Effect Of Mild Hypothermia Research Articles

Effect of mild hypothermia vs normothermia cardiopulmonary bypass on postoperative bleeding in patients undergoing coronary artery bypass grafting: protocol of a multi-center, randomized, controlled trial

BackgroundCoronary artery bypass grafting (CABG) is often performed with hypothermic cardiopulmonary bypass (CPB) to reduce metabolic demands and protect the myocardium. However, hypothermia can increase bleeding risks and other complications.MethodsThis is a prospective, multi-center, randomized controlled trial. From September 2023 to December 2024, a total of 336 eligible patients planning to undergo on-pump CABG will be enrolled. All participants will be randomly divided into mild hypothermia CPB group (target oxygenator arterial outlet blood temperature at 32–33℃) or normothermia CPB group (target oxygenator arterial outlet blood temperature at 35–36℃). The primary endpoint is Universal Definition of Perioperative Bleeding (UDPB) class 2–4. Secondary endpoints are class of UDPB, levels of coagulation and inflammatory factors, in-hospital mortality, perioperative related complications, ICU length of stay, and hospital length of stay.DiscussionThis clinical trial aims to compare the effects of different target temperature during CPB on postoperative bleeding and to explore optimal temperature strategy to provide new clinical evidence.Trial registrationChictr.org.cn: ChiCTR2300075405. The trial was prospectively registered on 4 September 2023.

The effects of mild hypothermia on the electrode insertion trauma in a murine whole organ cochlea culture.

Local therapeutic hypothermia (32°C) has been linked experimentally to an otoprotective effect in the electrode insertion trauma. The pathomechanism of the electrode insertion trauma is connected to the activation of apoptosis and necrosis pathways, pro-inflammatory and fibrotic mechanisms. In a whole organ cochlea culture setting the effect of therapeutic hypothermia in an electrode insertion trauma model is evaluated. The cochleae of C57Bl6/J mice (Charles River®, Freiburg, Germany) are cultured for 24 hours at 37°C and 32°C after inserting a fishing line through the round window simulating an insertion trauma. The resulting effect was evaluated for the apoptotic reaction - B-cell-Lymphoma-2-Associated-X-Protein (BAX), B-Cell-Lymphoma-2-Protein (BCL2) and Cleaved-Caspase-3 (CC3) -, the inflammatory response - Tumor-Necrosis-Factor-Alpha (TNFα), Interleukin-1-Beta (IL-1Imm) and Cyclooxygenase-2 (COX2) - and proliferation process - Transforming-Growth-Factor-Beta-1 (TGFβ1) - using immunohistochemistry and real-time PCR technique. A minimum of 12 cochlea per experiment were used. A pro-apoptotic situation was observed in the normothermic group (BAX, CC3 ˃ Bcl2) whereas an anti-apoptotic constellation was found at 32°C culture conditions (BAX, CC3 < Bcl2). Furthermore the effect of the IT knowing to effect the pro-inflammatory cytokine (TNFα, Il1β) and enzyme (COX2) expression has been reproduced. This reaction was reversed with the application of therapeutic hypothermia resulting in significant lower pro-inflammatory cytokine (TNFα, Il1β) and enzyme (COX2) expression. TGFβ1 was increased by hypothermia. Concluding a protective effect of hypothermia on the experimental electrode insertion trauma can be described by an anti-apoptotic and anti-inflammatory reaction.

Effect of Mild Hypothermia on Morbidity and Mortality in Post AMI Cardiogenic Shock

