The Protective Effect and Mechanism of Mild Hypothermia on Lung Injury after Cardiopulmonary Resuscitation in Pigs.

To explore the protective effect and mechanism of mild hypothermia on lung tissue damage after cardiopulmonary resuscitation in pigs. In this experiment, we electrically stimulated 16 pigs (30 ± 2 kg) for 10 min to cause ventricular fibrillation. The successfully resuscitated animals were randomly divided into two groups, a mild hypothermia group and a control group. We took arterial blood 0.5, 1, 3, and 6 h after ROSC recovery in the two groups of animals for blood gas analysis. We observed the structural changes of lung tissue under an electron microscope and calculate the wet weight/dry weight (W/D) ratio. We quantitatively analyzed the expression differences of representative inflammatory factors [interleukin-6 (IL-6) and tumor necrosis factor-alpha TNF-α)] through the ELISA test. We detected the expression levels of Bax, Bcl-2, and Caspase-3 proteins in lung tissues by Western blot. After 3 h and 6 h of spontaneous circulation was restored, compared with the control group, PaO2/FiO2 decreased significantly (P < 0.05). In addition, the pathological changes, lung W/D and lung MDA of the mild hypothermia group were better than those of the control group. The levels of IL-6 and TNF-α in the lung tissue of the mild hypothermia group were significantly lower than those of the control group (P < 0.05). The content of Caspase-3 and Bax in the mild hypothermia group was significantly lower than that of the control group. Our experiments have shown that mild hypothermia can reduce lung tissue damage after cardiopulmonary resuscitation.

Effect of RARC-ERAS nursing program on clinical outcomes in patients undergoing RARC surgery: a retrospective, propensity matching study.

Currently, there is no specific perioperative nursing standard for RARC based on the ERAS concept. This retrospective study investigates to analyze the effect of RARC-ERAS nursing program on VTE and other clinical outcomes in patients undergoing RARC surgery. This retrospective study included 216 patients undergoing RARC surgery From January 1, 2022 to December 30, 2023, and propensity score adjustment analysis was applied. The study compares a control group receiving traditional nursing and an observation group receiving RARC-ERAS nursing program. Perioperative variables and other postoperative complications were retrieved from the hospital medical records. After propensity score matching, there were no significant differences in the demographic and clinical characteristics between the two groups (p > 0.05). The ERAS group exhibited aa significantly higher rate of postoperative unobstructed venous blood flow in the lower extremities by color Doppler ultrasound as compared to the control group (94.6% VS 80.4%, p = 0.042). Before anesthesia induction, lower preoperative anxiety and surgical information needs scores were observed in the ERAS group than in the control group (p < 0.05). Compared to the control group, the ERAS group demonstrated a shorter surgical duration, a lower incidence of perioperative hypothermia, less time needed for getting out of bed, anal exhaust, and for defecation after returning to the ward (p < 0.05). RARC-ERAS nursing program significantly increased the rate of postoperative unobstructed venous blood flow in the lower extremities by color doppler ultrasound, lower preoperative anxiety and intraoperative hypothermia in patients undergoing RARC. This nursing approach presents a valuable strategy for enhancing patient outcomes and merits further exploration in clinical practice.Trial registration:ChiCTR2400081118; http://www.chictr.org.cn , Principal investigator: Mang-mang He, Date of registration: Feb 22, 2024.

An untargeted metabolomics approach to study changes of the medium during human cornea culture.

