the mild hypothermia group (P＜0.05). Conclusion Mild hypothermia treatment can significantly improve coagulation function and reduce the release of inflammatory factors in a swine model of ECPR after CA, so as to alleviate the occurrence of ECPRrelated complications and inflammatory reactions. [ABSTRACT FROM AUTHOR]

Background: Transplant candidates on the waiting list are increasingly challenged by the lack of organs. Most of the organs can only be kept viable within very limited timeframes (e.g., mere 4–6 h for heart and lungs exposed to refrigeration temperatures ex vivo). Donation after circulatory death (DCD) using extracorporeal membrane oxygenation (ECMO) can significantly enlarge the donor pool, organ yield per donor, and shelf life. Nevertheless, clinical attempts to recover organs for transplantation after uncontrolled DCD are extremely complex and hardly reproducible. Therefore, as a preliminary strategy to fulfill this task, experimental protocols using feasible animal models are highly warranted. The primary aim of the study was to develop a model of ECMO-based cadaver organ recovery in mice. Our model mimics uncontrolled organ donation after an "out-of-hospital" sudden unexpected death with subsequent "in-hospital" cadaver management post-mortem. The secondary aim was to assess blood gas parameters, cardiac activity as well as overall organ state. The study protocol included post-mortem heparin–streptokinase administration 10 min after confirmed death induced by cervical dislocation under full anesthesia. After cannulation, veno-arterial ECMO (V–A ECMO) was started 1 h after death and continued for 2 h under mild hypothermic conditions followed by organ harvest. Pressure- and flow-controlled oxygenated blood-based reperfusion of a cadaver body was accompanied by blood gas analysis (BGA), electrocardiography, and histological evaluation of ischemia–reperfusion injury. For the first time, we designed and implemented, a not yet reported, miniaturized murine hemodialysis circuit for the treatment of severe hyperkalemia and metabolic acidosis post-mortem. Results: BGA parameters confirmed profound ischemia typical for cadavers and incompatible with normal physiology, including extremely low blood pH, profound negative base excess, and enormously high levels of lactate. Two hours after ECMO implantation, blood pH values of a cadaver body restored from < 6.5 to 7.3 ± 0.05, pCO2 was lowered from > 130 to 41.7 ± 10.5 mmHg, sO2, base excess, and HCO3 were all elevated from below detection thresholds to 99.5 ± 0.6%, − 4 ± 6.2 and 22.0 ± 6.0 mmol/L, respectively (Student T test, p < 0.05). A substantial decrease in hyperlactatemia (from > 20 to 10.5 ± 1.7 mmol/L) and hyperkalemia (from > 9 to 6.9 ± 1.0 mmol/L) was observed when hemodialysis was implemented. On balance, the first signs of regained heart activity appeared on average 10 min after ECMO initiation without cardioplegia or any inotropic and vasopressor support. This was followed by restoration of myocardial contractility with a heart rate of up to 200 beats per minute (bpm) as detected by an electrocardiogram (ECG). Histological examinations revealed no evidence of heart injury 3 h post-mortem, whereas shock-specific morphological changes relevant to acute death and consequent cardiac/circulatory arrest were observed in the lungs, liver, and kidney of both control and ECMO-treated cadaver mice. Conclusions: Thus, our model represents a promising approach to facilitate studying perspectives of cadaveric multiorgan recovery for transplantation. Moreover, it opens new possibilities for cadaver organ treatment to extend and potentiate donation and, hence, contribute to solving the organ shortage dilemma. [ABSTRACT FROM AUTHOR]

After restoration of spontaneous circulation (ROSC) following cardiac arrest, complements can be activated and excessive autophagy can contribute to the brain ischemia–reperfusion (I/R) injury. Mild hypothermia (HT) protects against brain I/R injury after ROSC, but the mechanisms have not been fully elucidated. Here, we found that HT significantly inhibited the increases in serum NSE, S100β, and C5a, as well as neurologic deficit scores, TUNEL-positive cells, and autophagic vacuoles in the pig brain cortex after ROSC. The C5a receptor 1 (C5aR1) mRNA and the C5a, C5aR1, Beclin 1, LC3-II, and cleaved caspase-3 proteins were significantly increased, but the P62 protein and the PI3K/Akt/mTOR pathway-related proteins were significantly reduced in pigs after ROSC or neuronal oxygen–glucose deprivation/reoxygenation. HT could significantly attenuate the above changes in NT-treated neurons. Furthermore, C5a treatment induced autophagy and apoptosis and reduced the PI3K/Akt/mTOR pathway-related proteins in cultured neurons, which could be reversed by C5aR1 antagonist PMX205. Our findings demonstrated that C5a could bind to C5aR1 to induce neuronal autophagy during the brain I/R injury, which was associated with the inhibited PI3K/Akt/mTOR pathway. HT could inhibit C5a-induced neuronal autophagy by regulating the C5a–C5aR1 interaction and the PI3K/Akt/mTOR pathway, which might be one of the neuroprotective mechanisms underlying I/R injury. The C5a receptor 1 (C5aR1) mRNA and the C5a, C5aR1, Beclin 1, LC3-II, and cleaved caspase-3 proteins were significantly increased, but the P62 protein and the PI3K/Akt/mTOR pathway-related proteins were significantly reduced in pigs after ROSC or neuronal oxygen–glucose deprivation/reoxygenation. Mild hypothermia (HT) could significantly attenuate the above changes in NT-treated neurons. Furthermore, C5a treatment induced autophagy and apoptosis and reduced the PI3K/Akt/mTOR pathway-related proteins in cultured neurons, which could be reversed by C5aR1 antagonist PMX205. Proposed mechanism by which HT protects against brain I/R injury by repressing C5a–C5aR1-induced excessive autophagy. Complement activation in response to brain I/R injury generates C5a that can interact with C5aR1 to inactivate mTOR, probably through the PI3K-AKT pathway, which can finally lead to autophagy activation. The excessively activated autophagy ultimately contributes to cell apoptosis and brain injury. HT may alleviate complement activation and then reduce C5a-induced autophagy to protect against brain I/R injury. HT, mild hypothermia; I/R, ischemia reperfusion. [ABSTRACT FROM AUTHOR]

