Hours Of Rewarming Research Articles

Moderate Hypothermia Effectively Alleviates Acetaminophen-Induced Liver Injury With Prolonged Action Beyond Cooling.

Acetaminophen (APAP) overdose accounts for the highest incidence of acute liver failure, despite the availability of an antidote i.e. N-acetylcysteine. This calls for alternative strategies to manage APAP-induced liver injury (AILI). Therapeutic hypothermia has been explored in past studies for hepatoprotection, but these phenomenal reports lack clarification of its optimal window for application, and mechanistic effects in specific AILI. Hence, we conducted an in vitro study with transforming growth factor-α transgenic mouse hepatocytes cell line, TAMH, and human liver hepatocytes cell line, L-02, where cells were conditioned with deep (25°C) or moderate (32°C) hypothermia before, during or after APAP toxicity. Cell viability was evaluated as a hallmark of cytoprotection, along with cell death. Simultaneously, cold shock proteins (CSPs) and heat shock proteins expressions were monitored; key liver functions including drug-metabolizing ability and hepatic clearance were also investigated. Herein, we demonstrated significant hepatoprotection with 24-hour moderate hypothermic conditioning during AILI and this effect sustained for at least 24 hours of rewarming. Such liver preservation was associated with a CSP—RNA-binding motif protein 3 (RBM3) as its knockdown promptly abolished the cytoprotective effects of hypothermia. With mild and reversible liver perturbations, hypothermic therapy appears promising and its RBM3 involvement deserves future exploration.

Electrocardiographic changes in patients undergoing targeted temperature management.

ObjectivesTargeted temperature management is the recommended therapy for comatose patients after an out‐of‐hospital cardiac arrest resuscitation due to the reduction in neurological damage and improved outcomes. However, there may result in electrocardiographic instability depending on the degree of targeted temperature management, including minor or life‐threatening dysrhythmias or conduction delays. This project aims to describe the frequency of ECG interval changes and clinically relevant dysrhythmias in targeted temperature management patients.MethodsThis is a retrospective observational study from January 2009 to December 2015. Patients who qualified for the study had a non‐traumatic cardiac arrest with a return of spontaneous circulation, received targeted temperature management at 33.5°C for 24 hours followed by 16 hours of rewarming. ECG interval changes and dysrhythmias were recorded immediately after return of spontaneous circulation, and at 24 and 48 hours post return of spontaneous circulation.ResultsA total of 322 patients (age 61.0 ± 16.9 years) had targeted temperature management initiated during the study period, of which 169 had complete data and 13 died prior to completing 24 hours of hypothermia. There were statistically significant changes during targeted temperature management in heart rate (96.7 ± 26.0/min before targeted temperature management; 69.5 ± 19.1/min during, P < 0.001), QRS duration (115.1 ± 32.6 ms before targeted temperature management; 107.8 ± 27.9 ms during targeted temperature management, P < 0.001), and QTc (486.3 ± 52.8 ms before targeted temperature management; 526.9 ± 61.7 ms during targeted temperature management, P < 0.001). There were cardiac dysrhythmias that received treatment during cooling and rewarming.ConclusionDuring the period of targeted temperature management and rewarming, we observed few self‐limiting ECG interval changes and no clinically significant dysrhythmias in this population during the period of targeted temperature management.

Management of accidental hypothermia: an established extracorporeal membrane oxygenation centre experience.

