The effects of nickel chloride on papillary muscle contractility under normothermic and hypothermic conditions: Comparison of active and hibernating ground squirrels (Urocitellus undulatus) with Wistar rats.

Extracellular Ca2+ plays a pivotal role in the regulation of cardiac contractility under normal and extreme conditions. Here, by using nickel chloride (NiCl2), a non-specific blocker of extracellular Ca2+ influx, we studied the input of extracellular Ca2+ on the regulation of papillary muscle (PM) contractility under normal and hypothermic conditions in ground squirrels (GS), and rats. By measuring isometric force of contraction, we studied how NiCl2 affects force-frequency relationship and the rest effect in PM of these species at 30 °C and 10 °C. We found that at 30 °C 1.5 mM NiCl2 significantly reduced force of contraction across entire frequency range in active GS and rats, whereas in hibernating GS force of contraction was reduced at low and high frequency range. Additionally, NiCl2 evoked spontaneous contractility in rats but not GS PM. The rest effect was significantly reduced by NiCl2 for active GS and rats but not hibernating GS. At 10 °C, NiCl2 fully reduced contractility in active GS and, to a lesser extent, in rats, whereas in hibernating GS it was significant only at 0.3 Hz. The rest effect was significantly reduced by NiCl2 in both active and hibernating GS, whereas it was unmasked in rats that had high contractility under hypothermic conditions in control. Our results show a significant contribution of extracellular Ca2+ to myocardial contractility in GS not only in active but also in hibernating states, especially under hypothermic conditions, whereas limitation of extracellular Ca2+ influx in rats under hypothermia can play protective role for myocardial contractility.

Combined effects of mild hypothermia and nitrous-oxide-induced narcosis on manual and cognitive performance.

Divers are at enhanced risk of suffering from acute cognitive deterioration because of the low ambient temperatures and the narcotic action of inert gases inspired at high pressures. Yet, the behavioral effects of cold and inert gas narcosis have commonly been assessed in isolation and during short-term provocations. We therefore evaluated the interactive influence of mild hypothermia and narcosis engendered by a subanesthetic dose of nitrous oxide (N2O; a normobaric intervention analog of hyperbaric nitrogen) on cognitive function during prolonged iterative exposure. Fourteen men partook in two ∼12-h sessions (separated by ≥4 days), wherein they performed sequentially three 120-min cold (20°C) water immersions (CWIs), while inhaling, in a single-blinded manner, either normal air or a normoxic gas mixture containing 30% N2O. CWIs were separated by a 120-min rewarming in room-air breathing conditions. Before the first CWI and during each CWI, subjects performed a finger dexterity test, and the Spaceflight Cognitive Assessment Tool for Windows (WinSCAT) test assessing aspects of attention, memory, learning, and visuospatial ability. Rectal and skin temperatures were, on average, reduced by ∼1.2 °C and ∼8 °C, respectively (P < 0.001). Cooling per se impaired (P ≤ 0.01) only short-term memory (∼37%) and learning (∼18%); the impairments were limited to the first CWI. N2O also attenuated (P ≤ 0.02) short-term memory (∼37%) and learning (∼35%), but the reductions occurred in all CWIs. Furthermore, N2O invariably compromised finger dexterity, attention, concentration, working memory, and spatial processing (P < 0.05). The present results demonstrate that inert gas narcosis aggravates, in a persistent manner, basic and higher-order cognitive abilities during protracted cold exposure.

Proarrhythmic changes in human cardiomyocytes during hypothermia by milrinone and isoprenaline, but not levosimendan: an experimental in vitro study.

