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

In the feline intestine studies have implicated superoxide (O.-) and other oxygen derived free radicals as initiators of injury as measured by increased capillary permeability during the reperfusion period. Biochemical mechanisms of this free radical generation include: xanthine oxidase dependent O.- production, hydrogen peroxide (H2O2) formation by superoxide dismutase (SOD), hydroxyl radical (OH-) production via the Haber-Weiss reaction, and lipid radical formation from membrane peroxidation. Pathological consequences of these events include inflammatory neutrophil infiltration, damage to the collagen and mucosal basement membrane, increased capillary permeability, edema, cell degeneration and necrosis. Animal models of neonatal necrotizing enterocolitis (NNEC) indicate that intestinal injury occurs after the etiologic factors (hypothermia, hypoxia) are removed. In order to determine the role of active oxygen species in the pathogenesis of NNEC, weanling hamsters and neonatal piglets were cold stressed and activities of pro/antioxidant enzymes were determined, and histopathologic and ultrastructural studies were performed. Cold stressed weanling hamsters showed a 55.7% (P less than 0.05) decrease in xanthine dehydrogenase/xanthine oxidase activity ratio. Light microscopy revealed scattered colonic mucosal erosions and submucosal edema in 50% of cold stressed animals. Transmission electron microscopy demonstrated degeneration of colonic mucosal epithelial cells, enlarged intracellular spaces, cytoplasmic vacuolization, and nuclear membrane swelling. The colonic serosa was also edematous and infiltrated with bacteria. Large intestinal tissue from cold stressed neonatal piglets showed a significant increase (P less than 0.05) in Mn and Cu, Zn, SOD, CAT, GSH-Red, total GSH, and Glc6-PD at 0 and 12 hrs. post stress.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Intestinal post-ischemic reperfusion injury: studies with neonatal necrotizing enterocolitis. 259 24

Age-dependent differences in the effects of ischemia and reperfusion on ATP breakdown were studied in perfused adult and newborn (10 days old) rat hearts. No-flow ischemia (15 min at 37, 30, or 23 degrees C) was applied and reperfusion (20 min at 37 degrees C) was studied after ischemia at 23 or 37 degrees C. Hypothermia during ischemia protected both age groups to a similar degree against ATP decline, which was linear with temperature. Reperfusion after normothermic ischemia resulted in higher ATP levels in newborn hearts with less release of ATP catabolites (purines). We found no age-related differences in lactate release but large differences in purine release. During normoxia, adult hearts released mainly urate (80% of total) and inosine (7%), but newborns released hypoxanthine (64%) and inosine (15%). Early during reperfusion adult hearts released inosine (58%) and adenosine (18%), but newborns released inosine (53%) and hypoxanthine (38%). These data suggested a lower activity of the potentially deleterious enzyme xanthine oxidoreductase in newborn hearts, which was confirmed by enzymatic assay. ATP-catabolite release during reperfusion was less in newborn than adult hearts, and this coincided with lower xanthine oxidase activity.
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PMID:Different ATP-catabolism in reperfused adult and newborn rat hearts. 316 69

Little is known about postnatal changes in myocardial purine metabolism. We therefore studied how ATP catabolism was affected by hypothermia and ischaemia in neonatal and adult hearts. Hypothermia during ischaemia protected isolated adult and newborn hearts against ATP decline. Reperfusion after normothermic ischaemia resulted in higher ATP levels in newborn hearts with less release of ATP-catabolites. During normoxia adult hearts released mainly urate (80% of total purine release), while newborns released mainly hypoxanthine (64%). During early reperfusion adult and newborn hearts released mainly inosine (50-60%). The very low xanthine oxidase activity in the neonatal heart could be an important factor in the observed ATP preservation during reperfusion.
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PMID:Developmental differences in myocardial ATP metabolism. 366 14

Previous studies have demonstrated that reactive oxygen species are involved in ischemic injury. The present work was undertaken to determine in vivo the role of xanthine oxidase in the oxygen free radical production during rat liver ischemia and to examine the activity of antioxidant enzymes (superoxide dismutase, catalase and glutathione peroxidase) during the same period. Our results indicate a 4-fold increase in xanthine oxidase activity between 2 and 3 hours of normothermic ischemia, in parallel with a decrease in cell viability. Moderate hypothermia delays both events. Under the same conditions, the activity of oxygen radical scavenging enzymes remains unchanged. Moreover, we have compared in vitro the susceptibility of isolated liver cells to an oxidative stress induced by O2.-, H2O2 and .OH. Our results reveal that endothelial cells are much more susceptible to reactive oxygen species than hepatocytes, probably because they lack H2O2-detoxifying enzymes. These findings suggest that xanthine oxidase might play a major role in the ischemic injury mainly at the level of the sinusoidal space where most endothelial cells are located.
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PMID:Deleterious effects of xanthine oxidase on rat liver endothelial cells after ischemia/reperfusion. 748 47