Background: Acute myocardial infarction (AMI) complicated with cardiogenic shock is still associated with a significant death rate. Other interventions, including intra-aortic balloon counter pulsation and medical therapy, failed to improve prognosis in large-scale randomised studies, with the exception of early revascularization. Recently, mild therapeutic hypothermia, in which patients are lowered to 33°C over the course of 24 hours, has been proposed as a therapy option for cardiogenic shock patients. The purpose of this study is to determine the impact of mild hypothermia on morbidity and mortality associated with post-AMI cardiogenic shock.&#x0D; Methods: This randomized, controlled, unblinded trial was conducted on 50 patients with AMI complicated by CS. Patients were randomly allocated into two equal groups; group I received MTH to 33°C for 24-36 h and group II (control group) did not receive MTH. Patients were subjected to full history taking, general and clinical examination, laboratory examination, echo, chest ultrasound (US), coronary angiography data and mild therapeutic hypothermia protocol.&#x0D; Results: Stroke until day 30, duration of mechanical ventilation, length of ICU stay, duration of inotropic support, mortality and pulmonary congestion by US were insignificantly different between both groups. Arterial lactate and mean arterial blood pressure (MAP) at 4h, 6h, 8h, 10h, 12h, 14h, 16h, 18h, 20h were significantly increased in group I than Group II (P value&lt;0.05). and were insignificantly different between both groups at 0h, 2h, 22h, 24h, 26h, 28h, 30h. Serum creatinine at 24h, 48h was significantly increased in group I than Group II (p value &lt;0.05) and was insignificantly different between both groups at 0h.&#x0D; Conclusions: Therapeutic hypothermia (TH) didn’t improve short term outcomes in patients with post AMI cardiogenic shock.

Effect of Mild Hypothermia on the Catalytic Characteristics of Synaptic Acetylcholinesterase during Subtotal Global Cerebral Ischemia in Rats

Effect of Mild Hypothermia on the Catalytic Characteristics of Synaptic Acetylcholinesterase during Subtotal Global Cerebral Ischemia in Rats

Cardioprotective effect of combination therapy by mild hypothermia and local or remote ischemic preconditioning in isolated rat hearts

A multitargeted strategy to treat the consequences of ischemia and reperfusion (IR) injury in acute myocardial infarction may add cardioprotection beyond reperfusion therapy alone. We investigated the cardioprotective effect of mild hypothermia combined with local ischemic preconditioning (IPC) or remote ischemic conditioning (RIC) on IR injury in isolated rat hearts. Moreover, we aimed to define the optimum timing of initiating hypothermia and evaluate underlying cardioprotective mechanisms. Compared to infarct size in normothermic controls (56 ± 4%), mild hypothermia during the entire or final 20 min of the ischemic period reduced infarct size (34 ± 2%, p < 0.01; 35 ± 5%, p < 0.01, respectively), while no reduction was seen when hypothermia was initiated at reperfusion (51 ± 4%, p = 0.90). In all groups with effect of mild hypothermia, IPC further reduced infarct size. In contrast, we found no additive effect on infarct size between hypothermic controls (20 ± 3%) and the combination of mild hypothermia and RIC (33 ± 4%, p = 0.09). Differences in temporal lactate dehydrogenase release patterns suggested an anti-ischemic effect by mild hypothermia, while IPC and RIC preferentially targeted reperfusion injury. In conclusion, additive underlying mechanisms seem to provide an additive effect of mild hypothermia and IPC, whereas the more clinically applicable RIC does not add cardioprotection beyond mild hypothermia.

The effect of mild hypothermia plus rutin on the treatment of spinal cord injury and inflammatory factors by repressing TGF-β/smad pathway.

ABSTRACTPurposeTo probe the mechanism of mild hypothermia combined with rutin in the treatment of spinal cord injury (SCI).MethodsThirty rats were randomized into the following groups: control, sham, model, mild hypothermia (MH), and mild hypothermia plus rutin (MH+Rutin). We used modified Allen’s method to injure the spinal cord (T10) in rats, and then treated it with MH or/and rutin immediately. BBB scores were performed on all rats. We used HE staining for observing the injured spinal cord tissue; ELISA for assaying TNF-α, IL-1β, IL-8, Myeloperoxidase (MPO), and Malondialdehyde (MDA) contents; Dihydroethidium (DHE) for measuring the reactive oxygen species (ROS) content; flow cytometry for detecting apoptosis; and both RT-qPCR and Western blot for determining the expression levels of TGF-β/Smad pathway related proteins (TGF-β, Smad2, and Smad3).ResultsIn comparison with model group, the BBB score of MH increased to a certain extent and MH+Rutin group increased more than MH group (p < 0.05). After treatment with MH and MH+Rutin, the inflammatory infiltration diminished. MH and MH+Rutin tellingly dwindled TNF-β, MDA and ROS contents (p < 0.01), and minified spinal cord cell apoptosis. MH and MH+Rutin could patently diminished TGF-β1, Smad2, and Smad3 expression (p < 0.01).ConclusionsMH+Rutin can suppress the activation of TGF-β/Smad pathway, hence repressing the cellular inflammatory response after SCI.

