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)

We investigated the response of mitochondrial function and microsomal adenosine triphosphatase (ATPase) activity in rat liver tissue subjected to in vitro ischemia at either 0 degree C to 4 degrees C or 37 degrees C for 30 to 60 minutes. Mitochondrial coupling, expressed as respiratory control index, was preserved at up to 60 minutes' cold ischemia. However, respiratory control index was decreased significantly from control by 30 minutes of warm ischemia. Both microsomal magnesium-activated ATPase and sodium-potassium ATPase activity were significantly increased by 60 minutes of warm ischemia yet were unaltered by 60 minutes of ischemia at 0 degree C to 4 degrees C. Warm ischemia produces deleterious effects on energy-generating (mitochondria) and energy-utilizing (ATPase) activity. Hypothermia provides a significant prolongation of cellular viability in ischemic tissue in terms of bioenergetic status. In addition to organ procurement and transplantation, hypothermic cytoprotection may prove valuable in areas such as shock, ischemia, and other clinical conditions of compromised visceral perfusion.
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PMID:Hepatic microsomal adenosine triphosphatase and mitochondrial function. Response to cold and warm ischemia. 295 19

Of all tissues of the extremities, muscle is the least tolerant of ischemia. Hypothermia of tissue is considered beneficial for the maintenance of viability of muscle in amputated limbs before surgical replantation, but it has never been established that conventional cooling in an ice bath or its equivalent (temperature of tissue, approximately 1 degree Celsius) is the optimum level of hypothermia for minimizing metabolic derangement in ischemic muscle. In this study, we first defined the time course and level of metabolic derangement of muscle in twenty-eight ischemic hind limbs in cats at 22, 15, 10, 5, and 1 degree Celsius. The levels of adenosine triphosphate and phosphocreatine and the mean intracellular pH of the muscles in the lateral aspect of the thigh in each limb were monitored with phosphorus nuclear magnetic-resonance spectroscopy over time. The excised muscles from six freshly amputated legs of live humans were then similarly studied to determine whether muscles from cats and from humans exhibit comparable bioenergetic responses to hypothermic ischemia. A final series of ten ischemic hind limbs from cats was studied by nuclear magnetic resonance and muscle biopsy for direct biochemical assay of tissue energy metabolites to compare the metabolic benefits of two different methods of preserving limbs: continuous cooling in an ice bath, and a newly devised protocol for the rapid induction and maintenance of so-called intermediate (10 +/- 5 degrees Celsius) hypothermia of tissue. Ischemic skeletal muscle in cats exhibited a paradoxical metabolic response to extreme cold (1 degree Celsius). The rate of metabolic deterioration progressively declined with decreasing temperature of tissue to 10 degrees Celsius. However, at 5 degrees Celsius, no additional benefit was detected, and at 1 degree Celsius, there was a significant acceleration in the rates of degradation of adenosine triphosphate and phosphocreatine and in the production of lactate. The rate of degradation of adenosine triphosphate in human ischemic muscle was also faster at 1 degree Celsius than at 10 degrees Celsius. This paradoxical response is apparently due to a severe inhibition of the calcium pump of the sarcoplasmic reticulum of the muscle cell at temperatures of less than 5 degrees Celsius. The inhibition permits an efflux of calcium to the myofibrils, which stimulates both glycolysis and the degradation of adenosine triphosphate by myofibrillar adenosine triphosphatase.
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PMID:The bioenergetics of preservation of limbs before replantation. The rationale for intermediate hypothermia. 319 76

