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 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To study the molecular basis of ammonia toxicity, highly reproducible models of acute liver failure and acute hyperammonemia in the rabbit were developed. Acute liver failure was induced by two-stage liver devascularization, and acute hyperammonemia by prolonged ammonia infusion such that the plasma ammonia pattern found in acute liver failure was simulated. Clinical symptoms, spectral analysis of the EEG, biochemistry (blood gases, renal function, electrolytes and markers of hepatic injury) and the presence of cerebral edema were studied. During acute liver failure severe encephalopathy developed after 10.2 +/- 1.9 h (n = 6, mean +/- SEM). Other liver-failure-associated abnormalities were cerebral edema, lactic acidosis, renal dysfunction, hypothermia and septicemia. During acute hyperammonemia, severe encephalopathy developed after 18.2 +/- 0.4 h (n = 6, mean +/- SEM). Other abnormalities found were cerebral edema and lactic acidosis. In both animal models comparable EEG changes were observed (a decrease in mean dominant frequency and theta-activity, and an increase in delta activity). However, these changes were not statistically significant, and non-specific as they also occurred in control rabbits despite their clinical wellbeing. This study demonstrates in the rabbit the similarity between encephalopathy due to acute ischemic liver failure and that due to hyperammonemia. An observed difference in hyperammonemia-induced encephalopathy was pronounced ataxia, which did not occur during acute liver failure, whereas hypothermia, sepsis and renal failure occurred exclusively in acute liver failure. Our models appear satisfactory for the study of hepatic encephalopathy and ammonia toxicity.
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PMID:Encephalopathy from acute liver failure and from acute hyperammonemia in the rabbit. A clinical and biochemical study. 817 26

Energy substrate mobilization has been suggested as being a limiting factor for the rate of cold-induced thermogenesis (M), and consequently in delaying hypothermia. The evidence supporting this hypothesis in humans, however, is not convincing and the hypothesis has yet to be tested in a rigorous manner using a full heat balance analysis (partitional calorimetry). The goal of this study was therefore to re-investigate whether enhancing energy substrate mobilization by feeding cold-exposed subjects would improve M and affect heat debt (S; the minute-by-minute balance of M and heat losses) as well as rectal (Tre) and mean skin temperatures (Tsk). Nine healthy semi-nude fasted subjects were exposed to 5 degrees C (3 h at rest, 1 m.s-1 wind) on three occasions following the ingestion at min 0 and 90 of either: (1) a placebo, (2) 710 kJ of pure carbohydrates (100%-CHO), or (3) 710 kJ of a high-carbohydrate bar (High-CHO). As expected in the cold, Tre and Tsk decreased whereas M, S and heat losses increased (P < 0.01). However, there were no differences between treatments, including the final Tre [mean (SEM); 36.4 (0.2); 36.5 (0.3) and 36.5 (0.2) degrees C for the placebo, 100%-CHO and High-CHO tests, respectively]. During the 100%-CHO treatment, rates of carbohydrate oxidation were the highest and fat oxidation the lowest (P < 0.05), whereas the High-CHO treatment caused smaller changes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Is energy substrate mobilization a limiting factor for cold thermogenesis? 822 37

Fatty acid and glucose oxidation rates were measured in isolated rat hearts undergoing hypothermia and rewarming. The hearts were perfused in the Langendorff mode with Krebs-Henseleit bicarbonate buffer containing 11.1 mM glucose plus 0.6 mM albumin-bound oleic acid as energy substrates. The hearts were stabilized at 37 degrees C and thereafter cooled progressively to 15 degrees C over a period of 60 min. The hearts were kept at this temperature for 10 min and then rewarmed to 37 degrees C during the next 30 min. Control hearts were perfused at 37 degrees C throughout the whole perfusion period. Trace amounts of [14C]glucose or [14C]oleic acid were included in the perfusate, and the rate of substrate oxidation was determined on the basis of the radioactive CO2 production. In normothermic hearts steady state oxidation rates of glucose and oleate were found to be 0.17 +/- 0.01 and 0.51 +/- 0.07 mumol min-1 g-1 dry wt, respectively (mean +/- SEM). In response to hypothermia (15 degrees C) glucose oxidation was reduced by 76% (from 0.17 +/- 0.01 to 0.04 +/- 0.01 mumol min-1 g-1 dry wt) and oleate oxidation by 47% (from 0.51 +/- 0.07 to 0.27 +/- 0.02 mumol min-1 g-1 dry wt). Upon rewarming glucose and fatty acid oxidation rates returned to essentially the same values (0.12 +/- 0.02 and 0.45 +/- 0.04 mumol min-1 g-1 dry wt) as those observed under steady state normothermic conditions. The molar ratio between glucose and fatty acid oxidation was, however, significantly (P < 0.05) lower in hypothermic than in normothermic hearts.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Substrate preference of isolated perfused rat hearts during hypothermia and rewarming. 826 3