Data on management of severe accidental hypothermia published from an established high-volume extracorporeal membrane oxygenation centre are scarce. A total of 28 patients with intravesical temperature lower than 28°C on admission were either treated with veno-arterial extracorporeal membrane oxygenation or rewarmed conservatively. A total of 10 patients rewarmed on veno-arterial extracorporeal membrane oxygenation (age: 37 ± 12.6 years) and 18 conservatively (age: 55.2 ± 11.2 years) were collected over a course of 5 years. The dominant cause was alcohol intoxication with exposure to cold (39%), 12 patients were resuscitated prior to admission. The admission temperature in the extracorporeal membrane oxygenation group (23.8 ± 2.6°C) was lower than in the non-extracorporeal membrane oxygenation group (26.0 ± 1.5°C, p = 0.01). The peripheral percutaneous veno-arterial extracorporeal membrane oxygenation was always cannulated in malignant arrhythmias causing refractory cardiac arrest. The typical extracorporeal membrane oxygenation blood flow was 3-4 L/minute and sweep gas flow 2 L/minute, the median extracorporeal membrane oxygenation duration was 48.3 (28.1-86.7) hours. The median rates of rewarming did not differ (0.41 (0.35-0.7)°C/hour in extracorporeal membrane oxygenation and 0.77 (0.54-0.98)°C/hour in non-extracorporeal membrane oxygenation, p = 0.46) as well as the admission arterial lactate, pH and potassium. Their development was not different between the groups except for higher pH between the third and ninth hour of rewarming in the extracorporeal membrane oxygenation group. The hospital mortality was 10% in the extracorporeal membrane oxygenation group and 11.1% in the non-extracorporeal membrane oxygenation group with the median last Glasgow Coma Scale 15 and Cerebral Performance Score 1. Veno-arterial extracorporeal membrane oxygenation for severe hypothermia shows promising outcome data collected in an extracorporeal membrane oxygenation/extracorporeal cardiopulmonary resuscitation centre located in a European urban area. Except for presence of refractory cardiac arrest, the established hypothermia-related prognostic indicators did not differ between patients in need for extracorporeal membrane oxygenation and those rewarmed without extracorporeal membrane oxygenation.

ENERGY EXPENDITURE DURING TARGETED TEMPERATURE MANAGEMENT: A PROSPECTIVE COHORT STUDY

SESSION TITLE: Miscellaneous Critical Care SESSION TYPE: Original Investigations PRESENTED ON: 10/10/2018 07:30 AM - 08:30 AM PURPOSE: To measure and quantify the relationship between core body temperature and metabolic consumption during targeted temperature management. METHODS: Ten patients (mean age 39.7, range 24 to 65, 7 males, 3 females) undergoing targeted temperature management after cardiac arrest at 32OC to 33OC were included in this prospective cohort study.Mild therapeutic hypothermia was induced by active cooling using temperature controlled intravenous filters (Zoll Thermoguard XP). A triple lumen catheter was inserted into a femoral vein. Core body temperature was continuously monitored.After ROSC external passive and internal active cooling was started immediately in order to expedite the reduction of body temperature, once the thermometer reached 32O to 33OC the external cooling was stopped and internal active cooling was used to maintain the temperature over a period of 48 hours.The rewarming phase was undertaken over a period of 24 hours (1OC/3 hours).Indirect calorimetry was determined by computerized respiratory gas exchange (Deltatrac II, Datex-Ohmeda). Oxygen consumption and carbon dioxide production were measured every hour during induction, the 48 hours of hypothermia and 24 hours of rewarming. The basal metabolic rate (kilocalories/day) was calculated using the Harris-Benedict equation: RESULTS: Cooling was started within 15±7 minutes after ROSC. The core body target temperature was achieved after 95±30 minutes of initiating cooling. The average drop in temperature compared to the target temperature (32OC- 33OC) was 2.7OC per hour. During the stage of steady state of targeted temperature management, core body temperature was 31.5±0.9OC.The oxygen consumption compared with baseline temperature was reduced by 82 mL/min (95% CI 59 to 107 mL/min; p=0.003).The basal metabolic rate was decreased by 35.6% (95% CI 26.9 to 52.3%; p=0.004) during the stage of steady state targeted temperature management.Future analysis and calculations will compute correlation between temperature, time and energy expenditure as well as estimations of fat and protein oxidation rates by means of mathematical equations. CONCLUSIONS: The main finding of an immediate reduction in oxygen consumption achieved by targeted temperature management was directly proportional to the reduction in core body temperature. Other studies by Bruder, Tokutomi, and Saur have shown similar measured values and results.Some of the limitations of this study are the small number of patients leading to big differences in measurements. Ideally, a similar study with a larger number of patients should be conducted to confirm our results. Another limitation was the use of different core body thermometers for which differences were not calculated. CLINICAL IMPLICATIONS: From a clinical perspective, it would seem reasonable to reduce the caloric intake during targeted temperature management since the basal metabolic rate was decreased by 35.6%. DISCLOSURES: Speaker/Speaker's Bureau relationship with Sunovian Please note: $5001 - $20000 Added 11/20/2017 by Salim Surani, source=Web Response, value=Honoraria Advisory Committee Member relationship with Astra Zeneca Please note: $5001 - $20000 Added 11/20/2017 by Salim Surani, source=Web Response, value=Consulting fee No relevant relationships by Emmanuel Urquieta, source=Web Response No relevant relationships by Joseph Varon, source=Web Response

