Profound Hypothermia Research Articles

Olanzapine-Induced Hypothermia: A Case Report in an Elderly Black Male Patient Diagnosed with Bipolar 1 Type Disorder

There are few reports that describe incidence of hypothermia in patients treated with olanzapine. We report a case of an elderly 83-year-old black male, readmitted to the state psychiatric hospital December 2023 due to psychiatric exacerbation after 6 months of successful discharge to community, who experienced a fall and profound hypothermia with bradycardia that resulted in a 10-day acute hospitalization in January 2024. Medical workup was unrevealing except for multivessel disease found on CT stroke study of the brain. When patient returned to inpatient psychiatric hospital, his psychiatric medications, including both quetiapine and olanzapine, were restarted at half the dose. The next morning, the patient was again hypotensive, bradycardic and hypothermic. For this patient, only the olanzapine was new upon the most recent admission, and thus this case report supports the other few reports already published, implicating olanzapine in the pharmacologic adverse effect of drug induced hypothermia.

Normothermic Perfusion is Superior to Cold Perfusion in Porcine Ex Situ Lung Perfusion

BackgroundCold ex situ lung perfusion (ESLP) has demonstrated improved preservation in small animal ESLP compared to normothermic ESLP and cold static preservation. We hypothesized that cold negative pressure ventilation (NPV)-ESLP would improve graft function in a porcine transplantation model. MethodsFour perfusate temperatures were examined with 12 hours NPV-ESLP in a large animal transplantation model. Pig lungs were allotted to four groups: (1) Normothermia (38°C, n = 6); (2) profound hypothermia (10°C, n = 6); (3) moderate hypothermia (20°C, n = 3); (4) subnormothermia (32°C, n = 3). A fifth group subnormothermic low-flow (SNLF) perfusion was examined to assess the effect of reduced cardiac output with cold perfusion (32°C, 10% cardiac output, n = 6). ResultsOnly Normothermic and SNLF groups demonstrated acceptable oxygenation after 12 hours NPV-ESLP and were transplanted. All other groups failed prematurely. After 12 hours of ESLP, Normothermic lungs demonstrated significantly greater dynamic compliance compared to SNLF lungs (P = .03). Edema formation post-ESLP was significantly worse in the SNLF group (P = .01). There was no significant difference in pulmonary artery pressures after ESLP (P = .10); however, pulmonary vascular resistance was significantly greater in the SNLF (P = .04). Isolated left lung oxygenation 4-hours post-transplant and left lung edema formation was not significantly different between Normothermic and SNLF post-transplant (P = .09). Proinflammatory cytokines were significantly greater during SNLF-ESLP (tumor necrosis factor alpha, P < .05). ConclusionsProlonged normothermic (38°C) NPV-ESLP is superior to 10, 20, and 32°C perfusion. Normothermic ESLP of porcine lungs results in superior graft function and reduced inflammation versus SNLF-ESLP.

Hypothermia Inhibits Dexmedetomidine-Induced Contractions in Isolated Rat Aortae.

Dexmedetomidine is widely used to induce sedation in the perioperative period. This study examined the effect of hypothermia (33 and 25 °C) on dexmedetomidine-induced contraction in an endothelium-intact aorta with or without the nitric oxide synthase inhibitor NW-nitro-L-arginine methyl ester (L-NAME). In addition, the effect of hypothermia on the contraction induced by dexmedetomidine in an endothelium-denuded aorta with or without a calcium-free Krebs solution was examined. The effects of hypothermia on the protein kinase C (PKC), myosin light chain (MLC20) phosphorylation, and Rho-kinase membrane translocation induced by dexmedetomidine were examined. Hypothermia inhibited dexmedetomidine-induced contraction in the endothelium-intact aorta with L-NAME or endothelium-denuded aorta. Hypothermia had almost no effect on the dexmedetomidine-induced contraction in the endothelium-denuded aorta with the calcium-free Krebs solution; however, the subsequent contraction induced by the addition of calcium was inhibited by hypothermia. Conversely, the transition from profound hypothermia back to normothermia reversed the hypothermia-induced inhibition of subsequent calcium-induced contractions. Hypothermia inhibited any contraction induced by KCl, PDBu, and NaF, as well as PKC and MLC20 phosphorylation and Rho-kinase membrane translocation induced by dexmedetomidine. These results suggest that hypothermia inhibits dexmedetomidine-induced contraction, which is mediated mainly by the impediment of calcium influx and partially by the attenuation of pathways involving PKC and Rho-kinase activation.