Considerable evidence indicates that brain temperature during ischemia affects the extent and distribution of ischemic injury. However, only limited data have been presented concerning the influence of temperature on ischemic damage after reversible focal cerebral ischemia. Because focal ischemic events of this type resemble conditions observed in the clinic, studies were undertaken to examine the effects of mild and moderate hypothermia on the extent of cerebral infarction after focal neocortical ischemia. Under halothane anesthesia, the left middle cerebral artery and both carotid arteries were occluded reversibly for a period of 3 hours in adult Sprague-Dawley rats. The animals were killed 3 days later. Brain sections were stained with triphenyltetrazolium chloride and analyzed for infarction using a computerized image analysis system. Temporal muscle temperature and rectal temperature were monitored continuously. The following groups with different intraischemic temporal muscle temperatures were analyzed: 1) control, 35.8 to 36.2 degrees C; 2) mild hypothermia, 33.0 to 33.5 degrees C; and 3) moderate hypothermia, 27.5 to 29.2 degrees C. The volumes of infarction were 214.5 +/- 17.9, 166.5 +/- 6.8, and 108.2 +/- 5.9 mm3 (mean +/- SEM) for the control, mild hypothermia, and moderate hypothermia groups, respectively. These findings demonstrate that both mild and moderate hypothermia reduce the impact of temporary focal ischemia in Sprague-Dawley rats.
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PMID:Effects of intraischemic hypothermia on cerebral damage in a model of reversible focal ischemia. 832 2

Isolated embryonic retinas were metabolically stressed by inhibition of glycolysis either with iodoacetate (IOA) or by glucose withdrawal plus 10 mM 2-deoxy-D-glucose, and the effects of hypothermia were examined. Incubation at 30 versus 37 degrees C during 30 min of hypoglycemia with IOA completely reduced the rapid swelling-related GABA release [6 +/- 2 vs. 68 +/- 10 nmol/100 mg of protein (mean +/- SEM) for 30 and 37 degrees C, respectively]. Histology of the retina immediately following 30 min of metabolic stress at 30 degrees C appeared normal, whereas that at 37 degrees C showed a pattern of acute edema, characteristic of NMDA-mediated acute excitotoxicity. Coincubation with a competitive or noncompetitive NMDA antagonist, respectively, CGS-19755 (10 microM) or MK-801 (1 microM), during 30 min of hypoglycemia at 37 degrees C completely prevented tissue swelling, whereas extracellular GABA content remained at basal levels, indicating that the cytotoxic effects of IOA treatment for 30 min at 37 degrees C were NMDA receptor mediated. Longer periods of hypoglycemia at 37 degrees C produced acute toxicity that was only partially NMDA receptor mediated. Hypothermia delayed the onset of NMDA-mediated toxicity by 30-60 min. At 30 degrees C, the rate of loss of ATP was slowed during the first several minutes of hypoglycemia (82 and 58% of maximal tissue levels at 30 and 37 degrees C, respectively, at 5 min, but by 10 min, ATP levels were comparably reduced. After a transient exposure of retina to 50 microM NMDA in Mg(2+)-free medium, hypothermia significantly attenuated acute GABA release by 30%.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hypothermia, metabolic stress, and NMDA-mediated excitotoxicity. 837 98