BACKGROUND: Accidental hypothermia, recognized by core temperature below 35 °C, is a lethal condition with a mortality rate up to 25%. Hypothermia-induced cardiac dysfunction causing increased total peripheral resistance and reduced cardiac output contributes to the high mortality rate in this patient group. Recent studies, in vivo and in vitro, have suggested levosimendan, milrinone and isoprenaline as inotropic treatment strategies in this patient group. However, these drugs may pose increased risk of ventricular arrhythmias during hypothermia. Our aim was therefore to describe the effects of levosimendan, milrinone and isoprenaline on the action potential in human cardiomyocytes during hypothermia. METHODS: Using an experimental in vitro-design, levosimendan, milrinone and isoprenaline were incubated with iCell2 hiPSC-derived cardiomyocytes and cellular action potential waveforms and contraction were recorded from monolayers of cultured cells. Experiments were conducted at temperatures from 37 °C down to 26 °C. One-way repeated measures ANOVA was performed to evaluate differences from baseline recordings and one-way ANOVA was performed to evaluate differences between drugs, untreated control and between drug concentrations at the specific temperatures. RESULTS: Milrinone and isoprenaline both significantly increases action potential triangulation during hypothermia, and thereby the risk of ventricular arrhythmias. Levosimendan, however, does not increase triangulation and the contractile properties also remain preserved during hypothermia down to 26 °C. CONCLUSIONS: Levosimendan remains a promising candidate drug for inotropic treatment of hypothermic patients as it possesses ability to treat hypothermia-induced cardiac dysfunction and no increased risk of ventricular arrhythmias is detected. Milrinone and isoprenaline, on the other hand, appears more dangerous in the hypothermic setting.

Natural product P57 induces hypothermia through targeting pyridoxal kinase.

Induction of hypothermia during hibernation/torpor enables certain mammals to survive under extreme environmental conditions. However, pharmacological induction of hypothermia in most mammals remains a huge challenge. Here we show that a natural product P57 promptly induces hypothermia and decreases energy expenditure in mice. Mechanistically, P57 inhibits the kinase activity of pyridoxal kinase (PDXK), a key metabolic enzyme of vitamin B6 catalyzing phosphorylation of pyridoxal (PL), resulting in the accumulation of PL in hypothalamus to cause hypothermia. The hypothermia induced by P57 is significantly blunted in the mice with knockout of PDXK in the preoptic area (POA) of hypothalamus. We further found that P57 and PL have consistent effects on gene expression regulation in hypothalamus, and they may activate medial preoptic area (MPA) neurons in POA to induce hypothermia. Taken together, our findings demonstrate that P57 has a potential application in therapeutic hypothermia through regulation of vitamin B6 metabolism and PDXK serves as a previously unknown target of P57 in thermoregulation. In addition, P57 may serve as a chemical probe for exploring the neuron circuitry related to hypothermia state in mice.

Torpor-like Hypothermia Induced by A1 Adenosine Receptor Agonist: A Novel Approach to Protect against Neuroinflammation.

Hypothermia is a promising clinical therapy for acute injuries, including neural damage, but it also faces practical limitations due to the complexities of the equipment and procedures required. This study investigates the use of the A1 adenosine receptor (A1AR) agonist N6-cyclohexyladenosine (CHA) as a more accessible method to induce steady, torpor-like hypothermic states. Additionally, this study investigates the protective potential of CHA against LPS-induced sepsis and neuroinflammation. Our results reveal that CHA can successfully induce a hypothermic state by activating a neuronal circuit similar to the one that induces physiological torpor. This state is characterized by maintaining a steady core body temperature below 28 °C. We further found that this torpor-like state effectively mitigates neuroinflammation and preserves the integrity of the blood-brain barrier during sepsis, thereby limiting the infiltration of inflammatory factors into the central nervous system. Instead of being a direct effect of CHA, this protective effect is attributed to inhibiting pro-inflammatory responses in macrophages and reducing oxidative stress damage in endothelial cells under systemic hypothermia. These results suggest that A1AR agonists such as CHA could potentially be potent neuroprotective agents against neuroinflammation. They also shed light on possible future directions for the application of hypothermia-based therapies in the treatment of sepsis and other neuroinflammatory conditions.

Induction of a torpor-like hypothermic and hypometabolic state in rodents by ultrasound.

Torpor is an energy-conserving state in which animals dramatically decrease their metabolic rate and body temperature to survive harsh environmental conditions. Here, we report the noninvasive, precise and safe induction of a torpor-like hypothermic and hypometabolic state in rodents by remote transcranial ultrasound stimulation at the hypothalamus preoptic area (POA). We achieve a long-lasting (>24 h) torpor-like state in mice via closed-loop feedback control of ultrasound stimulation with automated detection of body temperature. Ultrasound-induced hypothermia and hypometabolism (UIH) is triggered by activation of POA neurons, involves the dorsomedial hypothalamus as a downstream brain region and subsequent inhibition of thermogenic brown adipose tissue. Single-nucleus RNA-sequencing of POA neurons reveals TRPM2 as an ultrasound-sensitive ion channel, the knockdown of which suppresses UIH. We also demonstrate that UIH is feasible in a non-torpid animal, the rat. Our findings establish UIH as a promising technology for the noninvasive and safe induction of a torpor-like state.