The main aim of this study was to explore the mechanism of mild hypothermia (MH) plus methylprednisolone (MPS) was in spinal cord injury (SCI) therapy. Application of modified Allen's method was for injury of the spinal cord (T10) in rats and treated SCI was with MH or/and MPS immediately. Conduction of Basso-Beattie-Bresnahan (BBB) scores was on all rats at different time points after surgery. Subsequently harvest of the serum and the spinal cord tissues was behind euthanasia of rats. Detection of biochemical indicators, observation of cell apoptosis, and determination of Bax, Bcl-2, p38 MAPK and Smad2 were clarified. We found that MH and MH+MPS could effectively reduce apoptotic cells, dramatically minify TNF-a, IL-6, IL-8, MDA and Bax contents (P < 0.01) and elevate GSH-Px and Bcl-2 level (P < 0.01). Additionally, the P38AMPK/Smad2 pathway proteins (phosphorylated p -P38MAPK and Samd2) were notably higher in the model versus the control and the sham, while MH and MH+MPS could patently down-regulate p-P38MAPK and Samd2 protein levels. To conclude, MH+MPS is available to refrain the activation of P38AMPK/Smad2 signal, hence repressing cell apoptosis after SCI, reducing secondary SCI, and benefiting the recovery of nerve function. [ABSTRACT FROM AUTHOR]

Background: Traumatic brain injury (TBI) is associated with a range of neural changes. A comprehensive understanding of the injury-induced lysine acetyltransferase 6A (KAT6A) response, particularly the temporal profile of biochemical alterations, is crucial to design effective therapeutic interventions. Methods: Experiments were performed in male Sprague-Dawley rats. The influence of post-traumatic hypothermia (32°C) or hyperthermia (39°C) on the temporal and regional expression profiles of KAT6A was assessed after moderate or severe TBI. qPCR and western blotting were used to determine the expression of KAT6A in different groups. Results: In the ipsilateral and contralateral hemispheres, significantly lower protein and mRNA expression of KAT6A was found after TBI than sham injury. Moreover, two expression minima of KAT6A were observed in the cortex and hippocampus of the ipsilateral hemisphere. A decrease in injury severity was associated with lower levels of KAT6A mRNA at 12 h and protein at 24 h, but KAT6A mRNA at 48 h and protein at 72 h had alterations. Compared with normothermia and hyperthermia, post-traumatic hypothermia intensified the decrease in KAT6A at both the mRNA and protein levels. In contrast, hyperthermia, as compared with normothermia, did not significantly affect the levels of KAT6A mRNA at 12 h and protein at 24 h, but triggered a significant increase in levels of KAT6A mRNA at 24 h and protein at 72 h. Furthermore, an overall upregulation of KAT6A after TBI was associated with greater injury severity in a time-dependent manner. Conclusions: Post-traumatic hypothermia plays a key role in the regulation of KAT6A expression and thus may at least partially explain the phenotype of post-traumatic temperature in secondary injury after TBI.

The brain ischemia/reperfusion (I/R) injury has a great impact on human life and property safety. As far as we know, mild hypothermia (MH) is an effective measure to reduce neuronal injury after I/R. However, the precise mechanism is not extremely clear. The purpose of this study was to investigate whether mild therapeutic hypothermia can play a protective role in nerve cells dealing with brain I/R injury and explore its specific mechanism in vitro. A flow cytometer, cell counting kit-8 (CCK-8) assay and lactate dehydrogenase (LDH) release assay were performed to detect apoptotic rate of cells, cell viability and cytotoxicity, respectively, reactive oxygen species (ROS) assay kit, JC-1 fluorescent methods, immunofluorescence and western blot were used to explore ROS, mitochondrial transmembrane potential (Δψm), mitochondrial permeability transition pore (MPTP) and protein expression, respectively. The result indicated that the cell activity was decreased, while the cytotoxicity and apoptosis rate were increased after treating with oxygen–glucose deprivation/reperfusion (OGD/R) in PC12 cells. However, MH could antagonize this phenomenon. Interestingly, treating with OGD/R increased the release of ROS and the transfer of Cytochrome C (Cyt-C) from mitochondria to cytoplasm. In addition, it up-regulated the expression of γH2AX, Bax and Clv-caspase3, down-regulated the expression of PCNA, Rad51 and Bcl-2, and inhibited the function of mitochondria in PC12 cells. Excitingly, the opposite trend was observed after MH treatment. Therefore, our results suggest that MH protects PC12 cells against OGD/R-induced injury with the mechanism of inhibiting cell apoptosis by reducing ROS production, improving mitochondrial function, reducing DNA damage, and enhancing DNA repair. [ABSTRACT FROM AUTHOR]