Research on the friction and wear mechanism of a polymer interface at low temperature based on molecular dynamics simulation

Two polymers and five metal pairs were tested at six low temperature points and three constant load speeds. The tribological properties were determined by joint iterative coupling of the temperature, load and friction velocity value. Molecular dynamics simulation was used to study the micro-tribological properties of friction pairs at the atomic scale. The macro-tribological performance test results were similar to the results of the molecular dynamics simulation and exhibited the same trend. Two profound hypothermia points were predicted. The evolution of the tribological mechanism and properties of the polymer interface under different working conditions at low temperature were revealed on the macroscopic and atomic scales.

Accidental hypothermia: pathophysiology, investigations and management.

Accidental hypothermia, defined as an unintentional decrease in core body temperature to below 35°C, adversely affects several body systems, including the cardiovascular, central nervous and renal systems. It is classified according to core body temperature from a maximum of 35°C in mild hypothermia to below 24°C in profound hypothermia. Patients with severe hypothermia (28°C-24°C) are at risk of cardiac arrythmias and cardiac arrest. In patients presenting with hypothermia, it is vital to prevent any further heat loss and quickly start rewarming them. Nurses working in the emergency department have a crucial role in supporting the optimal recovery of hypothermic patients. This article explains the pathophysiology of hypothermia, describes the investigations conducted in patients with accidental hypothermia and discusses management and nursing care.

Aortic arch repair: lessons learned over three decades at Baylor College of Medicine.

The treatment of complex aortic arch disease continues to be among the most demanding cardiovascular operations, with a considerable risk of death and stroke. Since January 1990, our single-practice service has performed over 3000 repairs of the aortic arch. Our aim was to describe the progression of our technical approach to open aortic arch repair. Our center's surgical technique has evolved considerably over the last three decades. When it comes to initial arterial cannulation, we have shifted away from femoral artery cannulation to innominate and axillary artery cannulation. During difficult repairs, this transition has made it easier to use antegrade cerebral perfusion rather than retrograde cerebral perfusion, which was commonly used in the early days. Brain protection tactics during open aortic arch procedures have evolved from profound (≤14 °C) hypothermia during circulatory arrest to moderate (22-24 °C) hypothermia. Aortic arch repair is performed through a median sternotomy and may treat acute aortic dissection, chronic aortic dissection, or degenerative aneurysm. Reoperative repair - that necessitating redo sternotomy - is common in patients undergoing aortic arch repair. The majority of repairs will include varying portions of the ascending aorta and may involve the aortic valve or the aortic root. In some patients, repair may extend into the proximal descending thoracic aorta; this includes elephant trunk, frozen elephant trunk, and antegrade hybrid approaches.

Induced Hypothermia as Cold as 3°C in Humans: Forgotten Cases Rediscovered.

Zafren, Ken, Raimund Lechner, Peter Paal, Hermann Brugger, Giles Peek, and Tomasz Darocha. Induced hypothermia as cold as 3°C in humans: Forgotten cases rediscovered. High Alt Med Biol. 23:105-113.-The lowest temperature from which humans can be successfully rewarmed from accidental hypothermia is unknown. The lowest published core temperature with survival from accidental hypothermia is 11.8°C. We recently reported a rediscovered case series of patients in whom profound hypothermia was induced for surgery. The patient in this case series with the lowest core temperature, 4.2°C, survived neurologically intact. We subsequently rediscovered several additional case series of induced hypothermia to core temperatures below 11.8°C. In one case series, at least one patient was cooled to 3°C. We do not know if any patient survived cooling to 3°C. As in the previous case series, the authors of the additional reports presented physiological data at various core temperatures, showing wide variations in individual responses to hypothermia. These data add to our understanding of the physiology of profound hypothermia. Although induced hypothermia for surgery differs from accidental hypothermia, survival from very low temperatures in induced hypothermia provides evidence that humans with accidental hypothermia can be resuscitated successfully from temperatures much lower than 11.8°C. We continue to advise against using core temperature alone to decide if a hypothermic patient in cardiac arrest has a chance of survival.