Hypothermia as a Possible Symptom of Serotonin Toxicity: A Case Report.

Background There are three commonly used sets of criteria to diagnose serotonin syndrome and all three diagnostic tools have all been shown to have shortcomings that do not fully encompass the possible symptoms of serotonin toxicity. Objective To describe a case of an atypical presentation of possible drug-induced serotonin syndrome, characterized by hypothermia, night sweats, muscle tremors, and confusion. Setting A rural and medically underserved area in eastern Washington State. Practice Description This patient case was identified as a part of a project to identify and intervene with complex and high-risk patients from local rural and underserved populations. The pharmacist identified the symptoms of possible drug-induced serotonin syndrome during a comprehensive medication review with the patient. Results The pharmacist identified a possible case of drug-induced serotonin syndrome and made a recommendation to the patient's physician that led to discontinuation of both fluoxetine and trazodone. At the follow-up visit, the patient reported that his symptoms had resolved completely. Discussion The three sets of diagnostic criteria for serotonin syndrome all include fever as a symptom, but do not list hypothermia. Effects at various 5-HT receptors and receptor subtypes have been linked to symptoms often seen in serotonin syndrome, but there are gaps in the currently used diagnostic criteria. Conclusion Pharmacists' comprehensive review of medications can allow identification of symptoms, such as hypothermia to identify possible serotonin syndrome.

Risk factors for delayed neurocognitive recovery in elderly patients undergoing thoracic surgery.

BACKGROUND: To investigate the risk factors for delayed neurocognitive recovery in elderly patients undergoing thoracic surgery. METHODS: A total of 215 elderly patients who underwent thoracic surgery between May 2022 and October 2022 were recruited in this prospective observational study. Cognitive function was tested by MoCA tests that were performed by the same trained physician before surgery, on postoperative day 4 (POD4), and on postoperative day 30 (POD30). Univariate and multivariate logistic regression models were used to analyze the risk factors for DNR. RESULTS: A total of 154 patients (55.8% men) with an average age of 67.99 ± 3.88 years were finally included. Patients had an average preoperative MoCA score of 24.68 ± 2.75. On the 30th day after surgery, 26 (16.88%) patients had delayed postoperative cognitive recovery, and 128 (83.12%) had postoperative cognitive function recovery. Diabetes mellitus (OR = 6.508 [2.049-20.664], P = 0.001), perioperative inadvertent hypothermia (< 35℃) (OR = 5.688 [1.693-19.109], P = 0.005), history of cerebrovascular events (OR = 10.211 [2.842-36.688], P < 0.001), and VICA (sevoflurane combined with propofol anesthesia) (OR = 5.306 [1.272-22.138], P = 0.022) resulted as independent risk factors of delayed neurocognitive recovery. On the POD4, DNR was found in 61 cases (39.6%), and age ≥ 70 years (OR = 2.311 [1.096-4.876], P = 0.028) and preoperative NLR ≥ 2.5 (OR = 0.428 [0.188-0.975], P = 0.043) were identified as independent risk factors. CONCLUSIONS: The risk factors for delayed neurocognitive recovery in elderly patients undergoing thoracic surgery include diabetes, perioperative inadvertent hypothermia (< 35℃), VICA (sevoflurane combined with propofol anesthesia), and history of cerebrovascular events.

[Antidepressant overdose resulting in coma and hypothermia]. / Coma en hypothermie door een antidepressivum.

BACKGROUND: Cognitive disorders lead to an increased risk of misuse of medication, resulting in possible auto-intoxication. CASE DESCRIPTION: We describe the case of a 68-year-old patient, with hypothermia and a coma, with accidental tricyclic antidepressant (TCA) intoxication. What is remarkable about this case is that there were no cardiac or hemodynamic abnormalities, which is to be expected with both hypothermia and TCA-intoxication. CONCLUSION: Intoxication should be considered in patients with hypothermia and a decreased level of consciousness, in addition to primarily neurological or metabolic causes. A good (hetero)anamnesis with attention to pre-existent cognitive functioning is important. Early screening for intoxication in patients with cognitive disorders with a coma and hypothermia is advisable, even in the absence of a typical toxidrome.