As a subtype of stroke, subarachnoid hemorrhage (SAH) has a notoriously high rate of disability and mortality owing to the lack of effective intervention. Early brain injury (EBI) is the main factor responsible for the dismal prognosis of SAH patients. The current study intends to explore the molecular mechanism underlying the effect of MH on EBI after SAH from a novel perspective of pyroptosis, a highly specific inflammatory programmed cell death, in the SAH rat model. Sprague-Dawley (SD) rats were divided into different groups in accordance with various treatments. In the treatment group, the rats underwent mild hypothermia for 4 h after modeling; in the inhibitor group, Compound C (an inhibitor of AMPK) was administered intravenous injections (i.v.) 30 min before modeling. Neurological score, neuronal death, brain water content, inflammatory reaction, and expression levels of pyroptosis-related proteins were evaluated in the rats. Our results indicate that the MH therapy significantly increased the neurological score and assuaged brain edema, neuronal injury, and inflammatory reaction induced by SAH. Meanwhile, MH therapy upregulated the level of AMPK phosphorylation whereas downregulated the protein expressions of NLRP3, ASC, cleaved caspase-1, GSDMD, IL-1β, and IL-18. The reversed effect of MH therapy by Compound C concretely indicated that MH therapy inhibited pyroptosis through an AMPK-dependent pathway. Our study also found that MH therapy potently curbed the increasing trend of brain temperature (BT), rectal temperature (RT), and ICP after SAH. Taken together, our data indicate that the neuroprotective effects of MH therapy were manifested by inhibiting pyroptosis via the AMPK/NLRP3 inflammasome pathway, which may serve as a promising therapy for the intervention of SAH. • Mild hypothermia (MH) plays a neuroprotective role in subarachnoid hemorrhage (SAH). • MH regulates inflammation, brain and rectal temperature, and ICP after SAH. • MH reduces SAH-induced early brain injury by suppressing pyroptosis. • MH exerts its neuroprotective by inhibiting pyroptosis via the AMPK/NLRP3 pathway. [ABSTRACT FROM AUTHOR]

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Multiple organ failure secondary to severe sepsis leads to increased morbidity and mortality and is often accompanied by inflammation and immune system dysfunction. Mild hypothermia has been shown to have anti-inflammatory properties, but whether it can exert a protective effect in cases of multiple organ failure remains unclear. Thus, in this study, we investigated the protective effect of mild hypothermia on septic multiple organ failure and the underlying mechanism for this effect. Sepsis was induced through the cecal ligation and puncture (CLP) method. Rats were then housed at normal (36–38°C) or mild hypothermic (32–34°C) temperature for 10 h. CLP-induced effects on inflammatory cytokines and biochemical markers in serum were reversed by mild hypothermia. The pathological injury score and the expressions of pyroptosis markers, including TLR4, MyD88 and NF-κB signaling molecules, showed a similar trend. Moreover, 3 d survival of CLP rats was improved by mild hypothermia. Mild hypothermia alleviated CLP-induced organ failure and the downstream effects on pyroptosis, probably through the TLR4/NF-κB/NLRP3 signaling pathway. [ABSTRACT FROM AUTHOR]

Liver ischemia reperfusion injury (IRI) is a serious complication of certain liver surgeries, and it is difficult to prevent. As a potential drug-free treatment, mild hypothermia has been shown to promote positive outcomes in patients with IRI. However, the protective mechanism remains unclear. We established in vivo and in vitro models of hepatic ischemia reperfusion (IR) and mild hypothermia pretreatment. Hepatocytes were transfected with RNA-binding motif protein 3 (RBM3) overexpression plasmids, and IR was performed. Cell, culture medium, blood and tissue samples were collected to assess hepatic injury, oxidative stress, apoptosis and changes in RBM3 expression in the liver. Upregulation of RBM3 expression by mild hypothermia reduced the aminotransferase release, liver tissue injury and mitochondrial injury induced by liver IR. Hepatic IR-induced p38 and c-Jun N-terminal kinase (JNK) signaling pathway activation, oxidative stress injury and apoptosis could be greatly reversed by mild hypothermia. Overexpression of RBM3 mimicked the hepatoprotective effect of mild hypothermia. Mild hypothermia protects the liver from ischemia reperfusion-induced p38 and JNK signaling pathway activation, oxidative stress injury and apoptosis through the upregulation of RBM3 expression. [ABSTRACT FROM AUTHOR]

Cardiopulmonary bypass (CPB) provides cerebral oxygenation and blood flow (CBF) during neonatal congenital heart surgery, but the impacts of CPB on brain oxygen supply and metabolic demands are generally unknown. To elucidate this physiology, we used diffuse correlation spectroscopy and frequency-domain diffuse optical spectroscopy to continuously measure CBF, oxygen extraction fraction (OEF), and oxygen metabolism (CMRO2) in 27 neonatal swine before, during, and up to 24 h after CPB. Concurrently, we sampled cerebral microdialysis biomarkers of metabolic distress (lactate–pyruvate ratio) and injury (glycerol). We applied a novel theoretical approach to correct for hematocrit variation during optical quantification of CBF in vivo. Without correction, a mean (95% CI) +53% (42, 63) increase in hematocrit resulted in a physiologically improbable +58% (27, 90) increase in CMRO2 relative to baseline at CPB initiation; following correction, CMRO2 did not differ from baseline at this timepoint. After CPB initiation, OEF increased but CBF and CMRO2 decreased with CPB time; these temporal trends persisted for 0–8 h following CPB and coincided with a 48% (7, 90) elevation of glycerol. The temporal trends and glycerol elevation resolved by 8–24 h. The hematocrit correction improved quantification of cerebral physiologic trends that precede and coincide with neurological injury following CPB.

