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Query: UMLS:C0020672 (hypothermia)
 17,327 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Deep hypothermic circulatory arrest facilitates repair of congenital cardiac anomalies in infants. It is known empirically that hypothermia protects against central nervous system (CNS) ischemic damage. The Q10O2 is only 2.2 for brain and thus a decrease in metabolic rate does not fully account for protective effects of hypothermia. Since enthalpy of dissociation of H2O is high (approximately 7 kcal/mole), its pH is temperature dependent (7.0 at 25 degrees C, 7.4 at 20 degrees C) and hypothermia may in part protect by its influence on hydrogen ion concentration. A manifestation of CNS susceptibility to ischemia is an obstruction of the microcirculation [no-reflow lesion (NRL)] demonstrated by infusion of carbon black into the cerebral circulation after a period of circulatory arrest. White lesions (NRL) against a gray background on cut section of brain increase in size with increasing time of arrest. The effect of anoxia versus circulatory arrest, brain temperature, and extracellular brain pH on NRL was studied in 45 mongrel dogs, subjected to varying periods of N2-induced anoxia on cardiopulmonary bypass (CPB) at 37 degrees C or 20 degrees C. In some studies jugular venous pH was adjusted by infusion of NaHCO3 or HCl. Control groups included normothermic CPB without anoxic and normothermic CPB, anoxia, and equimolar NaCl infusion. NRL was quantified by planimetry of photographs of cut sections of brain. These results confirm that NRL is abated by hypothermia and suggest that (1) NRL is a function of anoxia and not arrested circulation since perfusion with N2 at 37 degrees C does not protect the brain (i.e., NRL is not solely related to "critical reopening pressure") and (2) NRL is in part a function of extracellular pH.
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PMID:Cerebral anoxia: effect of deep hypothermia and pH. 3 7

The effects produced by IP administration of these three agents in the rat were compared because of in vitro evidence that each modulates the picrotoxinin site of the GABAA receptor. For each, hypothermia had the lowest threshold and convulsions the next, with hypophagia produced only by the highest dose of either Ro 5-4864 or lindane. Convulsant effects had a shorter latency and a shorter duration than did hypothermia. Hypophagia, when present, lasted the longest. Myoclonus was the seizure type with the lowest threshold for all three agents. At the highest dose, lindane produced a high incidence of maximal clonic (hopping) seizures, whereas Ro 5-4864 and picrotoxin produced a high incidence of maximal tonic seizures instead. On a mole/kg basis, picrotoxin was 40 times more effective than the other two agents and produced seizures which started later, peaked later, and persisted longest. Ro 5-4864 and lindane were effective at equimolar concentrations and, in combination, produced effects which suggested either dose-addition or synergism. The data are consistent with the hypothesis that the toxic effects of both Ro 5-4864 and lindane may be attributable, at least in part, to an action at a subpopulation of GABAA receptors.
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PMID:Toxicokinetics of Ro 5-4864, lindane and picrotoxin compared. 171 99

The irreversible muscarinic agonist, BM123 (63 mu moles kg-1, IV), was shown to produce central and peripheral physiological signs characteristic of cholinergic agonists. It also induced hypothermia, elevated nociceptive thresholds, reduced locomotor activity and disrupted spontaneous alternation performance in rats. The centrally acting muscarinic antagonist, atropine (50 mu mole kg-1) prevented or reduced all the above effects of BM123 when given SC 40 min prior to the BM123 injection. In contrast, the peripherally acting muscarinic antagonist, N-methyl atropine, prevented only the peripheral effects and the elevated nociceptive thresholds. Habituation of activity during a 20 min session was observed in all groups despite different levels of general activity. These findings are consistent with a model in which atropine and N-methyl atropine compete with BM123 for reversible association with the muscarinic receptor. In the case of BM123 administered alone, the association results, first, in agonist effects and proceeds to form an irreversible complex. Our present results show that by competing with BM123 for mAChR sites during the initial, reversible state of the interaction, atropine blocks the cholinomimetic effects of the agonist during both this state and its otherwise subsequent irreversible state.
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PMID:Influence of atropine and N-methyl atropine pretreatments on behavioral and physiological effects of the irreversible muscarinic agonist, BM123. 357 64