In vivo phenotypic validation of adenosine receptor-dependent activity of non-adenosine drugs.

Some non-adenosinergic drugs are reported to also act through adenosine receptors (ARs). We used mouse hypothermia, which can be induced by agonism at any of the four ARs, as an in vivo screen for adenosinergic effects. An AR contribution was identified when a drug caused hypothermia in wild type mice that was diminished in mice lacking all four ARs (quadruple knockout, QKO). Alternatively, an adenosinergic effect was identified if a drug potentiated adenosine-induced hypothermia. Four drugs (dipyridamole, nimodipine, cilostazol, cyclosporin A) increased the hypothermia caused by adenosine. Dipyridamole and nimodipine probably achieved this by inhibition of adenosine clearance via ENT1. Two drugs (cannabidiol, canrenoate) did not cause hypothermia in wild type mice. Four other drugs (nifedipine, ranolazine, ketamine, ethanol) caused hypothermia, but the hypothermia was unchanged in QKO mice indicating non-adenosinergic mechanisms. Zinc chloride caused hypothermia and hypoactivity; the hypoactivity was blunted in the QKO mice. Interestingly, the antidepressant amitriptyline caused hypothermia in wild type mice that was amplified in the QKO mice. Thus, we have identified adenosine-related effects for some drugs, while other candidates do not affect adenosine signaling by this in vivo assay. The adenosine-modulating drugs could be considered for repurposing based on predicted effects on AR activation.

An unusual case of fatal hypothermia involving topical diphenhydramine.

PURPOSE: Diphenhydramine is an antihistamine drug widely used to alleviate symptoms caused by allergies and the common cold. Diphenhydramine-involved fatalities have been reported in the past but usually involving overdose by ingestion. We report a peculiar case of fatal hypothermia during non-winter season involving topical diphenhydramine. METHODS: A 23-year-old male with no known preexisting medical conditions was found dead in the bathroom of his apartment with a small amount of running water on his back. Postmortem examinations and toxicological analysis on blood and urine were performed. RESULTS: Color difference was apparent between the right and left cardiac blood. Wischnewski spots were observed in the gastric mucosa. Histological examination revealed no obvious findings that could attribute to serious cardiovascular events. Drug screening by gas chromatograph-tandem mass spectrometry (GC/MS/MS) detected diphenhydramine in blood and urine. Further quantification revealed the postmortem concentrations to be 0.44 µg/mL in blood and 2500 µg/mL in urine. CONCLUSIONS: The cause of death was determined to be hypothermia. Diphenhydramine-induced drowsiness and possible intrinsic cardiac factor may have led to prolonged impaired consciousness, preventing his ability to escape from the running cold water leading to hypothermia and death.

Retrospective investigation of decreasing body temperature trends during anaesthesia in dogs.

BACKGROUND: Hypothermia during the perianaesthetic period may lead to an increased risk of morbidity in veterinary patients. However, the timeline of the decrease in body temperature during general anaesthesia has been minimally investigated. METHODS: Anaesthetic records of 1097 client-owned dogs were examined. Change in body temperature (ΔBT = baseline temperature - time point temperature) was plotted over time for all dogs. The slope of ΔBT was calculated for each 15-minute interval, and the magnitude of the largest ΔBT and the time point at which the largest ΔBT occurred were determined for each record. RESULTS: A rapid decline in ΔBT occurred from 0 to 15 minutes, a slower decline occurred from 15 to 60 minutes and a plateau occurred from 60 to 240 minutes. The largest ΔBT occurred at 75 (15-240) minutes from baseline, with a maximum ΔBT of -2.06°C (-0.06°C to -8.72°C). LIMITATIONS: This is a retrospective study. As such, there were missing data points and potential confounding factors could not be controlled for. CONCLUSIONS: Anaesthetised dogs exhibited a distinct pattern of decrease in body temperature, with the most rapid reduction occurring within the first 15 minutes. The effects of procedures and anaesthetic agents on the timeline and pattern of heat loss warrant further investigation.