Cor triatriatum dexter (CTD) is an uncommon congenital cardiac anomaly in dogs. This case report describes successful membranectomy for CTD via partial venous inflow occlusion under mild hypothermia in a dog. A 7-month-old intact male mixed-breed dog weighing 20.5 kg presented with a history of abdominal distention, lethargy, and anorexia. Clinical examination, radiography, echocardiography, microbubble testing, and computed tomography revealed a remnant right atrium membrane obscuring the venous blood inflow from the vena cava. Considering the potential risk of re-stenosis following interventional treatment, curative resection involving surgical membranectomy via venous inflow occlusion was performed. By performing partial venous inflow occlusion under mild hypothermia (34.5 °C), sufficient time was obtained to explore the defect and resect the remnant membrane. The dog recovered without any complications, and the clinical signs were relieved. This case illustrates that partial venous inflow occlusion under mild hypothermia is feasible for achieving curative resection of cor triatriatum dexter in dogs.

ObjectiveErythropoietin (EPO) seems to have a good application prospect both in experimental models and patients with hypoxic ischaemic encephalopathy (HIE). Data regarding the effect of EPO on death or neurodevelopmental impairment are conflicting.MethodsA search was conducted by two investigators involved in this research in PubMed, Embase, and Cochrane databases for studies in English, in Wanfang, VIP, and Cnki databases for Chinese studies (all last launched on 2022/08/31). Ultimately, we identified 11 original studies, including the EPO group (n = 636) and the control group (n = 626). Odds ratio (OR) and weighted mean difference were calculated using a random effects or fixed effects model, depending on the data type and heterogeneity of the included studies.Results1. The comparison of effectiveness of EPO treatment on HIE: (1) With respect to death, data showed no significant difference between EPO and control groups (OR = 0.97, 95% CI, 0.66–1.43; P = 0.88); Considering the additional effect of mild hypothermia treatment (MHT), no significant difference was found between EPO + MHT/control + MHT groups either (OR = 1.09, 95% CI, 0.69–1.73; P = 0.72); With respect to the interference of different routes of medication administration, Meta-analysis further showed no difference between intravenous EPO/control groups (OR = 1.13, 95% CI, 0.70–1.82; P = 0.62). (2) With respect to cerebral palsy, the analysis showed no significant difference (OR = 0.76, 95% CI, 0.50–1.15; P = 0.20); Considering the effect of MHT and routes of medication administration, data further showed no difference between EPO group and control group (OR = 1.26, 95% CI, 0.73–2.19; P = 0.41). (3) Regarding epilepsy, no significant difference was found (OR = 0.49, 95% CI, 0.20–1.19; P = 0.12). MR abnormality was less common in EPO group (OR = 0.39, 95% CI, 0.19–0.79; P = 0.008). 2. The comparison of possible adverse events of EPO: EPO treatment would not increase the risk of thrombocytopenia, hypotension, and hepatic and kidney injury.ConclusionsThis meta-analysis showed that EPO treatment is not beneficial for reducing death and improving neurological impairment, though it would not increase the risk of adverse events.

To assess the effectiveness and molecular mechanisms of mild hypothermia and remote ischemic postconditioning (RIPC) in patients with acute ischemic stroke (AIS) who have undergone thrombolysis therapy. A total of 58 AIS patients who received recombinant tissue plasmin activator (rt-PA) intravenous thrombolysis were included in this prospective study. Participants were randomly allocated to the experimental group (rt-PA intravenous thrombolysis plus mild hypothermic ice cap plus remote ischemic brain protection, n  = 30) and the control group (rt-PA intravenous thrombolysis plus 0.9% saline, n  = 28). The RIPC was performed for 14 consecutive days on both upper limb arteries spaced 2 minutes apart. Five cycles of ischemia-reperfusion were performed sequentially (2-2, 3-3, 4-4, 5-5, 5-0 minutes, respectively). The outcome measures of the National Institute of Health stroke scale (NIHSS) score, volume of cerebral infarction, serum levels of superoxide dismutase (SOD), malondialdehyde (MDA), interleukin-1β, tumor necrosis factor α, nuclear factors kappa B (NF-κB), and NOD-1ike receptor pyrin 3 (NLRP3) were evaluated at different time points after treatment. Similarly, the 90-day modified Rankin Scale (mRS) scores were compared between the two groups. After treatment, the NIHSS score, MDA, NF-κB, and NLRP3 levels in the experimental group were significantly lower than those in the control group ( p  < 0.05). While the SOD in the experimental group was significantly higher than in the control group ( p  < 0.05), the NIHSS scores decreased within groups (all p  < 0.05) in both experimental and control groups. The 90-day mRS score (0-2 points) in the experimental group was significantly higher than that in the control group (73.33% vs. 53.57%, p  < 0.05) and no significant differences were observed in the safety indices between the two groups (all p  > 0.05). Our study shows that combining mild hypothermia and RIPC has a positive effect on brain protection and can significantly reduce the oxidative stress and associated outburst of inflammatory response. The Clinical Trial Registration number is ChiCTR2300073136.