Etomidate is a nonbarbiturate hypnotic agent which, like the barbiturates, decreases the cerebral metabolic rate of oxygen consumption (CMRO2) 35-50%. The present studies assessed whether etomidate decreased CMRO2 through temperature-dependent mechanisms and whether the combination of etomidate and moderate hypothermia (28 degrees C) decreased CMRO2 more than hypothermia alone. Nineteen anesthetized dogs were treated with saline, etomidate (burst-suppressive doses), etomidate with hypothermia, or hypothermia alone. Etomidate did not affect (p > 0.05) the mean arterial pressure (MAP, mm Hg) but modestly lowered the heart rate [HR; 124 +/- 6 to 105 +/- 14, (mean +/- SEM); p < 0.05] whereas hypothermia (without or with etomidate) lowered (p < 0.05) both MAP (141 +/- 4 to 116 +/- 5 and 135 +/- 6 to 81 +/- 7) and HR (135 +/- 14 to 84 +/- 3 and 135 +/- 10 to 69 +/- 5, respectively). Etomidate administration did not result in a change (p > 0.05) in the esophageal, brain parenchymal, or subdural temperature. CMRO2 (ml/100 g/min) decreased (p < 0.05) during etomidate administration (3.2 +/- 0.4 to 1.7 +/- 0.2) and hypothermia (3.5 +/- 0.2 to 1.1 +/- 0.2), but the addition of etomidate to hypothermia did not further reduce CMRO2 in the animals (3.1 +/- 0.5 to 1.3 +/- 0.2) despite decreasing their brain hemispheric electrical activity from 9 +/- 1 Hz to a burst-suppressive state.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of etomidate and hypothermia on cerebral metabolism and blood flow in a canine model of hypoperfusion. 849 Mar 7

For preventing graft failure, the effects of hypothermic management of brain dead dogs was investigated. Forty-three brain dead dogs were divided into two groups according to the degree of esophageal temperature; a normothermic group (37.2 +/- 0.3 degree C, mean +/- SEM, n = 22), and a hypothermic group (31.8 +/- 0.3 degree C, n = 21) which was obtained by introducing ice slush in the peritoneal cavity. During the management of brain dead dogs, 1) heart rate, pressure product, and a total amount of catecholamine were significantly lower (p < 0.05) in the hypothermic group than in the normothermic group, 2) mean blood pressure, the maximum rate of the rise of left ventricle (LVdp/dt) and cardiac output were not different between both groups, 3) lactate content in the coronary sinus, and O2-extraction rate of the heart tended to be lower in the hypothermic group than in the normothermic group. After transplantation, the recovery of cardiac function was better in the hypothermic group than in the normothermic group. Hypothermic management of brain dead dogs may safely decrease cardiac stress, and keep cardiac aerobic circumstances.
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PMID:[Hypothermic management of brain dead dogs]. 875 82

The effect of mild (32 degrees C) and moderate (27 degrees C) hypothermia was analyzed on the cell volume and intracellular pH (pHi) of C6 glioma cells at normal pH and during lactacidosis at pH 6.2 in vitro. The cells were suspended in an incubation chamber under continuous control of pH, PO2 and temperature. Cell swelling was quantified by an advanced Coulter-system. pHi was measured by flow cytometry using the fluorescent dye bis-carboxyethyl carboxyfluorescein (BCECF). Following a control period at 37 degrees C, the ambient temperature was decreased to 32 degrees C for 30 min, and subsequently to 27 degrees C for another 30 min. Hypothermia alone led to an immediate and significant cell volume increase of 107.3 +/- 0.4% (mean +/- SEM) of control after 30 min at 32 degrees C, and further swelling to 110.5 +/- 0.9% after 30 min at 27 degrees C. Yet, hypothermia (27 degrees C) afforded partial protection against the acidosis-induced cell swelling at pH 6.2, which was reaching to 120.4 +/- 0.9% in the normothermic control group after 60 min, while only to 111.3 +/- 0.9% at 27 degrees C. Hypothermia, however, was associated with a more pronounced decrease of the pHi during acidosis (6.3 +/- 0.04) as compared to that of the normothermic control falling then to 6.5 +/- 0.03. The results demonstrate that mild and moderate hypothermia induce glial cell swelling, but simultaneously inhibit cell swelling from acidosis. The protection against cell swelling, however, has its price as indicated by the enhancement of the intracellular acidification.
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PMID:Effect of mild and moderate hypothermia on the acidosis-induced swelling of glial cells. 941 41