Clinical observation of mild hypothermia combined with intravenous thrombolysis in treating patients with acute cerebral infarction.

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 (30-35°C) 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.

The effect of mild hypothermia on interleukin-3 expression in septic mice

To investigate whether or not mild hypothermia can inhibit the expression and release of interleukin-3 (IL-3) in septic mice and whether it has a protective effect on septic mice. According to random number table method, 120 male C57BL/6 mice were divided into sham operation group (Sham group), sepsis normal temperature group (NT group) and sepsis mild hypothermia group (HT group), with 40 mice in each group. The acute septic mice model was established by cecal ligation and puncture (CLP) method. In the HT group, body temperature decreased to 32-34 centigrade at 1 hour after CLP and was maintained for 8 hours, followed by rewarming slowly to 36-38 centigrade. In the NT group, mice were resuscitated after CLP and body temperature was maintained at 36-38 centigrade throughout the experimental periods, while in Sham group, the cecum was not ligated or punctured and resuscitated routinely. The average arterial pressure (MAP) of 20 mice in each group was monitored for 12 hours after CLP, and the survival time was observed for 4 days. The serum of remaining mice was collected at 12 hours after CLP, and the mice were killed for organ tissues. The serum levels of IL-3, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were determined by enzyme linked immunosorbent assay (ELISA). Western blotting was used to detect IL-3 protein expression in spleen and lung tissues. The pathological changes of lung and liver tissues were observed under microscope and the semi-quantitative scoring was performed. MAP of NT group and HT group decreased after CLP with the prolongation of time. MAP (mmHg, 1 mmHg = 0.133 kPa) of HT group at 10 hours and 12 hours after CLP were significantly higher than those of NT group (10 hours: 74.4±12.4 vs. 62.9±7.2, 12 hours: 68.4±3.7 vs. 57.5±9.6, both P < 0.01). Compared with Sham group, serum levels of IL-3, IL-6 and TNF-α in NT group and HT group were significantly increased at 12 hours after CLP [IL-3 (ng/L): 2.21±0.87, 0.18±0.04 vs. 0, IL-6 (ng/L): 51.22±18.65, 24.68±6.20 vs. 1.36±0.34, TNF-α (ng/L): 101.43±38.60, 72.15±25.12 vs. 14.49±5.17, all P < 0.01]. IL-3 protein expressions of spleen and lung tissues in NT group and HT group were significantly increased compared to those in Sham group (IL-3/β-actin: spleen tissue 0.200±0.039, 0.135±0.023 vs. 0.090±0.023, lung tissue 0.085±0.009, 0.056±0.009 vs. 0.039±0.005, all P < 0.01). The serum levels of IL-3, IL-6 and TNF-α were significantly lower in HT group than those in the NT group [IL-3 (ng/L): 0.18±0.04 vs. 2.21±0.87, IL-6 (ng/L): 24.68±6.20 vs. 51.22±18.65, TNF-α (ng/L): 72.15±25.12 vs. 101.43±38.60, all P < 0.01]. The expressions of IL-3 protein in HT group were significantly lower than those in NT group (IL-3/β-actin: spleen tissue 0.135±0.023 vs. 0.200±0.039, lung tissue 0.056±0.009 vs. 0.085±0.009, both P < 0.01). The lung tissue injury and liver tissue injury scores in HT group were significantly lower than those in NT group (lung tissue injury score: 4.00±1.41 vs. 6.67±2.16, P = 0.03, liver tissue injury score: 3.83±1.47 vs. 7.17±2.14, P = 0.01). Compared to NT group, the 4-day survival rate of HT group was significantly improved (50% vs. 30%, P < 0.01). Mild hypothermia can significantly inhibit the expression and release of IL-3 in septic mice, attenuate organ injury, and protecte septic mice.

