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

In order to reduce the operative injury of the endothelium in free reversed vein grafts, cultured human endothelial cells were used to test the optimal concentration of the constituents of a flushing solution for improved protection of the endothelium. The following solution proved to be the most suitable when tested at 20 degrees C; mannitol 160 mmol l-1, glucose 15 mmol l-1, NaCl 30 mmol l-1, KHCO3 5 mmol l-1, K2SO4 10 mmol l-1, KH2PO4 4 mmol l-1, MgSO4 20 mmol l-1, CaCl2 1.5 mmol l-1, potassium citrate 1.0 mmol l-1, Pluronic F-68 20 mg l-1, HEPES 4 mmol l-1, HEPES-Na 6 mmol l-1, pH 7.25, osmolality 325 mosmol kg-1 H2O. When endothelial cell injury was measured by a 51Cr-release assay, the new solution protected human endothelial cells in culture during hypothermic incubation better than isotonic NaCl, St Thomas' cardioplegic solution or Krebs-Henseleit's buffer. Transmission and scanning electron microscopy showed that the endothelium of human saphenous vein grafts was well preserved following 6 h of incubation at 20 degrees C with the new solution. As determined by morphometry using scanning electron microscopy, the endothelium of free porcine vein grafts was better preserved after incubation for 2 h at 20 degrees C with the new solution than with either isotonic NaCl (p = 0.02) or diluted, heparinized blood (p = 0.02) as the incubation medium, all cases observed following 2 h of subsequent arterial flow. The present study indicates that the endothelium of free vein grafts can be well protected against hypothermia when the flushing and irrigation fluid has a composition favouring endothelial protection. It appears likely that such treatment of vein grafts will reduce the frequency of vein graft narrowing and occlusion, post-operatively.
 ...
PMID:A new protective solution for hypothermic storage of free vein grafts in cardiovascular surgery. 158

Organic cosolvents are used in many intramuscular formulations for solubilization of drugs and have been shown to cause skeletal muscle damage (myotoxicity). This study explored the influence of organic cosolvent-induced myotoxicity on the bioavailability of a model compound, diazepam. A tracer (C14) dose of diazepam was selected which did not elicit any systemic pharmacologic effects (viz., hypothermia and sedation) that might alter the pharmacokinetics of the drug. Male New Zealand White rabbits were injected with diazepam dissolved in three cosolvent: water mixtures (20% v/v propylene glycol, 20% v/v polyethylene glycol 400, and 50% v/v polyethylene glycol 400). These mixtures have similar physicochemical properties, but vary 10-fold in their in vitro myotoxicity. Using plasma total radioactivity following intramuscular administration of diazepam, statistical differences were not detected in the area under the curve (AUC), the peak concentration, and the time of the observed peak concentration among these treatments, although the in vivo myotoxicity of these systems (measured by the plasma creatine kinase AUC) varied by 10-fold (p less than 0.01). Limited data on unchanged diazepam levels confirmed these observations. Thus, the degree of skeletal muscle damage caused by these organic cosolvent systems does not seem to affect the bioavailability of a tracer dose of intramuscular diazepam.
 ...
PMID:Effect of organic cosolvent-induced skeletal muscle damage on the bioavailability of intramuscular [14C]diazepam. 227 57

The cellular response to hypotonic stimulation was studied with videometric methods in 266 proximal renal tubules dissected from Carassius auratus (goldfish). In hypotonic solutions (low NaCl), cells underwent rapid swelling followed by gradual shrinking toward isotonic volume (volume-regulatory decrease phase, VRD). Hypothermia (8 degrees C), increased extracellular potassium (15, 25, and 40 mM), quinine (0.1 mM), barium (0.5 mM), 4,4'-diisothio-cyanostilbene-2,2'-disulfonic acid (DIDS; 0.02 mM), acetazolamide (0.1 mM), decrements in extracellular bicarbonate, and increases in extracellular chloride impaired VRD. Ouabain (1.0 mM), furosemide (0.1 mM), and the chloride channel blocker 5-nitro-2-(3-phenylpropylalanine) benzoate (NPPB; 0.001 mM) had no effect. While VRD occurred in the absence of extracellular calcium influx, addition of the calcium ionophore A23187 (0.01 mM) in the presence of ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA; 2.0 mM) impaired this process both in acidic and alkaline media. Trifluoroperazine (0.01 mM) reversibly inhibited VRD. The effect of this calmodulin inhibitor could not be overridden with the cationic ionophore gramicidin (0.5 microM). The data suggest that Carassius proximal renal tubular cells volume regulate in hypotonic solutions by the loss of KCl and osmotically obligated water. We postulate that the main efflux of potassium is through a calcium-gated potassium channel with its counter ion extruded through a calmodulin-regulated Cl(-)-HCO3- exchanger.
 ...
PMID:Possible role of basolateral cell membrane in proximal renal tubule osmoregulation. 233 Oct 23