The present study was undertaken to demonstrate and characterize potentiation of ventricular overdrive suppression by adenosine. To substantiate that adenosine has an enhanced effect on overdrive suppression, it would be necessary to demonstrate that adenosine increases pause duration independent of slowing spontaneous pre-drive rate. In isolated perfused guinea pig hearts with surgically induced complete atrioventricular block, the effect of adenosine (2-20 microM) on pause duration was compared to two alternative means of slowing the pre-drive rate, i.e., hypothermia (28.0 degrees C to 34.0 degrees C) and cesium chloride (0.3-1.0 mM). The slope value of the linear regression line describing the relationship between pre-drive cycle length and pause duration for adenosine (15.8) was significantly greater than control (1.7), hypothermia (1.7), and cesium chloride (5.4). The competitive adenosine antagonist, aminophylline (60 microM), when infused at the initiation of overdrive during adenosine administration, significantly reduced the effect of adenosine on pause duration by 72.9 +/- 4.2% (mean +/- SEM). The reduction in pause duration by aminophylline was specific for adenosine and did not occur under control conditions or during cesium chloride administration. During hypoxia, aminophylline and adenosine deaminase, when infused at the initiation of overdrive, caused 72.3 +/- 5.6 and 63.3 +/- 6.1% reductions in pause duration, respectively. Endogenous adenosine levels rose significantly with hypoxia (1,687 +/- 202 vs. 36 +/- 4 pmol/min per g during normoxia) and increased significantly further during hypoxic overdrive (3,004 +/- 323 pmol/min per g). In isolated guinea pig Purkinje fibers (n = 4), adenosine (20 microM) increased pause duration by 73.6 +/- 9.9% while only minimally affecting the pre-drive cycle length (7.6 +/- 3.8%). These fibers, when stimulated at 1.5 Hz, also displayed an adenosine-induced reduction in action potential duration at 90% repolarization (16 +/- 2 msec). In addition, we demonstrated that adenosine had an enhanced effect on pause duration in the presence of ouabain (1 microM)-induced attenuation of overdrive suppression. Thus, in isolated Purkinje fibers, it is unlikely that the potentiating effect of adenosine on pause duration, which is independent of its chronotropic effect, is mediated via an enhancement of sodium potassium adenosine triphosphatase pump activity. The effect of adenosine is likely to be secondary to a direct action on outward potassium conductance.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Role of adenosine on ventricular overdrive suppression in isolated guinea pig hearts and Purkinje fibers. 404 82

Procainamide is an organic cation and commonly prescribed drug that is actively secreted into the urine by renal proximal tubules. In order to elucidate further the mechanisms involved in this secretion, [3H]procainamide uptake into dissected S2 segments of superficial proximal tubule cells was studied. Uptake of [3H]procainamide was reduced by hypothermia and in a dose-related manner by the organic cations nonradiolabeled procainamide, cimetidine and quinidine and also by the carbonic anhydrase inhibitors acetazolamide and benzolamide, but not by ouabain. All these drugs were shown previously to inhibit transtubular secretion of [3H]procainamide in isolated perfused proximal tubules. The results of these and our previous studies suggest that 1) organic cations reduce the tubular secretion of each other, in part, by competing for uptake across the basolateral membrane of renal tubule cells, 2) acetazolamide and benzolamide reduce urinary excretion of organic cations, in part, by inhibiting proximal tubular secretion and 3) the potential difference across the basolateral cell membrane (due to activity of Na+-K+-dependent adenosine triphosphatase) is not the only driving force for uptake of organic cations into intact renal tubule cells.
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PMID:Procainamide uptake by rabbit proximal tubules. 682 56

Recent experimental work implicates oxygen free radicals as mediators of ischemia/reperfusion injury. A simple cardioplegic solution was designed to scavenge superoxide anion and hydroxyl free radical with superoxide dismutase (10 micrograms/ml), mannitol (325 mOsm/L), and KCl 25 mEq/L (FRS). Hemodynamic and subcellular functions were studied in seven in situ canine models of hypothermic global ischemia receiving FRS, compared to a group (n = 7) receiving hyperosmolar, hyperkalemic saline (HSK) and to a standard model of topical hypothermia (TH, n = 5). Following 60 minutes of ischemia (10 degrees to 15 degrees C), hearts were reperfused and rewarmed. After 45 minutes of reperfusion, left ventricular peak systolic pressure (LVPSP), developed pressure (LVDP), dP/dt max, -dP/dt max, compliance, and elastic stiffness constant (K) were improved in the FRS group and not significantly different from control. Sarcoplasmic reticulum (SR) calcium transport in the FRS group was significantly improved (control = 1.077 +/- 0.022, TH = 0.754 +/- 0.018, HSK = 0.725 +/- 0.05, and FRS = 0.966 +/- 0.05 mumol/mg-min). Calcium adenosine triphosphatase (ATPase) activity did not differ significantly from control at pH 7.0. In this model of hypothermic global ischemia and reperfusion, free radical scavengers provide significant protection of mechanical and subcellular function. These findings support the hypothesis that oxygen free radicals are important mediators of myocardial ischemia and reperfusion injury.
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PMID:Inhibition of surgically induced ischemia/reperfusion injury by oxygen free radical scavengers. 687 62