The Effect of Mild Hypothermia on Nogo-A and Neurological Function in the Brain after Cardiopulmonary Resuscitation in Rats

Objective We investigated the dynamic changes of Nogo-A protein in brain and the effects of mild therapeutic hypothermia (MTH) on its expression after cardiopulmonary resuscitation (CPR). Methods: Western-blotting and neurological scoring of 45 rats subjected to cardiac arrest and CPR with and without MTR were performed to investigate the changes in the expression of Nogo-A protein in the hippocampus and cortex over a period of time ranging from 6 h to 72 h after restoration of spontaneous circulation (ROSC). Results: Nogo-A expression levels were increased at 6 h after CPR in the hippocampus and cortex, peaked at 24 h in the cortex, and at 48 h in the hippocampus. The expression of Nogo-A in the MTR group was significantly lower at 12 h (p < 0.05) compared to those with no MTR after ROSC. Conclusions: MTR blunts the expression of Nogo-A protein in the hippocampus and cortex after cardiac arrest and resuscitation, and MTR may provide cerebral protection after ischemia.

Effect of Mild Hypothermia on the Diaphragmatic Microcirculation and Function in A Murine Cardiopulmonary Resuscitated Model.

Diaphragm dysfunction often occurs in patients with prolonged mechanical ventilation (MV) after resuscitation. Mild hypothermia (MHT) is a classical treatment to improve the outcomes of cardiac arrest (CA); however, the effect of MHT on diaphragm function remains unclear. In the present study, we aim to investigate the effect of MHT on diaphragmatic microcirculation and function using a murine cardiopulmonary resuscitation model. Thirty-two rats were randomly assigned into a resuscitation normothermia group (RNT), an intraresuscitation hypothermia group (IRH), a postresuscitation hypothermia group (PRH), or a sham control group. CA was induced by airway occlusion, and resuscitation was implemented by precordial compression and MV. The diaphragmatic microvascular blood flow velocity, diaphragmatic microcirculation flow index (MFI), and perfused vascular density (PVD) were measured. The diaphragm was then removed for in vitro contractile property examination and cross-sectional area measurement. The lipid peroxidation and superoxide dismutase (SOD) levels in the diaphragm were also assayed. Either early or delayed MHT intervention did not improve the diaphragmatic microvascular blood flow velocity, MFI, and PVD, which were significantly decreased during prolonged MV after resuscitation. Compared with the RNT group, treatment with MHT increased the diaphragm contractility, fiber dimensions, and SOD levels and decreased diaphragm lipid peroxidation. A more significant change in these indices was observed in the IRH group compared with that in the PRH group. MHT preserves the diaphragm contractility and fiber dimensions and decreases oxidative stress but does not improve the microcirculatory blood supply during prolonged MV after resuscitation. Early MHT intervention is more efficient in preventing diaphragm dysfunction than delayed intervention after CA.

Effect of mild hypothermia on expression of cortical Mfn2 during cerebral ischemia-reperfusion in rats

Objective To evaluate the effect of mild hypothermia on the expression of mitofusin 2 (Mfn2) during cerebral ischemia-reperfusion (I/R) in rats. Methods Sixty healthy clean-grade male Sprague-Dawley rats, aged 8 weeks, weighing 200-250 g, were divided into 3 groups (n=20 each) using a random number table method: sham operation group (group S), group I/R and mild hypothermia group (group H). In I/R and H groups, cerebral I/R was induced by inserting a nylon thread with rounded tip into the right internal carotid artery which was occluded for 2 h and then released for reperfusion.In group H, the surface cooling was started immediately after removing the nylon thread, and the rectal temperature was maintained at 32-34 ℃ for 3 h. The neurological deficit were assessed and scored at 24 and 48 h of reperfusion.Animals were then sacrificed, the cerebral cortex in ischemic area was then removed for determination of the viable neuron count (by HE staining), apoptotic neurons (by TUNEL), and expression of Mfn2 (by Western blot). Apoptosis rate was calculated. Results Compared with group S, the neurological deficit score and apoptosis rate were significantly increased, and the count of viable neurons was decreased, the expression of Mfn2 was down-regulated at each time of reperfusion in I/R and H groups (P<0.05). Compared with group I/R, the neurological deficit score and apoptosis rate were significantly deereased, and the count of viable neurons was increased, and the expression of Mfn2 was up-regulated at each time of reperfusion in group H (P<0.05). Conclusion The mechanism by which mild hypothermia attenuates cerebral I/R injury may be associated with up-regulating the expression of Mfn2 in cerebral cortex of rats. Key words: Hypothermia, induced; Reperfusion injury; Brain; Mitochondrial proteins

Effect of mild hypothermia on lung injury after cardiac arrest in swine based on lung ultrasound

