Subsequent Hypothermia Research Articles

Differential Mitochondrial Bioenergetics in Neurons and Astrocytes Following Ischemia-Reperfusion Injury and Hypothermia.

The close interaction between neurons and astrocytes has been extensively studied. However, the specific behavior of these cells after ischemia-reperfusion injury and hypothermia remains poorly characterized. A growing body of evidence suggests that mitochondria function and putative transference between neurons and astrocytes may play a fundamental role in adaptive and homeostatic responses after systemic insults such as cardiac arrest, which highlights the importance of a better understanding of how neurons and astrocytes behave individually in these settings. Brain injury is one of the most important challenges in post-cardiac arrest syndrome, and therapeutic hypothermia remains the single, gold standard treatment for neuroprotection after cardiac arrest. In our study, we modeled ischemia-reperfusion injury by using in vitro enhanced oxygen-glucose deprivation and reperfusion (eOGD-R) and subsequent hypothermia (HPT) (31.5 °C) to cell lines of neurons (HT-22) and astrocytes (C8-D1A) with/without hypothermia. Using cell lysis (LDH; lactate dehydrogenase) as a measure of membrane integrity and cell viability, we found that neurons were more susceptible to eOGD-R when compared with astrocytes. However, they benefited significantly from HPT, while the HPT effect after eOGD-R on astrocytes was negligible. Similarly, eOGD-R caused a more significant reduction in adenosine triphosphate (ATP) in neurons than astrocytes, and the ATP-enhancing effects from HPT were more prominent in neurons than astrocytes. In both neurons and astrocytes, measurement of reactive oxygen species (ROS) revealed higher ROS output following eOGD-R, with a non-significant trend of differential reduction observed in neurons. HPT after eOGD-R effectively downregulated ROS in both cells; however, the effect was significantly more effective in neurons. Lipid peroxidation was higher after eOGD-R in neurons, while in astrocytes, the increase was not statistically significant. Interestingly, HPT had similar effects on the reduction in lipoperoxidation after eOGD-R with both types of cells. While glutathione (GSH) levels were downregulated after eOGD-R in both cells, HPT enhanced GSH in astrocytes, but worsened GSH in neurons. In conclusion, neuron and astrocyte cultures respond differently to eOGD-R and eOGD-R + HTP treatments. Neurons showed higher sensitivity to ischemia-reperfusion insults than astrocytes; however, they benefited more from HPT therapy. These data suggest that given the differential effects from HPT in neurons and astrocytes, future therapeutic developments could potentially enhance HPT outcomes by means of neuronal and astrocytic targeted therapies.

Abstract 151: The PRINCESS 2 Trial: A Randomized Study to Assess the Impact of Ultrafast Hypothermia on Neurologic Function in Out-of-Hospital Cardiac Arrest With Initial Shockable Rhythm

Background: The impact of ultrafast hypothermia, i.e. delivered intra-arrest or immediately after return of spontaneous circulation (ROSC), on functional neurologic outcome after out-of-hospital cardiac arrest (OHCA) is unclear. In two prior trials, prehospital transnasal evaporative intra-arrest cooling was safe, feasible and reduced time to target temperature. Both studies showed trends towards improved neurologic recovery in patients with shockable rhythms. The aim of the PRINCESS2-study is to assess whether cooling, initiated either intra-arrest or immediately after ROSC, followed by in-hospital hypothermia, significantly increases survival with complete neurologic recovery as compared to standard normothermia care, in OHCA patients with shockable rhythms. Methods/Design: This investigator-initiated, randomized, controlled trial will randomize patients at the scene of cardiac arrest to either transnasal cooling within 20 minutes from Emergency Medical System arrival with subsequent hypothermia at 33°C for 24 hours after hospital admission (intervention), or to standard of care with no prehospital or in-hospital cooling (control). Fever (>37,7 o C) will be avoided for the first 72 hours in both groups. All patients will receive post resuscitation care and withdrawal of life support procedures according to current guidelines. Primary outcome is survival with complete neurologic recovery at 90 days, defined as modified Rankin scale (mRS) 0-1. Key secondary outcomes include survival to hospital discharge, survival at 90 days and mRS 0-3 at 90 days. In total, 970 patients are required to detect an absolute difference of 9 % (from 45 to 54 %) in survival with neurologic recovery (80 % power and 2-sided α=0,5). Recruitment starts in Q3 2023 and we expect maximum enrolment to be achieved during 2024 at 20-25 European and US sites. Discussion: This trial will assess the impact of ultrafast hypothermia applied on the scene of cardiac arrest on survival with complete neurologic recovery in patients with OHCA and shockable rhythm