Hypothermic hyperkalemic circulatory arrest has been widely used for myocardial protection during heart surgery. Recent data showed that administration of triiodo-L-thyronine (T3) postoperatively enhanced ventricular function. The effect of hyperkalemic arrest in conjunction with thyroid hormone on the plasma membrane enzyme sodium/potassium-adenosine triphosphatase (Na/K-ATPase), was determined in cultured neonatal rat atrial and ventricular myocytes. Exposure of ventricular myocytes to hyperkalemic medium (50 mM KCl) in the absence of T3 increased expression of the Na/K-ATPase catalytic subunit mRNAs, alpha1 and alpha3 isoforms, by 1.9- and 1.5-fold, respectively (p<0.01), which were accompanied by similar increases (1.4- and 1.8-fold) in protein content. Addition of T3 to the hyperkalemic cultures attenuated these increases in Na/K-ATPase mRNA isoforms to levels of expression observed in cells treated with T3 (10(-8) M) alone. Similarly, expression of the alpha1 mRNA isoform in atrial myocytes was increased (p<0.05) by hyperkalemic conditions, and T3 treatment attenuated this effect. In contrast, although expression of the Na/K-ATPase beta1 mRNA in both atrial and ventricular myocytes was significantly increased by hyperkalemia, addition of T3 did not prevent the hyperkalemic response, and in atrial myocytes T3 significantly increased beta1 mRNA expression 1.8-fold. These results show that expression of cardiac Na/K-ATPase is regulated by T3 and hyperkalemia in an isoform and chamber specific manner, and suggest that use of hyperkalemic cardioplegia during heart surgery may alter plasma membrane ion function.
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PMID:Regulation of Na/K-ATPase gene expression by thyroid hormone and hyperkalemia in the heart. 1003 77

Inflammasomes activate caspase-1 for processing and secretion of the cytokines interleukin-1beta (IL-1beta) and IL-18. Cryopyrin/NALP3/NLRP3 is an essential component of inflammasomes triggered by microbial ligands, danger-associated molecular patterns (DAMPs), and crystals. Inappropriate Cryopyrin activity has been incriminated in the pathogenesis of gouty arthritis, Alzheimer's, and silicosis. Therefore, inhibitors of the Nalp3 inflammasome offer considerable therapeutic promise. In this study, we show that the type 2 diabetes drug glyburide prevented activation of the Cryopyrin inflammasome. Glyburide's cyclohexylurea group, which binds to adenosine triphosphatase (ATP)-sensitive K(+) (K(ATP)) channels for insulin secretion, is dispensable for inflammasome inhibition. Macrophages lacking K(ATP) subunits or ATP-binding cassette transporters also activate the Cryopyrin inflammasome normally. Glyburide analogues inhibit ATP- but not hypothermia-induced IL-1beta secretion from human monocytes expressing familial cold-associated autoinflammatory syndrome-associated Cryopyrin mutations, thus suggesting that inhibition occurs upstream of Cryopyrin. Concurrent with the role of Cryopyrin in endotoxemia, glyburide significantly delays lipopolysaccharide-induced lethality in mice. Therefore, glyburide is the first identified compound to prevent Cryopyrin activation and microbial ligand-, DAMP-, and crystal-induced IL-1beta secretion.
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PMID:Glyburide inhibits the Cryopyrin/Nalp3 inflammasome. 1980 29