Effects of systemic hypothermia on the brain-stem auditory evoked responses (BAERs) in 4 pentobarbital anesthetized adult cats placed on total cardiopulmonary bypass were investigated. Hypothermia was achieved by slowly cooling the bypass blood through a heat exchanger. Serial BAERs were recorded at 2 min intervals as brain temperature was lowered from 37 to 22 degrees C and then rewarmed over a 1-2 h period. Temperatures were recorded from the brain, esophagus and rectum. Three effects were produced by controlled systemic hypothermia. First, latencies of each component wave (I-V) of the BAER increased exponentially as brain temperature was lowered to 19 degrees C. Latencies of earlier waves (I-III) increased less than those of the later waves (IV-V). Arrhenius plots of inverse latency (rate) versus reciprocal of the absolute temperature generated a family of straight lines of similar slope for each of the 5 component waves of the BAER. The activation energy for each of the 5 BAER waves was derived from the slope of the Arrhenius plot. The mean and standard deviation of the activation energy of all 5 waves was 9.7 +/- 0.5 kcal/mole degree C. The fact that the activation energy was similar for each BAER component wave (I-V) indicated that the increase in latencies for all 5 waves was governed by the same rate-limiting, temperature-dependent process(es). Second, the rise time and duration of each of the component waves of the BAER increased with decreasing temperature. Third, wave amplitudes increased from 37 to 32 degrees C in a quasiparabolic relation and then, decreased at approximately a linear rate. The BAER wave form completely disappeared below 20.3 degrees C. Slow rewarming of the brain to its initial temperature restored the BAER component waves to their original latencies and amplitudes.
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PMID:Effects of hypothermia on the cat brain-stem auditory evoked response. 619 55

1. Intrahypothalamic injection of either dopamine or 5-hydroxytryptamine (5-HT) in a dose volume of 1 microliters caused a fall in core temperature in lightly restrained rats maintained at an ambient temperature of 17 +/- 1 degree C. 2. Haloperidol (6.5 n-mole), a dopamine antagonist, prevented the hypothermic effect of dopamine (65 n-mole), but was ineffective against the response to either intrahypothalamic 5-HT (114 n-mole) or oxotremorine (6.0 n-mole). 3. Methysergide (14 n-mole) and cryproheptadine (17 n-mole) blocked the effect of both 5-HT and dopamine. However, these same doses failed to antagonise the effect of oxotremorine. 4. Rats placed on 0.65 m below a 250 W infra-red lamp responded to the imposed heat load vasodilation of tail skin blood vessels, as indicated by an increased tail skin temperature. 5. Rats tested 2 weeks after bilateral intrahypothalamic injection of 5,6-dihydroxytryptamine (42 n-mole in 2 microliters) showed a significant reduction in their tail skin temperature response and were less able to withstand the imposed heat load. 6. Three serial sections (0.8 mm thick) were prepared from the preoptic area of the rat brain, one anterior, one posterior and one corresponding to the previously defined dopamine-sensitive site. 7. Pretreatment with 5,6-dihydroxytryptamine significantly reduced the 5-HT concentration in the dopamine sensitive site, but had no effect on the concentration of dopamine. This pretreatment blocked dopamine but not 5-HT-induced hypothermia. 8. The 5-hydroxyindoleacetic acid (5HIAA) concentration in the hypothalamus of the normal rat exposed to a heat load was found to be significantly elevated, whereas there was no change in the 5HIAA concentration in the cortex. 9. Slices of rat preoptic hypothalamus and hippocampus were incubated with [3H]5-HT (0.2-2 microM). These slices accumulated 5-HT with properties characteristic of a neuronal uptake process. 10. Perfusion with either dopamine (greater than 50 microM) or apomorphine (greater than 200 microM) enhanced the release of [3H]5-HT from the prelabelled hypothalamic slices, but failed to stimulate release from hippocampal slices. 11. The release of [3H]5-HT from preoptic slices by dopamine and apomorphine was antagonised by the dopamine antagonists haloperidol (2 microM) and (+) isomer of butaclamol (1 microM), the (-) isomer of butaclamol was inactive. 12. These results support the hypothesis of a dopamine-5HT link in the hypothalamic thermoregulatory pathways of the rat.
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PMID:A dopamine-5-hydroxytryptamine link in the hypothalamic pathways which mediate heat loss in the rat. 743 Dec 48