INTRODUCTION: Two main approaches (organ culture and hypothermia) for the preservation and storage of human donor corneas are globally adopted for corneal preservation before the transplant. Hypothermia is a hypothermic storage which slows down cellular metabolism while organ culture, a corneal culture performed at 28-37 °C, maintains an active corneal metabolism. Researchers, till now, have just studied the impact of organ culture on human cornea after manipulating and disrupting tissues. OBJECTIVES: The aim of the current work was to optimize an analytical procedure which can be useful for discovering biomarkers capable of predicting tissue health status. For the first time, this research proposed a preliminary metabolomics study on medium for organ culture without manipulating and disrupting the valuable human tissues which could be still used for transplantation. METHODS: In particular, the present research proposed a method for investigating changes in the medium, over a storage period of 20 days, in presence and absence of a human donor cornea. An untargeted metabolomics approach using UHPLC-QTOF was developed to deeply investigate the differences on metabolites and metabolic pathways and the influence of the presence of the cornea inside the medium. RESULTS: Differences in the expression of some compounds emerged from this preliminary metabolomics approach, in particular in medium maintained for 10 and 20 days in presence but also in the absence of cornea. A total of 173 metabolites have been annotated and 36 pathways were enriched by pathway analysis. CONCLUSION: The results revealed a valuable untargeted metabolomics approach which can be applied in organ culture metabolomics.

Incidence and Risk Factors for Postoperative Visual Loss after Cardiac Surgical Procedures: A Systematic Review.

ABSTRACT: Postoperative visual loss (POVL) is an infrequent yet consequential complication that can follow cardiac surgical interventions. This systematic review aims to provide a comprehensive analysis of the incidence of POVL after cardiac surgery and to delineate the associated risk factors. A comprehensive search was conducted in major medical databases for relevant studies published up to September 2022. Eligible studies reporting on the incidence of POVL and identifying risk factors in patients undergoing cardiac surgery were included. Data extraction was performed independently by two reviewers. The pooled incidence rates and the identified risk factors were synthesized qualitatively. POVL after cardiac surgery has an overall incidence of 0.015%, that is, 15 cases per 100,000 cardiac surgical procedures. Risk factors for POVL include patient characteristics (advanced age, diabetes, hypertension, and preexisting ocular conditions), procedural factors (prolonged surgery duration, cardiopulmonary bypass time, and aortic cross-clamping), anesthetic considerations (hypotension, blood pressure fluctuations, and specific techniques), and postoperative complications (stroke, hypotension, and systemic hypoperfusion). Ischemic optic neuropathy (ION) is an uncommon complication, associated with factors like prolonged cardiopulmonary bypass, low hematocrit levels, excessive body weight gain, specific medications, hypothermia, anemia, raised intraocular pressure, and micro-embolization. Diabetic patients with severe postoperative anemia are at increased risk for anterior ischemic optic neuropathy (AION). Posterior ischemic optic neuropathy (PION) can occur with factors like hypertension, postoperative edema, prolonged mechanical ventilation, micro-embolization, inflammation, hemodilution, and hypothermia.While the overall incidence of POVL postcardiac surgery remains modest, its potential impact is substantial, necessitating meticulous consideration of modifiable risk factors. Notably, prolonged surgical duration, intraoperative hypotension, anemia, and reduced hematocrit levels remain salient contributors. Vigilance is indispensable to promptly detect this infrequent yet visually debilitating phenomenon in the context of postcardiac surgical care.

Changes in temperature in preheated crystalloids at ambient temperatures relevant to a prehospital setting: an experimental simulation study with the application of prehospital treatment of trauma patients suffering from accidental hypothermia.

BACKGROUND: Accidental hypothermia is common in all trauma patients and contributes to the lethal diamond, increasing both morbidity and mortality. In hypotensive shock, fluid resuscitation is recommended using fluids with a temperature of 37-42°, as fluid temperature can decrease the patient's body temperature. In Sweden, virtually all prehospital services use preheated fluids. The aim of the present study was to investigate how the temperature of preheated infusion fluids is affected by the ambient temperatures and flow rates relevant for prehospital emergency care. METHODS: In this experimental simulation study, temperature changes in crystalloids preheated to 39 °C were evaluated. The fluid temperature changes were measured both in the infusion bag and at the patient end of the infusion system. Measurements were conducted in conditions relevant to prehospital emergency care, with ambient temperatures varying between - 4 and 28 °C and flow rates of 1000 ml/h and 6000 ml/h, through an uninsulated infusion set at a length of 175 cm. RESULTS: The flow rate and ambient temperature affected the temperature in the infusion fluid both in the infusion bag and at the patient end of the system. A lower ambient temperature and lower flow rate were both associated with a greater temperature loss in the infusion fluid. CONCLUSION: This study shows that both a high infusion rate and a high ambient temperature are needed if an infusion fluid preheated to 39 °C is to remain above 37 °C when it reaches the patient using a 175-cm-long uninsulated infusion set. It is apparent that the lower the ambient temperature, the higher the flow rate needs to be to limit temperature loss of the fluid.

