Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020672 (hypothermia)
 17,327 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To characterize the efflux system of digoxin, a cardiac glycoside, from the brain to the blood through the blood-brain barrier and blood-cerebrospinal fluid (CSF) barrier, the accumulation of digoxin by the brain microvessel or the choroid plexus isolated from guinea pig brain was investigated. The accumulation of digoxin by the brain microvessel has a saturable component (Km = 0.163 microM, Vmax = 0.142 nmol/mL of tissue/min), with a nonsaturable component [Kd = 0.203 cell-to-medium (C:M) ratio/min] that was decreased by hypothermia (Q10 = 2.9), sulfhydryl reagent, and quinidine, but not by a metabolic inhibitor [2,4-dinitrophenol (DNP)]. It was concentration- and Na+-dependent. The accumulation of digoxin by the choroid plexus was also saturable (Km = 1.9 microM, Vmax = 3.8 nmol/mL of tissue/min), and was decreased by hypothermia (Q10 = 4.4), sulfhydryl reagents, ouabain, and quinidine, but not by metabolic inhibitors (DNP, KCN); it was also concentration- and Na+-dependent. The binding of digoxin to the homogenate of choroid plexus was one-tenth of digoxin accumulation by the intact choroid plexus, suggesting that digoxin is transported into the cells and bound to the cytosol fraction. The value of (Vmax/Km + Kd) multiplied by the total tissue weight of the microvessel per guinea pig is approximately 10-fold that of Vmax/Km multiplied by the tissue weight of the choroid plexus, although (Vmax/Km + Kd) per milliliter of the microvessel is half the Vmax/Km value of the choroid plexus. These findings suggest that digoxin can be excreted from both the brain and the cerebrospinal fluid to blood by a carrier-mediated diffusion system which is inhibited by quinidine, and that a main route of digoxin efflux from the brain to the blood is not through the blood-CSF barrier, but through the blood-brain barrier.
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PMID:Transport of digoxin into brain microvessels and choroid plexuses isolated from guinea pig. 337 95

To study the transport system of propranolol (PL), a basic drug, in the blood-brain barrier, the uptake of PL into isolated bovine brain microvessels was investigated. The uptake of PL was a concentrative one via saturable process (Km = 42.5 microM) that was decreased by hypothermia (Q10 = 2.2), but not by metabolic inhibitors (2,4-dinitrophenol, KCN, ouabain). Although basic drugs such as quinidine and imipramine decreased both the initial rate of uptake and the steady-state cell-to-medium concentration ratio (C/M) of PL, acidic drugs (phenobarbital, salicylic acid) did not affect them. These results suggest that PL is taken up by the endothelial cells of the isolated brain microvessels by facilitated diffusion which is specific for basic drugs and then binds to certain binding sites in the cells.
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PMID:Uptake of propranolol by microvessels isolated from bovine brain. 343 Mar 39

Using guinea pig hippocampal slice preparations, the effect of temperature on the electrical activity and the protective effect of hypothermia against deprivation of both oxygen and glucose were studied by recording field potentials of pyramidal cell layer (CA3-4 area) and by measuring the content of adenosine triphosphate (ATP), phosphocreatine (PCr) and lactate of each slice. Cooling the perfusion medium from 37 to 21 degrees C caused a decrease in the amplitude of field potentials, although the amplitude increased (120%) transiently at around 33 degrees C. The electrical activity ceased at around 22 degrees C. When the temperature was raised from 21 to 37 degrees C, the activity recovered reversibly. However, when the temperature was raised to above 38 degrees C, the amplitude decreased and disappeared irreversibly at 42 degrees C. During deprivation, energy consumption (total approximately P used; 2 X delta ATP + delta PCr + 1.3 X delta lactate) was suppressed by lowering the tissue temperature and the initial (0-2.5 min deprivation) energy use rate was calculated to be 42.2 at 37 degrees C, 22.8 at 28 degrees C and 7.0 at 21 degrees C (approximately P m mol/kg protein/min), respectively. From these values, Q10 was estimated to be 2.05. With regard to the protective effect of hypothermia, the critical survival time (period of deprivation of oxygen and glucose for the complete recovery in neural activity and the level of high energy phosphates) was 10 min at 37 degrees C, 15 min at 28 degrees C, and 45 min at 21 degrees C, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The protective effect of hypothermia on hippocampal slices from guinea pig during deprivation of oxygen and glucose. 365 15

