Hypothermia-induced hypokalemia

Hypothermia may be seen both as a presenting problem and as a part of therapeutic strategy. An illustrative case is presented. In our case of severe head trauma, hypothermia was used as a therapeutic modality to minimize the brain injury. While hypothermic, the patient developed severe hypokalemia and was supplemented with 400 mEq of potassium. Upon rewarming, severe hyperkalemia occurred with resultant fatal arrhythmias. Severe hypokalemia may be seen in hypothermic patients, which represents a shift of potassium rather than a true loss. Careful management of this electrolyte problem must be given to avoid hyperkalemia with rewarming.     

Site accessibility and the pH dependence of the saturation capacity of a highly cross-linked matrix. Immobilized metal affinity chromatography of bovine serum albumin on chelating Superose

Striatal and cortical neurons containing nitric oxide synthase (NOS) were studied in adult rats subjected to different periods of perinatal asphyxia (PA) using immunohistochemistry at both light microscopy (LM) and electron microscopy (EM). Another group was subjected to PA + hypothermia to study its neuroprotective effect. Quantitative image analysis was performed on the striatum and neocortex in order to count the number of immunoreactive neurons and to compare the pattern of staining between the different groups. Six-month-old rats that suffered subsevere and severe PA demonstrated, at LM, cytomegaly of the striatal and neocortical neurons containing NOS. Control and hypothermic neurons were more weakly immunostained than PA neurons. Subsevere and severe asphyctic rats showed an important neuronal loss that was reduced by hypothermic treatment. The PA group disclosed, at EM, dense electronic bodies distributed in terminals surrounding synaptic vesicles and in dendrites. Non-NOS-containing neurons showed signs of degeneration, such as dark cytoplasm and shrunken nuclei. Surrounding the blood vessels, we observed a clear edema. The immunolabeling in hypothermic rats resembled that observed in controls. These data suggest that subsevere and severe PA induces chronic changes in the neuronal content of NOS in the striatum and neocortex. Degeneration observed in neurons surrounding cytomegalic NOS-containing cells may be due to the excess of NO in their environment. Moreover, the chronic alterations produced by PA seem to be prevented by hypothermia.     

Effect of extracellular ATP on breast tumor cell growth, implication of intracellular calcium

The aim of this retrospective study was to investigate whether plasma potassium, pH and activated clotting time (ACT), obtained from a central venous blood sample immediately after admission to hospital, could predict outcome in patients with severe accidental hypothermia and cardiocirculatory arrest. Twenty-two patients rewarmed with cardiopulmonary bypass were studied retrospectively (12 patients after avalanche accidents, seven patients after cold water submersion and three patients after prolonged exposure to cold). In 12 patients stable spontaneous circulation could not be restored. In 10 patients stable spontaneous circulation could be restored. Two of these 10 patients survived long-term. Plasma potassium, central venous pH and ACT were clinically useful prognostic markers in hypothermic arrest victims after avalanche accidents: a plasma potassium value exceeding 9 mmol/l, a pH equal to or less than 6.50 or an ACT exceeding 400 s was seen in patients in whom spontaneous circulation could not be restored. Plasma potassium, central venous pH and ACT were of only limited prognostic value in hypothermic arrest victims following cold water submersion or prolonged exposure to cold. In hypothermic arrest victims after cold water submersion a central venous pH as low as 6.51 on admission did not exclude long-term survival. Moderate and severe hyperkalemia in arrest victims after prolonged exposure to cold need not necessarily indicate postmortem autolysis. A decision to continue or terminate resuscitation cannot be based on laboratory parameters. Nevertheless, our data suggest that plasma potassium, central venous pH and ACT on admission can be used to identify hypothermic arrest victims in whom death preceded cooling. If several hypothermic arrest victims are admitted simultaneously after avalanche accidents, these 3 parameters can help not to waste limited cardiopulmonary bypass facilities for patients with no hope of survival.     

Arterial-venous carbon dioxide tension difference after hypothermic cardiopulmonary bypass

Arterial-venous carbon dioxide tension difference (Pv-aCO2) is known to become high after severe hemorrhage shock and resuscitation. We hypothesized that Pv-aCO2 might be high after cardiac surgery because of the oxygen debt occurred during hypothermic cardiopulmonary bypass (CPB). Blood pressure, cardiac index, hemoglobin, the arterial and mixed venous blood gases were repeatedly measured every 6 hours for 24 hours following cardiac surgery in 60 adult patients who underwent hypothermic CPB. Immediately after the surgery, Pv-aCO2 was extremely high, then gradually decreased to within normal ranges 12 hours later (8.0 +/- 2.9 mmHg vs 5.9 +/- 3.1 mmHg. p < 0.01). Factors which significantly correlated to Pv-aCO2 were cardiac index, oxygen delivery, minimum rectal temperature and duration of CPB. Oxygen debt during hypothermic CPB might cause significantly high Pv-aDO2. At least 12 hours were necessary to recover from anaerobic status to physiological condition.     