Impact of intraoperative hypothermia on the recovery period of anesthesia in elderly patients undergoing abdominal surgery.

BACKGROUND: This study aimed to investigate the impact of intraoperative hypothermia on the recovery period of anesthesia in elderly patients undergoing abdominal surgery. METHODS: A prospective observational study was conducted based on inclusion and exclusion criteria. A total of 384 elderly patients undergoing abdominal surgery under general anesthesia were enrolled in a grade A tertiary hospital in Chengdu, Sichuan Province from October 2021 and October 2022. After anesthesia induction, inflatable warming blankets were routinely used for active heat preservation, and nasopharyngeal temperature was monitored to observe the occurrence of intraoperative hypothermia. Patients were divided into hypothermia group and nonhypothermia group according to whether hypothermia occurred during the operation. Anesthesia recovery time and the incidence of adverse events or unwanted events during anesthesia recovery between the two groups were compared. RESULTS: The numbers (percentage) of 384 patients who underwent abdominal surgery developed intraoperative hypothermia occurred in 240 (62.5%) patients, all of whom had mild hypothermia. There were statistically significant differences between mild hypothermia after active warming and nonhypothermia in the occurrence of shivering (χ2 = 5.197, P = 0.023) and anesthesia recovery time (Z = -2.269, P = 0.02) in elderly patients undergoing abdominal surgery during anesthesia recovery, and there were no statistically significant differences in hypoxemia, nausea or vomiting, hypertension, hypokalemia, hypocalcemia, analgesic drug use,postoperative wound infection or postoperative hospitalization days. CONCLUSIONS: The incidence of intraoperative mild hypothermia after active warming was high in elderly patients who underwent abdominal surgery. Mild hypothermia increased the incidence of shivering and prolonged anesthesia recovery time in elderly patients undergoing abdominal surgery.

Hypothermia effects on neuronal plasticity post spinal cord injury.

BACKGROUND: SCI is a time-sensitive debilitating neurological condition without treatment options. Although the central nervous system is not programmed for effective endogenous repairs or regeneration, neuroplasticity partially compensates for the dysfunction consequences of SCI. OBJECTIVE AND HYPOTHESIS: The purpose of our study is to investigate whether early induction of hypothermia impacts neuronal tissue compensatory mechanisms. Our hypothesis is that although neuroplasticity happens within the neuropathways, both above (forelimbs) and below (hindlimbs) the site of spinal cord injury (SCI), hypothermia further influences the upper limbs' SSEP signals, even when the SCI is mid-thoracic. STUDY DESIGN: A total of 30 male and female adult rats are randomly assigned to four groups (n = 7): sham group, control group undergoing only laminectomy, injury group with normothermia (37°C), and injury group with hypothermia (32°C +/-0.5°C). METHODS: The NYU-Impactor is used to induce mid-thoracic (T8) moderate (12.5 mm) midline contusive injury in rats. Somatosensory evoked potential (SSEP) is an objective and non-invasive procedure to assess the functionality of selective neuropathways. SSEP monitoring of baseline, and on days 4 and 7 post-SCI are performed. RESULTS: Statistical analysis shows that there are significant differences between the SSEP signal amplitudes recorded when stimulating either forelimb in the group of rats with normothermia compared to the rats treated with 2h of hypothermia on day 4 (left forelimb, p = 0.0417 and right forelimb, p = 0.0012) and on day 7 (left forelimb, p = 0.0332 and right forelimb, p = 0.0133) post-SCI. CONCLUSION: Our results show that the forelimbs SSEP signals from the two groups of injuries with and without hypothermia have statistically significant differences on days 4 and 7. This indicates the neuroprotective effect of early hypothermia and its influences on stimulating further the neuroplasticity within the upper limbs neural network post-SCI. Timely detection of neuroplasticity and identifying the endogenous and exogenous factors have clinical applications in planning a more effective rehabilitation and functional electrical stimulation (FES) interventions in SCI patients.