The efficacy of benidipine hydrochloride in preventing myocardial ischemia and reperfusion injury was evaluated in isolated rabbit hearts (n = 28). Isovolumic left ventricular function, coronary flow, creatine phosphokinase (CPK) release, and myocardial water content were measured after ischemia during both normothermia (37 degrees C; Group I) and hypothermia (23 degrees C; Group II). After baseline measurements, hearts were induced to arrest by chilled cardioplegic solution. Each group was divided into two subgroups, depending upon whether benidipine hydrochloride (10(-9) mole/liter) was added in the cardioplegia (A, without benidipine; B, with benidipine). After 30 min of ischemia for Group I and 180 min for Group II (which added another cardioplegia every 30 min), hearts were reperfused. Measurements the same as those at baseline were carried out every 15 or 30 min for up to 60 min. Benidipine-treated hearts started beating in a shorter time than did control hearts (Group I-B, 38.7 +/- 3.7 sec vs Group I-A, 59.9 +/- 5.6; Group II-B, 36.7 +/- 2.0 vs Group II-A, 47.8 +/- 3.3). The percentage of recovery of left ventricular developed pressure after 60 min of reperfusion was significantly better in benidipine groups (P < 0.05). With respect to changes in coronary flow and CPK release after reperfusion, benidipine groups were preserved extremely well. We conclude that the addition of benidipine hydrochloride to cardioplegic solution significantly improves ventricular function after myocardial ischemia and reperfusion.
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PMID:Efficacy of benidipine hydrochloride on myocardial ischemia and reperfusion. 764 89

Metabolic and body temperature (Tb) responses of star-nosed moles (Condylura cristata) exposed to air temperatures ranging from 0 to 33 degrees C were investigated. The thermoneutral zone of this semi-aquatic mole extended from 24.5 to 33 degrees C, over which its basal rate of metabolism averaged 2.25 ml O2 g-1 h-1 (45.16 J g-1 h-1). This rate of metabolism is higher than predicted for terrestrial forms, and substantially higher than for other moles examined to date. Minimum thermal conductance was nearly identical to that predicted for similar-sized eutherians and may represent a compromise between the need to dissipate heat while digging and foraging in subterranean burrows, and the need to conserve heat and avoid hypothermia during exposure to cold. C. cristata precisely regulated Tb (mean +/- SE = 37.7 +/- 0.05 degrees C) over the entire range of test temperatures. Over three separate 24-h periods, Tb of a radio-implanted mole varied from 36.6 to 38.8 degrees C, and generally tracked level of activity. No obvious circadian variation in Tb and activity was apparent, although cyclic 2-4 h intervals of activity punctuated by periods of inactivity lasting 3-5 h were routinely observed. We suggest that the elevated basal metabolic rate and relatively high Tb of star-nosed moles may reflect the semi-aquatic habits of this unique talpid.
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PMID:Fasting metabolism and thermoregulatory competence of the star-nosed mole, Condylura cristata (Talpidae: Condylurinae). 1050 Oct 21