We have previously reported that hyberbaric oxygen (HBO) improved the survival rate of experimental free flaps. The purpose of this study was to evaluate the effects of combined hypothermia and HBO administered during storage on free flaps and on the xanthine oxidase system in rats. Epigastric skin flaps were stored cold for 48 and 72 hours either in room air or under HBO (2.9 atmospheres absolute, 100% oxygen) before free flap transfer. The success rates of free flaps were 80% (8/10) after 48 hours and 20% (2/10) after 72 hours of cold storage in room air. HBO produced no effect after 48 hours but significantly increased the success rate to 70% (7/10) after 72 hours of cold storage. Tissue hypoxanthine (plus xanthine) levels increased to 210% of normal after 48 hours of cold storage in room air and to 176% in HBO. Elevated hypoxanthine levels returned toward normal by 72 hours of cold storage in room air, while the increased levels remained under HBO. Xanthine oxidase activities significantly increased by 60 to 80% during 72 hours of room air storage. HBO treatment inhibited xanthine oxidase activity to 48% of normal by 72 hours of storage. Free flaps exhibited no significant alterations in GR and G6PDH activity after 48 hours of cold storage in room air or HBO. After 72 hours of cold storage, the room air control displayed a trend of decreasing GR activity and a significant 20% decrease in G6PDH activity, while HBO groups showed no significant alterations in both GR and G6PDH activity compared to normal. Protection of the antioxidative enzymes by hypothermia and inhibition of the xanthine oxidase activity by HBO appear to be one of the mechanisms of improved skin flap survival in free flaps.
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PMID:Effects of combined cold and hyperbaric oxygen storage on free flap survival. 784 94

After prolonged ischemia, reperfusion of the myocardium with oxygenated blood results in high levels of superoxide anions. Several mechanisms for superoxide anion generation have been proposed, including increased xanthine oxidase activity, neutrophil activation, and arachidonate cascade activation. Superoxide anion accumulation may cause enzyme inactivation and lipid peroxidation in the sarcolemma with resultant intracellular calcium accumulation and excitation-contraction uncoupling. A review of a number of animal studies has shown that free radical scavengers such as superoxide dismutase and catalase can preserve myocardial function and metabolism during transplantation. In addition, other data indicate a role for inhibitors of free radical generation (i.e., allopurinol or oxypurinol), iron chelators (i.e., deferoxamine), or metabolic substrates such as L-glutamate in the inhibition of free radical myocardial injury. In addition, glutathione has been demonstrated to produce faster recovery of ventricular function in hypothermia preserved and reperfused rat hearts, presumably by inhibiting free radical production. Confirmatory data for human cardiac transplantation is not yet available.
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PMID:Oxygen free radicals in cardiac transplantation. 838

The hypothesis was tested that treatment with allopurinol, a xanthine oxidase inhibitor, or deferoxamine, a chelator of nonprotein-bound iron, preserved cerebral energy metabolism, attenuated development of edema, and improved histologic outcome in the newborn piglet at 24 h after hypoxia-ischemia. Thirty-two newborn piglets were subjected to 1 h of hypoxia-ischemia by occluding both carotid arteries and reducing the fraction of inspired oxygen; five newborn piglets served as sham-operated controls. The depth of hypoxia-ischemia was controlled by phosphorous magnetic resonance spectroscopy. Upon reperfusion and reoxygenation, piglets received vehicle (n= 12), allopurinol (30 mg/kg/d, n = 10), or deferoxamine (12.5 mg/kg/d, n = 10). The cerebral energy status was determined with phosphorous magnetic resonance spectroscopy. The presence of vasogenic edema was assessed by T2-weighted magnetic resonance imaging. Brain cell injury was assessed with caspase-3 activity, histology, and terminal deoxynucleotidyl transferase-mediated dUTP-biotin in situ nick end (TUNEL)-labeling. At 24 h after hypoxia-ischemia, the phosphocreatine/inorganic phosphate ratios were significantly decreased in vehicle-treated, but not in allopurinol- or deferoxamine-treated piglets. Water T2 values were significantly increased at 24 h after hypoxia-ischemia in cerebral cortex, thalamus, and striatum of vehicle-treated piglets, but not in allopurinol- and deferoxamine-treated piglets. No differences in caspase-3 activity, histologic outcome, or TUNEL-labeling were demonstrated between the three treatment groups. We suggest that allopurinol and deferoxamine may have an additional value in the treatment of perinatal hypoxia-ischemia with other neuroprotective agents or in combination with hypothermia.
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PMID:Effects of allopurinol and deferoxamine on reperfusion injury of the brain in newborn piglets after neonatal hypoxia-ischemia. 1281 12