Código encefalopatía hipóxico-isquémica: revisión sistematizada para entornos con recursos limitados / Hypoxic-ischaemic encephalopathy code: a systematic review for resource-limited settings

Se estima que el 96% de los recién nacidos (RN) con encefalopatía hipóxico-isquémica (EHI) nacen en entornos con recursos limitados (ERL) sin capacidad para ofrecer el estándar asistencial vigente desde hace cerca de 15 años en los países con altos recursos y que incluye hipotermia terapéutica, neuromonitorización continua electroencefalográfica y resonancia magnética, además de un control intensivo de las constantes vitales y del equilibrio homeostático. Esta situación no parece estar cambiando; sin embargo y aún con estas limitaciones, el conocimiento actualmente disponible permite mejorar la asistencia de los pacientes con EHI atendidos en ERL. El propósito de esta revisión sistematizada es ofrecer, bajo el término «código EHI», recomendaciones de prácticas asistenciales basadas en evidencia científica y factibles en ERL, que permitan optimizar la atención del RN con EHI y ayuden potencialmente a reducir los riesgos asociados a la comorbilidad y a mejorar los resultados neuroevolutivos. El contenido del código EHI se agrupó en nueve epígrafes: 1) prevención de la EHI, 2) reanimación, 3) primeras seis horas de vida, 4) identificación y graduación de la EHI, 5) manejo de las convulsiones, 6) otras intervenciones terapéuticas, 7) disfunción multiorgánica, 8) estudios complementarios, y 9) atención a la familia. (AU)

It is estimated that 96% of infants with hypoxic-ischaemic encephalopathy (HIE) are born in resource-limited settings with no capacity to provide the standard of care that has been established for nearly 15 years in high-resource countries, which includes therapeutic hypothermia, continuous electroencephalographic monitoring and magnetic resonance imaging in addition to close vital signs and haemodynamic monitoring. This situation does not seem to be changing; however, even with these limitations, currently available knowledge can help improve the care of HIE patients in resource-limited settings. The purpose of this systematic review was to provide, under the term «HIE Code», evidence-based recommendations for feasible care practices to optimise the care of infants with HIE and potentially help reduce the risks associated with comorbidity and improve neurodevelopmental outcomes. The content of the HIE code was grouped under 9 headings: 1) prevention of HIE, 2) resuscitation, 3) first 6hours post birth, 4) identification and grading of encephalopathy, 5) seizure management, 6) other therapeutic interventions, 7) multiple organ dysfunction, 8) diagnostic tests and 9) family care. (AU)

The combination treatment of hypothermia and intranasal insulin ameliorates the structural and functional changes in a rat model of traumatic brain injury.

The present study aimed to investigate the combination effects of hypothermia (HT) and intranasal insulin (INS) on structural changes of the hippocampus and cognitive impairments in the traumatic brain injury (TBI) rat model. The rats were divided randomly into the following five groups (n = 10): Sham, TBI, TBI with HT treatment for 3 h (TBI + HT), TBI with INS (ten microliters of insulin) treatment daily for 7 days (TBI + INS), and TBI with combining HT and INS (TBI + HT + INS). At the end of the 7th day, the open field and the Morris water maze tests were done for evaluation of anxiety-like behavior and memory performance. Then, after sacrificing, the brain was removed for stereological study. TBI led to an increase in the total volume of hippocampal subfields CA1 and DG and a decrease in the total number of neurons and non-neuronal cells in both sub-regions, which was associated with anxiety-like behavior and memory impairment. Although, the combination of HT and INS prevented the increased hippocampal volume and cell loss and improved behavioral performances in the TBI group. Our study suggests that the combined treatment of HT and INS could prevent increased hippocampal volume and cell loss in CA1 and DG sub-regions and consequently improve anxiety-like behaviors and memory impairment following TBI.

Structural Changes in Rat Hepatocyte Nucleolus under Nucleolar Stress Caused by Hypothermia.