Objective: Temperature during cardiopulmonary bypass (CPB) for cardiac surgery has been controversial. The aim of the current study is to compare the outcomes for patients with mild hypothermia versus normothermic CPB temperatures. Methods: All patients who underwent cardiac surgery with CPB and temperatures ≥32°C from 2011 to 2018 were included, which consisted of mild hypothermia (32°C-35°C) and normothermia (>35°C) cohorts. Propensity matching (1:1) was performed for risk adjustment. Primary outcomes included operative and long-term survival. Secondary outcomes included postoperative complications. Results: A total of 6525 patients comprised 2 cohorts: mild hypothermia (32°C-35°C; n = 3148) versus normothermia (>35°C; n = 3377). Following adjustment for surgeon preference, there were 1601 propensity-matched patients who had similar baseline characteristics (standard mean difference, ≤0.10), including CPB time, crossclamp time, and intra-aortic balloon pump placement. Kaplan-Meier analysis showed no difference in long-term survival (82.6% vs 81.6%; P = .81). Over a median follow-up of 4.4 years, there were no differences in overall mortality (18.1% vs 18.1%; P = 1.1) or readmission (50.3% vs 48.3%; P = .2). Acute renal failure (3.7% vs 2.4%; P = .03) and intensive care unit hours (46.5 vs 45.1; P = .04) were significantly higher with hypothermia. There was no difference between cohorts for postoperative stroke (2.0% vs 2.0%; P = 1.0), reoperation (5.9% vs 6.0%; P = .9), or operative intra-aortic balloon pump placement (1.7% vs 1.8%; P = .9). Conclusions: Patients with mild hypothermia during CPB had increased postoperative renal failure and length of intensive care unit stay. Although there was no difference in long-term survival, mild hypothermia does not appear to offer patients appreciable benefits, compared with normothermia.

Background: Traumatic brain injury (TBI) is the leading cause of death and disability worldwide. Mild hypothermia (32–35°C) has been found to show neuroprotective effects against TBI. However, the specific mechanism is still elusive. In the current study, we explored the relationship between oxidative damage after TBI and treatment with mild hypothermia as well as the underlying molecular mechanisms. Methods: We used the closed cortex injury model to perform the brain injury and a temperature monitoring and control system to regulate the body temperature of mice after injury. Adult male C57BL/6 mice were adopted in this study and divided into four experimental groups. Tissue samples were harvested 24 h after injury. Results: First, our results showed that treatment with mild hypothermia significantly improved neurobehavioral dysfunction and alleviated brain edema after TBI. Moreover, treatment with mild hypothermia enhanced the activity of the antioxidant enzymes superoxide dismutase and glutathione peroxidase and reduced the accumulation of lipid peroxidation malondialdehyde. Importantly, the expression and activation of the nuclear factor erythroid 2‐related factor 2‐antioxidant response element (Nrf2‐ARE) pathway were upregulated by mild hypothermia after TBI. Finally, treatment with hypothermia significantly decreased the cell apoptosis induced by TBI. Conclusion: Our results showed that the protective effects of mild hypothermia after TBI may be achieved by the upregulation of the Nrf2‐ARE pathway and revealed Nrf2 as a potentially important target to improve the prognosis of TBI. [ABSTRACT FROM AUTHOR]

Abstract Background Traumatic brain injury (TBI) is the leading cause of death and disability worldwide. Mild hypothermia (32–35°C) has been found to show neuroprotective effects against TBI. However, the specific mechanism is still elusive. In the current study, we explored the relationship between oxidative damage after TBI and treatment with mild hypothermia as well as the underlying molecular mechanisms. Methods We used the closed cortex injury model to perform the brain injury and a temperature monitoring and control system to regulate the body temperature of mice after injury. Adult male C57BL/6 mice were adopted in this study and divided into four experimental groups. Tissue samples were harvested 24 h after injury. Results First, our results showed that treatment with mild hypothermia significantly improved neurobehavioral dysfunction and alleviated brain edema after TBI. Moreover, treatment with mild hypothermia enhanced the activity of the antioxidant enzymes superoxide dismutase and glutathione peroxidase and reduced the accumulation of lipid peroxidation malondialdehyde. Importantly, the expression and activation of the nuclear factor erythroid 2‐related factor 2‐antioxidant response element (Nrf2‐ARE) pathway were upregulated by mild hypothermia after TBI. Finally, treatment with hypothermia significantly decreased the cell apoptosis induced by TBI. Conclusion Our results showed that the protective effects of mild hypothermia after TBI may be achieved by the upregulation of the Nrf2‐ARE pathway and revealed Nrf2 as a potentially important target to improve the prognosis of TBI.

To explore the mechanism regarding the regulation of spinal cord ischemia (SCI) in rats by mild hypothermia. A SCI rat model was established through aorta occlusion, and in some cases, the rats were intervened with mild hypothermia, after which motor function, microglia activation, and M1/M2 polarization in rats were measured. Also, the expression of inflammatory cytokines (IL-1β, IL-6 and TNF-α) and neuronal apoptosis were examined. Lipopolysaccharide (LPS)-induced M1 microglia and IL-4-induced M2 microglia were intrathecally injected into rats to evaluate the effect of microglial polarization on SCI. In in vitro experiments, primary microglial cells were treated under hypothermic condition, in which M1/M2 polarization and microglia apoptosis, the levels of iNOS, CD86, CD206, Arg-1 and inflammatory cytokines were assessed. Western blot analysis detected the activation of the TLR4/NF-κB pathway to investigate the role of this pathway in M1/M2 polarization. SCI treatment impaired motor function, induced higher M1 microglia proportion, and increased the levels of pro-inflammatory cytokines in rats, and mild hypothermic treatment attenuated these trends. Moreover, injection of M1 microglia increased M1 microglia proportion and increased the levels of pro-inflammatory cytokines, while injection of M2 microglia induced the reverse results, i.e. decreased M1 microglia proportion and reduced pro-inflammatory cytokine levels. In LPS-induced microglial cells, mild hypothermia treatment increased M2 microglia proportion and decreased pro-inflammatory cytokine levels, relative to normothermia. Mild hypothermia inactivated the TLR4/NF-κB pathway in LPS-treated microglia. TLR4 overexpression reversed the function of mild hypothermia in LPS-stimulated microglia, and under normal condition, TLR4/NF-κB pathway suppressed microglial M2 polarization. Mild hypothermia inhibits TLR4/NF-κB pathway and promotes microglial M2 polarization, thus attenuating SCI-induced injury and inflammation. [ABSTRACT FROM AUTHOR]