We have evaluated the efficacy of new electric warming blankets, which meet the requirements of the international standard for perioperative electrical and thermal safety, in preventing intraoperative hypothermia. We studied 18 patients undergoing abdominal surgery, allocated to one of two groups: in the control group, there was no prevention of intraoperative hypothermia (n = 8) and in the electric blanket group, two electric blankets covered the legs and upper body (n = 10). Anaesthesia duration was similar in the two groups (mean 201 (SEM 11) min), as was ambient temperature (20.5 (0.1) degrees C). Core temperature decreased during operation by 1.5 (0.1) degrees C in the control group, but only by 0.3 (0.2) degree C in the electric blanket group (P < 0.01). Five patients shivered in the control group compared with one in the electric blanket group (P < 0.05). We conclude that cutaneous warming with electric blankets was an effective means of preventing intraoperative hypothermia during prolonged abdominal surgery.
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PMID:Prevention of hypothermia by cutaneous warming with new electric blankets during abdominal surgery. 949 15

We employed a bile duct ligation (BDL) model of cholestatic liver injury to test the hypothesis that this form of preexisting hepatic dysfunction alters the kinetics of circulating TNF-alpha and IL-6 after Escherichia coli endotoxemia, thereby augmenting mortality and lung injury by a TNF-alpha:leukotriene (LT) axis of inflammation. Male rats were catheterized 13 d after BDL or sham surgery and studied while awake 18 to 24 h later. Cholestasis after BDL was confirmed by baseline serum bilirubin (BDL = 7.34 +/- 0.72 mg/dl, mean +/- SEM, n = 17 versus Sham = 0.25 +/- 0.07, n = 20; p < 0.005) and histopathology. Sham and BDL animals received E. coli lipopolysaccharide serotype O55:B5 (LPS, 5 mg/kg i.v.) or 0.9% NaCl (NS) ending at t = 0 and were monitored over 24 h for vital signs and hemodynamics. In parallel studies, lipoxygenase inhibition was performed using diethylcarbamazine or the 5-lipoxygenase activating-protein inhibitor MK-886. Blood was collected at baseline and at t = 1.5, 3.5, and 24 h for formed elements and for serum endotoxin, TNF-alpha, IL-6, bilirubin, and alanine aminotransferase (ALT). Organs were evaluated at 24 h for histopathology, including neutrophil (PMN) densities and wet/dry weight (W/D) ratios. Cholestasis reduced survival after otherwise nonlethal endotoxemia, with seven of 11 BDL + LPS rats dying within 24 h versus no deaths in BDL + NS (n = 6), Sham + LPS (n = 14), or Sham + NS (n = 6) animals (p < 0.01). Despite equivalent serum endotoxin between groups, circulating TNF-alpha was 8-fold higher in BDL + LPS than in Sham + LPS rats at 1.5 and 3.5 h (p < 0.001), whereas serum TNF-alpha did not differ between BDL + NS and Sham + NS rats. IL-6 likewise was increased differentially by 1.5 h in BDL + LPS animals (11.98 +/- 2.42 ng/ml) versus Sham + LPS rats (3.05 +/- 0.58 ng/ml, p < 0.05). Hypothermia, bradycardic hypotension, and leukopenia were most severe and prolonged in BDL + LPS rats, which also had significantly higher ALT values, W/D ratios, and organ PMN counts. LT inhibition failed to reduce BDL-related differences in serum cytokines or survival after endotoxemia. Thus, cholestasis augments inflammatory responses to gram-negative endotoxemia, sensitizing the host to enhanced fluid flux in multiple organs and to mortality by a LT-independent mechanism.
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PMID:Cholestatic liver injury increases circulating TNF-alpha and IL-6 and mortality after Escherichia coli endotoxemia. 960 37


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