Intracerebroventricular injection of taurine induces hypothermia through modifying monoaminergic pathways in chicks.

Brain monoamines are reported to regulate body temperature and food intake. The objective of this study was to investigate the mechanism of brain monoamine metabolism in taurine-induced hypothermia and appetite suppression. In Experiment 1, 5-day-old male Julia layer chicks (n = 10) were subjected to intracerebroventricular (ICV) injection with saline or taurine (5 µmol/10 µL). In Experiment 2, the chicks were ICV injected with saline, taurine, fusaric acid (dopamine-ß-hydroxylase inhibitor: 558 nmol), or taurine with fusaric acid. In Experiment 3, the chicks were ICV injected with saline, taurine, para-chlorophenylalanine (PCPA, tryptophan hydroxylase inhibitor: 400 nmol), or taurine with PCPA. In Experiment 4, the chicks were ICV injected with saline, taurine, clorgyline (monoamine oxidase inhibitor: 81 nmol), or taurine with clorgyline. Central taurine lowered rectal temperature at 30 min post-injection and increased norepinephrine in the brainstem and its metabolite 3-methoxy-4-hydroxyphenylglycol in both the diencephalon and brainstem. Similarly, taurine treatment induced increases in serotonin (5-HT) and its metabolite 5-hydroxyindoleacetic acid in the diencephalon. Fusaric acid completely and PCPA partially, but not clorgyline, attenuated taurine-induced hypothermia. The anorexigenic effect of taurine was partially attenuated by PCPA, but not fusaric acid nor clorgyline. In conclusion, central taurine activates dopamine-ß-hydroxylase and tryptophan hydroxylase to produce norepinephrine and 5-HT, and then induces hypothermia, but 5-HT alone may be linked with taurine-induced anorexia in chicks.

Cannabimimetic effects of abused indazole-carboxamide synthetic cannabinoid receptor agonists AB-PINACA, 5F-AB-PINACA and 5F-ADB-PINACA in mice: Tolerance, dependence and withdrawal.

BACKGROUND: Chronic abuse of synthetic cannabinoid receptor agonists (SCRAs), known as "K2″ or "Spice", threatens public health and safety. Recently, SCRAs of the indazole-carboxamide structural class have become more prevalent. Preclinical studies investigating the tolerance and dependence potentially involved in chronic SCRA abuse is limited. The present study determined the in vivo effects of chronic exposure to indazole-carboxamide SCRAs, AB-PINACA, 5F-AB-PINACA and 5F-ADB-PINACA compared to the first-generation SCRA, JWH-018. METHODS: Adult male C57Bl/6 mice were used for dose-effect determinations of hypothermic effects. Adult male NIH Swiss mice were used in biotelemetry studies to assess tolerance to hypothermic effects following repeated SCRA administration over 5 consecutive days, and to determine the role of Phase I drug metabolism via acute CYP450 inhibition in the presence of 1-ABT, a nonspecific CYP450 inhibitor. SCRA dependence was determined in adult male NIH Swiss mice via assessment of rimonabant-precipitated observable sign of withdrawal (i.e., front paw tremors). RESULTS: All SCRAs elicited dose-dependent hypothermia mediated through cannabinoid CB1 receptors (CB1Rs). 1-ABT increased duration of hypothermia for all SCRAs tested, and increased the magnitude of hypothermia for all SCRAs except 5F-ADB-PINACA. Upon repeated administration, tolerance to hypothermic effects of AB-PINACA, 5F-AB-PINACA and 5F-ADB-PINACA was much less than that of JWH-018. Similarly, rimonabant-precipitated front paw tremors were much less frequent in mice treated with 5F-AB-PINACA and 5F-ADB-PINACA than in mice treated with JWH-018. CONCLUSIONS: These findings suggest a decreased potential for tolerance and withdrawal among indazole-carboxamide SCRAs, and may imply structural class-dependent profiles of in vivo effects among SCRAs.

Comparison of the effects of dexmedetomidine and propofol on hypothermia in patients under spinal anesthesia: a prospective, randomized, and controlled trial.