Performance of Intravenous Insertion is Impaired Following Cold Water Immersion in Military Medical Providers

Accidental cold water immersion or unprepared exposure to extreme cold temperatures can negatively impact warfighter performance and mission outcomes by hindering hands and feet use due to numbness. Skin or extremity temperature has been identified as a relevant variable that predicts impairment in manual dexterity and tactile sensitivity, yet no data have been presented showing performance of medically-specific tasks, such as intravenous (IV) insertion following a cold water immersion. PURPOSE: To determine the influence of cold water immersion and rewarming on IV insertion performance among military medical providers. METHODS: Thirty-eight military personnel (mean ± SD age: 25.8 ± 5.4 yrs, height: 179.5 ± 9.9 cm, weight: 83.2 ± 10.9 kg), trained in the technique of IV insertion, participated in a Cold Weather Medicine course. During the training exercise, students completed six stations: baseline in a classroom (5 min, 23° C), pre-immersion (pre) outdoors (5 min, -4.6° C), immersion in cold water (10 min, 0.2° C), post-immersion (post) (5 min, wet clothing, -4.6° C), transition (5 min, change into dry clothing), and rewarming (60 min, using various techniques). An IV insertion task was performed upon arrival at baseline, pre- and post-immersion, and after rewarming. The IV insertion task required students to insert an IV using a manikin arm. Students were assessed for time to insert IV and success of administering fluid. RESULTS: Assessment revealed a significant increase in IV insertion time (p<0.001) and a decrease in IV insertion success rate following cold water immersion. IV insertion times (seconds) for each station were: baseline 82 ± 17, pre 70 ± 12, post 168 ± 45, and rewarm 73 ± 14. IV insertion success rates were similar among baseline (76%), pre (71%), and rewarm (84%) stations; however, post-immersion, IV success trended downward (47%). CONCLUSION: Results were consistent with the expected loss of manual dexterity following cold water immersion. When given one hour of rewarming, performance returned to baseline. It is essential that military personnel are educated and trained on the effects of accidental cold exposure, the impact it may have on their performance as medical providers, and appropriate extremity rewarming techniques.

A New Proposal for Management of Severe Frostbite in the Austere Environment

Despite advances in outdoor clothing and medical management of frostbite, individuals still experience catastrophic amputations. This is a particular risk for those in austere environments, due to resource limitations and delayed definitive treatment. The emerging best therapies for severe frostbite are thrombolytics and iloprost. However, they must be started within 24 hours after rewarming for recombinant tissue plasminogen activator (rt-PA) and within 48 hours for iloprost. Evacuation of individuals experiencing frostbite from remote environments within 24 to 48 hours is often impossible. To date, use of these agents has been confined to hospitals, thus depriving most individuals in the austere environment of the best treatment. We propose that thrombolytics and iloprost be considered for field treatment to maximize chances for recovery and reduce amputations. Given the small but potentially serious risk of complications, rt-PA should only be used for grade 4 frostbite where amputation is inevitable, and within 24 hours of rewarming. Prostacyclin has less risk and can be used for grades 2 to 4 frostbite within 48 hours of rewarming. Until more field experience is reported with these agents, their use should probably be restricted to experienced physicians. Other modalities, such as local nerve blocks and improving oxygenation at high altitude may also be considered. We submit that it remains possible to improve frostbite outcomes despite delayed evacuation using resource-limited treatment strategies. We present 2 cases of frostbite treated with rt-PA at K2 basecamp to illustrate feasibility and important considerations.