Background: Sphingomyelin, composed of ceramide (CER), sphingosine (Sph), and sphingosine-1-phosphate (S1P), is an essential structural component of cellular membranes and plays an important role in the signal transduction regulating cell proliferation, differentiation, and apoptosis. CER is mainly metabolized to Sph, and under the action of sphingosine kinases (SphKs), Sph produces S1P, which can be converted back to Sph by S1P phosphatase. It is suggested that the fate of cells is controlled partly by the interconversion of CER and intracellular S1P. SphK2 is considered the main kinase of S1P synthesis in the central nervous system. The objective of this study was to explore the hypothesis that SphK2 and sphingomyelin metabolism participated in the process of cell apoptosis and the protection of mild hypothermia. Methods: Rat brain microvascular endothelial cells were divided into groups for intervention of SphK2 inhibitor, SphK2 small interfering RNA (SiRNA) transfection, ischemia–reperfusion, and mild hypothermia. After interventions, cell apoptosis was detected by 4,6-diamino-2-phenyl indole (DAPI) and flow cytometry, the expression of apoptosis-related protein was detected by Western Blot, and SphK2 enzyme activity and the content of sphingomyelin were determined. Results: ABC294640 and transfection of SphK2 SiRNA could increase apoptosis, accompanied by the increase of the expression of proapoptotic genes Caspase3 and Bax and the decrease of the expression of BCL-2. This effect could be partially reversed with mild hypothermia. Ischemia–reperfusion injury, transfection of SphK2 SiRNA, and the addition of ABC294640 could significantly inhibit the activity of SphK2, accompanied by the increase of CERs and the decrease of S1P. Mild hypothermia could reverse the changes of sphingolipids but have no significant effect on the activity of sphk2. Conclusions: Mild hypothermia can inhibit the occurrence of apoptosis and reverse the changes of apoptosis-related genes and sphingomyelin content induced by ischemia–reperfusion injury, but the effect on sphk2 enzyme activity was not significant. [ABSTRACT FROM AUTHOR]

Oxidative stress injury (OSI) is involved in brain injury induced by cardiac arrest (CA)/cardiopulmonary resuscitation (CPR), and endoplasmic reticulum stress (ERS) is closely related to OSI. Mild hypothermia (MT) has been used to treat different kinds of brain injury but the mechanism remains unclear. Therefore, this study aimed to examine the effects of MT on OSI in a rat model of CA/CPR and determine the relationship between MT and ERS. The rats were divided into the sham, non-hypothermia (NT), and MT groups, which were then each divided into two subgroups consisting of rats that were sacrificed at 4.5 h and 24 h after the return of spontaneous circulation, respectively (NT-4.5, NT-24, MT-4.5, and MT-24 subgroups) (n = 6). A CA/CPR model was established by asphyxiation in the NT and MT groups, and MT was administered to rats in the MT group. Roughly 73% (24/33) of the rats survived until the end of the study. Compared with the sham group, the neurological deficit score (NDS) decreased, and the OSI, apoptosis, water content increased after model establishment (p lower than 0.05). Compared with those in the NT-4.5 and NT-24 groups, rats in the MT-4.5 and MT-24 groups showed improved NDS (65.3 ± 5.1 vs. 52.8 ± 4.7; 59.7 ± 6.0 vs. 50.5 ± 5.4), lower MDA activity (4.7 ± 0.3 vs. 6.5 ± 0.6; 5.1 ± 0.4 vs. 7.7 ± 0.6) (nmol mg-1 protein), higher SOD (84.7 ± 5.2 vs. 67.4 ± 5.8; 73.9 ± 6.4 vs. 55.8 ± 4.1) (U mg-1 protein) and CAT activities (83.1 ± 6.9 vs. 77.2 ± 6.5; 71.9 ± 3.6 vs. 62.7 ± 4.9) (U mg-1 protein), lower water content (79.2 ± 1.1% vs. 80.6 ± 0.8%; 81.0 ± 0.9% vs. 83.7 ± 1.7%), and lower expression of the ERS-related proteins GRP78, CHOP, caspase-12, and cleaved-caspase-3 (p lower than 0.05). The results also showed that after the MT was stopped, the effects were maintained for a period of time. In conclusion, MT protected against brain injury induced by CA/CPR by decreasing OSI by inhibiting of ERS.

