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 have developed a nondepolarizing solution (NDS) that retards myocardial calcium accumulation during cardioplegia. This study compares 1) the membrane resting potential (Em) in Purkinje fibers during cardioplegia induced by NDS or University of Wisconsin solution (UW) at normothermia and hypothermia for 6 h, 2) left ventricular (LV) diastolic function of isolated canine hearts preserved with NDS or UW for 6- and 12 h in hypothermia to elucidate the relationship between diastolic function and myocyte physiology (n = 8, each group), and 3) the effect of Non-depolarizing solution (NDS) compared with Bretschneider's HTK solution on LV diastolic function in isolated rabbit hearts using the Langendorff model in normothermia (n = 10, each group). The membrane resting potential (Em) was as follows: NDS in normothermia, -71 mV (2 min), -65 mV (30 min), and -52 mV (60 min); NDS in hypothermia, -40 mV (1 h) and -32 mV (6 h), while UW in hypothermia 0 mV (6 h). Myocardial calcium accumulation during reperfusion in the NDS groups was minimal and significantly lower than in the UW groups after the 6- and 12 h preservations. Postreperfusion myocardial cyclic adenosin monophosphate (cAMP) and adenosin triphosphate (ATP) concentrations in the NDS groups were closer to normal than in the UW groups after the 6- and 12 h preservations. The postreperfusion myocardial Ca concentration correlated with the cAMP (r = -0.68, n = 25, P = 0.003) and cyclic guanosine monophosphate (cGMP) concentrations (r = -0.69, n = 25, P = 0.003). The left ventricular end-diastolic pressure (LVEDP) after reperfusion correlated with myocardial ATP (r = -0.65, n = 25, P = 0.003) and Ca concentrations (r = -0.68, n = 25, P = 0005). However, the parameter indicating LV elasticity (max LV -dp/dt) correlated with neither the Ca or ATP concentration following reperfusion. NDS prevented stiffness (increased LVEDP) better than HTK during normethermic cardioplegia for 30 min. These results in vitro suggest that NDS prevents myocardial Ca accumulation, depletion of ATP and cAMP, and preserves LV diastolic function, particularly stiffness after reperfusion, for up to 12 h. Furthermore, the myocardial Ca concentration is inversely correlated with the cAMP and cGMP concentrations.
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PMID:The use of a nondepolarizing cardioplegic solution for cardiac preservation has a beneficial effect on the left ventricular diastolic function. 1137 Jan 70

The safety and myocardial protective effect of perfused ventricular fibrillation (VF) under moderate hypothermia were investigated. Through a midline sternotomy and opening the left atrium from the right side, isolated mitral valve surgery was performed under aortic cross-clamping (ACC) and cardioplegic arrest using Bretschneider HTK solution in 96 patients, and under perfused VF in 20 patients (VF Group). Patient characteristics, clinical outcomes, and perioperative variables were compared. A satisfactory surgical view was obtained in all VF Group patients. Patient characteristics in the 2 groups were similar, and both groups had comparable results for mortality and morbidity, operation time, cardiopulmonary bypass time, peak levels of creatine kinase (CK) and its myocardial fraction, hours of mechanical ventilation, intensive care unit stay, and postoperative left ventricular ejection fraction. Even in VF Group patients with preoperative critical hemodynamic compromise, inotropes could be discontinued within 3 days. Thus, no detrimental effect of perfused VF was observed. On the other hand, in patients who underwent ACC and cardioplegic arrest of 120min or longer, peak levels of CK and its myocardial fraction were significantly higher than those of the rest of C group patients and VF Group patients. Perfused VF under moderate hypothermia can be a good alternative myocardial protection strategy during mitral valve surgery, particularly in patients in whom ACC is unsuitable or the duration of ACC is expected to be long.
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PMID:Mitral valve surgery under perfused ventricular fibrillation with moderate hypothermia. 1203 Mar 38