Effect of systematic graded rewarming measures on body temperature and prognosis of patients undergoing emergency trauma surgery

To observe the effect of systematic graded rewarming measures on body temperature and prognosis of patients with moderate and severe trauma [revised trauma score (RTS) < 12] requiring emergency operation. A prospective randomized double-blind controlled study was conducted. From January 2020 to January 2021, 104 patients who underwent emergency trauma surgery in the Second Affiliated Hospital of Wenzhou Medical University were selected as the research object. According to random number table method, the patients were divided into traditional rewarming group and systematic graded rewarming group, with 52 cases in each group. Patients in traditional rewarming group (only record the body temperature without intervention, and start the rewarming process when the body temperature at any time was less than 36 centigrade); the patients in the system graded rewarming group start the preventive measures as soon as they were admitted to the hospital, and record the body temperature. When the body temperature at any time was less than 36 centigrade, start the graded rewarming process. Observe the rewarming effect, coagulation function, blood gas analysis and postoperative anesthesia recovery time of the two groups and final outcome. With the extension of time, the body temperature of the two groups increased gradually. The body temperature of the systematic grade rewarming group was significantly higher than that of the traditional rewarming group at 2 hours after rewarming and at discharge (centigrade: 36.23±0.77 vs. 35.84±0.93 at 2 hours after rewarming, 36.54±0.87 vs. 35.82±0.92 at discharge, both P < 0.05). The incidence of subsequent hypothermia was significantly lower than that in the traditional rewarming group [7.7% (4/52) vs. 25.0% (13/52), P < 0.05]. The postoperative activated partial thromboplastin time (APTT) of the two groups was significantly shorter than that at admission (s: 35.74±8.05 vs. 45.55±28.02 in the systematic rewarming group, P < 0.05; 38.35±6.48 vs. 42.40±13.18 in the traditional rewarming group, P < 0.05); the intraoperative and postoperative pH values in the systematic rewarming group were significantly higher than those at admission (7.33±0.05, 7.36±0.06 vs. 7.30±0.07, both P < 0.05), while there was no significant difference between the intraoperative and postoperative pH values in the traditional rewarming group and those at admission (7.31±0.06, 7.33±0.06 vs. 7.31±0.05, both P > 0.05). The postoperative prothrombin time (PT) and anesthesia recovery time in the systematic graded rewarming group were significantly shorter than those in the traditional rewarming group [PT (s): 15.05±2.44 vs. 17.94±3.48, anesthesia recovery time (hours): 14.40±11.76 vs. 17.35±10.51, all P < 0.05], and the pH value was significantly higher than that in the traditional rewarming group (7.36±0.06 vs. 7.33±0.06, P < 0.05). The systematic graded rewarming group had higher improvement rate and lower disability rate than the traditional rewarming group (76.9% vs. 65.4% and 17.3% vs. 25.0%, both P < 0.05). Systematic graded rewarming measures can improve the hypothermia of emergency trauma patients who received surgery, reduce the incidence of subsequent hypothermia of trauma patients, shorten the time of postoperative resuscitation, improve the coagulation function and blood gas indexes, improve the treatment rate, and reduce the incidence of disability.

Ultra-mini Pcnl with clear Petra® suction–evacuation access sheath and warming irrigation fluid system (Rocamed®) for stone treatment in children

Inadvertent perioperative hypothermia (a drop in core temperature to below 36°C) occurs because of interference with normal temperature regulation by anaesthetic drugs, skin exposure for prolonged periods and the introduction of large volumes of intravenous and irrigation fluids. If the temperature of these fluids is below core body temperature, they can cause significant heat loss. Warming irrigation fluids might prevent some of this heat loss and subsequent hypothermia and that is the role of warming irrigation fluid systems. The video describes prone ultra mini PCNL with suction-evacuation access sheath under warming irrigation fluid system in a 15 month-old boy with a 2cm-600HU staghorn calculi and one stone of 7mm-500HU in proximal ureter. The surgery was performed without intraoperative complications and perioperative hypothermia was prevented. The patient started the surgery at 35.4°C and the final temperature was 36.3°C in 90min of procedure, in addition to being free of stones. The warming irrigation fluid system can be helpful in preventing inadvertent perioperative hypothermia in children, improving the safety of ultra mini PCNL with suction-evacuation access sheath and shows promising results with high stone-free rates and low complications.