Hybrid Approach in Acute and Chronic Aortic Disease

The management of patients with aortic disease that involves the ascending aorta, the aortic arch, and the descending aorta represent a surgical challenge. Open surgical repair remains the gold standard for aortic arch pathologies. However, this operation requires a cardiopulmonary bypass and a period of profound hypothermia and circulatory arrest, which carries a substantial rate of mortality and morbidity. For these reasons, hybrid arch repair that involves a combination of open surgery with endovascular aortic stent graft placement has been introduced as a therapeutic alternative for those patients deemed unfit for open surgical procedures. Hybrid repair requires varying degrees of invasiveness and can be performed as a single-stage procedure or as a two-stage procedure. The choice of the technique is multifactorial, depending on the characteristics of the diseased arch with regard to position of the stent graft proximal landing zone, patient fitness and comorbid status, as well as surgical expertise and hospital facilities. Among the evolving hybrid procedures is the so-called “frozen” or stented elephant trunk technique. Adapted from the classical elephant trunk technique, this approach facilitates the repair of a concomitant aortic arch and proximal descending aortic aneurysms in a single stage under circulatory arrest. This technique is increasingly being used to treat extensive thoracic aortic disease and has shown promising results.

Extracorporeal Life Support in Accidental Hypothermia with Cardiac Arrest-A Narrative Review.

Severely hypothermic patients, especially suffering cardiac arrest, require highly specialized treatment. The most common problems affecting the recognition and treatment seem to be awareness, logistics, and proper planning. In severe hypothermia, pathophysiologic changes occur in the cardiovascular system leading to dysrhythmias, decreased cardiac output, decreased central nervous system electrical activity, cold diuresis, and noncardiogenic pulmonary edema. Cardiac arrest, multiple organ dysfunction, and refractory vasoplegia are indicative of profound hypothermia. The aim of these narrative reviews is to describe the peculiar pathophysiology of patients suffering cardiac arrest from accidental hypothermia. We describe the good chances of neurologic recovery in certain circumstances, even in patients presenting with unwitnessed cardiac arrest, asystole, and the absence of bystander cardiopulmonary resuscitation. Guidance on patient selection, prognostication, and treatment, including extracorporeal life support, is given.

Administration of Intravenous Amino Acids Attenuates Postoperative Hypothermia in Patients Undergoing Percutaneous Nephrolithotomy.

Amino acids attenuate hypothermia during the perioperative period by increasing thermogenesis and stimulating energy consumption. Percutaneous nephrolithotomy (PCNL) induces profound hypothermia owing to the use of large volumes of irrigating fluids. The role of amino acids in this group of surgeries for hypothermia and shivering prevention has been evaluated in this study because there is no available literature of concern. This prospective randomised controlled trial was conducted in patients undergoing PCNL. Group A received amino acids at 60 mL h-1 an hour before surgery until the end of surgery. Group C received normal saline infusion. Perioperative nasopharyngeal temperature, haemodynamics, and postoperative shivering were recorded. Although there was no significant difference in temperature in the intraoperative period, postoperative decrease in the temperature was less in the amino acid group. In the postoperative period, 2 patients in the amino acid group and 11 patients in the control group experienced shivering. Intravenous administration of amino acids attenuated postoperative hypothermia and reduced shivering in patients undergoing PCNL without any adverse effects.

Stuart Craig Lennox

Stuart Craig Lennox was born on 25 May 1932 in Aberdeen and died on 4 August 2018 at his home in Little Hadham, Hertfordshire. He qualified from the London Hospital...