Introduction: We studied field rewarming using a typical winter sleeping bag versus two heated hypothermia wrap systems in a semi-realistic lab simulation., Methods: 10 participants (8 M, 2 F) were cooled to 36.1°C core temperature through 10.5-11.5°C water immersion, then performed 60 min of passive rewarming in 0°C air. The rewarming methods tested were: 1) a -9°C rated mummy-style Sleeping Bag; 2) Doctor Down Rescue Wrap; and 3) Thermal Yielding Vascular Airway Capsule (TYVAC) system; the latter two methods included vapor barriers and two heating pads. Rectal and skin temperatures, along with metabolic heat production calculated via indirect calorimetry, were measured throughout rewarming., Results: One male participant was removed from analysis due to lack of sufficient cooling. Rectal temperature decreased in the remaining participants by ∼1.1-1.2°C to 36.1°C during the initial immersion phase. Over the 60 min of rewarming, rectal temperature changes were Δ0.0 ± 0.6°C in a sleeping bag, Δ+0.2 ± 0.3°C in Doctor Down, and Δ+0.2 ± 0.3°C in TYVAC, with no significant differences across methods. Mean skin temperatures, metabolic heat production, and perceptual measures were also similar across methods with no method×time interactions., Conclusions: After 60 min of passive rewarming in cold conditions, all three rewarming methods were able to stall continued core cooling to levels at or slightly above post-immersion temperatures. With no differences in any physiological measures, it appears that all three rewarming methods are equally viable options for wilderness responders, and the choice should come down to environmetal conditions, availability, convenience, and ergonomics rather than rewarming efficacy.

• Mild hypothermia reduced the activation of microglia activation in ISCI rats. • Mild hypothermia enhanced the autophagy in activated microglia. • Rapamycin inhibited OGD induced microglia activation. Delayed paralysis occurs within some patients suffered from ischemic spinal cord injury (ISCI) due to the aorta occlusion during the repair surgery of thoracic and thoracoabdominal aortic aneurysms. Although mild hypothermia has been reported to improve ISCI and prolong the tolerance of rats to ISCI without inducing immediate paralysis, the mechanism remains unclear. Herein, the study revealed that the mild hypothermia treatment indeed partially improved the ISCI in rats caused by cross-clamping at the descending aorta. ISCI induced the excessive activation of microglia and moderate autophagy in the spinal cord tissues of rats, while mild hypothermia significantly induced autophagy and reversed the excessive activation of microglia in the spinal cord tissues of rats. In OGD-stimulated mouse microglia BV-2 cells, the excessive activation of microglia and moderate autophagy were also observed; in the rapamycin-treated OGD model in BV-2 cells, autophagy was significantly enhanced whereas the excessive activation of microglia was reversed. In both in vivo ISCI model in rats and in vitro OGD model in BV-2 cells, the PI3K/AKT/mTOR pathway showed to be inhibited, whereas the PI3K/AKT/mTOR pathway was further inhibited by mild hypothermia in ISCI rats or rapamycin treatment in OGD-stimulated BV-2 cells. In conclusion, enhanced autophagy might be the mechanism of inhibited microglia activation by hypothermia treatment in ISCI rats and by rapamycin treatment in OGD-stimulated BV-2 cells. Autophagy could be enhanced through inhibiting the PI3K/AKT/mTOR pathway. [ABSTRACT FROM AUTHOR]

BackgroundTotal arch replacement (TAR) with Frozen elephant trunk (FET) treatment of acute DeBakey type I aortic dissection (ADIAD) is complicated, carries a high complication/mortality risk and remains controversial on the optimal hypothermic level, cerebral perfusion and visceral organ protection strategy. We developed a new strategy named “Brain-Heart-first” in which the surgical procedures and the management of cardiac perfusion/cerebral protection during Cardiopulmonary bypass (CPB) were redesigned, and TAR with FET technique can be performed under mild hypothermia with satisfactory outcomes.ObjectiveOur aims were to describe a new surgical strategy under mild hypothermia (≥30°C) for the treatment of ADIAD and to report the operative outcomes of 215 patients.MethodsWe conducted a retrospective analysis of 215 consecutive cases of ADIAD treated with our new strategy.ResultsThe durations of CPB, aortic cross-clamping, antegrade cerebral perfusion, operation, mechanical ventilation support, and Intensive Care Unit stay were 139.7 ± 52.3 min, 55.6 ± 27.4 min, 14.1 ± 3.1 min, 6.0 ± 1.7 h, 40.0 h and 4.0 d, respectively. The 30-day mortality was 9.8%, with cerebral stroke occurring in nine patients (4.2%), paraplegia in one patient (0.5%) and postoperative renal injury requiring dialysis in 21 patients (9.8%). The blood transfusion of red blood cells and fresh frozen plasma during surgery and the first 24 h after surgery was 4.0 u and 200.0 ml, respectively.ConclusionsThe Brain-Heart-first strategy can be widely used with low technical and resource requirements and provides a safe alternative for conventional TAR with FET technique in ADIAD patients with satisfactory operative results.