Effect of valproic acid combined with therapeutic hypothermia on neurologic outcome in asphyxial cardiac arrest model of rats

BackgroundsValproic acid (VPA) has been reported to have survival and neuroprotective effects in a cardiac arrest rat model. This study was designed to investigate the effect of VPA combined with therapeutic hypothermia (HT) in an asphyxial cardiac arrest rat model. MethodsRats were subjected to 6 minutes of asphyxial cardiac arrest. Cardiopulmonary resuscitation was performed and then the randomly allocated to 1 of 4 groups (normal saline [NS]/normothermia [NT], VPA/NT, NS/HT, and VPA/HT). Hypothermia (32.5°C ± 0.5°C, 4 hours of HT and 2 hours of rewarming) or NT (37°C ± 0.5°C for 6 hours) was applied, and VPA (300 mg/kg) or NS was administered immediately after the return of spontaneous circulation. Neurologic deficit score was measured, and a tape removal test was performed for 3 days. Histologic injury of hippocampus was evaluated. ResultsValproic acid significantly improved neurologic deficit score at 48 and 72 hours in the NT-treated rats and at 72 hours in the HT-treated rats (all P < .05). Although the latency and success rate were not significantly different between the VPA/NT and NS/NT groups, the VPA/HT group showed significantly lower latency and higher success rates compared to the NS/HT group (P < .05). The histologic injury score in the hippocampal CA1 sector was significantly lower in the VPA/NT group than the NS/NT group (P < .05) and showed a tendency to be decreased in the VPA/HT group compared with the NS/HT group (P = .06). ConclusionIn an asphyxial cardiac arrest rat model, administration of VPA improved neurologic outcomes and added a neuroprotective effect to HT.

Effect of cryotherapy on the ankle temperature in athletes: ice pack and cold water immersion

Introduction Cryotherapy is often used for rehabilitation of injured athletes. Objective To compare the effectiveness of ice pack (IP) and cold water immersion (CWI) on lowering the ankle skin surface temperature in athletes. Materials and methods Thirteen athletes (seven women and six men), age 19.53 (± 2.9) years. IP and CWI were applied on the anterior talofibular ligament (ATFL) of the dominant leg for 30 minutes. The skin surface temperature was measured with an infrared digital thermometer prior to the application and during cryotherapy (10, 15, 20, 25 and 30 minutes) and up to two hours of rewarming. During rewarming, the athletes remained at rest and the temperature was measured every 1 minute until 10 minutes, every 5 minutes for up to an hour and every 15 minutes until 2 hours. Results The two types of cold application were effective in lowering the skin surface temperature after the 30-minute procedure. Significant differences were observed among the following temperatures: pre-application (IP = 29.8 ± 2.4 °C and CWI = 27.5 ± 3 °C – P &lt; 0.05); after 30 minutes (IP = 5 ± 2.4 °C and CWI = 7.8 ± 3 °C – P &lt; 0.01). For rewarming, after 25 minutes (IP = 20.8 ± 3.3 °C and CWI = 18.2 ± 2.7 °C – P &lt; 0.04); after 45 minutes (IP = 24.5 ± 2.3 °C and IP = 22.1 ± 3.5 °C – P &lt; 0.05); after 75 minutes (IP = 26.4 ± 2.2 °C and CWI = 24 ± 2.7 °C – P &lt; 0.02). Conclusion After the 30-minute application, both IP and CWI produced the appropriate temperature; however the application of CWI produced the lowest temperature during rewarming.

Rapid rewarming after therapeutic hypothermia worsens outcome in sepsis.

ObjectiveThis study was performed to investigate the effect of the rewarming rate on survival and acute lung injury in sepsis.MethodsMale Sprague-Dawley rats underwent cecal ligation and incision. After 1 hour of sepsis induction, normothermia (37°C±0.5°C, NT group) or hypothermia (32°C±0.5°C) was induced. Hypothermia was maintained for 4 hours and rats were divided into two groups according to the rewarming rate: RW1 group, 1 hour of rewarming; and RW2 group, 2 hours of rewarming. In the survival study, rats were observed for 12 hours after sepsis induction (n=6 per group). In the second experiment, rats were sacrificed 7 hours after sepsis induction, and lung tissues and plasma were harvested (n=10 per group).ResultsIn the survival study, the RW2 group survived longer than the RW1 group (P<0.05), but the RW1 and NT groups showed no significant difference in survival duration (P>0.05). The histological lung injury score and malondialdehyde concentrations in the lung tissues were significantly higher in the RW1 group than in the RW2 group (P<0.05). Plasma interleukin (IL)-6 concentration and the ratio of IL-6 to IL-10 were higher in the RW1 group than in the RW2 group (P<0.05).ConclusionRapid rewarming after therapeutic hypothermia results in a shorter survival period and acute lung injury in sepsis, which could be associated with the inflammatory responses.