Structural changes in rat hepatocyte nucleoli were studied during deep hypothermia simulated by immersion in water at 5°C for 40 min (ambient air temperature 7°C). In comparison with the control, phenomena of nucleolar stress occurred in rats during hypothermia: the number of fibrillar centers (FC) per nucleus (by 1.7 times) and per nucleolus (by 1.6 times), nucleolonemal nucleoli per nucleus (by 2.8 times), and the relative content of nucleolonemal nucleoli per nucleus (by 2.6 times) significantly decreased (p=0.0000001); the number of FC per nucleolonemal nucleolus also decreased by 1.4 times (p=0.01). In the hepatocyte nuclei, we observed an increase in the relative content of transitional type nucleoli per nucleus (by 1.3 times; p=0.01), the number of FC per transitional type nucleolus (by 1.4 times; p=0.003), the content of free FC per nucleus (by 3 times; p=0.00004), and the percentage of free FC per nucleus (by 3.5 times; p=0.00004). These changes can be considered as compensatory and adaptive reactions, and transitional type nucleoli can be attributed to the "reserve" nucleolar pool.

Clinical Characteristics, Etiology, and Outcomes of Hypothermia in Well-appearing Children Referred to the Emergency Department.

BACKGROUND: Hypothermia, as a sign of serious bacterial infection (SBI) in children and infants older than 90 days is poorly characterized, especially in the post-pneumococcal vaccine era. OBJECTIVES: To assess the prevalence of SBI in children and infants presenting to the pediatric emergency department (PED) with reported or documented hypothermia. METHODS: Retrospective data analysis was conducted of all well-appearing children aged 0-16 years who presented with a diagnosis of hypothermia at two tertiary PEDs from 2010 to 2019. RESULTS: The study comprised 99 children, 15 (15.2%) age 0-3 months, 71 (71.7%) 3-36 months, and 13 (13.1%) > 36 months. The youngest age group had increased length of stay in the hospital (P < 0.001) and increased rates of pediatric intensive care unit admissions (P < 0.001). Empirical antibiotic coverage was initiated in 80% of the children in the 0-3 months group, 21.1% in the 3-36 months group, and 15.4% in > 36 months (P < 0.001). Only one case of SBI was recorded and no bacteremia or meningitis. Hypothermia of unknown origin was the most common diagnosis in all age groups (34%, 42%, 46%), respectively, followed by bronchiolitis (26%) and hypoglycemia (13.3%) for 0-3 month-old children, unspecified viral infection (20%) and otitis media (7%) for 3-36-month old, and unspecified viral infection (23%) and alcohol intoxication (15.2%) in > 36 months. CONCLUSIONS: There is a low incidence of SBI in well-appearing children presenting to the PED with hypothermia and a benign course and outcome in those older than 3 months.

[Design and application of a warming fixation device for premature infants].