Cerebral high energy phosphates were studied in the intact rabbit brain using nuclear magnetic resonance spectroscopy. The effect of hypothermia on degradation kinetics in total ischemia due to circulatory arrest was examined, measuring phosphocreatine, adenosine triphosphate, and inorganic phosphate as a function of time at three different temperatures (35, 24, 21 degrees C). Phosphocreatine- and ATP-decays followed single exponential functions at all three temperatures. The half-life times increased by approximately a factor of three upon lowering the temperature from 35 to 21 degrees C with activation energies of 15-20 kcal/mol, which corresponds to values of Q10 between 2.4 and 3.2. In the temperature range studied, no critical temperature was found below which metabolism would stop completely. We conclude that nuclear magnetic resonance spectroscopy allows, in the intact animal, quantitative assessment of the influence of hypothermia on energy metabolism in the brain. This influence is a major concern in the field of cardiac surgery in infants and children who are often operated in total circulatory arrest under deep hypothermia.
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PMID:Cerebral metabolic studies in situ by 31P-nuclear magnetic resonance after hypothermic circulatory arrest. 374 59

To characterize the transport system of cimetidine, an organic cation, in the blood-cerebrospinal fluid barrier, the accumulation of cimetidine by the isolated rat choroid plexus was examined. Accumulation of cimetidine was against a concentration gradient via a saturable process (Km = 53 microM, Vmax = 12 nmol/ml/min) that was inhibited by sulfhydryl reagents (p-hydroxymercuribenzoate), metabolic inhibitors (KCN and 2,4-dinitrophenol) and hypothermia (Q10 = 4.5), but did not require inward Na+ gradient. Organic cations such as 1N-methylnicotinamide, tetraethylammonium, choline, histamine and creatinine did not affect the accumulation of cimetidine at the concentration of 1 mM. Cimetidine did not affect the accumulation of tetraethylammonium. More lipophilic cations such as quinidine and quinine inhibited not only the accumulation of cimetidine but also that of an organic anion, benzylpenicillin, although the inhibitory mechanisms are not known. One millimolar of organic anions, such as 5-hydroxyindoleacetic acid, p-aminohippuric acid, homovanillic acid, salicylic acid and benzylpenicillin, inhibited the accumulation of cimetidine. Furthermore, the accumulation of organic anions (benzylpenicillin and salicylic acid) showed saturability and was inhibited by cimetidine. Cimetidine and the organic anions thus showed a mutual inhibition. Oligopeptides also inhibited the accumulation of cimetidine. These findings suggested that cimetidine transport in the choroid plexus is via carrier-mediated active transport process, but does not require inward Na+ gradient. This transport is inhibited by several compounds with different properties like oligopeptides, lipophilic cations and organic anions, although the inhibitory mechanism is not known.
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PMID:Transport of cimetidine by the rat choroid plexus in vitro. 379 52

Two patients were rewarmed from hypothermia (esophageal temperature 27.2 degrees C, 27.5 degrees C respectively). The first case suffered from head-injury after alcohol ingestion and was deeply comatose. A metabolic or cardiovascular regulatory response to cold was not observed in this patient. The relationship between esophageal temperature and whole-body-oxygen consumption was quantified with a Q10 of 2.75 during rewarming (27.2-37.2 degrees C). His epinephrine levels were greatly elevated to 1,000 pg/ml whereas norepinephrine levels were only moderately increased to 250 pg/ml. Premature ventricular contractions (PVCs) during intubation or from the pulmonary artery catheter were not observed. The second patient was a 87 year old man with accidental hypothermia. He exhibited shivering at an esophageal temperature of 27.5 degrees C which indicated persistent thermoregulation. In contrast to the first case his norepinephrine levels were elevated to 1,500 pg/ml and his epinephrine levels only to 450 pg/ml. After onset of surface rewarming an additional increase in norepinephrine levels was observed and an increasing rate of PVC's (15/min) recorded, which ceased when temperature returned to normal. Our observations indicate that part of the cardiac complications during rewarming from deep hypothermia may result from thermoregulation and additional catecholamine liberation.
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PMID:[Rewarming from moderate to deep hypothermia: plasma catecholamine content, metabolism and circulatory function. 2 case reports]. 648 85