Glutamate excitotoxicity: a mechanism of neurologic injury associated with hypothermic circulatory arrest

Glutamate, the major central nervous system neurotransmitter, may have potent neurotoxic activity under conditions of metabolic stress. By receptor autoradiography, we have demonstrated that brain regions most vulnerable to injury during prolonged hypothermic circulatory arrest have the highest density of glutamate receptors. To test the hypothesis that such injury could be mediated by glutamate excitotoxicity, we used dizocilpine (MK-801), a selective N-methyl-D-aspartate-glutamate receptor antagonist in a canine survival model of hypothermic circulatory arrest. Eighteen male dogs (20 to 25 kg) were supported by closed-chest cardiopulmonary bypass, subjected to 2 hours of hypothermic circulatory arrest at 18 degrees C, and rewarmed on cardiopulmonary bypass. All were mechanically ventilated and monitored for 20 hours before extubation and survived for 3 days. Group A dogs (n = 9) received a prearrest intravenous bolus of dizocilpine (0.75 mg/kg) followed by continuous infusion (75 micrograms/kg per hour), resulting in electroencephalographic silence. Dizocilpine was weaned before extubation. Group B dogs received vehicle only. According to a species-specific behavior scale that yielded a neurologic deficit score ranging from 0 (normal) to 500 (brain dead), all animals were neurologically assessed every 12 hours. After the dogs were killed at 72 hours, brains were examined by receptor autoradiography and histologically for patterns of selective neuronal necrosis; they were scored blindly from 0 (normal) to 100 (severe injury). Group A dogs had better neurologic function than group B (neurologic deficit score 21 +/- 15 versus 192 +/- 40, p < 0.001) and had less neuronal injury (7.3 +/- 3 versus 48.3 +/- 9, p < 0.0001). Densitometric receptor autoradiography revealed preservation of neuronal N-methyl-D-aspartate-glutamate receptor expression in group A only. These results represent the first direct evidence of a role for glutamate excitotoxicity in the development of hypothermic circulatory arrest-induced brain injury and suggest that selective glutamate receptor antagonists may have a neuroprotective capacity in prolonged periods of hypothermic circulatory arrest.     

Mitral valve repair in a patient with severe porcelain aorta

We repaired the mitral valve in a patient with severe porcelain aorta. Significant mitral regurgitation developed in a 66-year-old woman with heavy calcification throughout the whole aorta. At operation, cardiopulmonary bypass was properly established by combined axillary and femoral arterial cannulations for sufficient systemic flow. Likewise, the combination of a superior mitral approach and profound hypothermic fibrillatory arrest in conjunction with low-flow cardiopulmonary bypass allowed us to repair the mitral valve successfully.     

Cerebral oxygenation during cardiopulmonary bypass in children

OBJECTIVE: Previous work has found cerebral oxygen extraction to decrease during hypothermic cardiopulmonary bypass in children. To elucidate cardiopulmonary bypass factors controlling cerebral oxygen extraction, we examined the effect of perfusate temperature, pump flow rate, and hematocrit value on cerebral hemoglobin-oxygen saturation as measured by near infrared spectroscopy. METHODS: Forty children less than 7 years of age scheduled for cardiac operations with continuous cardiopulmonary bypass were randomly assigned to warm bypass, hypothermic bypass, hypothermic low-flow bypass, or hypothermic low-hematocrit bypass. For warm bypass, arterial perfusate was 37 degrees C, hematocrit value 23%, and pump flow 150 ml/kg per minute. Hypothermic bypass differed from warm bypass only in initial perfusate temperature (22 degrees C); hypothermic low-flow bypass and low-hematocrit bypass differed from hypothermic bypass only in pump flow (75 ml/kg per minute) and hematocrit value (16%), respectively. Cerebral oxygen saturation was recorded before bypass (baseline), during bypass, and for 15 minutes after bypass had been discontinued. RESULTS: In the warm bypass group, cerebral oxygen saturation remained at baseline levels during and after bypass. In the hypothermic bypass group, cerebral oxygen saturation increased 20% +/- 2% during bypass cooling (p < 0.001), returned to baseline during bypass rewarming, and remained at baseline after bypass. In the hypothermic low-flow and hypothermic low-hematocrit bypass groups, cerebral oxygen saturation remained at baseline levels during bypass but increased 6% +/- 2% (p = 0.05) and 10% +/- 2% (p < 0.03), respectively, after bypass was discontinued. CONCLUSIONS: In children, cortical oxygen extraction is maintained during warm cardiopulmonary bypass at full flow and moderate hemodilution. Bypass cooling can decrease cortical oxygen extraction but requires a certain pump flow and hematocrit value to do so. Low-hematocrit hypothermic bypass and low-flow hypothermic bypass can also alter cortical oxygen extraction after discontinuation of cardiopulmonary bypass.     