OBJECTIVE: A warming fixation device for premature infants was made and its clinical application effect was discussed. METHODS: The warming fixation device for premature infants was designed and used in clinic. Sixty premature infants admitted to the neonatal ward of Baoding Hospital, Beijing Children's Hospital, Capital Medical University from January to June 2022 were selected as the control group, and 60 premature infants admitted from July to December 2022 were selected as the experimental group. In the control group, umbilical vein catheterization or central vein catheterization were performed using Astro Boy heating box, restraint band or artificial restraint. The preterm infants in the experimental group were radiated into the Astro Boy warm box with self-designed preterm warming fixation device for catheterization. The time of catheterization, the number of limb protrusion, the number of participants in catheterization operation, and the body temperature from 20 minutes of catheterization operation to the end of catheterization operation were recorded in the two groups. The frequency of hypothermia (< 36.5 centigrade) was calculated, and the differences in various indexes between the two groups were compared. RESULTS: (1) The warming fixation device for premature babies consists of two parts: warm sleeping bag and soft pad. The warm sleeping bag includes 4 parts: head, arm, chest and abdomen, and lower limbs. The chest and abdomen were designed with rectangular covering cloth, which can be opened to facilitate umbilical vein puncture for premature infants. There were 3 groups of restraint belts on the rectangular soft pad, which can respectively fix the arms, chest and abdomen of the warm sleeping bag and the lower limbs. During the catheterization operation, use Velcro to secure the warm sleeping bag to the cushioned surface, and select the area of exposed skin according to the piercing site. (2) There were no significant differences in gender, body weight and gestational age between the experimental group and the control group [male: 48.3% vs. 46.7%, body weight (kg): 1.86±0.06 vs. 1.82±0.06, gestational age (weeks): 31.33±0.31 vs. 32.25±0.34, all P > 0.05]. Compared with the control group, the catheterization time of experimental group was significantly shortened (minutes: 21.30±0.43 vs. 30.02±0.64, P < 0.01), the number of limb protrusion was significantly reduced (0 time: 70.0% vs. 33.3%, 1 time: 26.7% vs. 50.0%, P < 0.01), and the number of participants in catheterization operation was significantly reduced (people: 1.77±0.06 vs. 2.37±0.06, P < 0.01). The frequency of hypothermia in experimental group was significantly lower than that in the control group [6.12% (6/98) vs. 26.50% (31/117), χ2 = 15.536, P < 0.01]. CONCLUSIONS: The warming fixation device for premature infants is convenient to use, which can effectively shorten the tube placement time, save human resources, and reduce the incidence of hypothermia in premature infants.

Transient changes in the ST-T waveform mimicking myocardial infarction in a child with near-drowning: a case report.

Drowning is a common cause of childhood morbidity and mortality worldwide. Anoxia, hypothermia, and metabolic acidosis are mainly responsible for this morbidity. Drowning may lead to multiple organ damage, especially cardiac damage, in cases in which severe hypothermia and hypoxemia occur. We report a case of a 4-year-old girl who was admitted to our hospital's Emergency Department because of drowning. She had elevated troponin I concentrations and ST-segment elevation with T wave inversion. However, cardiovascular computed tomography showed no obvious abnormalities in the coronary arteries. We suggest that cardiac damage in this situation is caused by coronary artery spasms. To the best of our knowledge, this is the first case of cardiac damage with electrocardiographic changes after drowning in a preschool child.

Biofilm exopolysaccharides alter sensory-neuron-mediated sickness during lung infection.

Infections of the lung cause observable sickness thought to be secondary to inflammation. Signs of sickness are crucial to alert others via behavioral-immune responses to limit contact with contagious individuals. Gram-negative bacteria produce exopolysaccharide (EPS) that provides microbial protection; however, the impact of EPS on sickness remains uncertain. Using genome-engineered Pseudomonas aeruginosa (P. aeruginosa) strains, we compared EPS-producers versus non-producers and a virulent Escherichia coli (E. coli) lung infection model in male and female mice. EPS-negative P. aeruginosa and virulent E. coli infection caused severe sickness, behavioral alterations, inflammation, and hypothermia mediated by TLR4 detection of the exposed lipopolysaccharide (LPS) in lung TRPV1+ sensory neurons. However, inflammation did not account for sickness. Stimulation of lung nociceptors induced acute stress responses in the paraventricular hypothalamic nuclei by activating corticotropin-releasing hormone neurons responsible for sickness behavior and hypothermia. Thus, EPS-producing biofilm pathogens evade initiating a lung-brain sensory neuronal response that results in sickness.

Factors Influencing the Occurrence of Intraoperative Hypothermia in Patients Undergoing General Anesthesia Intervention: A Study in a Tertiary Care Hospital.