Management of Cold Water-induced Hypothermia: A Simulation Scenario for Layperson Training Delivered via a Mobile Tele-simulation Unit.

Newfoundland and Labrador (NL) has one of the highest provincial drowning rates in Canada, largely due to the many rural communities located near bodies of water. Factor in the province’s cold climate (average NL’s freshwater temperature is below 5.4°C)and the prevalence of winter recreational activities among the population, there exists an inherent risk of ice-related injuries and subsequent hypothermia. Oftentimes, these injuries occur in remote/rural settings where immediate support from Emergency Medical Services (EMS) may not be available. During this critical period, it frequently falls on individuals without formal healthcare training to provide lifesaving measures until help arrives.Training individuals in rural communities plays an important role in ensuring public safety. In recent years, simulation-based education has become an essential tool in medical, marine and first aid training. It provides learners with a safe environment to hone their skills and has been shown to be superior to traditional clinical teaching methods. The following case aims to train laypeople from rural settings in the immediate management of an individual who becomes hypothermic following immersion into cold water.However, reaching these individuals to provide training can be a challenge in a province with such a vast geography. To assist with overcoming this, the development of a simulation center that is portable between communities (or Mobile Tele-Simulation Unit) has occurred. By utilizing modern technology, this paper also proposes an innovative method of connecting with learners in more difficult to reach regions.

Warming of intravenous and irrigation fluids for preventing inadvertent perioperative hypothermia.

Inadvertent perioperative hypothermia (a drop in core temperature to below 36°C) occurs because of interference with normal temperature regulation by anaesthetic drugs, exposure of skin for prolonged periods and receipt of large volumes of intravenous and irrigation fluids. If the temperature of these fluids is below core body temperature, they can cause significant heat loss. Warming intravenous and irrigation fluids to core body temperature or above might prevent some of this heat loss and subsequent hypothermia. To estimate the effectiveness of preoperative or intraoperative warming, or both, of intravenous and irrigation fluids in preventing perioperative hypothermia and its complications during surgery in adults. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2014, Issue 2), MEDLINE Ovid SP (1956 to 4 February 2014), EMBASE Ovid SP (1982 to 4 February 2014), the Institute for Scientific Information (ISI) Web of Science (1950 to 4 February 2014), Cumulative Index to Nursing and Allied Health Literature (CINAHL) EBSCOhost (1980 to 4 February 2014) and reference lists of identified articles. We also searched the Current Controlled Trials website and ClinicalTrials.gov. We included randomized controlled trials or quasi-randomized controlled trials comparing fluid warming methods versus standard care or versus other warming methods used to maintain normothermia. Two review authors independently extracted data from eligible trials and settled disputes with a third review author. We contacted study authors to ask for additional details when needed. We collected data on adverse events only if they were reported in the trials. We included in this review 24 studies with a total of 1250 participants. The trials included various numbers and types of participants. Investigators used a range of methods to warm fluids to temperatures between 37°C and 41°C. We found that evidence was of moderate quality because descriptions of trial design were often unclear, resulting in high or unclear risk of bias due to inappropriate or unclear randomization and blinding procedures. These factors may have influenced results in some way. Our protocol specified the risk of hypothermia as the primary outcome; as no trials reported this, we decided to include data related to mean core temperature. The only secondary outcome reported in the trials that provided useable data was shivering. Evidence was unclear regarding the effects of fluid warming on bleeding. No data were reported on our other specified outcomes of cardiovascular complications, infection, pressure ulcers, bleeding, mortality, length of stay, unplanned intensive care admission and adverse events.Researchers found that warmed intravenous fluids kept the core temperature of study participants about half a degree warmer than that of participants given room temperature intravenous fluids at 30, 60, 90 and 120 minutes, and at the end of surgery. Warmed intravenous fluids also further reduced the risk of shivering compared with room temperature intravenous fluidsInvestigators reported no statistically significant differences in core body temperature or shivering between individuals given warmed and room temperature irrigation fluids. Warm intravenous fluids appear to keep patients warmer during surgery than room temperature fluids. It is unclear whether the actual differences in temperature are clinically meaningful, or if other benefits or harms are associated with the use of warmed fluids. It is also unclear if using fluid warming in addition to other warming methods confers any benefit, as a ceiling effect is likely when multiple methods of warming are used.