Signal transduction pathways and transcription factors are likely to be important mediators of stress responses to ischaemia and reperfusion injury following renal transplantation. We have investigated the activation of the transcription factor nuclear factor kappaB (NF-kappaB) and the mitogen activated protein kinases (MAPK), p44/42 (ERK 1/2), p38 and c-Jun N-terminal kinase (JNK) during cold stress at 4 degrees C. Human umbilical vein endothelial cells (HUVECs) were subjected to 72 h of hypothermia in a renal preservation solution. NF-kappaB activation was assessed by electromobility shift assays and MAPK activation by immunoblotting. Cell viability and apoptosis was assessed. Hypothermia activated the NF-kappaB complex, ERK 1/2 and p38 MAPK pathway. There was a 6-fold increase in NF-kappaB in the nucleus within minutes of hypothermia, correlating with p38 (p = 0.01) and ERK 1/2 activation (p = 0.03). A significant relationship was found between ERK 1/2, p38 and NF-kappaB throughout the 72 h time course (p = 0.01). In contrast, hypothermia had no effect on JNK phosphorylation. Inhibition of MAPK with an MEK inhibitor (PD098059) blocked the activation of NF-kappaB but a specific p38 inhibitor (SB203580) had no effect on NF-kappaB. Increased lactate production after 48 h indicated a switch towards anaerobic metabolism during prolonged hypothermia. Endothelial cells had a high viability and no DNA fragmentation throughout the experiment. Activation of stress pathways during organ procurement may be important in the quality of stored grafts.
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PMID:Activation of NF-kappaB and MAP kinase cascades by hypothermic stress in endothelial cells. 1215 Dec 71

Natural infection of humans with human T-cell lymphotropic virus type I (HTLV-I) and of old world nonhuman primates with the simian counterpart, STLV-I, is associated with development of neoplastic disease in a small percentage of individuals after long latent periods. HTLV-I is also the etiologic agent of a more rapidly progressive neurologic disease, HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Macaques have been used experimentally in studies to evaluate HTLV-I candidate vaccines for efficacy, but no evidence of disease was observed. Here we report experimental infection of pig-tailed macaques with STLV-I(sm) and HTLV-I(ACH), both of which were associated with a disease syndrome characterized by rapid onset, hypothermia, lethargy, and death within hours to days. Other pathologic sequelae included diarrhea, rash, bladder dysfunction, weight loss, and, in one animal, arthropathy. Both retroviruses were detected in the central nervous systems of some animals, either by culture or by direct antigen capture for p19 Gag in cerebrospinal fluid. Although virus was recovered throughout infection from peripheral blood mononuclear cells (PBMC), all infected macaques maintained low antiviral antibody titers and stable proviral burdens, which generally ranged between 10 and 100 copies per 10(6) PBMC. However, of 13 macaques infected with HTLV-I(ACH) or STLV-I(sm), seven animals (54%) died between 35 weeks and 412 years after infection. This unexpected high mortality within a relatively short time suggests that infection of pig-tailed macaques might be a useful model for studying immune responses to and pathologic events resulting from HTLV-I infection.
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PMID:Association of primate T-cell lymphotropic virus infection of pig-tailed macaques with high mortality. 1250 76

Cold preservation results in cell death via iron-dependent formation of reactive oxygen species, leading to apoptosis during rewarming. We aimed to study cold-induced damage (i.e., injury as a consequence of hypothermia itself and not cold ischemia) in proximal tubular cells (PTC) in various preservation solutions presently applied and to clarify the role of mitochondria in this injury. Primary cultures of rat PTC were incubated at 4 degrees C for 24 h in culture medium, UW, Euro-Collins or HTK solution with and without the iron chelator desferal and rewarmed at 37 degrees C in culture medium. Cell damage, morphology, and apoptosis were studied and mitochondrial membrane potential was assessed by fluorescence microscopy. Cold incubation of PTC in culture medium followed by rewarming caused marked cell damage compared to warm incubation alone (LDH release 39+/-10% vs. 1.6+/-0.3%). Cold-induced damage was aggravated in all preservation solutions (LDH release 85+/-2% for UW; similar in Euro-Collins and HTK). After rewarming, cells showed features suggestive for apoptosis. Desferal prevented cell injury in all solutions (e.g., 8+/-2% for UW). Mitochondrial membrane potential was lost during rewarming and this loss could also be inhibited by desferal. Trifluoperazine, which is known to inhibit mitochondrial permeability transition (MPT), was able to prevent cold-induced injury (LDH 85+/-5% vs. 12+/-2%). We conclude that cold-induced injury occurs in PTC and is aggravated by UW, Euro-Collins, and HTK solution. Iron-dependent MPT is suggested to play a role in this damage. Strategies to prevent cold-induced injury should aim at reducing the availability of "free" iron.
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PMID:Hypothermia causes a marked injury to rat proximal tubular cells that is aggravated by all currently used preservation solutions. 1296 15