BackgroundLung injury is common in post-cardiac arrest syndrome, and is associated with increased morbidity and mortality. The aim of this study was to evaluate the effect of mild hypothermia on lung injury after cardiac arrest in swine based on lung ultrasound.MethodsTwenty-three male domestic swine weighing 36 ± 2 kg were randomly assigned to three groups: therapeutic hypothermia (TH, n = 9), normothermia (NT, n = 9), and sham control (control, n = 5) groups. Sham animals only underwent surgical preparation. The animal model was established with 8 min of ventricular fibrillation followed by 5 min of cardiopulmonary resuscitation. Therapeutic hypothermia was induced and maintained until 24 h post-resuscitation in the TH group by surface blanket cooling, followed by rewarming at a rate of 1 °C/h for 5 h. The extravascular lung water index (ELWI), pulmonary vascular permeability index (PVPI), PO2/FiO2, and lung ultrasound score (LUS) were measured at baseline and at 1, 3, 6, 12, 24, and 30 h after resuscitation. After euthanizing the swine, their lung tissues were quickly obtained to evaluate inflammation.ResultsAfter resuscitation, ELWI and PVPI in the NT group were higher, and PO2/FiO2 was lower, than in the sham group. However, those measures were significantly better in the TH group than the NT group. The LUS was higher in the NT group than in the sham group at 1, 3, 6, 12, 24, and 30 h after resuscitation. The LUS was significantly better in the TH group compared to the NT group. The lung tissue biopsy revealed that lung injury was more severe in the NT group than in the TH group. Increases in LUS were highly correlated with increases in ELWI (r = 0.613; p < 0.001) and PVPI (r = 0.683; p < 0.001), and decreases in PO2/FiO2 (r = − 0.468; p < 0.001).ConclusionsMild hypothermia protected against post-resuscitation lung injury in a swine model of cardiac arrest. Lung ultrasound was useful to dynamically evaluate the role of TH in lung protection.

Effect of mild hypothermia on the expression of IL-10 and IL-18 in neonates with hypoxic ischemic encephalopathy.

The effect of mild hypothermia on the expression of interleukin (IL)-10 and IL-18 in neonates with hypoxic ischemic encephalopathy was investigated. A retrospective analysis was performed on 97 neonates with hypoxic-ischemic encephalopathy (HIE) admitted to the neonatal intensive care unit of Xuzhou Children's Hospital, Xuzhou Medical University from September 2016 to August 2018. Of these patients, 54 with mild hypothermia were included in the experimental group (moderate + severe), and 43 patients who received conventional therapy were included in the control group (moderate + severe). The effect of mild hypothermia on IL-10 and IL-18 expression levels was analyzed, and the relationship between IL-10, IL-18 and disease severity in children with hypoxic ischemic encephalopathy was analyzed. The concentration of IL-10 in the experimental group was significantly lower than that in the control group at 1, 2, 3 and 5 days (P<0.05). The concentration of IL-18 in the experimental group was significantly lower than that in the control group at the 2, 3 and 5 days (P<0.05). NBNA scores of the experimental group were significantly higher than those of the control group at 14 and 28 days after birth (P<0.05). Before treatment, the expression levels of IL-10 and IL-18 in severe children were significantly higher than those in moderate children (P<0.05). IL-10 was positively correlated with the severity of the disease (r=0.521, P<0.05), and IL-18 was also positively correlated with the severity of the disease (r=0.616 P<0.05). Mild hypothermia treatment can effectively improve the neurological function of children with HIE, reduce the expression of IL-10 and IL-18 in serum, and inhibit the inflammatory response. Therefore, the expression of IL-10 and IL-18 was positively correlated with the severity of disease in children with HIE, and could be used as an indicator to judge the severity of HIE.