Abstract Background Aortic arch surgery remains the only viable life-saving treatment for aortic arch disease. However, the necessity for cessation of systemic blood flow with hypothermic cardiac arrest carries substantial risk of morbidity and mortality, including poor neurological outcomes and kidney failure. While uncontrolled studies have suggested the safety of operating at warmer temperatures, significant variables remain un-investigated, supporting the need for a randomized clinical trial (RCT) to produce evidence-based guidelines for perfusion strategies in aortic surgery. This study proposes a multi-center RCT in order to compare outcomes of warmer hypothermic strategies during aortic hemiarch surgery on a composite endpoint of neurologic and acute kidney injury (AKI). Methods/design This is a prospective multi-center, single-blind two-arm RCT comparing mild (32 °C) versus moderate (26 °C) hypothermic cardiac arrest in patients (n = 282) undergoing hemiarch surgery with antegrade cerebral perfusion (ACP). The primary endpoint is a composite of neurological injury (incidence of transient ischemic attack and/or stroke) and Kidney Disease Improving Global Outcomes (KDIGO) stage 1 or higher AKI. Secondary outcomes include death, cardiopulmonary bypass time, bleeding, transfusion rates, prolonged mechanical ventilation, myocardial infarction, length of stay, and quality of life measures. Patients will undergo 1:1 block randomization to each treatment arm on day of surgery. Sequence of operation will be at the surgeon’s discretion with mandatory guidelines for temperature and ACP administration. Perioperative management will occur as per enrolling center standard of care. Neurocognitive function will be assessed for neurological injury using validated neurological screening tests: NIHSS, MOCA, BI, and MRS throughout patient follow-up. Diagnosis and classification of AKI will be based on rising creatinine values as per the KDIGO criteria. Study duration for each patient will be 60 ± 14 days. Discussion It is hoped that performing hemiarch surgery using mild hypothermia (32 °C) and selective ACP will result in a 15% absolute risk reduction in the composite outcomes. The potential of this risk reduction will translate into improved patient outcomes, survival, and long-term financial savings to the health care system. In addition, the results of this trial will be used to create the first-ever guidelines for temperature management strategy during aortic surgery. Trial registration This trial is registered on ClinicalTrials.gov with the registration number NCT02860364. Registration date August 9th, 2016.

Objective: To determine the efficacy of mechanical thrombectomy combined with prolonged mild hypothermia compared with conventional treatment in managing acute middle cerebral artery occlusion, and to explore whether extending the duration of hypothermia can improve neurological function., Method: From 2018 to June 2023, a retrospective analysis was conducted on 45 patients with acute middle cerebral artery occlusion treated at the NICU of Suzhou Kowloon Hospital, affiliated with Shanghai Jiao Tong University School of Medicine. After thrombectomy, patients were admitted to the neurological intensive care unit (NICU) for targeted temperature management. Patients were divided into two groups: the mild hypothermia group (34.5-35.9°C) receiving 5-7 days of treatment, and the normothermia group (control group) whose body temperature was kept between 36 and 37.5°C using pharmacological and physical cooling methods. Baseline characteristics and temperature changes were compared between the two groups of patients. The primary outcome was the modified Rankin Scale (mRS) score at 3 month after surgery, and the secondary outcomes were related complications and mortality rate. Prognostic risk factors were investigated using both univariate and multivariate logistic regression analyses., Results: Among 45 patients, 21 underwent prolonged mild hypothermia, and 24 received normothermia, with no significant differences in baseline characteristics between the two groups. The duration of mild hypothermia ranged from 5 to 7 days. The incidence of chills (33.3% vs. 8.3%, p  = 0.031) and constipation (57.1% vs. 20.8%, p  = 0.028) was significantly higher in the mild hypothermia group compared with the control group. There was no significant difference in mortality rates between the mild hypothermia and the control group (4.76% vs. 8.33%, p  = 1.000, OR = 1.75, 95% CI, 0.171-17.949). At 3 month, there was no significant difference in the modified mRS (0-3) score between the mild hypothermia and control groups (52.4% vs. 25%, p  = 0.114, OR = 0.477, 95% CI, 0.214-1.066). Infarct core volume was an independent risk factor for adverse neurological outcomes., Conclusion: Prolonged mild hypothermia following mechanical thrombectomy had no severe complications and shows a trend to improve the prognosis of neurological function. The Infarct core volume on CTP was an independent risk factor for predicting neurological function., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Meng, Chen, Chu, Zhou, Jiang and Wang.)

Objectives: To investigate the clinical effect of mild hypothermia combined with intravenous thrombolysis in the treatment of acute cerebral infarction. Methods: Eighty-eight patients with acute cerebral infarction in Binzhou People's Hospital between May 2018 and August 2019 were randomly selected and divided into a control group and an observation group according to the random number table method, with 44 patients in each group. The control group was given intravenous thrombolysis; the observation group was treated with mild hypothermia (30-350C) in addition to intravenous thrombolytic thrombolysis. The clinical efficacy, incidence of complications, oxidative stress indexes, inflammatory factor level, neurological function, and mental state of the two groups before and after treatment were compared. Results: The clinical efficacy of the observation group was significantly better than that of the control group, and the difference was statistically significant (P<0.05). There was no significant difference in the levels of oxidative stress indexes and inflammatory factors between the two groups before treatment (P<0.05). After treatment, the levels of oxidative stress indexes and inflammatory factors of the two groups significantly improved, and the improvement of the observation group was better than that of the control group; the differences were statistically significant (P<0.05). There was no significant difference in the neurological function and mental state between the two groups before treatment (P<0.05). After treatment, the neurological function and mental state of the two groups significantly improved, and the improvement of the observation group was better than that of the control group; the differences were statistically significant (P<0.05). There was no significant difference in the incidence of complications and mortality between the two groups (P>0.05). Conclusion: Thrombolytic therapy combined with mild hypothermia has a good efficacy in the treatment of acute cerebral infarction. The therapy can improve the neurological function of patients with acute cerebral infarction by significantly improving the oxidative stress index and relieving the inflammatory reaction. Its efficacy is better than single thrombolytic therapy. [ABSTRACT FROM AUTHOR]