Fifty-Three Hours of Total Sleep Deprivation Has No Effect on Rewarming From Cold Air Exposure

Sleep deprivation and cold air exposure are both experienced in occupational and military settings but the combined effects of these 2 stressors is unknown. The purpose of this study was to determine the effects of 53 hours of total sleep deprivation on thermoregulation during the rewarming phase (25°C air) after acute cold air exposure (10°C air). Eight young men underwent 2 trials in which they either received 7 hours of sleep at night or were totally sleep deprived. On 3 consecutive mornings, the subjects underwent 2 hours of cold air exposure followed by 2 hours of rewarming. Rectal temperature, mean skin temperature, oxygen consumption, and thermal sensation were measured. Rewarming from acute cold air exposure caused a decline in rectal temperature (~0.5°C) each day but this was not different between subjects who were totally sleep deprived and subjects who received 7 hours of sleep at night. During this same period, mean skin temperature increased (from ~22°C to 27°C), oxygen consumption decreased (from ~7 to 4 mL·kg(-1)·min(-1)), and the participants felt warmer. Under the conditions of the present study, sleep-deprived persons are not at a greater risk for a decline in rectal temperature (ie, a hypothermic afterdrop) during rewarming from cold air.

Prolonged and profound therapeutic hypothermia for the treatment of “brain death” after a suicidal intoxication. Challenging conventional wisdoms

Therapeutic hypothermia has been reported to improve the neurologic outcome of comatose survivors of out-of-hospital cardiac arrest. The use of therapeutic hypothermia in patients who have had an acute ischemic-hypoxic brain injury after a suicidal intoxication has not been previously reported. We present the case of a young woman who presented comatose to our emergency department after attempting suicide by ingesting diazepam and a bottle of antifreeze (ethylene-glycol). Despite aggressive supportive care, the patient progressed to what appeared to be clinical brain death. At this point, the patient was managed with therapeutic hypothermia for 36 hours. The patient awoke within 48 hours of rewarming and made a complete and full neurologic recovery. In conclusion, this case has important implications in the management of patients who have had an acute ischemichypoxic brain injury. Inappropriately labeling such patients as "brain dead" will result in the failure to institute therapeutic hypothermia and other advanced neuroprotective interventions in patients who could be salvaged with a good neurologic outcome.

Combined Neuroprotective Modalities Coupled with Thrombolysis in Acute Ischemic Stroke: A Pilot Study of Caffeinol and Mild Hypothermia

Both caffeinol and hypothermia are neuroprotective in preclinical models of transient middle cerebral artery occlusion. We tested whether combining caffeinol and hypothermia with tissue plasminogen activator (t-PA) in patients with acute stroke is safe and feasible. Twenty patients with acute ischemic stroke were treated with caffeinol (caffeine 8-9 mg/kg + ethanol 0.4 g/kg intravenously [IV] x 2 hours, started by 4 hours after symptom onset) and hypothermia (started by 5 hours and continued for 24 hours [target temperature 33-35 degrees C] followed by 12 hours of rewarming). IV t-PA was given to eligible patients. Meperidine and buspirone were used to suppress shivering. All patients received caffeinol, and most reached target blood levels. Cooling was attempted in 18 patients via endovascular (n = 8) or surface (n = 10) approaches. Two patients were not cooled due to catheter or machine failure. Thirteen patients reached target temperature; average time from symptom onset was 9 hours and 43 minutes. The last 5 hypothermia patients received surface cooling with iced saline induction and larger doses of meperidine; all patients reached target temperature, on average within 2 hours and 30 minutes from induction and 6 hours and 21 minutes from symptom onset. Three patients died: one from symptomatic hemorrhage, one from malignant cerebral edema, and one from unrelated medical complications. No adverse events were attributed to caffeinol. One patient had reduced respiratory drive due to meperidine, requiring BiPAP. Combining caffeinol with hypothermia in patients with acute stroke given IV t-PA is feasible. A prospective placebo-controlled randomized study is needed to further assess safety and to test the efficacy of caffeinol, hypothermia, or both.