To investigate the effects on the central nervous system of severe cold stress with and without chlorpromazine, guinea pigs were treated with chlorpromazine or 0.9% NaCl and exposed to -20 degrees C or +23 degrees C for 1 h. Hypothalamic noradrenaline (NA), dopamine (DA), 5-hydroxy-tryptamine (5-HT), 3-methoxy-4-hydroxyphenyl ethylene glycol (MHPG), homovanillinic acid (HVA) and 5-hydroxy-indoleacetic acid (5-HIAA) were determined by high-performance liquid chromatography. Serum, urinary and vitreous fluid catecholamines, muscle and liver glycogen, and blood glucose were also measured. Chlorpromazine caused distinct hypothermia at -20 degrees C and slight hypothermia at +23 degrees C. The rise in hypothalamic MHPG, 5-HIAA and MHPG/NA and in 5-HIAA/5-HT ratios in the cold indicate increased noradrenergic and serotonergic activity. The latter was inhibited by chlorpromazine and a drug-induced inhibition of noradrenergic neurons could not be ruled out. Chlorpromazine increased the turnover of DA at room temperature and the same tendency was seen in the cold. The hypothermic animals had low serum catecholamines, indicating diminished sympathetic activity. The chlorpromazine-treated cold-exposed animals did not react to the environmental stress by sympathetic activation, as urinary NA and adrenaline were not elevated, but DA was excreted by all the drug-treated animals. Vitreous fluid NA and DA were elevated as an indicator of cold stress, and no drug effect was seen in this fluid.
 ...
PMID:Chlorpromazine-induced alterations in hypothalamic amine metabolism and stress responses in severe cold. 247 37

Hepatocytes from isolated rat livers were hypothermically incubated (5 degrees C) in an oxygenated environment with continuous shaking (to simulate organ perfusion preservation). The incubation solution was either a tissue culture medium (L-15), an organ preservation perfusate (UW gluconate), or a simple cold-storage solution used for organ preservation (UW lactobionate). Hepatocyte viability was assessed from the release of lactate dehydrogenase (LDH) into the incubation medium. Cell swelling (due to the uptake of water) was also measured. Within 24 hr, hepatocytes hypothermically stored in each of the three incubation solutions became swollen (30 to 40% water gain) and lost a significant amount of LDH (as much as 60%). The addition of polyethylene glycol (PEG; relative molecular mass 8000; 5 g%) to the solutions suppressed cell swelling and allowed the incubated hepatocytes to remain relatively well preserved (30% LDH release) for as long as 120 hr. Adding either dextran (relative molecular mass 10,000 to 78,000; 5 g%) or saccharides (100 mmol/liter) instead of PEG neither prevented cell swelling nor prevented the cells from dying. The results of this study suggest (i) there is a direct correlation (r = 0.873) between hypothermia-induced cell swelling and cell death (i.e., the suppression of cell swelling prevents cell death); (ii) the mechanism by which PEG prevents cell swelling (and thus maintains cell viability) is not related to the osmotic or oncotic properties of the molecule but instead is apparently related to some unknown interaction between PEG and the cell, an interaction that provides stability during hypothermic incubation; and (iii) hypothermia-induced cell swelling must be prevented if isolated hepatocytes are to be used as a model for studying the mechanism by which cell damage occurs during hypothermic organ preservation. By eliminating cell death due to cell swelling, the biochemical mechanisms of cell death can be studied.
 ...
PMID:Hypothermic preservation of hepatocytes. I. Role of cell swelling. 248 Aug 65

We looked at FiO2, choice of anesthetic, nutritional status, and body temperature in a gerbil model of forebrain ischemia to determine their effect on data interpretation, ischemic outcome, and extent of pharmacologic protection. We subjected 484 gerbils to 5 minutes of forebrain ischemia under different experimental conditions. The gerbils were anesthetized with 3% halothane and inspired 21% O2, 37% O2 and 60% N2O, or 97% O2. Six groups of gerbils pretreated with 200 mg/kg phenytoin or 2 ml/kg polyethylene glycol (vehicle) underwent ischemia in the fasted or fed state. Three groups of gerbils receiving no pretreatment underwent ischemia with rectal temperatures of 32-33 degrees C, 34-35 degrees C, or 37 degrees C. We counted intact neurons in the CA1 hippocampal sector in brains fixed on Day 7 after ischemia. t tests of square-root-transformed cell counts were used to assess the effect of hypothermia, and analysis of variance of the transformed data was used to test for the effects of phenytoin, FiO2, and nutritional status. Phenytoin pretreatment provided significant protection from CA1 neuron loss in all groups tested (p less than 0.001), but the degree of protection varied from 20% to 44%. In spite of significantly higher serum glucose concentrations in fed than in fasted gerbils (173 and 118 mg/dl, respectively), we found no significant effect of nutritional status upon neuron loss in phenytoin- or vehicle-pretreated gerbils. An FiO2 of 21% significantly decreased the number of viable neurons in both vehicle- and phenytoin-pretreated groups (p less than 0.03), despite the lack of an effect of hypoxemia on arterial blood gases.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Conditions for pharmacologic evaluation in the gerbil model of forebrain ischemia. 281 90