Blind male hamsters were maintained in running-wheel cages in a LD 12:12 light-dark cycle. After regular running patterns were established hypothermia was induced by ether anesthesia, wetting of the fur with ethanol, and cooling with ice. The hamsters were kept hypothermic for 3-24 h at colonic temperatures from 10 to 20 degrees C. Following hypothermia the animals were rewarmed and replaced in their home cages. Examination of the locomotor activity records showed phase shifts (delays) in activity onset that were correlated with the temperature and duration of the hypothermia but not with the circadian time at which the hypothermia was administered. The data were interpreted to mean that the circadian pacemaker was running at a reduced rate during the hypothermic bout. Calculation of the Q10 for the rate of the clock during hypothermia produced a range from 1.08 to 1.34 depending on the method of calculation. When compared with earlier data gathered from rats under similar conditions, the hamsters circadian pacemaker appears to be better temperature compensated.
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PMID:Temperature dependence of the hamster circadian pacemaker. 684 68

Constant heat loss studied by direct calorimetry is decreased during acute hypothermia induced by 30-40 min exposure at -6 degrees C, and body temperature falls by 7-9 degrees. Heat production is restored within 35-40 min. Cooling of the animals at -11.8 degrees leads to a fall in body temperature by more than 10 degrees, and restitution sets in about 25 min. Brain tissue respiration (incubation at 23 and 33 degrees) is increased at the 5th and 45th min after hypothermia with no changes in Q10-respiration. The metabolism of heart and liver tissues and skeletal muscles is increased at 5th, 40th and 105th min of restitution; Q10 of skeletal muscle respiration is decreased after 105-min restitution. Temperature compensation for metabolism as the mechanism of tissue homeostasis obvious during arousal in hibernating animals, is absent in non-hibernating heterothermal animals.
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PMID:[Heat loss and tissue metabolism in albino mice after acute hypothermia]. 717 26

Blind female rats were maintained in running-wheel cages in a 12-h light-dark cycle. Hypothermia was induced by ether anesthesia, wetting of the fur by ethanol, and covering with ice. Rats were put in restraining cages and colonic temperatures were maintained between 20 and 32 degrees C for 3-16 h by cooling with ice and water. On recovery from hypothermia, the rats were replaced in their home wheels. Examination of the activity records showed significant phase delays associated with temperatures lower than 28 degrees C. At 20 degrees C, the phase delays indicated that the clock was running at about 64% normal speed giving a mean Q10 of 1.33, which is quite a bit higher than previously reported. It is speculated that, because the rat maintains its body temperature within narrow limits after the neonatal stage, it has lost the precise temperature compensation for the period of its biological clock that has been so well documented in other organisms.
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PMID:Temperature dependence of rat circadian pacemaker. 724 97

The Arrhenius hypothesis suggests that change in temperature has a less marked effect on the rate of physical processes than on biological reactions. We have investigated the process underlying recovery from neuromuscular block in man by studying the effect of cooling on the rate of recovery from depolarising and non-depolarising block. Vecuronium, rocuronium and decamethonium (C10) neuromuscular block were investigated using the isolated forearm technique on awake human volunteers. In these experiments, one arm was cooled whilst the other was used as control. Moderate hypothermia decreased the rate of recovery from all three agents, but this was significantly less marked with the depolarising drug. The mean Q10 (the anticipated change in rate of a reaction across of 10 degrees C temperature gradient) of the rate of recovery for vecuronium was 3.21, rocuronium 2.86 and decamethonium 1.29. This suggests a different process in the recovery of these two types of drug. According to the Arrhenius hypothesis this would suggest that the recovery from non-depolarising drugs is likely to involve a biochemical mechanism and that recovery from decamethonium is controlled by a physical process.
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PMID:The influence of cold on the recovery of three neuromuscular blocking agents in man. 871 23


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