Cardiovascular and thermoregulatory biomarkers of heat stroke severity in a conscious rat model.

Multiorgan failure is a catastrophic consequence of heat stroke (HS) and considered the underlying etiology of mortality. Identifying novel biomarkers capable of predicting the extent of HS-induced organ damage will enhance point-of-care triage and treatment. Conscious male F344 rats (n = 32) were radiotelemetered for continuous core temperature (Tc), heart rate, and arterial pressure measurement. Twenty-two animals were exposed to ambient temperature of 37°C to a maximum Tc of 41.9 ± 0.1°C. Rats were euthanized at 24 h of recovery for analysis of plasma biomarkers [cardiac troponin I (cTnI), blood urea nitrogen (BUN), alanine aminotransferase (ALT), albumin, glucose] and histology. Tc profiles observed during recovery stratified HS severity into Mild, Moderate, and Severe. Eleven (50%) animals exhibited an acute compensatory hemodynamic response to heat exposure and a monophasic Tc profile consisting of sustained hyperthermia (∼1°C). Five (23%) rats displayed hemodynamic challenge and a biphasic Tc profile with rapid return to baseline followed by rebound hyperthermia. All biomarkers were significantly altered from control values (P < 0.05). Four (18%) animals exhibited significant hemodynamic compromise during heat and a triphasic profile characterized by rapid cooling to baseline Tc, rebound hyperthermia, and subsequent hypothermia (∼35°C) through 24 h. cTnI showed a 40-fold increase over CON (P < 0.001) and correlated with BUN (r = 0.912) consistent with cardiorenal failure. Hypoglycemia correlated with ALT (r = 0.824) suggestive of liver dysfunction. Histology demonstrated myocardial infarction, renal tubular necrosis, and acute liver necrosis. Two (9%) animals succumbed during HS recovery. This study identified novel biomarkers that predict HS severity and organ damage during acute recovery that could provide clinical significance for identifying key biomarkers of HS pathogenesis.

Partners' ambivalence towards cardiac arrest and hypothermia treatment: a qualitative study

The purpose of this study was to examine the experiences of partners of patients who had cardiac arrest and subsequent hypothermia treatment in an intensive care unit (ICU). Nine in-depth interviews were conducted 5 months to 1 year after hospitalization. The participants were partners of patients who had survived cardiac arrest and had undergone hypothermia treatment without serious brain damage. All the interviews were analysed using Giorgi's phenomenological method. Six main themes emerged from the analysis: (1) terrified by witnessing the cardiac arrest; (2) ambivalence towards the ICU room and the cold body; (3) need for honest and realistic information; (4) anticipating the awakening; (5) social network as support and burden; and (6) the frightening homecoming. The essential structure of the partners' experiences of loved ones' cardiac arrest and hypothermia treatment was characterized by ambivalence; they experienced both fear and relief. There may be a relationship between experiences before entering the ICU and reactions during hypothermia treatment and afterwards. Some partners experienced a feeling of guilt after the resuscitation event, and especially during the awakening phase. After discharge, the partners described feeling anxiety. Nurses play a pivotal role in providing partners with information and in nurturing hope and feelings of security. Partners need to fully understand the reason for hypothermia treatment to enable them to accept the cold body as part of a life-saving process. We recommend follow-up after discharge. This may increase the partners' sense of security and control.