Effects of Graft Preservation Conditions on Coronary Endothelium and Functional Recovery in a Rat Model of Donation after Circulatory Death

Purpose Donation after circulatory death (DCD) could significantly improve cardiac graft availability. However, DCD hearts are subjected to potentially damaging conditions prior to circulatory arrest and during warm ischemia and reperfusion. Although the feasibility of DCD heart transplantation has been demonstrated, protocols for graft preservation and storage require optimization to ensure graft quality. Therefore, we aimed to compare the current clinical conditions used for heart preservation (St. Thomas n°2) with a potentially more suitable solution for DCD hearts, evaluating endothelial and cardiac function to investigate differences in cardioprotective effects. Methods Following anaesthesia, diaphragm transection, and circulatory arrest in male Wistar rats to simulate DCD conditions, hearts were subjected to either 0 or 18 minutes of warm, in-situ ischemia. At end-ischemia, hearts were perfused with either: St. Thomas n°2 cardioplegia at 4°C as in current clinical practice, or normokalemic, adenosine-lidocaine cardioplegia (A-L) at 4°C or 22°C. Afterwards, hearts were stored for 15 min in their respective solutions, and then reperfused ex-situ for either 30 min (to assess endothelial function) or 60 min (to assess cardiac function and biochemical parameters). Results A-L cardioplegia at 22°C better preserves vascular function as compared to cold A-L or St. T cardioplegia, as demonstrated by greater eNOS coupling (p Conclusion Use of A-L and avoidance of profound hypothermia and hyperkalemic cardioplegia could improve endothelial and contractile function, potentially through the promotion of eNOS dimerization and activation of the RISK pathway; these approaches should help to optimize clinical protocols in DCD heart transplantation and facilitate its widespread adoption in clinical practice.

Prolonged Circulatory Arrest is Not Associated with Stroke or Mortality after Pulmonary Thromboendarterectomy

Purpose Patients with chronic thromboembolic pulmonary hypertension (CTEPH) frequently present with extensive distal clot burden, which adds complexity to pulmonary thromboendarterectomy (PTE). Complete endarterectomy often necessitates prolonged periods of hypothermic circulatory arrest (HCA), the ramifications of which are poorly understood. Objectives were to describe the association of HCA time with post-operative neurologic complications, operative mortality and other major morbidity after PTE. Methods From 2013 to 2019, 163 patients underwent PTE at a single academic institution. Median age was 51 [IQR 23] and 55% (N=89) were female. Operative approach involved profound hypothermia with multiple brief periods of HCA without aortic crossclamping. As event rates were low, the primary outcome was a composite of operative mortality, stroke, respiratory failure requiring tracheostomy and renal failure requiring dialysis. Both univariate and multivariable logistic regression analyses were performed to examine association between HCA and this composite outcome. Results Overall operative mortality was 6.8% (N=11), while 1% of patients (n=2) suffered stroke, 5% (n=8) required dialysis and 10% (n=17) required tracheostomy. In terms of hemodynamic outcomes, median improvement in mean PA pressures was 15mmHg [IQR 16] comparing pre-operative to last post-operative invasive monitoring. Median HCA time was 46 minutes [IQR 32] over a median of 3 [IQR 2] arrest periods at median core temperature of 17°C [IQR 2.2]. When grouped by HCA time less than or greater than 60 minutes, there was no significant difference in the composite outcome (15% versus 12%, p=0.720). Among nine patients with very prolonged HCA time greater than 90 minutes, the composite outcome occurred in one (11%). In a univariate logistic regression analysis, neither HCA time (OR 1.00, CI 0.99-1.01) nor number of arrests (OR 0.98, CI 0.94-1.02) were significant predictors of the composite. In a multivariable model, increasing age was the only significant predictor of the composite (OR 1.05, CI 1.01-1.10). Conclusion Prolonged HCA during PTE does not appear to confer increased risk of neurologic or other major complications. Therefore, more extensive endarterectomy should be pursued, when appropriate, to achieve the best hemodynamic outcome for patients with distal and bilateral disease.

Stem Cell Behavior at Hypothermia: A Review Article.

Temperature is a fundamental factor that affects many functions and structural aspects of physiological systems. Despite its importance, few studies have been performed so far for investigating the compartments and mechanisms engaged in the response of cellular systems to temperature perturbation. In this review, focusing on stem cells, we tried to perform a literature review for investigating the possible ways through which the temperature reduction (hypothermia) affects stem cell function and behavior. Besides, using the obtained results of this investigation, the possible mechanisms are proposed. The survey indicates that profound hypothermia enhances cell adhesion by increasing the stability of E-cadherins. Furthermore, mild hypothermia increases stem cell survival by reducing oxidative stress and prevents apoptosis via the overexpression of anti-apoptotic heat shock proteins. Mild-hypothermia also promotes cell proliferation by affecting gene expression in several ways. Even though it seems that hypothermia generally reduced stem cell differentiation, some inconsistencies are observed between obtained results from the literature. Based on the obtained results, mechanisms responsible for the temperature effect of hypothermia in profound and mild ranges are given that might help the researcher in real experiments.