Effect of mild hypothermia combined with hydrogen-rich saline on cerebral injury after cardiac arrest and resuscitation in rats

Objective To evaluate the effect of mild hypothermia combined with hydrogen-rich saline on cerebral injury after cardiac arrest and resuscitation in rats. Methods Healthy male Sprague-Dawley rats, aged 7-8 weeks, weighing 280-320 g, were divided into 5 groups (n=33 each) using a random number table method: sham operation group (group S), cardiac arrest and resuscitation group(group CA-R), hydrogen-rich saline group (group H2), mild hypothermia group (group MH), and mild hypothermia plus hydrogen-rich saline group (group MH+ H2). Cardiac arrest was induced with transoesophageal cardiac pacing followed by cardiopulmonary resuscitation to establish the cerebral injury model.Hydrogen-rich saline 5 ml/kg was intraperitoneally injected immediately after return of spontaneous circulation (ROSC) in H2 and MH+ H2 groups, while the equal volume of normal saline was given instead in the other groups.The body temperature of rats was cooled down to 32-34℃ within 15 min starting from the time point immediately after ROSC and maintained for 4 h in MH and MH+ H2 groups.Fifteen rats were selected at 24 h after ROSC to assess the neurological function score (NDS). Eighteen rats in each group were sacrificed at 24 h after ROSC, and brains were removed for microscopic examination of the pathological changes in hippocampal CA1 region after hematoxylin and eosin staining and for determination of pyramidal cell count and expression of glucose-regulated protein 78 (GRP78), C/EBP-homologous protein (CHOP), caspase-12, caspase-3, Bcl-2 and Bax in hippocampal CA1 region (by Western blot). Results Compared with group S, the NDS was significantly decreased, the pyramidal cell count was reduced, the expression of GRP78, CHOP, caspase-12, caspase-3 and Bax was up-regulated, and the expression of Bcl-2 was down-regulated in the other four groups (P 0.05). Conclusion Combination of mild hypothermia and hydrogen-rich saline offers enhanced efficacy in reducing cerebral injury after cardiac arrest and resuscitation over mild hypothermia or hydrogen-rich saline alone in rats. Key words: Hypothermia, induced; Hydrogen; Heart arrest; Cardiopulmonary resuscitation; Reperfusion injury; Brain

Comparison of different durations of mild hypothermia on neuroprotection in septic rats

Objective To investigate the protective effect of mild hypothermia on septic rats and to find suitable hypothermia duration time. Methods After cecal ligation and puncture (or sham), male Sprague-Dawley rats were divided into a sham operation group(Sham group, n=20), a normal temperature group[Norm group, (37.0±0.2) °C, n=43], and hypothermia group (34.0±0.5) °C[a hypothermia 6 h group (Hypo 6 group, n=41), a hypothermia 12 h group (Hypo 12 group, n=33), a hypothermia 24 h group (Hypo 24 group, n=27)], and the electrodes were placed on the head 10 days before the operation. Electrocardiogram (EEG) and behavioral tests were performed before and 24 h after surgery. The blood samples were collected 24 h after surgery. The blood levels of S100β protein were detected by enzyme-linked immunosorbent assay (ELISA) to determine the degree of brain damage. Results Twenty rats in each group survived. The survival rates of Sham group, Norm group and Hypo 6, 12 and 24 groups were 100% (20/20), 46.51% (20/43), 48.78% (20/41), 60.61% (20/33) and 74.07% (20/27), the survival rate of Hypo 24 group was significantly higher than that of Norm group and Hypo 6 group (P 0.05). Compared with the Sham group, rats in Norm group and Hypo groups presented remarkably lowerd neurobiological scores 24 h after surgery(P 0.05), and no significant difference was found between Hypo 12 and Hypo 6 groups (P>0.05). Compared with the sham groups, remarkly higher levels of plasma S100β protein and EEG δ waves were detected in the operation group(P 0.05), and no significant difference between Hypo 6 and Hypo 12 groups (P>0.05). According to the biological score and EEG monitoring results, sepsis-associated encephalopathy was was detected in 13(65%), 13(65%), 11(55%), and 8(40%) rats in the Norm group, Hypo 6, 12, 24 groups, and no statistically significant differences in the incidence was found among the groups(P>0.05). Conclusions Although mild hypothermia cannot reduce the incidence of sepsis-associated encephalopathy in rats with sepsis, it can reduce there brain damage, and protect the brain as hypothermia time extends. Key words: Hypothermia; Sepsis; Sepsis-associated encephalopathy; Neuroprotection

The effect of mild hypothermia on the myocardial and microcirculatory dysfunction induced by epinephrine during early post-resuscitation