Severe Hypothermia Increases the Risk for Intensive Care Unit-Acquired Infection

Although hypothermia is widely accepted as a risk factor for subsequent infection in surgical patients, it has not been well defined in medical patients. We sought to assess the risk of acquiring intensive care unit (ICU)--acquired infection after hypothermia among medical ICU patients. Adults (≥18 years) admitted to French ICUs for at least 2 days between April 2000 and November 2010 were included. Surgical patients were excluded. Patient were classified as having had mild hypothermia (35.0°C-35.9°C), moderate hypothermia (32°C-34.9°C), or severe hypothermia (<32°C), and were followed for the development of pneumonia or bloodstream infection until ICU discharge. A total of 6237 patients were included. Within the first day of admission, 648 (10%) patients had mild hypothermia, 288 (5%) patients had moderate hypothermia, and 45 (1%) patients had severe hypothermia. Among the 5256 patients who did not have any hypothermia at day 1, subsequent hypothermia developed in 868 (17%), of which 673 (13%), 176 (3%), and 19 (<1%) patients had lowest temperatures of 35.0°C-35.9°C, 32.0°C-34.9°C, and <32°C, respectively. During the course of ICU admission, 320 (5%) patients developed ICU-acquired bloodstream infection and 724 (12%) patients developed ICU-acquired pneumonia. After controlling for confounding variables in multivariable analyses, severe hypothermia was found to increase the risk for subsequent ICU-acquired infection, particularly in patients who did not present with severe sepsis or septic shock. The presence of severe hypothermia is a risk factor for development of ICU-acquired infection in medical patients.

Early protective effect of hypothermia in newborn pigs after hyperoxic, but not after normoxic, reoxygenation

Abstract Mild hypothermia can attenuate the development of brain damage after asphyxia. Supplemental oxygen during resuscitation increases generation of reactive oxygen species, compared to room air. It is unknown if supplemental oxygen affects hypothermic neuroprotection. We studied the early effects of hyperoxic reoxygenation and subsequent hypothermia on tissue oxygenation, microcirculation, inflammation and brain damage after global hypoxia. Anesthetized newborn pigs were randomized to control (n=6), or severe global hypoxia (n=46). Three pigs died during hypoxia or reoxygenation. After 20-min reoxygenation with room air (n=22) or 100% oxygen (n=21), pigs were randomized to normothermia (deep rectal temperature 39 degrees C, n=22) or total body cooling (35 degrees C, n=21) for 6.5 h before the experiment was terminated. We demonstrated a differential effect of post-hypoxic hypothermia between animals reoxygenated with 100% oxygen and with room air, with reduced damage only in hypothermic animals reoxygenated with 100% oxygen (P=0.001). Hyperoxic reoxygenation resulted in a significant overshoot in striatal oxygen tension, without affecting microcirculation. Inflammatory response after the insult did not differ between groups. The results indicate an early protective effect of hypothermia which may vary with oxygen level used during reoxygenation.

Intra-Operative Warming with a Forced-Air Warmer in Preventing Hypothermia after Tourniquet Deflation in Elderly Patients

This randomized, single-blind study aimed to explore the effects of intra-operative warming with a forced-air warmer in the prevention of hypothermia after tourniquet deflation in elderly patients undergoing unilateral total knee replacement arthroplasty under general anaesthesia. Patients were randomized to receive either intra-operative warming using a forced-air warmer with an upper body blanket (warming group; n = 12) or no intra-operative warming (nonwarming group; n = 12). Oesophageal temperature was measured as core body temperature. At 30 min following tourniquet inflation, the core body temperature started to increase in the warming group whereas it continued to drop in the non-warming group. This difference was statistically significant. The final core body temperature after tourniquet deflation was significantly higher in the warming group (mean +/- SD 36.1 +/- 0.2 degrees C) than in the non-warming group (35.4 +/- 0.3 degrees C). Intra-operative forced-air warming increased the core body temperature before tourniquet deflation and prevented subsequent hypothermia in elderly patients under general anaesthesia.

Diazoxide preconditioning plus subsequent hypothermia increased resistance of rat cultured hippocampal neurons against hypoxia-reoxygenation injury