Endothelial dysfunction in cerebral microcirculation during hypothermic cardiopulmonary bypass in newborn lambs

OBJECTIVES: Inflammatory stimuli or mechanical stresses associated with hypothermic cardiopulmonary bypass could potentially impair cerebrovascular function, resulting in inadequate cerebral perfusion. We hypothesize that hypothermic cardiopulmonary bypass is associated with endothelial or vascular smooth muscle dysfunction and associated cerebral hypoperfusion. Therefore we studied the cerebrovascular response to endothelium-dependent vasodilator, acetylcholine, endothelium-independent nitric oxide donor, sodium nitroprusside, and vasoactive amine, serotonin, in newborn lambs undergoing hypothermic cardiopulmonary bypass (nasopharygeal temperature = 18 degrees C). METHODS: Studies were performed on 13 newborn lambs equipped with a closed cranial window, allowing for direct visualization of surface pial arterioles. Six animals were studied while undergoing hypothermic cardiopulmonary bypass, whereas seven served as nonbypass, warm (37 degrees C) controls. Pial arteriolar caliber (range = 111 to 316 microm diameter) was monitored using video microscopy. RESULTS: Topical application of acetylcholine caused a dose-dependent increase in arteriolar diameter in the control group that was absent in animals undergoing hypothermic cardiopulmonary bypass. Hypothermic cardiopulmonary bypass did not alter the vasodilation in response to sodium nitroprusside. Furthermore, the contractile response to serotonin was fully expressed during hypothermic cardiopulmonary bypass. CONCLUSIONS: The specific loss of acetylcholine-induced vasodilation suggests endothelial cell dysfunction rather than impaired ability of vascular smooth muscle to respond to nitric oxide. It is speculated that loss of endothelium-dependent regulatory factors in the cerebral microcirculation during hypothermic cardiopulmonary bypass may enhance vasoconstriction, and impaired cerebrovascular function may be a basis for associated neurologic injury during or after hypothermic cardiopulmonary bypass.     

Metabolism in the hypothermically perfused dog kidney. Incorporation rate of leucine and threonine into proteins

The incorporation of [14C]leucine and [14C]threonine into kidney cortex proteins was studied during 6 days' hypothermic perfusion of dog kidneys at 8-10 degrees C and during in vitro incubation of dog kidney cortex slices at 37 degrees C. Leucine carbon was incorporated into proteins at a higher rate than threonine carbon both during in vitro incubation of kidney cortex slices and during hypothermic kidney perfusion. The incorporation of leucine and threonine during hypothermic perfusion was linear for 6 days but 50-100 times lower than the incorporation of leucine and threonine in kidney cortex slices at 37 degrees C. During hypothermic perfusion there was a decrease in specific activity of leucine and threonine in the perfusate corresponding to a degradation of proteins which was greater than protein synthesis as calculated from the incorporation of label into proteins. Leucine carbon was recovered in CO2 during hypothermic perfusion and in vitro incubation of kidney cortex slices at 37 degrees C. The incorporation of threonine carbon into CO2 was about 10% of the corresponding value for leucine both during hypothermic kidney perfusion and during in vitro incubation of kidney cortex slices at 37 degrees C. It is concluded that there is a turnover of kidney proteins during hypothermic perfusion with a perfusate containing amino acids.     