Vascular Smooth Muscle Cell Apoptosis Induced by “Supercooling” and Rewarming

The underlying mechanisms for the reduction in restenosis caused by cryoplasty for peripheral atherosclerotic lesions are not well understood. Because vascular smooth muscle cells (SMCs) are known to play a critical role in restenosis and neointimal hyperplasia, the aim of this study was to determine SMC survival under conditions of "supercooling" and/or rewarming. Bovine aortic SMCs were supercooled to -10 degrees C for 0, 60, or 120 seconds with a custom-designed conduction cooling stage and then rewarmed to 37 degrees C in an incubator for 0, 12, or 24 hours. A terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay was used to measure the degree of apoptosis. Activation of Akt (ie, protein kinase B), a key signal protein involved in cell survival, was assessed by Western blot analysis. An increase in apoptotic SMCs was observed with increasing supercooling and rewarming time. Akt was significantly activated at only the most severe condition (120 seconds of supercooling and 24 hours of rewarming), which showed a 2.03-fold increase compared with the group without rewarming. The data suggest that SMC apoptosis occurs with supercooling and rewarming. Protective cell survival mechanisms were activated only late in the rewarming phase. This may partially explain the long-term patency observed with cryoplasty of atherosclerotic peripheral lesions.

Heat Production and Body Temperature During Cooling and Rewarming in Overweight and Lean Men

To compare overweight and lean subjects with respect to thermogenesis and physiological insulation in response to mild cold and rewarming. Ten overweight men (mean BMI, 29.2 +/- 2.8 kg/m(2)) and 10 lean men (mean BMI, 21.1 +/- 2.0 kg/m(2)) were exposed to cold air for 1 hour, followed by 1 hour of rewarming. Body composition was determined by hydrodensitometry and deuterium dilution. Heat production and body temperatures were measured continuously by indirect calorimetry and thermistors, respectively. Muscle activity was recorded using electromyography. In both groups, heat production increased significantly during cooling (lean, p = 0.004; overweight, p = 0.006). The increase was larger in the lean group compared with the overweight group (p = 0.04). During rewarming, heat production returned to baseline in the overweight group and stayed higher compared with baseline in the lean group (p = 0.003). The difference in heat production between rewarming and baseline was larger in the lean (p = 0.01) than in the overweight subjects. Weighted body temperature of both groups decreased during cold exposure (lean, p = 0.002; overweight, p < 0.001) and did not return to baseline during rewarming. Overweight subjects showed a blunted mild cold-induced thermogenesis. The insulative cold response was not different among the groups. The energy-efficient response of the overweight subjects can have consequences for energy balance in the long term. The results support the concept of a dynamic heat regulation model instead of temperature regulation around a fixed set point.

Pharmacologically induced preconditioning with diazoxide: a novel approach to brain protection