Stroke is a devastating disease and a leading cause of death and disability. Currently, the only FDA approved therapy for acute ischemic stroke is the intravenous administration of the thrombolytic medication, recombinant tissue plasminogen activator (tPA). However, this treatment has many contraindications and can have dangerous side effects such as intra-cerebral hemorrhage. These treatment limitations have led to much interest in potential adjunctive therapies, such as therapeutic hypothermia (T <or 35 degrees C) and ultrasound enhanced thrombolysis. Such interest may lead to combining these therapies with tPA to treat stroke, however little is known about the effects of temperature on the thrombolytic efficacy of tPA. In this work, we measure the temperature dependence of the fractional clot mass loss Deltam(T) resulting from tPA exposure in an in vitro human clot model. We find that the temperature dependence is well described by an Arrhenius temperature dependence with an effective activation energy E(eff) of 42.0 +/- 0.9 kJ mole(-1). E(eff) approximates the activation energy of the plasminogen-to-plasmin reaction of 48.9 kJ mole(-1). A model to explain this temperature dependence is proposed. These results will be useful in predicting the effects of temperature in future lytic therapies.
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PMID:Arrhenius temperature dependence of in vitro tissue plasminogen activator thrombolysis. 1750 82

Furred subterranean mammals face the problem of dissipating heat to the environment because high humidity and absence of air flow in sealed belowground tunnels constrain heat loss from body by convection and evaporation. In order to detect body areas responsible for heat loss, surface temperatures in two species of African mole-rats were measured at different ambient air temperatures by infrared thermography. Fur characteristics were also evaluated. Thinner pelage of the ventrum, its moderate temperature and large size suggest that ventral side of the body is the main thermal avenue for heat loss in both species. Interspecific differences could be explained by different fur characteristics connected with social thermoregulation. Compared to the social Fukomys mechowii, the solitary Heliophobius argenteocinereus has denser and longer fur on most of its body; its surface temperature was thus lower than in F. mechowii at lowered ambient temperatures. On the other hand, the denser and longer hair cover in H. argenteocinereus impedes heat dissipation at highest ambient temperatures (and probably also during digging activity) resulting in increase of core body temperature. H. argenteocinereus seems to be more sensitive to overheating than F. mechowii. At lower air temperatures, the social species may uses huddling to combat hypothermia.
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PMID:Patterns of surface temperatures in two mole-rats (Bathyergidae) with different social systems as revealed by IR-thermography. 1754 16

Tau is the major microtubule associated protein (MAP) of a mature neuron. The other two neuronal MAPs are MAP1 and MAP2. An established function of MAPs is their interaction with tubulin and promotion of its assembly into microtubules and stabilization of the microtubule network. The microtubule assembly promoting activity of tau, a phosphoprotein, is regulated by its degree of phosphorylation. Normal adult human brain tau contains 2-3 moles phosphate/mole of tau protein. Hyperphosphorylation of tau depresses this biological activity of tau. In Alzheimer disease (AD) brain tau is ~three to four-fold more hyperphosphorylated than the normal adult brain tau and in this hyperphosphorylated state it is polymerized into paired helical filaments ([PHF) admixed with straight filaments (SF) forming neurofibrillary tangles. Tau is transiently hyperphosphorylated during development and during anesthesia and hypothermia but not to the same state as in AD brain. The abnormally hyperphosphorylated tau in AD brain is distinguished from transiently hyperphosphorylated tau by its ability (1) to sequester normal tau, MAP1 and MAP2 and disrupt microtubules, and (2) to self-assemble into PHF/SF. The cytosolic abnormally hyperphosphorylated tau, because of oligomerization, unlike normal tau, is sedimentable and on self-assembly into PHF/SF, loses its ability to sequester normal MAPs. Some of the tau in AD brain is truncated which also promotes its self-assembly. Tau mutations found in frontotemporal dementia apparently promote its abnormal hyperphosphorylation. Thus, the AD abnormally hyperphosphorylated tau (1) is distinguishable from both normal and transiently hyperphosphorylated taus, and (2) is inhibitory when in a cytosolic/oligomeric state but not when it is self-assembled into PHF/SF. Inhibition of abnormal hyperphosphorylation of tau offers a promising therapeutic target for AD and related tauopathies.
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PMID:Tau in Alzheimer disease and related tauopathies. 2067 74


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