Preservation of myocyte contractile function after hypothermic, hyperkalemic cardioplegic arrest with 2, 3-butanedione monoxime

One proposed contributory mechanism for depressed ventricular performance after hypothermic, hyperkalemic cardioplegic arrest is a reduction in myocyte contractile function caused by alterations in intracellular calcium homeostasis. Because 2,3-butanedione monoxime decreases intracellular calcium transients, this study tested the hypothesis that 2,3-butanedione monoxime supplementation of the hyperkalemic cardioplegic solution could preserve isolated myocyte contractile function after hypothermic, hyperkalemic cardioplegic arrest. Myocytes were isolated from the left ventricles of six pigs. Magnitude and velocity of myocyte shortening were measured after 2 hours of incubation under normothermic conditions (37 degrees C, standard medium), hypothermic, hyperkalemic cardioplegic arrest (4 degrees C in Ringer's solution with 20 mEq potassium chloride and 20 mmol/L 2,3-butanedione monoxime). Because beta-adrenergic agonists are commonly employed after cardioplegic arrest, myocyte contractile function was examined in the presence of the beta-agonist isoproterenol (25 nmol/L). Hypothermic, hyperkalemic cardioplegic arrest and rewarming reduced the velocity (32%) and percentage of myocyte shortening (27%, p < 0.05). Supplementation with 2,3 butanedione monoxime normalized myocyte contractile function after hypothermic, hyperkalemic cardioplegic arrest. Although beta-adrenergic stimulation significantly increased myocyte contractile function under normothermic conditions and after hypothermic, hyperkalemic cardioplegic arrest, contractile function of myocytes exposed to beta-agonist after hypothermic, hyperkalemic cardioplegic arrest remained significantly reduced relative to the normothermic control group. Supplementation with 2,3-butanedione monoxime restored beta-adrenergic responsiveness of myocytes after hypothermic, hyperkalemic cardioplegic arrest. Thus, supplementation of a hyperkalemic cardioplegic solution with 2,3-butanedione monoxime had direct and beneficial effects on myocyte contractile function and beta-adrenergic responsiveness after cardioplegic arrest. A potential mechanism for the effects of 2,3-butanedione monoxime includes modulation of intracellular calcium transients or alterations in sensitivity to calcium. Supplementation with 2,3-butanedione monoxime may have clinical utility in improving myocardial contractile function after hypothermic, hyperkalemic cardioplegic arrest.     

Does hypothermic perfusion have beneficial effects for ischemic liver during extended hepatectomy with hepatic inflow occlusion of canine liver? A comparative study with topical cooling

BACKGROUND/AIMS: The present study was designed to elucidate the effect of topical cooling and hypothermic perfusion in extended hepatectomy under hepatic inflow occlusion. Hypothermic perfusion has provided to have a protective effect on the ischemic liver. However, it has not been determined whether hypothermia or perfusion had salutary effects on the ischemic liver. METHODOLOGY: Seventy-five percent of the liver was resected under hepatic inflow occlusion for 60 minutes in each adult mongrel dog. The animals were divided into three groups; no cooling group (n = 8), topical cooling group (n = 7) using ice slush and hypothermic perfusion group (n = 7). Blood from the hepatic vein was sampled for measurement of ALT, AST, LDH and purine nucleoside phosphorylase. RESULTS: The seven-day survival in topical cooling group and hypothermic perfusion group was better compared with that in no cooling group. ALT, AST and LDH levels showed no significant differences among the groups. PNP levels were significantly lower in topical cooling group (p < 0.01) and hypothermic perfusion group (p < 0.05) than in no cooling group, but no significant differences between topical cooling group and hypothermic perfusion group. CONCLUSIONS: In the hepatic ischemia for 60 minutes, hypothermic perfusion did not demonstrate markedly better effects compared with topical cooling.     

Protective efficacy of a hypothermic pharmacological agent in gerbil forebrain ischemia