Background. Ischemic preconditioning is an endogenous mechanism whereby brief periods of ischemia render neurons resistant to subsequent lethal insults. This protection appears to alter cellular apoptosis and can be induced by potassium channel openers acting on the inner membrane of the mitochondria (mitoK ATP). To test the hypothesis that pharmacologic preconditioning could provide neuroprotection, the mitoK ATP opener diazoxide was used in a canine model of brain injury induced by hypothermic circulatory arrest (HCA). Methods. Seventeen dogs were placed on cardiopulmonary bypass (CPB) and cooled to 18°C. After 2 hours of HCA, animals were rewarmed and weaned from CPB. Six dogs received intravenous diazoxide (2.5 mg/kg bolus 15 minutes prior to CPB, then 0.5 mg/min until circulatory arrest, then restarted for the first hour of rewarming). Six animals received vehicle only. Five received diazoxide and the mitoK ATP blocker 5-hydroxydecanoate (5-HD). Using a modified Pittsburgh Canine Neurological Scoring System (0 = normal, 500 = brain death), animals were evaluated every 24 hours for 3 days. The brains were removed and histologic sections of four regions characteristically injured in this model were scored (0 = no injury, 4 = infarction) by a neuropathologist in a blinded fashion. Results. Clinical scoring showed marked improvement in the diazoxide group at 48 hours (101 ± 10.5 vs 165 ± 14.8, p < 0.01) and 72 hours (54 ± 9.3 vs 137 ± 12.1, p < 0.01). This neuroprotection was attenuated when 5-HD was concomitantly administered. Three of four brain regions typically injured in this model (cortex, hippocampus, and entorhinal cortex) had significant neuron preservation in the diazoxide group. Likewise, combined region scores were significantly improved in the treatment group (1.18 ± 0.2 vs 2.46 ± 0.2, p < 0.01). Conclusions. Pretreatment with diazoxide resulted in significant improvement in both clinical neurologic scores and histopathology in our model of HCA. This suggests that pharmacologic preconditioning with the mitoK ATP channel opener diazoxide may offer effective neuroprotection during HCA.

Safety of 65 °C intravenous fluid for the treatment of hypothermia

To demonstrate the safety and efficacy of 65 degrees C (149 degrees F) centrally administered intravenous fluid (CIVF) compared to conventional 40 degrees C (104 degrees F) CIVF in the treatment of hypothermia. Ten beagles (9-13 kg) were prospectively randomized to receive 65 degrees C or 40 degrees C CIVF. They were anesthetized and data were collected at baseline, during hypothermia, and after 1 and 2 hours of rewarming. The plasma free/total hemoglobin (PFHb/THb) was measured to detect hemolysis. Each subject was cooled to 30 degrees C (86 degrees F) and then received either 65 degrees C or 40 degrees C CIVF through a specialized catheter in the superior vena cava for 2 hours in addition to conventional rewarming techniques. All subjects survived 7 days, after which they were sacrificed and a complete autopsy was performed. The rewarming rate was 3.7 degrees C/hr in the 65 degrees C CIVF group and 1.75 degrees C/hr in the 40 degrees C CIVF group. Core temperatures were significantly different after 1 hour (33.4 degrees +/- 0.77 degrees versus 31.7 degrees +/- 0.57 degrees, P < 0.01) and 2 hours (37 degrees +/- 1.03 degrees versus 33.4 degrees +/- 0.89 degrees, P < 0.001). PFHb/THb was not different. Two intimal injuries occurred in each group but these were remote from the infusion site. Blinded examination by two pathologists could not differentiate the etiology of these injuries from mechanical trauma. CIVF at 65 degrees C is a safe and effective means of treating hypothermia.

VERY HOT INTRAVENOUS FLUID IN THE TREATMENT OF HYPOTHERMIA

The efficacy and safety of very hot (65 degrees C/149 degrees F) intravenous fluid (IVF) were compared with those of conventional warm (38 degrees C/100.4 degrees F) IVF in the treatment of hypothermia. Eight anesthetized beagles (11-20 kg) were studied. Blood pressure (BP), pulse (P), and core temperature (cT degrees) were recorded at baseline, during hypothermia, and during rewarming. The plasma free hemoglobin (PFHg) was measured to assess hemolysis. Each subject was cooled to 32 degrees C/89.6 degrees F and assigned to receive either 65 degrees C or 38 degrees C IVF via a specially designed multiport balloon-tipped catheter in the superior vena cava (SVC). The IV fluid rate was 80% of the blood volume per hour. Conventional rewarming methods were used in all subjects. After 2 hours the subjects were killed and the SVC was examined for injury. The rate of rewarming was 2.9 degrees C/hour in the 65 degrees C IVF group and 1.25 degrees C/hour in the 38 degrees C IVF group. The cT degrees was significantly different in all subjects after 1 (35.2 degrees +/- 1.03 degrees C vs. 33.2 degrees +/- 0.5 degrees C; p < 0.006) and 2 (37.6 degrees +/- 1.17 degrees C vs. 34.3 degrees +/- 0.9 degrees C; p < 0.004) hours of rewarming. The BP, P, and PFHg were not different. Visual examination of the SVC revealed two lesions in the 65 degrees C IVF group and one in the 38 degrees C group. Mechanical or thermal injury could not be differentiated.(ABSTRACT TRUNCATED AT 250 WORDS)

Centrioles as microtubule-organizing centers for marginal bands of molluscan erythrocytes.