Objective To investigate the effect of mild hypothermia on the myocardial and microcirculation dysfunction induced by epinephrine during early post-resuscitation in a rat model of cardiac arrest and cardiopulmonary resuscitation (CPR). Methods Transesophageal cardiac pacing was performed in order to elicit cardiac arrest for 5 min in SD male rats. Totally 40 rats were randomly (random number) divided into 4 groups (n=10): normothermic control group (N), normothermic epinephrine group (N+E), hypothermic control group (H), and hypothermic epinephrine group (H+E). Chest compression was then initiated. Epinephrine (0.02 mg/kg) or saline was administrated at 1 min during CPR. Restoration of spontaneous circulation (ROSC) was recorded, and the rates of ROSC were observed. Myocardial and microcirculatory function were observed at 1, 2, 3, and 4 h during early post-resuscitation. Serum lactate level was assessed at baseline and ROSC 4 h. Results The ROSC rates were 10/10 in the H+E group, 9/10 in the N+E group, 4/10 in the H group, and 1/10 in the N group, respectively. Ejection fraction (EF) and cardiac output (CO) in the H+E group were significantly higher than that of other groups (P<0.05). Total vessel density, perfused vessel density, proportion of perfused vessels, and microvascular flow index in the H+E group were also significantly higher than those of other groups during early post-resuscitation. The serum lactate level in the H+E group was significantly lower than that in the N+E and H groups.. Conclusions Both epinephrine and mild hypothermia can improve the success rate of resuscitation. However, mild hypothermia can improve the epinephrine induced myocardial and microcirculatory dysfunction during postresuscitation in the rat cardiac arrest. Key words: Cardiac arrest; Cardiopulmonary resuscitation; Epinephrine; Mild hypothermia; Myocardial dysfunction; Microcirculation

Propofol Does Not Attenuate the Cardioprotective Effect of Mild Hypothermia in Swine

ObjectivePrevious experimental studies have demonstrated that mild reductions in body temperature can decrease infarct size in the setting of acute myocardial infarction (MI). However, it has been suggested that the cardioprotective effects of mild hypothermia and other conditioning interventions are attenuated by concomitant administration of propofol. To address this issue, we evaluated the relationship between body temperature and infarct size in propofol‐anesthetized swine subjected to prolonged myocardial ischemia and reperfusion.MethodsSwine (n=17) were anesthetized with propofol (10 mg/kg/hour) and subjected to a 60‐minute balloon occlusion of the distal left anterior descending coronary artery (LAD) in the closed‐chest state. Serum cTnI values were quantified by a porcine‐specific ELISA at baseline and 1‐hour after reperfusion. Infarct size (triphenyl tetrazolium chloride) and ischemic area‐at‐risk (AAR; phthalocyanine blue during coronary re‐occlusion) were assessed post‐mortem 3‐hours (n=2), 24 hours (n=5), or 7 days (n=10) after reperfusion.ResultsDirect, statistically significant (p&lt;0.01) correlations were observed between body temperature at reperfusion and infarct size relative to AAR (r=0.75), infarct size relative to LV mass (r=0.70), and serum cTnI 1‐hour after reperfusion (r=0.78). When animals were divided into two groups based on median body temperature at reperfusion (37.5 °C), animals with a body temperature &lt;37.5 °C exhibited significantly smaller infarcts and lower serum cTnI values than animals with a body temperature &gt; 37.5 °C (Table). Importantly, low body temperature‐related reductions in infarct size were observed in the absence of group differences in the duration of reperfusion, LV mass, and ischemic AAR.ConclusionThese results demonstrate that the cardioprotective effect of mild hypothermia is not attenuated in the setting of propofol anesthesia. Furthermore, the marked reduction in infarct size associated with relatively minor diminutions in body temperature provides further support for the notion that even modest reductions in body temperature within a normothermic range may be an effective approach to limit infarct size in patients with acute MI.Support or Funding InformationThe National Heart Lung and Blood Institute (HL‐061610), the American Heart Association (17SDG33660200), the National Center for Advancing Translational Sciences (UL1TR001412), the Department of Veterans Affairs (1IO1BX002659), the New York State Department of Health (NYSTEM CO24351, the UB Center for Undergraduate Research and Creative Activities, and the Albert and Elizabeth Rekate Fund in Cardiovascular Medicine.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Effect of mild hypothermia on cerebral microcirculation in a murine cardiopulmonary resuscitation model.