BACKGROUND AND PURPOSE: The novel muscarinic cholinergic partial agonist U-80816E was tested in the gerbil brief bilateral carotid occlusion ischemia model based on the rationale that the compound's hypothermic properties might afford effective protection of the selectively vulnerable hippocampal CA1 region. METHODS: Male gerbils were subjected to either 10 or 15 minutes of bilateral carotid occlusion, followed by histopathological assessment of the CA1 neuronal survival 7 days later. RESULTS: In saline-treated animals, 10 minutes of bilateral carotid occlusion resulted in a 30.5% loss of CA1 neurons, whereas a 15-minute insult resulted in a 49.6% loss. Administration of U-80816E (6 mg/kg i.p. 30 minutes before bilateral carotid occlusion and again 2 hours after reperfusion) resulted in a significant protective effect of the CA1 neuronal population with either duration of ischemia; neuronal loss was reduced to 12.6% in the milder model (p < 0.05 versus saline-treated) and 24.9% in the more severe model (p < 0.04 versus saline). However, the 6 mg/kg i.p. dose of U-80816E was found to produce a 1.0 degree C decrease in brain temperature (measured with a tympanic temperature probe) at 10 minutes of ischemia compared with that of saline-treated gerbils. At 10 minutes of reperfusion, after the 10-minute episode of ischemia, the brain temperature of the U-80816E-treated gerbils was 2.2 degrees C lower than that of saline-treated animals. When the U-80816E-treated gerbils were subjected to either 10 or 15 minutes of ischemia but placed in a heated chamber that prevented the hypothermic effects, no cerebroprotection was observed. CONCLUSIONS: These results show that the anti-ischemic efficacy of U-80816E is mediated through its hypothermic properties, thus suggesting the feasibility of pharmacologically induced hypothermia as a cerebroprotective approach.     

Protective effect of hypothermia on contractile force in skeletal muscle

The clinical success of limb replantation and tissue transfer is partly dependent on the duration of ischemia experienced by the amputated part. This study focused primarily on the damage that occurs during this ischemic period. An experimental system was implemented that allowed the observation of contractile function in totally isolated skeletal muscle after ischemia. Contractile function was selected as an indicator of ischemic damage because normal function is the ultimate goal of replantation. All experiments were performed on the rat extensor digitorum longus. The muscles were subjected to ischemic periods of 1.5, 3.0, and 5.0 hours and were stored in either a hypothermic (4 degrees C) or a room-temperature (23 degrees C) environment during the ischemic interval. After the ischemic period, all muscles were transferred to a tissue bath and were subjected to contractility testing, followed by fatigue testing. In both groups, muscle function decreased as the ischemic interval was increased. A significant difference in function between the normal control and the muscles of both ischemic groups implied that ischemic injury had occurred in the hypothermic and room-temperature muscles, even with the relatively short 1.5-hour ischemic interval. After each ischemic interval however, the hypothermic muscles produced significantly greater contractile force than the room-temperature muscles in both the contractility and the fatigue tests. After 1.5 hours of ischemia, the contractile force in the hypothermic group was about three times as great as that observed in the room-temperature group. These results indicated that muscle function after a period of totally isolated ischemia is protected by hypothermic preservation. They also support the advisability of storage of amputated parts and free muscle flaps in hypothermic environments before replantation even after relatively brief intervals of ischemia.     

Postoperative management of hypothermia of intra-operative origin--experience with a forced-air convective warming device

Hypothermia develops during the intra-operative period partly as a result of disordered thermoregulation induced by anaesthesia, and partly because of the nature of the operation or injury and the surgical environment. Both the hypothermic state and the consequences of physiological attempts to return the core temperature to normal, which take place during the postoperative period, are associated with non-beneficial effects. Attempts to prevent an intra-operative decline in core temperature are a part of anaesthesia management. However, most of the traditional options available are inefficient or ineffective, especially if used as a single intervention and particularly in adults. This study evaluates the performance of a new device, the forced-air convective warmer, in the management of the postoperative hypothermic state. Results show that the device made a significant difference to the thermal state of a group of hypothermic postoperative patients when compared with a hypothermic control group, but only if used for at least 2 hours after the operation.     

Interaction of the Na(+)-Ca2+ exchanger with small molecules on cell Ca2+ signaling

BACKGROUND: Evaluation of outcome after CPR in severe hypothermic patients. DESIGN: Perspective study from October 1995 to April 1996. SETTING: First aid team of Italian Red Cross, Busto Arsizio (Varese), Italy. METHODS: A population of 22 patients in cardiac arrest in which CPR was performed immediately after rescue team's arrival is studied. ECG, core temperature, SpO2 and MAP were monitored whereas vital parameters were present during Basic Life Support. Outcome after CPR was evaluated with GOS scale. RESULTS: It has been observed that severe hypothermia and time of cardiac arrest impact on the clinical outcome after CPR. The high mortality rate after CPR with BLS standard is worsened by a core temperature < or = 33 degrees C. CONCLUSIONS: Severe hypothermia seems to have a dangerous effect upon outcome after cardiopulmonary resuscitation; heating systems for body temperature could prevent this situation improving CPR results.     