Cerebral ischemia-reperfusion/hypoxia-reoxygenation insult triggers lots of pathophysiological and biochemical events that separately affect the evolution of cerebral damage. Accordingly, all known effective neuroprotective measures should be taken to get the optimal efficacy of therapy. This study was undertaken to investigate whether diazoxide (DZ) preconditioning combined with the following hypothermia could contribute to synergistic neuroprotection compared with either hypothermia or DZ preconditioning alone. Cultured for 9-10 days in vitro, the hippocampal neurons of SD rats were preconditioned with DZ 0 micromol/L or DZ 250 micromol/L for 1 hour per day and this treatment lasted for 3 days. Subsequently, neurons were subjected to deprivation of oxygen for 4 hours at 37 degrees C, 34 degrees C, 30 degrees C and 22 degrees C, respectively. This experiment consisted of 8 groups (4 temperature groups and 4 combination groups) and each group contained 12-well or 2-dish cells. Survival rate, expression of Bcl-2, fluorescence magnitude of intracellular calcium, and concentration of malondialdehyde (MDA) were determined at 24 hours after reoxygenation. The survival rate and expression of Bcl-2 were both increased in individually hypothermic conditions compared with those at 37 degrees C (P < 0.05), whereas intracellular calcium and MDA did the opposite exhibition simultaneously (P < 0.05). 22 degrees C contributed to a higher survival rate and greater expression of Bcl-2 in comparison with other hypothermia (P < 0.05). Preceding administration of 250 micromol/L DZ took the similar effects on the neurons like hypothermia. Moreover, compared with individual hypothermia or DZ preconditioning, the neuronal survival rate and expression of Bcl-2 in the combination group were increased significantly (P < 0.05), whereas the calcium fluorescence density and concentration of MDA were reduced further (P < 0.05). 250 micromol/L DZ preconditioning combined with 22 degrees C provided a maximal neuroprotection. Compared with either individual hypothermia or DZ preconditioning, the combination of both treatments conferred synergistic protection for cultured hippocampal neurons in vitro against hypoxia-reoxygenation insult.

Diazoxide preconditioning combined with subsequent hypothermia alleviates anoxia-re-oxygenation injury: experiment with rat hippocampal neurons

To observe the alleviative effects of preconditioning with diazoxide (DZ), a mitochondrial ATP-sensitive potassium channel opener, combined with subsequent hypothermia on anoxia-re-oxygenation injury. Hippocampal neurons of new-born SD rat were cultured. DZ of the concentration of 250 micromol/L was added into the culture fluid. The group of preconditioned cultured neurons were re-divided into 4 subgroups to be treated by hypothermia of different levels: 37 degrees C, 34 degrees C, 30 degrees C, and 22 degrees C, and then were derived of oxygen for 4 hours. The group of neurons without addition of DZ was re-divided into 4 subgroup too to be exposed to different temperatures and then underwent anoxia-re-oxygenation as described above. Thus the experiment was performed on 8 subgroups in total. Twenty-four hours after re-oxygenation the neurons were stained with dimethyl sulfoxide and their levels of absorptivity were measured so as to calculate the survival rate. Modified thiobarbital method was used to detect the concentration of malondialdehyde (MDA) in the culture fluid. Fluorescence probe Fluo-3-AM was added to detect the Ca(2+) concentration in the neurons. The survival rates of the DZ-preconditioned neurons of the 22 degrees C, 30 degrees C, and 34 degrees C subgroups were (94 +/- 8)%, (73 +/- 9)%, (67 +/- 8)% respectively, all significantly higher than that of the 37 degrees C subgroup (57 +/- 6%, all P < 0.01), with significant differences between the 22 degrees C subgroup and the 30 degrees C and 34 degrees C subgroups (both P < 0.01). The survival rates of the non-DZ-preconditioned neurons of the 22 degrees C, 30 degrees C, and 34 degrees C subgroups were 66 +/- 10%, 52 +/- 910%, 48 +/- 9% respectively, all significantly higher than that of the 37 degrees C subgroup (41% +/- 7%, all P < 0.01), with significant differences between the 22 degrees C subgroup and the 30 degrees C and 34 degrees C subgroups (both P < 0.01). The survival rates at different temperatures in the DZ-preconditioned group were all significantly higher than those in the corresponding non-preconditioned subgroups (all P < 0.01). The MDA concentration in the culture fluid of the 22 degrees C subgroup was significantly lower than those of the 30 degrees C, 34 degrees C, and 37 degrees C subgroups in both the DZ-preconditioned and non-preconditioned groups (all P < 0.01). The MDA concentrations of the preconditioned subgroups at different temperatures were all significantly lower than those of the corresponding non-preconditioned subgroups (all P < 0.01). The fluorescent value of the intracellular Ca(2+) of the 22 degrees C subgroup was significantly lower than those of the 30 degrees C, 34 degrees C, and 37 degrees C subgroups in both the DZ-preconditioned and non-preconditioned groups (all P < 0.01). The fluorescent value of the intracellular Ca(2+) of the preconditioned subgroups at different temperatures were all significantly lower than those of the corresponding non-preconditioned subgroups (all P < 0.01). Hypothermia alleviates the anoxia-re-oxygenation injury: DZ preconditioning enhances the neuroprotection by hypothermia.