The release of oxygen free radicals from ischemic myocardium has been implicated as a causative factor of cardiac dysfunction after thermal injury. In this study, isolated coronary perfused guinea pig hearts were used to determine if free radical scavengers improve left ventricular (LV) intrinsic contractile response to burn shock. Parameters measured included peak isovolumic LV pressure (LVP) and maximal rate of LVP rise (+dP/dtmax) and fall (-dP/dtmax) at a constant preload. Control animals were immersed in body temperature water and divided into four groups: Group 1, untreated N = 10; Group 2, control animals treated with unbound superoxide dismutase (SOD), N = 5; Group 3, control animals treated with ficoll-SOD, N = 5; and Group 4, control animals treated with PEG-SOD, N = 5. Scald burn equivalent to 45% of total body surface area was produced in 64 animals. Fluid resuscitation was initiated immediately after burn in all animals, and animals were then divided into seven burn experimental groups. In Group 5, 10 animals were treated with fluid alone, lactated Ringer's, 4 mL/kg/% burn. Burned animals in Group 6 (N = 10) received a reduced volume of Ringer's 2 mL/kg/% burn plus unbound-SOD, 50 mg/kg; 10 animals in Group 7 received this volume of Ringer's plus ficoll-SOD, 50 mg/kg. In groups 8, 9, and 10 animals were given fluid, lactated Ringer's, 2 mL/kg/% burn plus varying doses of PEG-SOD (Group 8: N = 9, 1,000 U; Group 9: N = 10, 6,000 U; Group 10: N = 5, 12,000 U). In Group 11 (N = 10), animals received SOD-PEG, 6,000 U, plus catalase, CAT-PEG, 6,000 U, given with 4 mL/kg/% burn lactated Ringer's solution. Hypotension, hypothermia, and hemoconcentration were similar in all animals after thermal injury, regardless of treatment regimen. Burn hearts showed significantly lower LVP, +dP/dt max, and -dP/dt max than control hearts (P less than 0.05). Compared to controls, coronary pressure and coronary vascular resistance were significantly higher in all treated burn groups. There was no significant difference in heart rate or time to peak pressure or time to maximal contraction or relaxation among the groups. Left ventricular function curves for burned hearts were shifted downward and to the right of curves obtained from control hearts (P less than 0.01), regardless of scavenger treatment. PEG-SOD, 6,000 U, improved left ventricular contractility (+dP/dt) at maximal levels of end-diastolic pressure but deficits in left ventricular pressure and relaxation persisted.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:The role of oxygen-derived free radicals in burn-induced myocardial contractile depression. 322 Aug 65

The in situ rat gut technique was used to study the effects of hypothermia on the intestinal absorption of a 1 mg/ml solution of sodium pentobarbital in 0.01 M phosphate buffer (pH 6.0). Male Sprague-Dawley rats weighing between 300 and 370 g were exposed to an atmosphere of helox (helium:oxygen, 80:20) at 0-4 degrees C for 5 hr. This procedure lowers the rectal temperature of the rats from 38 to 20 degrees C. The animals were prepared for surgery using ether as anesthetic after their rectal temperature reached 20 degrees C. Water flux in and out of the intestinal lumen was estimated from tritiated polyethylene glycol 4000 concentrations in the perfusate. The disappearance rate constant of pentobarbital from the intestinal lumen was 0.0638 +/- 0.007 min-1 for hypothermic rats, in comparison to 0.114 +/- 0.0123 min-1 for normothermic rats.
 ...
PMID:Effects of hypothermia on drug absorption. 350 90

Clinicopathologic findings were retrospectively evaluated in 26 cats and 24 dogs with ethylene glycol intoxication. Common clinical signs were ataxia, depression, vomiting, and hypothermia. Characteristic alterations in the hemogram and serum chemical profile included neutrophilia, lymphopenia, azotemia, hyperphosphatemia, hypocalcemia, hyperglycemia, and decreased whole blood bicarbonate. Common urinalysis findings included isosthenuria, proteinuria, glucosuria, hematuria, calcium oxalate and hippurate crystalluria, and the presence of renal epithelial cells, white blood cells, and granular and cellular casts in the urine sediment. The high death rate (78%) was attributed to delays in presentation, diagnosis, and therapy.
 ...
PMID:Clinicopathologic findings in dogs and cats with ethylene glycol intoxication. 669 34

The flexibility of an automated, modified Langendorff perfusion column is illustrated by a series of experiments on isolated rat hearts under the following conditions:L normothermia, hypothermia, the addition of a cryoprotective agent--ethylene glycol and cooling to -13 degrees C and -22 degrees C. Successful normothermic perfusions of up to 14 h were achieved. Hypothermia prevented a rise in vascular resistance with time and improved the electrocardiograms. Ethylene glycol was administered during the cooling period to -22 degrees C at temperatures below 23 degrees C. It was removed upon warming and before toxic effects were visible, thus leading to good recovery. By controlling the speed of the perfusate's peristaltic pump, the perfusion pressure was not allowed to exceed a pre-set level. A constant and standard vascular resistance at any selected perfusion temperature, normal heart rate and electrocardiograms were the criteria for normality.
 ...
PMID:Variations in vascular resistance of isolated rat hearts during normothermic and hypothermic experiments. 701 12


1 2 3 Next >>