Hypothermia is an important preservation method for tissues and solid organs. The aim of the present study was to assess in rat cremaster muscle the effect of hypothermia, without or with pre-ischaemic HTK (histidine-tryptophan-ketoglutarate-Bretschneider solution) perfusion, on microvascular consequences of 4 or 6 h ischaemia and 2 h of reperfusion. Intravital microscopy was applied to examine capillary perfusion and leucocyte-endothelium interactions. The cremaster muscle was subjected to 4 or 6 h of cold (4 degrees C) or warm (33-34 degrees C) ischaemia and 2 h of reperfusion. Measurements were performed at baseline, prior to HTK perfusion and ischaemia, and at 0, 1 and 2 h after blood flow restoration. Hypothermia completely prevented the 50% reduction in capillary perfusion that was observed previously at start of reperfusion after 4 h warm ischaemia. After 6 h of warm ischaemia, perfusion resumed in only 45% of capillaries and remained at this low level during reperfusion. In contrast, only a slight decrease (< 10%) in capillary perfusion was observed after 6 h of cold ischaemia. Pre-ischaemic HTK perfusion had no beneficial effect on tissue perfusion. Both hypothermia and HTK attenuated the significant increase in venular leucocyte-vessel wall interactions, which was observed after 4 h of warm ischaemia in a previous study. Combined application of both interventions had no additional effects. After 6 h of warm ischaemia, no increase in leucocyte-vessel wall interactions was observed, possibly due to venular flow reduction. In conclusion, hypothermia preserves capillary perfusion and prevents an increase in leucocyte-vessel wall interactions during reperfusion after muscle tissue ischaemia. Preischaemic perfusion of the vasculature with HTK does not improve the effects of cold storage on tissue perfusion, but attenuates the inflammatory response independently of temperature effect.
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PMID:Effect of hypothermia and HTK on the microcirculation in the rat cremaster muscle after ischaemia. 1561 71

While alterations in dopamine (DA) uptake appear to be a critical mechanism underlying locomotor and reinforcing effects of cocaine (COC), many centrally mediated physiological and affective effects of this drug are resistant to DA receptor blockade and are expressed more quickly following an intravenous (i.v.) injection than expected based on the dynamics of drug concentration in the brain. Because COC is also a potent local anesthetic, its rapid action on Na+ channels may be responsible for triggering these effects. We monitored temperatures in the nucleus accumbens, temporal muscle and skin together with conventional locomotion during a single i.v. injection of COC (1 mg/kg), procaine (PRO, 5 mg/kg; equipotential anesthetic dose), a short-acting local anesthetic drug that, like COC, interacts with Na+ channels, and cocaine methiodide (COC-MET, 1.31 mg/kg, equimolar dose), a quaternary COC derivative that is unable to cross the blood-brain barrier. In this way, we explored not only the importance of Na+ channels in general, but also the importance of central vs. peripheral Na+ channels specifically. COC induced locomotor activation, temperature increase in the brain and muscle, and a biphasic temperature fluctuation in skin. Though PRO did not induce locomotor activation, it mimicked, to a greater degree, the temperature effects of COC. Therefore, Na+ channels appear to be a key substrate for COC-induced temperature fluctuations in the brain and periphery. Similar to PRO, COC-MET had minimal effects on locomotion, but mimicked COC in its ability to increase brain and muscle temperature, and induce transient skin hypothermia. It appears therefore that COC's interaction with peripherally located Na+ channels triggers its central excitatory effects manifested by brain temperature increase, thereby playing a major role in drug sensing and possibly contributing to COC reinforcement.
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PMID:The role of peripheral Na(+) channels in triggering the central excitatory effects of intravenous cocaine. 1693 Apr 44