BACKGROUND Intraoperative and postoperative hypothermia of patients can be caused by the use of anesthetic drugs and the complicated and time-consuming procedures of interventional surgery. This retrospective study included 184 patients to investigate the incidence and factors associated with hypothermia during intraoperative anesthesia in a single center in China between January and October 2023. MATERIAL AND METHODS A convenient sampling method was used to select 184 patients who underwent general anesthesia intervention in a tertiary hospital in Sichuan Province from January to October 2023 as the study population. The independent factors influencing the occurrence of intraoperative hypothermia were analyzed. A survey was conducted to collect 5 demographic factors, 4 preoperative-related factors, and 10 surgically related factors. According to the occurrence of intraoperative hypothermia, the independent influencing factors of unplanned hypothermia during perioperative period were further analyzed. RESULTS Among 184 patients, 64 (34.78%) experienced perioperative unplanned hypothermia, of which 5 (7.81%) cases occurred before the start of surgery, 7 (10.94%) occurred before the start of surgery after anesthesia, and 52 (81.25%) occurred during surgery. Logistic regression analysis showed that body temperature at the beginning of surgery (P<0.001), set operating room temperature (P<0.001), duration of anesthesia (P=0.006), and age (P=0.001) were independent influencing factors for unplanned hypothermia during perioperative period. CONCLUSIONS The incidence of intraoperative hypothermia is high in patients undergoing general anesthesia interventions. Age, duration of anesthesia, set operating room temperature, and body temperature at the beginning of the operation were independent influencing factors for the occurrence of unplanned hypothermia during the perioperative period.

Delayed Rewarming Thrombocytopenia: A Suggested Preventable and Treatable Cause of Rewarming Deaths.

The lack of a consensus of accepted prognostic factors in hypothermia suggests an additional factor has been overlooked. Delayed rewarming thrombocytopenia (DRT) is a novel candidate for such a role. At body temperature, platelets undergoing a first stage of aggregation are capable of progression to a second irreversible stage of aggregation. However, we have shown that the second stage of aggregation does not occur below 32°C and that this causes the first stage to become augmented (first-stage platelet hyperaggregation). In aggregometer studies performed below 32°C, the use of quantities of ADP that cause a marked first-stage hyperaggregation can cause an augmented second-stage activation of the platelets during rewarming (second-stage platelet hyperaggregation). In vivo, after 24 hours of hypothermia, platelets on rewarming seem to undergo second-stage hyperaggregation, from ADP released from erythrocytes, leading to life-threatening thrombocytopenia. This hyperaggregation is avoidable if heparin is given before the hypothermia or if aspirin, alcohol or platelet transfusion is given during the hypothermia before reaching 32°C on rewarming. Many of the open questions existing in this field are explained by DRT. Prevention and treatment of DRT could be of significant value in preventing rewarming deaths and some cases of rescue collapse. Performing platelet counts during rewarming will demonstrate potentially fatal thrombocytopenia and enable treatment with platelet infusions aspirin or alcohol.

Mild hypothermia reduces lipopolysaccharide-induced microglial activation via down-regulation of Tent5c.

Microglial activation is a critical factor in the pathogenesis and progression of neuroinflammatory diseases. Mild hypothermia, known for its neuroprotective properties, has been shown to alleviate microglial activation. In this study, we explore the differentially expressed (DE) mRNAs and long non-coding RNAs (lncRNAs) in BV-2 microglial cells under different conditions: normal temperature (CN), mild hypothermia (YT), normal temperature with lipopolysaccharide (LPS), and mild hypothermia with LPS (LPS + YT). Venn analysis revealed 119 DE mRNAs that were down-regulated in the LPS + YT vs LPS comparison but up-regulated in the CN vs LPS comparison, primarily enriched in Gene Ontology terms related to immune and inflammatory responses. Furthermore, through Venn analysis of YT vs CN and LPS + YT vs LPS comparisons, we identified 178 DE mRNAs and 432 DE lncRNAs. Among these transcripts, we validated the expression of Tent5c at the protein and mRNA levels. Additionally, siRNA-knockdown of Tent5c attenuated the expression of pro-inflammatory genes (TNF-α, IL-1ß, Agrn, and Fpr2), cellular morphological changes, NLRP3 and p-P65 protein levels, immunofluorescence staining of p-P65 and number of cells with ASC-speck induced by LPS. Furthermore, Tent5c overexpression further potentiated the aforementioned indicators in the context of mild hypothermia with LPS treatment. Collectively, our findings highlight the significant role of Tent5c down-regulation in mediating the anti-inflammatory effects of mild hypothermia.