Dosing Heat: Expected Core Temperature Change with Warmed or Cooled Intravenous Fluids.

Emergent modification of a patient's body temperature is crucial in certain disease or injury states. Advanced targeted temperature management techniques such as central venous catheter devices are not universally available, however, virtually all medical centers have access to intravenous fluids. This study approximates the change in body temperature for a given volume of room temperature, chilled, or heated isotonic crystalloid bolus. Using thermodynamic principles, a mathematical model was created to approximate change in body core temperature in response to a given volume and temperature of intravenous fluid. The model assumes rapid fluid infusion and the previously published specific heat capacity of the human body of 3.47 J/kg · °C. Values were calculated under conditions of varying body temperatures from profound hypothermia to hyperthermia (18°C-45°C). Various crystalloid temperatures representing iced, room temperature, and warmed (4°C, 20°C, 42°C) were used in the calculations. Each 30 mL/kg dose of 20°C crystalloid is expected to cool a hyperthermic (38°C-45°C) patient by 0.6°C-0.9°C. Each 30 mL/kg dose of 4°C crystalloid is expected to cool a hyperthermic (38°C-45°C) patient by 1.2°C-1.4°C. Each dose of 42°C crystalloid is expected to warm a hypothermic patient by 0.2°C-0.8°C. Using the results in this study, clinicians may roughly estimate the effect of temperature management with varying doses of intravenous fluids and thus assess the benefits of this technique. Risk should be evaluated based on inevitable coadministered volume and electrolytes. Individuals with volume-sensitive conditions such as heart, liver, or kidney failure deserve particular attention. Based on a mathematical model, typical expected core temperature change is about 0.2°C-1.4°C per 30 mL/kg crystalloid bolus, depending on patient and fluid temperature.

Dual benefit of combined neuroprotection: Cholesterol depletion restores membrane microviscosity but not lipid order and enhances neuroprotective action of hypothermia in rat cortex nerve terminals

Here, both neuroprotectants, i.e. cholesterol depletion of the plasma membrane of rat brain nerve terminals (synaptosomes) using methyl-β-cyclodextrin (MβCD) and deep/propound hypothermia, were analyzed during their combined administration and regarding additive neuroprotective effect. The extracellular synaptosomal level of L-[14C]glutamate significantly increased after treatment with MβCD in both deep and profound hypothermia. Cholesterol depletion gradually enhanced inhibiting effect of deep and profound hypothermia on glutamate uptake and “excitotoxic” transporter-mediated release of L-[14C]glutamate. A decrease in L-[14C]glutamate release via heteroexchange from nerve terminals in deep and profound hypothermia was enhanced by cholesterol deficiency that confirmed previous result. Fluorometric studies with probes NR12S and DCVJ revealed oppositely directed effects of cholesterol depletion and hypothermia on synaptosomal membrane lipid order and microviscosity showing that cholesterol depletion can normalise up to the control hypothermia-induced increase in microviscosity, but not the lipid order of the synaptosomal membrane. Dynamics of changes in exocytosis in nerve terminals, which involved membrane fusion stage, was different from transporter-dependent ones. Hypothermia did not augment effects of cholesterol depletion on exocytotic L-[14C]glutamate release and lowering cholesterol enhanced the impact of deep, but not profound hypothermia on this parameter. Therefore, dual benefit of combined neuroprotection was demonstrated. Cholesterol depletion enhanced neuroprotective effects of hypothermia intensifying inhibition of “excitotoxic” transporter-mediated glutamate release and can normalise a hypothermia-induced increase in microviscosity of the synaptosomal membrane. This feature is prospective in mitigation of side effects of therapeutic hypothermia, and also for brain conservation preserving normal physical and chemical properties of the cellular membranes.