Hypothermic perfusion is a standard method for neuroprotection during cardiac surgery in children. However, the cellular responses underlying these mechanisms have not been clearly elucidated. In the present study we demonstrated that the inflammatory response of stimulated microglial cells is significantly reduced after moderate hypothermia. Continuous hypothermia caused a diminished NO release. Moderate hypothermia and rewarming caused a downregulation of phosphorylated MEK, ERK and iNOS-expression, diminished cytokine release and reduced CD-11a and ICAM-1 expression. Thus, neuroprotection offered by hypothermia could be attributed to reduced cytotoxic products released from stimulated microglial cells mediated by the MEK/ERK signal transduction pathway.
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PMID:Hypothermia suppresses inflammation via ERK signaling pathway in stimulated microglial cells. 1765 18

Hypothermia is a standard method for organ protection during cardiac surgery in children. However, the mechanisms of hypothermia-induced cell protection have not yet been clearly established. Therefore, the aim of our studies was to elucidate molecular effects of clinically relevant mild and deep hypothermia on endothelial cells. The endothelium plays a pivotal role in the interaction between blood cells and actively participates in complex inflammatory events. We isolated primary human umbilical vein endothelial cells (HUVEC) and investigated cell viability, proliferation and inflammatory characteristics after TNF-alpha stimulation under mild (32 degrees C) and deep (17 degrees C) hypothermia in comparison to normothermia (37 degrees C). As a protective mechanism of endothelial cells kept under hypothermic conditions we found a significant upregulation of the antiapoptotic protein Bcl-2, resulting in the same cell viability under hypothermic conditions. Unexpectedly we demonstrated significantly higher IL-6 release after 6h of mild hypothermia. In contrast, hypothermia diminished inflammatory chemokines such as IL-8, MCP-1 and COX-2 protein expression which could lead to reduced leukocyte recruitment under hypothermia. Underlying mechanisms of this downregulation were found to be reduced ERK 1/2 phosphorylation and incomplete IkappaB-alpha degradation resulting in reduced NFkappaB-dependent proinflammatory gene expression. The upregulation of Bcl-2 protein and the higher IL-6 release after 6h of mild hypothermia are new and interesting cellular mechanisms of hypothermia in endothelial cell biology. Both factors may play a major role as cell protective mechanisms in hypothermia.
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PMID:Hypothermia downregulates inflammation but enhances IL-6 secretion by stimulated endothelial cells. 1879 Jun 95

Neuronal injury results in increased mineralocorticoid receptor (MR) expression and is associated with increased neuronal survival, suggesting that enhancing MR signalling may have therapeutic implications. MR has a complex gene structure with at least three untranslated exons (alpha, beta, gamma) each with unique promoters and a common coding region. We examined whether distinct cellular stressors differentially regulate exon-specific MR transcripts. MRbeta transcript was specifically upregulated in rat primary cortical cultures undergoing hypothermic oxygen-glucose deprivation (OGD/H) through activation of its own promoter. This effect was mediated in part by ERK signalling as blockade with PD98059 inhibited OGD/H-induced MRbeta promoter activity. A specific increase in MRbeta transcript expression was also found in vivo in hypothermic anoxic neonatal rat hippocampus. These results demonstrate a novel key role for the MRbeta transcript in response to injury and suggest that some of the known neuroprotective effects of hypothermia may be mediated through increased MR expression.
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PMID:Injury-induced mineralocorticoid receptor expression involves differential promoter usage: a novel role for the rat MRbeta variant. 1943 61


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