Was the biblical King David affected by hypothermia?

The elderly population has suffered from hypothermia for thousands of years. This report analyzes the first documented case of hypothermia as described in the Bible. The sentence "Now King David was old and stricken in years, and they covered him with clothes, but he gained no warmth" indicates that hypothermia afflicted the biblical King David, the second and the greatest of Israel's kings, who ruled the country 3000 years ago. Environmental factors did not play a significant role in the development of hypothermia. Among various diseases, the most likely to cause immobility and subsequent hypothermia are dementia, senile osteoporosis, hyperparathyroidism, and malignancy. Among these diseases, malignancy is the most likely. Viewed by a modern physician, the story of King David unfolds as possibly the earliest description of a patient affected by hypothermia, features of which have changed little through the ages. This report shows that the roots of contemporary geriatrics lead back to biblical times.

The effects of core and peripheral warming methods on temperature and physiologic variables in injured children

Injured children are at risk for thermoregulatory compromise, where temperature maintenance mechanisms are overwhelmed by severe injury, environmental exposure, and resuscitation measures. Adequate thermoregulation can be maintained, and heat loss can be prevented, by core (administration of warmed intravenous fluid) and peripheral (application of convective air warming) methods. It is not known which warming method is better to maintain thermoregulation and prevent heat loss in injured children during their trauma resuscitations. The purpose of this feasibility study was to compare the effects of core and peripheral warming measures on body temperature and physiologic changes in a small sample of injured children during their initial emergency department (ED) treatment. A prospective, randomized experimental design was used. Eight injured children aged 3 to 14 years (mean = 6.87, SD = 3.44 ) treated in the ED of Children's Hospital of Pittsburgh were enrolled. Physiologic responses (eg, heart rate, blood pressure, respiratory rate, arterial oxygen saturation, core, peripheral temperatures) and level of consciousness were continuously measured and recorded every 5 minutes to detect early thermoregulatory compromise and to determine the child's response to warming. Data were collected throughout the resuscitation period, including transport to CT scan, the inpatient nursing unit, intensive care unit, operating room or discharge to home. Core warming was accomplished with the Hotline Fluid Warmer (Sims Level 1, Inc., Rockland, MA), and peripheral warming was accomplished with the Snuggle Warm Convective Warming System (Sins Level 1, Inc., Rockland, MA). Data were analyzed using descriptive and inferential statistics. There were no statistically significant differences between the two groups on age (t = -0.485, P = 0.645); weight (t = -0.005, P = 0.996); amount of prehospital intravenous (IV) fluid (t = 0314, P = 0.766); temperature on ED arrival (t = 0.287, P = 0.784); total amount of infused IV fluid (t = -0.21, P = 0.8); and length of time from ED admission to hospital admission (t = -0.613, P = 0.56). There were no statistically significant differences between the two groups on RTS (t = -0.516, P = 0.633). When comparing the mean differences in temperature upon hospital admission, no statistically significant differences were found (t = -1.572, P = 0.167). There were no statistically significant differences between the two groups in tympanic [F(15) = 0.71, P = 0.44] and skin [F(15) = 0.06, P = 0.81] temperature measurements over time. Core and peripheral warming methods appeared to e effective in preventing heat loss in this stable patient population. A reasonable next step would be to continue this trial in a larger sample of patients who are at greater risk for heat loss and subsequent hypothermia and to use a control group.

The effects of selective dopamine receptor agonists and antagonists on body temperature in rats

Body temperature was measured at repeated time intervals following the administration of various dopamine agonists and antagonists. The D-1 and D-2 receptor agonist, apomorphine, produced dose-dependent hypothermia. This effect was inhibited by the D-2 receptor antagonist, spiroperidol. Stimulation of D-2 receptor by LY171555 produced dose-dependent hypothermia, which was attenuated by pretreatment with spiroperidol and not altered by the D-1 receptor antagonist SCH23390. The D-1 receptor agonist, SK&F38393 had no effect on body temperature. SCH23390 administered alone produced initial hyperthermia and subsequent hypothermia. When administered with apomorphine, SCH23390 both attenuated and potentiated the hypothermic response, depending on the dose and time of administration of each drug. The results suggest that dopamine receptor agonists induce hypothermia by stimulation of the D-2 receptor subtype.