Background: Redistribution hypothermia caused by vasodilation during anesthesia is the primary cause of perioperative hypothermia. Propofol exerts a dose-dependent vasodilatory effect, whereas dexmedetomidine induces peripheral vasoconstriction at high plasma concentrations. This study compared the effects of dexmedetomidine and propofol on core temperature in patients undergoing surgery under spinal anesthesia. Methods: This prospective study included 40 patients (aged 19-70 years) with American Society of Anesthesiologists Physical Status class I-III who underwent elective orthopedic lower-limb surgery under spinal anesthesia. Patients were randomly allocated to a dexmedetomidine or propofol group (n = 20 per group). After induction of spinal anesthesia, patients received dexmedetomidine (loading dose: 1 µg/kg over 10 min; maintenance dose: 0.2-0.7 µg/kg/h) or propofol (loading dose: 75 µg/kg over 10 min; maintenance dose: 12.5-75 µg/kg/min). The doses of sedatives were titrated to maintain moderate sedation. During the perioperative period, tympanic temperatures, thermal comfort score, and shivering grade were recorded. Results: Core temperature at the end of surgery did not differ significantly between the groups (36.4 ± 0.4 and 36.1 ± 0.7°C in the dexmedetomidine and propofol groups, respectively; P = 0.118). The lowest perioperative temperature, incidence and severity of perioperative hypothermia, thermal comfort score, and shivering grade did not differ significantly between the groups (all P > 0.05). Conclusions: In patients undergoing spinal anesthesia with moderate sedation, the effect of dexmedetomidine on patients' core temperature was similar to that of propofol.

[Antidepressant overdose resulting in coma and hypothermia]. / Coma en hypothermie door een antidepressivum.

BACKGROUND: Cognitive disorders lead to an increased risk of misuse of medication, resulting in possible auto-intoxication. CASE DESCRIPTION: We describe the case of a 68-year-old patient, with hypothermia and a coma, with accidental tricyclic antidepressant (TCA) intoxication. What is remarkable about this case is that there were no cardiac or hemodynamic abnormalities, which is to be expected with both hypothermia and TCA-intoxication. CONCLUSION: Intoxication should be considered in patients with hypothermia and a decreased level of consciousness, in addition to primarily neurological or metabolic causes. A good (hetero)anamnesis with attention to pre-existent cognitive functioning is important. Early screening for intoxication in patients with cognitive disorders with a coma and hypothermia is advisable, even in the absence of a typical toxidrome.

Lessons of the month 2: Olanzapine-induced hypothermia and hand oedema.

INTRODUCTION: We describe a case of olanzapine-induced hypothermia and hand oedema in an older adult with behavioural and psychological symptoms of dementia (BPSD). CASE PRESENTATION: An 82-year-old woman with hypothyroidism and dementia was reviewed by the geriatric team at a nursing home in view of lethargy and an unrecordable oral temperature. She was noted to have a bilateral hand oedema and right basal crackles. Investigations revealed high white cell count and inflammatory markers. She was treated as per hypothermia and communityacquired pneumonia protocols. The patient did not have the expected response to treatment. Olanzapine was tailed down and stopped with good effect as it was suspected to be a contributory cause to both the hypothermia and oedema. DISCUSSION AND CONCLUSION: Potentially inappropriate polypharmacy can be specifically targeted with effective deprescribing. Treatment review should be encouraged on a regular basis, especially in frail older adults with polypharmacy.

Recommended doses of medetomidine-midazolam-butorphanol with atipamezole for preventing hypothermia in mice.

A non-narcotic anesthetic combination (Me/Mi/Bu) of medetomidine (Me), midazolam (Mi), and butorphanol (Bu) has been recommended as the injectable anesthesia in mice. An original dose of Me/Mi/Bu (0.3/4.0/5.0 mg/kg) has provided sufficient anesthetic duration of 40-50 min in mice. In addition, atipamezole is available for reversal of Me/Mi/Bu anesthesia. As an adverse effect of Me/Mi/Bu anesthesia, however, severe hypothermia has been also observed in mice. In the present study, we investigated 1) the main agent in Me/Mi/Bu to cause of hypothermia, 2) the effects of the differential doses of atipamezole on hypothermia induced by Me/Mi/Bu anesthesia and on the plasma levels of creatinine phosphokinase and transaminases, and 3) those recommended doses for preventing hypothermia induced by Me/Mi/Bu anesthesia in mice. The results suggested that 1) the α2-agonist medetomidine is most likely to induce hypothermia in mice under Me/Mi/Bu anesthesia, 2) the antagonism of atipamezole within proper dose range is effective in promoting the recovery from Me/Mi/Bu-induced hypothermia, and 3) Me/Mi/Bu at the recommended dose of 0.2/6.0/10.0 mg/kg enable to provide anesthetic effects for 40 min and is more considerable to prevent the hypothermia than that at the original dose of 0.3/4.0/5.0 mg/kg.