The erythrocytes of blood clams (arcidae) are flattened, elliptical, and nucleated. They contain elliptical marginal bands (MBs) of microtubules, each physically associated with a pair of centrioles marginal bands (MBs) of microtubles, each physically associated with a pair of centrioles (Cohen, W., and I. Nemhauser, 1980, J. Cell Biol., 86:286-291). The MBs were found to be cold labile in living cells, disappearing within 1-2 h at 0 degrees C. After the cells had been rewarmed for 1-2 h, continuous MBs with associated centrioles were once again present. Time-course studies utilizing phase contrast, antitubulin immunofluorescence, and electron microscopy of cytoskeletons prepared during rewarming revealed structural evidence of centriole participation in MB reassembly. At the earliest stage of reassembly, a continuous MB was not present. Instead, relatively short and straight microtubules focused on a pointed centriolar "pole," and none were present elsewhere in the cytoskeleton. Thin continuous MBs then formed, still pointed in the centriolar region. Subsequently, the MBs regained ellipticity, with their thickness gradually increasing but not reaching that of controls even after several hours of rewarming. At these later time points, microtubules still radiated from the centrioles and joined the MBs some distance away. In the presence of 0.1 mM colchicines, MB reassembly was arrested at the pointed stage. Electron microscopic observations indicate that pericentriolar material is involved in microtubule nucleation in this system, rather than the centriolar triplets directly. The results suggest a model in which the centrioles and associated material nucleate assembly and growth of microtubules in diverging directions around the cell periphery. Microtubules of opposite polarity would then pass each other at the end of the cell distal to the centrioles, with continued elongation eventually closing the MB ellipse behind the centriole pair.

Compartments of sodium in a small artery.

Viable tail artery samples, in a modified Krebs medium, gain Na in exchange for K during cooling and reverse the process during rewarming. The process, within the margin of experimental error, is usually in a 1:1 ratio and has a long time constant, about 8 to 9 meq/100 g dry weight being exchanged within 3 h of cooling, and up to 15 meq/100 g within 24 h. Three hours of rewarming of tissues prepared by overnight (18 h) cooling is sufficient for an exchange of at least 10 meq/100 g. A second component of Na, equal to approximately 10 meq/100 g in tissue incubated in a Tris-buffered medium [Formula: see text], is apparently paracellular, for it is fully mobilized within 30 min of exposure to a sodium-free environment, even at 2°. Since even 3 h of exposure to such a medium at 2° fails to mobilize metabolism-dependent cellular Na it is possible to differentiate these two components. Evidence is also presented to show that Na transport, ordinarily associated with K accumulation, can occur without it.

Effects of cooling and rewarming on Na, K, and tension changes in rat tail artery.

The relation of cell Na and K to vascular smooth muscle tension was studied in the isolated, perfused rat tail artery. Glass electrodes were used to measure ion exchanges; cooling and rewarming were used to modify cell ion content and exchange rates. The cells, made Na-rich and K-poor by overnight cooling of the artery at 2 °C, responded weakly to vasoactive agents (norepinephrine, L-8 vasopressin, and angiotensin) and characteristically showed a slow rate of rise followed by a still slower rate of fall in tension. Within minutes of initiating rewarming to 37 °C the rate of rise was accelerated even in the presence of metabolic inhibitors. The degree of rise depended on the degree of restoration of ionic gradients; it increased progressively with the time allowed for extrusion of Na and reaccumulation of K, a process which could be blocked by iodoacetate. During rewarming, the Na/K exchange rate rose from zero at 2 °C to reach a maximum toward the end of the first hour of rewarming, and in this interval the rate of relaxation following stimulation returned to normal. Stimulation of the cold artery with angiotensin enhanced subsequent Na outflow during rewarming without affecting K inflow, and the tissue was unable to respond to a second stimulus.