Peroperative hypothermia.

Heat loss during anesthesia and operation and subsequent hypothermia will increase the postoperative oxygen demand and may endanger patients with restricted cardiopulmonary reserves. Forty patients scheduled for intra-abdominal aortic surgery and 40 patients scheduled for peripheral vascular surgery on the lower limbs were investigated using a warming blanket, humidified heated inspired anesthetic gases at 37-40 degrees C, or both these methods together. A fourth group of patients received no active warming. A warming blanket used alone gave no protection against hypothermia when compared with no active warming. In the abdominal surgical group, there was a steady fall in temperature throughout the operation if no warming method was employed. In this group the use of humidified, heated inspired gases was significantly better than no treatment after 2 h of anesthesia (P less than 0.05). The combination of humidified and heated inspired gases and a warming blanket gave significantly better heat preservation after 40 min (P less than 0.05). Patients undergoing peripheral vascular surgery had similar but smaller drops in temperature with the different types of warming procedures employed. The differences in temperature between the intra-abdominal and extra-abdominal operations were statistically significant after 3 h (P less than 0.05).

The effects of bombesin injected into the anterior and posterior hypothalamus on body temperature and oxygen consumption

Bombesin was microinjected into the lateral ventricle, preoptic area, and posterior hypothalamus of cold-exposed rats. Preoptic and ventricular injections produced dose-dependent depressions in metabolism with subsequent hypothermia. Furthermore, injections into the preoptic area elicited greater depressions in body temperature than equivalent doses injected into the lateral ventricle. No changes in oxygen consumption or body temperature resulted from posterior hypothalamic administration of the peptide. The data suggest that the preoptic area may be an important site of action for bombesin and that bombesin-induced hypothermia is mediated, at least in part, by a reduction in metabolic rate.

Genetical differences in sensitivity to tremorine and oxotremorine in mice

Male mice from 14 straind were injected i.p. with tremorine (3.0 mg/kg) or oxotremorine (0.15 pr 0.1 mg/kg). Large inter-strain differences in the degree and duration of the subsequent hypothermia were noted. 2 strains, BALB/c and Simpson, were particularly sensitive to the hypothermic effect of oxotremorine. The offspring from a cross between BALB/c and Simpson were less sensitive than the parental strains, suggesting genetic complementation. A set of 7 recombinant inbred (RI) lines derived from the strains C57BL and BALB/c were tested with oxotremorine. 5 RI lines resembled strain C57BL in their response and 2 RI lines resembled strain BALB/c. It was concluded that strains C57BL and BALB/c differ at a gene which has a major effect on the response to oxotremorine.

Sympathetic inhibition of thermogenesis in the infant rat: possible glucostatic control.

Nonshivering thermogenesis (NST) was examined during cold exposure (30 degrees C) in 5-day-old rats, during food deprivation. NST in the fed state doubled the O2 consumption observed at neutral temperatures. With fasting, the additional O2 consumption stimulated by cold dropped to that observed at thermoneutrality within 6 h, and colonic temperature (Tco) dropped concomitantly. Blood glucose (BG) concentration was halved. Oxygen consumption and Tco in the cold varied linearly with BG changes during food deprivation. 6-Hydroxydopamine transiently stimulated norepinephrine release and elevated metabolism nonadditively with cold stimulation in fed animals, and also stimulated O2 consumption. The drug also partially restored BG concentration, after it had declined during fasting. NST and BG were also restored by gastric infusion of glucose. These data suggest that the decline of NST, and the subsequent hypothermia during food deprivation, is in large part a sympathetically mediated reflex response to low cerebral BG concentration. However, glucose injection in doses sufficient to restore BG after fasting did not restore NST, nor was NST abolished by intracellular glucoprivation with 2-deoxy-D-glucose in fed rats. Thus, it is not argued that BG concentration is in itself an adequate signal for controlling NST.