Antiplatelet Therapy in Acute Myocardial Infarction and Cardiogenic Shock: Insights From the National Cardiogenic Shock Initiative.

BACKGROUND: Patients presenting with acute myocardial infarction complicated by cardiogenic shock (AMI-CS) are at high risk for impaired antiplatelet activity secondary to malabsorption, systemic hypoperfusion, hypothermia, need for mechanical ventilation, and high use of analgesics. The use of antiplatelet therapy in these high-risk patients is not well studied. METHODS: Using the National Cardiogenic Shock Initiative database, we analyzed patients who presented with AMI-CS at 60 hospitals from March 2018 to December 2020. All patients were treated using a standard shock protocol. Herein, the patterns of antiplatelet use are described. RESULTS: A total of 204 patients were included in the analysis, of which 174 (85.3%) presented with ST-segment elevation myocardial infarction (STEMI). The majority (84.3%) received antiplatelet therapy before percutaneous coronary intervention (PCI); of those who received antiplatelets, 77.9% received aspirin, 55.2% received an oral P2Y12 inhibitor, and 19.2% received intravenous (IV) antiplatelet therapy. Ticagrelor was the most common P2Y12 inhibitor administered (41.9%), followed by clopidogrel (12.2%) and prasugrel (1.2%). Only 18.6% of oral antiplatelet agents were crushed. Baseline characteristics of patients who received IV vs non-IV antiplatelet agents were similar. Thrombolysis in Myocardial Infarction (TIMI) 0 flow was present in 69.6% of patients before PCI and aspiration thrombectomy was performed in 24.5% of patients. The presence of STEMI, cardiac arrest, cardiopulmonary resuscitation, hypothermia, vasopressor use, elevated lactate levels, or number of vessels treated did not influence the use of IV antiplatelet agents. CONCLUSIONS: The use of crushed and IV antiplatelet agents in AMI-CS is low. Further studies are needed in this high-risk population to assess whether more potent antiplatelet inhibition will improve outcomes.

Hypothermic preconditioning attenuates hypobaric hypoxia induced spatial memory impairment in rats.

Hypobaric Hypoxia (HH) is known to cause oxidative stress in the brain that leads to spatial memory deficit and neurodegeneration. For decades therapeutic hypothermia is used to treat global and focal ischemia in preserving brain functions that proved to be beneficial in humans and rodents. Considering these previous reports, the present study was designed to establish the therapeutic potential of hypothermia preconditioning on HH induced spatial memory, biochemical and morphological changes in adult rats. Male Sprague Dawley rats were exposed to HH (7620 m, ~ 282 mmHg) for 1, 3 and 7 days with and without hypothermic preconditioning. Spatial learning memory was assessed by Morris water maze (MWM) test along with evaluation of hippocampal pyramidal neuron damage by histological study. Oxidative stress was measured by studying the levels of nitric oxide (NO), reactive oxygen species (ROS), lipid peroxidation (LPO), oxidized and reduced glutathione (GSSG and GSH). Results of MWM test indicated prolonged path length and latency to reach the platform in HH groups that regained to normal in cold pre-treated groups. A likely neurodegeneration was evident in HH groups that lessen in the cold pre-treated groups. Hypothermic preconditioning prevented spatial memory impairment and neurodegeneration in animals subjected to HH via decreasing the NO, ROS and LPO compared to control animals. The GSH level and GSH/GSSG ratio was found to be higher in preconditioned animals as compared to respective HH exposed animals, indicative of redox scavenging and restoration of hippocampal neuronal structure as well as spatial memory. Therefore, hypothermic preconditioning improves spatial memory deficit by reducing HH induced oxidative stress and hippocampal neurodegeneration, hence can be used as a multi-target prophylactic measure to combat HH induced neurodegeneration.