We hypothesized that mild hypothermia may improve brain microcirculation by reducing cerebral microvascular endothelial cells apoptosis, and this effect may be maximized by moving up the initiation of mild hypothermia from after return of spontaneous circulation (ROSC) to the start of cardiopulmonary resuscitation (CPR). A total of 35 rats were randomized into the intra-arrest hypothermia group (IAH), post-resuscitation hypothermia group (PRH), normothermia group (NT), or the sham control group. A craniotomy exposed the parietal cortex for visualization of microcirculation. Ventricular fibrillation was electrically induced and untreated for 8minutes, followed by 8minutes of precordial compression and mechanical ventilation. Hypothermia (33±0.5°C) in the IAH and PRH group was induced and maintained for 6hours at the beginning of CPR or after ROSC, respectively. At baseline, 1, 3, and 6hours, hemodynamic parameters were measured and the pial microcirculations were visualized with a sidestream dark field imaging video microscope. Microvascular flow index and perfused microvessel density (PMD) were calculated. Rats were euthanized, and brain tissues were removed at 3 and 6hours separately. Expression of Bax, Bcl-2, and Caspase 3 in brain microvascular endothelial cells was examined by Western blot. Microvascular flow index and PMD were significantly reduced after cardiac arrest and resuscitation (all P<0.05), and the former was largely preserved by hypothermia regardless when the hypothermia treatment was induced (P<0.05). Bax and Caspase 3 increased and Bcl-2 decreased significantly after resuscitation, and hypothermia treatment reversed the trend partly (all P<0.05). A moderate correlation was observed between MFI and those proteins (Bcl-2/BAX: 3hours: r=0.730, P=0.002; 6hours: r=0.743, P=0.002). Mild hypothermia improves cerebral microcirculatory blood supply, partly by inhibiting endothelial cell apoptosis. Mild hypothermia induced simultaneously with CPR has shown no additional benefit in microcirculation or endothelial cell apoptosis.

Mild hypothermia reduces endoplasmic reticulum stress-induced apoptosis and improves neuronal functions after severe traumatic brain injury.

BackgroundMild hypothermia is wildly used in clinical treatment of traumatic brain injury (TBI). However, the effect of mild hypothermia on endoplasmic reticulum (ER) stress‐induced apoptosis after severe TBI is still unknown.MethodsIn the present study, we used BALB/c mice to investigate the efficacy of posttraumatic mild hypothermia in reducing ER stress. Severe TBI was induced by controlled cortical impact injury. Mild hypothermia treatment was performed immediately after surgery and maintained for 4 hr. The animals were euthanized at 1 and 7 days after severe TBI. The expression levels of ER stress marker proteins were evaluated using Western blot and immunofluorescence. Cell apoptosis rate was analyzed by TUNEL staining. Neuronal functions of the mice were assessed using rotarod test and Morris water maze.ResultsOur results revealed that mild hypothermia significantly attenuated ER stress marker proteins, including p‐eIF2α/eIF2α, ATF4, CHOP and IRE‐1α, and reduced apoptosis rate in the pericontusion region at 1 and 7 days after severe TBI. Interestingly, mild hypothermia also prevented the translocation of CHOP into nucleus. In addition, posttraumatic mild hypothermia significantly improved neuronal functions after severe TBI.ConclusionsOur findings illustrated that mild hypothermia could reduce ER stress‐induced apoptosis and improve neuronal functions after severe traumatic brain injury.

Mild hypothermia promotes the viability of in vitro-produced bovine blastocysts and their transcriptional expression of the cold-inducible transcription factor Rbm3 during in vitro culture.

In this study, we evaluated the effects of holding in vitro-produced bovine blastocysts under mild hypothermia (33°C or 35°C), by examining viability and hatching rates of day 7 blastocysts (day 0: in vitro fertilization) cultured for 6 days and transcriptional expression of cold-inducible transcription factors Cirp and Rbm3, implicated in mild hypothermia-induced cellular protection against various types of stress. In the normothermic control (38.5°C), viability of the embryos decreased rapidly after day 10, and most samples were degenerated on day 13. However, mild hypothermia, particularly at 33°C, resulted in maintenance of high embryonic survival rates until day 13 (77.1% on day 13) and significant increases in transcriptional expression of Rbm3 in day 11 embryos compared with those at 38.5°C. Thus, our results suggested that upregulation of Rbm3 may occur in response to mild hypothermia in many bovine embryos, providing insights into the effects of mild hypothermia on embryo quality.