Experimental studies on myocardial metabolism of carbohydrate and lipid in surface-induced deep hypothermia

In surface-induced deep hypothermia, metabolic acidosis resulting from lactacidemia was observed. In the aspect of myocardial metabolism, the rate of reduction in coronary A-V difference ratio of lactate, pyruvate and NEFA was less than that of coronary flow and myocardial oxygen consumption in the hypothermic heart. Namely, it seems that lactate, pyruvate and NEFA play an important role as energy fuel in the hypothermic heart. On the other hand, myocardial metabolism of glucose was reduced in the hypothermic heart. Moreover, it seems that exogenous corticosteroid and ATP do not influence on the myocardial metabolism of carbohydrate and lipid in the hypothermic heart.     

Hypothermic vocalizations of rat pups (Rattus norvegicus) and direct maternal search behavior.

Emissions of ultrasonic vocalizations (USVs) by rat pups (Rattus norvegicus) during hypothermia have consequences for recovery and warming. The effects on dam behavior of USVs emitted by 3- to 11-day-old pups during hypothermia at rectal temperatures between 18 and 22°C was investigated Rat dams were tested in a Y maze with the home cage as a start box. Dams were given, in one condition, a choice between a hypothermic pup emitting USVs or a hypothermic, silent (anesthetized) pup and, in the other, a choice between 2 hypothermic, silent pups. Although differing in some acoustic properties from normal isolation calls, USVs emitted by hypothermic pups both elicited maternal search behavior and acted as directional cues for dams, in comparisons with control dams exposed only to silent pups. Thus USVs of pups recovering from extreme hypothermia have communicative as well as physiological significance. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Body temperature in mice: a quantitative measure of alcohol tolerance and physical dependence

Mice undergoing withdrawal after chronic ethanol consumption were found to be hypothermic if kept at room temperature. The extent of the hypothermia correlated well with the behavioral withdrawal symptoms and could be used as a quantitative measure of the severity and time course of the withdrawal syndrome. Placing mice in a cold environment (4 degrees C) exacerbated the hypothermia whereas placing animals at 34 degrees C reversed the hypothermia and produced hyperthermia. It was concluded that the temperature set point mechanism and the ability to regulate around this set point was disturbed in animals physically dependent on alcohol. During consumption of the ethanol-containing diets, mice exhibited tolerance to the hypothermic effects of an acutely administered dose od ethanol. Tolerance to the hypothermic effects of ethanol mirrored the development of behavioral tolerance as measured by performance on a tilting plane. Temperature and behavioral tolerance were both shown to extend well beyond the period of the withdrawal syndrome. Ethanol-treated mice were found to be cross-tolerant to the hypothermic effects of barbiturates but not to the hypothermia produced by the monoamine oxidase inhibitor, pargyline.     

Tissue and plasma peptidase activity is altered during hypothermic hibernation in the 13 lined ground squirrel (Spermophilus tridecemlineatus)

Adult 13 lined ground squirrels were monitored for entry into a state of hypothermic hibernation or arousal in a cold room on a photoperiod LD 2:22. Once animals developed predictable hibernation patterns, animals were killed at the mid point of hypothermic hibernation or arousal for determination of plasma and tissue angiotensin-1-converting enzyme (Kininase II) activity. Enzyme was extracted from plasma, lung, kidney, liver, forebrain and brainstem and assayed in vitro. During hypothermic hibernation enzyme activity is significantly decreased in all tissues examined. These data suggest that the activity of tissue and plasma peptidases are altered during the cyclic torporous periods characteristics of hibernation in this species.     

Conspiring to succeed: the process of a joint military health care merger

The exact mechanism of hypothermic cerebroprotection after traumatic brain injury (TBI) is not fully understood. The present study was conducted to investigate the effects of mild hypothermia on trauma-induced synthesis of nitric oxide (NO), which has been implicated in the pathogenesis of ischemic brain damage associated with glutamate neurotoxicity. Cerebral contusion was created in the rat parietal cortex by a weight-drop method, and extracellular concentrations of the NO end products nitrite and nitrate were measured using in vivo brain microdialysis and capillary electrophoresis under normothermic (37 degrees C) and mild hypothermic (32 degrees C) conditions. In normothermic animals, the level of NO end products increased markedly 10 min after contusion, reaching a maximum level at 20 min. In the hypothermic rats, such increases were absent. Although it is unknown whether endothelial NO synthase, neuronal NO synthase, or both caused the elevation of the NO end products seen in the normothermic animals, the present results indicate that inhibition of NO synthesis may play a part in hypothermic cerebroprotection following TBI.