Total Arch Replacement with Hypothermic Circulatory Arrest, Antegrade Cerebral Perfusion and the Y-graft

This study examines postoperative morbidity and mortality and long-term survival after total arch replacement (TAR) using deep to moderate hypothermic circulatory arrest (HCA), antegrade cerebral perfusion (ACP), and the Y-graft. Seventy-five patients underwent TAR with the Y graft. Deep to moderate HCA was initiated at 18-22°C. ACP was either initiated immediately (early ACP) or after the distal anastomosis was performed (late ACP). The arch vessels were then serially anastomosed to the individual limbs of the Y-graft. The median age was 66 years (range = 32-82). Etiology of aneurysmal dilatation included 20 (27%) patients with medial degenerations, 25 (33%) with chronic dissections, 14 (19%) with acute dissections, 9 (12%) with atherosclerosis and 2 (3%) with Marfan syndrome. In-hospital mortality was 5%. Neurologic complications occurred in 8 (11%) patients; 2 (3%) had strokes and 6 (8%) had transient neurologic deficits. Patients undergoing TAR with moderate hypothermia had a significantly higher incidence of new-onset renal insufficiency (3 [23%] vs [0%], P < 0.001) and TND (3 (23%) vs 3 (5%), P = 0.028) than the profound and deep hypothermia cohort. Excluding the 1 patient who died intraoperatively, 89% (95%CI: 79-94%) were alive at 1 year, 78% at 5 years (95%CI: 66-86%), and 73% at 10 years (95%CI: 59-82%). The combination of deep to moderate HCA, ACP, and the Y-graft is a safe and reproducible technique. Further inquiry is needed to assess if early ACP provides superior clinical outcomes.

The effects of graded hyperthermic (32, 20 ℃) on spinal cord protection during ischemia-reperfusion in rat

Objective To study the neuroprotective effects of moderate hypothermia (32 ℃) and profound hypothermia (20 ℃) on spinal cord ischemia-reperfusion in rats. Methods A subcutaneous heat exchanger is used to produce a low temperature of the spinal cord. The balloon blocked the thoracic aorta to induce spinal cord ischemia for 10 minutes. 42 SD rats were randomly divided into 4 groups, group Ⅰ. Non-blocking group (37 ℃, 6); Ⅱ. Normal temperature ischemia group (37 ℃, 12); Ⅲ. moderate hypothermia group (32 ℃, 12); Ⅳ. Profound Hyperthermia group (20℃, 12). Six rats in groups Ⅱ, Ⅲ and Ⅳ were given ischemia for 10 minutes and the lumbar spinal cord was taken. The other 6 rats in each group were given reperfusion, and the neurological function was evaluated at 1, 2, 4, and 8 hours. All the samples from all three rats were examined by histological examination and analyzed. The release of neurotransmitter amino acids was observed by high pressure liquid chromatography, and N-Methyl-D-Aspartate R1 (NMDAR1) mRNA was detected by in situ hybridization. The test results were analyzed by t test. Results Hard palate and neuron necrosis occurred in the normal temperature ischemia-reperfusion group. In terms of histopathological findings, the Moderate Hyperthermia (32 ℃) group and the profound hypothermia (20 ℃) group were significantly better than normal temperature ischemia after reperfusion. After 10 minutes of spinal cord ischemia, The glutamate concentration and NMDAR1 mRNA expression in the profound hypothermia in the Moderate Hyperthermia (32 ℃) group and (20 ℃) group were significantly lower than those in the normal temperature ischemia group. After 8 hours of reperfusion, the concentrations of glutamate and NMDAR1 mRNA in the Moderate Hyperthermia (32 ℃) group and the profound hypothermia (20 ℃) group were significantly higher than those in the normal temperature control group. Spinal cord ischemia was 10 min. The glutamate concentration in the medium-low temperature (32 ℃) group was 10.88±1.17 (t=27.292, P 0.05), and that in the low temperature (20 ℃) group was (12.57±2.59) cells (t=4.154, P<0.01), which was significantly lower than that in the normal temperature ischemia group [(17.36±2.56) cells]. After reperfusion for 8 hours, the glutamate concentration in the medium-low temperature (32 ℃) group was 49.38±13.26 (t=-8.407, P<0.01), and the deep hypothermia (20 ℃) group was 44.95±2.12 (t=-23.933, P<0.01), which was significantly higher than the normal temperature ischemia group (14.08±3.70); the number of NMDAR1 mRNA positive cells in the low temperature (32 ℃) group was (22.47±5.40) cells (t=-5.437, P<0.01), and that in the deep hypothermia (20 ℃) group was (18.89±3.98) cells (t=-4.042, P<0.01), which was significantly higher than that in the normal temperature ischemia group [(12.06±3.45) cells]. Conclusion Mode moderate hyperthermia (32 ℃) and profound hypothermia (20 ℃) have protective effects on histopathology of spinal ischemia-reperfusion cord. The results of spinal ischemia-reperfusion after 8 hours indicate that spinal cord protection are still needed during reperfusion. Key words: Spinal cord ischemia-reperfusion; Moderate hyperthermia; Profound hyperthermia; Glutamate