Nitrite (NO(2)(-)), previously viewed as a physiologically inert metabolite and biomarker of the endogenous vasodilator NO, was recently identified as an important biological NO reservoir in vasculature and tissues, where it contributes to hypoxic signaling, vasodilation, and cytoprotection after ischemia-reperfusion injury. Reduction of nitrite to NO may occur enzymatically at low pH and oxygen tension by deoxyhemoglobin, deoxymyoglobin, xanthine oxidase, mitochondrial complexes, or NO synthase (NOS). We show that nitrite treatment, in sharp contrast with the worsening effect of NOS inhibition, significantly attenuates hypothermia, mitochondrial damage, oxidative stress and dysfunction, tissue infarction, and mortality in a mouse shock model induced by a lethal tumor necrosis factor challenge. Mechanistically, nitrite-dependent protection was not associated with inhibition of mitochondrial complex I activity, as previously demonstrated for ischemia-reperfusion, but was largely abolished in mice deficient for the soluble guanylate cyclase (sGC) alpha1 subunit, one of the principal intracellular NO receptors and signal transducers in the cardiovasculature. Nitrite could also provide protection against toxicity induced by Gram-negative lipopolysaccharide, although higher doses were required. In conclusion, we show that nitrite can protect against toxicity in shock via sGC-dependent signaling, which may include hypoxic vasodilation necessary to maintain microcirculation and organ function, and cardioprotection.
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PMID:Nitrite protects against morbidity and mortality associated with TNF- or LPS-induced shock in a soluble guanylate cyclase-dependent manner. 1993 18

Nitric oxide (NO) is a key regulator of vascular tone. Endothelial nitric oxide synthase (eNOS) is responsible for NO generation under normoxic conditions. Under hypoxia however, eNOS is inactive and red blood cells (RBC) provide an alternative NO generation pathway from nitrite to regulate hypoxic vasodilation. While nitrite reductase activity of hemoglobin is well acknowledged, little is known about generation of NO by intact RBC with physiological hemoglobin concentrations. We aimed to develop and apply a new approach to provide insights in the ability of RBC to convert nitrite into NO under hypoxic conditions. We established a novel experimental setup to evaluate nitrite uptake and the release of NO from RBC into the gas-phase under different conditions. NO measurements were similar to well-established clinical measurements of exhaled NO. Nitrite uptake was rapid, and after an initial lag phase NO release from RBC was constant in time under hypoxic conditions. The presence of oxygen greatly reduced NO release, whereas inhibition of eNOS and xanthine oxidoreductase (XOR) did not affect NO release. A decreased pH increased NO release under hypoxic conditions. Hypothermia lowered NO release, while hyperthermia increased NO release. Whereas fetal hemoglobin did not alter NO release compared to adult hemoglobin, sickle RBC showed an increased ability to release NO. Under all conditions nitrite uptake by RBC was similar. This study shows that nitrite uptake into RBC is rapid and release of NO into the gas-phase continues for prolonged periods of time under hypoxic conditions. Changes in the RBC environment such as pH, temperature or hemoglobin type, affect NO release.
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PMID:The capacity of red blood cells to reduce nitrite determines nitric oxide generation under hypoxic conditions. 2500 72

Neonatal hypoxic-ischaemic encephalopathy due to the lack of oxygen at birth can have severe neurological consequences, such as cerebral palsy, or even the death of the asphyxiated newborn. Hypothermia is currently the only therapy included in intensive care neonatal units. This shows a clinical benefit in neonates suffering from hypoxic-ischaemic encephalopathy, mainly because of its ability to decrease the accumulation of excitatory amino acids and its anti-inflammatory, antioxidant, and anti-apoptotic effects. However, hypothermia is not effective in half of the cases, making it necessary to search for new, or to optimize current therapies, with the aim on reducing asphyxia-derived neurological consequences, either as single treatments or in combination with cooling. Within current potential therapies, melatonin, allopurinol, and erythropoietin stand out among the others, with clinical trials on the way. While, stem cells, N-acetylcysteine and noble gases have obtained promising pre-clinical results. Melatonin produces a powerful antioxidant and anti-inflammatory effect, acting as free radical scavenger and regulating pro-inflammatory mediators. Through the inhibition of xanthine oxidase, allopurinol can decrease oxidative stress. Erythropoietin has cell death and neurogenesis as its main therapeutic targets. Keeping in mind the whole scenario of current therapies, management of neonates suffering from neonatal asphyxia could rely on the combination of one or some of these treatments, together with therapeutic hypothermia.
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PMID:[Combined therapy in neonatal hypoxic-ischaemic encephalopathy]. 3110 85


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