Annexin A1 Bioactive Peptide Promotes Resolution of Neuroinflammation in a Rat Model of Exsanguinating Cardiac Arrest Treated by Emergency Preservation and Resuscitation.

Neuroinflammation initiated by damage-associated molecular patterns, including high mobility group box 1 protein (HMGB1), has been implicated in adverse neurological outcomes following lethal hemorrhagic shock and polytrauma. Emergency preservation and resuscitation (EPR) is a novel method of resuscitation for victims of exsanguinating cardiac arrest, shown in preclinical studies to improve survival with acceptable neurological recovery. Sirtuin 3 (SIRT3), the primary mitochondrial deacetylase, has emerged as a key regulator of metabolic and energy stress response pathways in the brain and a pharmacological target to induce a neuronal pro-survival phenotype. This study aims to examine whether systemic administration of an Annexin-A1 bioactive peptide (ANXA1sp) could resolve neuroinflammation and induce sirtuin-3 regulated cytoprotective pathways in a novel rat model of exsanguinating cardiac arrest and EPR. Adult male rats underwent hemorrhagic shock and ventricular fibrillation, induction of profound hypothermia, followed by resuscitation and rewarming using cardiopulmonary bypass (EPR). Animals randomly received ANXA1sp (3 mg/kg, in divided doses) or vehicle. Neuroinflammation (HMGB1, TNFα, IL-6, and IL-10 levels), cerebral cell death (TUNEL, caspase-3, pro and antiapoptotic protein levels), and neurologic scores were assessed to evaluate the inflammation resolving effects of ANXA1sp following EPR. Furthermore, western blot analysis and immunohistochemistry were used to interrogate the mechanisms involved. Compared to vehicle controls, ANXA1sp effectively reduced expression of cerebral HMGB1, IL-6, and TNFα and increased IL-10 expression, which were associated with improved neurological scores. ANXA1sp reversed EPR-induced increases in expression of proapoptotic protein Bax and reduction in antiapoptotic protein Bcl-2, with a corresponding decrease in cerebral levels of cleaved caspase-3. Furthermore, ANXA1sp induced autophagic flux (increased LC3II and reduced p62 expression) in the brain. Mechanistically, these findings were accompanied by upregulation of the mitochondrial protein deacetylase Sirtuin-3, and its downstream targets FOXO3a and MnSOD in ANXA1sp-treated animals. Our data provide new evidence that engaging pro-resolving pharmacological strategies such as Annexin-A1 biomimetic peptides can effectively attenuate neuroinflammation and enhance the neuroprotective effects of EPR after exsanguinating cardiac arrest.

Myxedema Coma in a Hypothermic, Obtunded Patient with Post-renal Acute Kidney Injury and Bacteremia in the Intensive Care Unit

We present a case of a hypothermic, unconscious patient transferred to our Intensive Care Unit with sepsis requiring mechanical ventilation. The absence of any known past medical history as well as concurrent obstructive uropathy and bacteremia made initial diagnosis challenging. He was eventually found to be in myxedema coma in light of evolving signs and laboratory investigations. This case emphasizes the need to consider myxedema coma in the differential diagnosis of profound hypothermia, especially when other clinical signs and symptoms may obscure its initial diagnosis, and lead clinicians to focus on the triggering event in isolation rather than concurrently managing hypothyroidism. This case highlights a challenging presentation of an uncommon, but life-threatening condition. We discuss the signs and symptoms present in the hypothyroid patient with myxedema coma; emphasize the pathophysiology of myxedema coma as well as the evidence-based acute management of this condition.