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 non-adult hearts, hypothermia influences protection of the myocardium by exerting effects on specific ion transporters, thereby altering the normal balance between ion pumps and ion leaks. We studied the effects of hypothermia on individual ion transporters in cardiac myocytes to better understand how to preserve the normal ion balance at reduced temperatures, and thereby enhance myocardial protection. Cardiocytes obtained from 11 day chick embryos were cultured for 3 days, and then equilibrated in a glucose containing HEPES-TRIS buffered salt solution at 37 degrees C (pH = 7.4). The cells were incubated at 10 +/- 2 degrees C for 5 to 360 min in the absence or presence of specific ion transport inhibitors, and ion contents were assessed by atomic absorption spectrophotometry. Intracellular Na content increased from approximately 90 nmol/mg protein (control) to 2-3 times this value within 30 min, and then returned to control levels by 60 min. This increase in Na was accompanied by a small rise in total Ca (1.5 times control). Acidotic pH (6.4) and/or ethylisopropyl amiloride (100 microM), but not bumetanide (100 microM) prevented the rise in Na content, suggesting the Na/H exchanger contributed to the initial Na influx. Ouabain (1 mM), exacerbated the Na rise and prevented its recovery to control values at 10 degrees C, although Rb flux measurements revealed only a low level of Na/K ATPase activity throughout 240 min at 10 degrees C (15% of 37 degrees C activity). Calcium content rose to 10 times control values in the presence of ouabain at 37 degrees C only, consistent with a lack of significant Na/Ca exchange activity during hypothermia. In conclusion, the effects of hypothermia on ion pumps and ion leaks in embryonic heart cells are as follows: (1) a low level of Na/K ATPase activity contributes significantly to ion regulation; (2) activity of the Na/H exchanger must be attenuated to minimize Na loading; (3) slowing of the Na/Ca exchange may reduce Ca induced cell injury. We suggest that reducing Na/H exchange activity during hypothermia, using cardioplegic solutions with a slightly acidic pH or with added ethylisopropyl amiloride, may enhance the protective effects of hypothermia in non-adult hearts.
 ...
PMID:Ion transport during hypothermia in cultured heart cells: implications for protection of the immature myocardium. 838 88

After O2 deprivation, tissue acidosis rapidly self-corrects. This study assessed the effect of this pH correction on the induction, and pathways, of posthypoxic proximal tubular injury. In addition, ways to prevent the resultant injury were explored. Isolated rat proximal tubular segments (PTSs) were subjected to hypoxia/reoxygenation (50/30 or 30/50 minutes) under the following incubation conditions: 1) continuous pH 7.4, 2) continuous pH 6.8, or 3) hypoxia at pH 6.8 and reoxygenation at pH 7.4 (NaHCO3 or Tris base addition). Continuously oxygenated PTSs maintained under these same pH conditions served as controls. Lethal cell injury was assessed by lactate dehydrogenase (LDH) release. pH effects on several purported pathways of hypoxia/reoxygenation injury were also assessed (ATP depletion, lipid peroxidation, and membrane deacylation). Acidosis blocked hypoxic LDH release (pH 7.4, 50 +/- 2%; pH 6.8, 6 +/- 1%) without mitigating membrane deacylation or ATP depletion. During reoxygenation, minimal LDH was released (3-5%) if pH was held constant. However, if posthypoxic pH was corrected, immediate (< or = 5 minutes) and marked cell death (e.g., 55 +/- 3% with Tris) occurred. This was dissociated from lipid peroxidation or new deacylation, and it was preceded by a depressed ATP/ADP ratio (suggesting an acidosis-associated defect in hypoxic/posthypoxic cell energetics). Realkalinization injury was not inevitable, since it could be substantially blocked by 1) posthypoxic glycine addition, 2) transient posthypoxic hypothermia, or 3) allowing a 10-minute reoxygenation (cell recovery) period before base addition. Neither mannitol nor graded buffer Ca2+ deletion conferred protection. Acute pH correction caused no injury to continuously oxygenated PTSs. Conclusions are as follows: 1) Posthypoxic "pH shock" causes virtually immediate cell death, not by causing de novo injury but, rather, by removing the cytoprotective effect of acidosis. 2) This injury can be prevented by a variety of methods, indicating a great potential for salvaging severely damaged posthypoxic PTSs.
 ...
PMID:Physiological pH. Effects on posthypoxic proximal tubular injury. 844 71

Some stroke patients suffering acute middle cerebral artery (MCA) infarction develop massive brain edema and herniation, a condition known as malignant MCA infarction. Severe swelling increases intracranial pressure (ICP) and leads to progressive brainstem dysfunction. Once ICP reaches critical values (>30 mm Hg) herniation occurs, usually within 2 to 5 days. Patients rarely survive (80% mortality) with standard treatment, and those who do are often severely disabled. Malignant MCA infarction is often missed by neurologists, despite well-defined clinical and neuroimaging (CT scan) diagnostic criteria. After diagnosis, conventional treatments such as osmotherapy, barbiturates, buffers, and hyperventilation center on reducing ICP. The goal of hyperosmolar therapy is to increase the serum osmolarity to approximately 315-320 mOsm/L. Enteric glycerol is used routinely to reduce ICP. In more severe cases and when glycerol fails, mannitol may be administered. Other therapies are also available, including hypertonic saline solution, THAM (Tris-hydroxy-methyl-aminomethane) buffer, and high-dose barbiturates. Hyperventilation also helps reduce ICP. All measures work effectively for a short time only. Other approaches to control elevated ICP, including decompression surgery and hypothermia, have shown promising results. In the Heidelberg decompression surgery trial, mortality in surgically treated patients was significantly lower (32%) than in non-treated patients (76%) despite conventional treatment. Importantly, of the surviving treated patients, 66% were rated independent with only mild to moderate disability. Moderate hypothermia (33-36 degrees C) has recently been shown to be effective in severe MCA infarction. Hypothermia induction within 14 hours of ischemic injury and maintained for 72 hours significantly reduced ICP and mortality (44%).
 ...
PMID:Treatment options for large hemispheric stroke. 1155 58

Brain ischemia is the leading pathopysiological mechanism in the development of secondary brain damage after acute subdural hematoma (SDH). Hypothermia has been employed as an effective cerebroprotective treatment on brain injuries, but the control of the general condition is very difficult under hypothermia, and various severe complications have been reported. Cerebral acidosis in the ischemic area is one of the important factors augmenting the brain edema formation. Tris-(hydroxymethyl)-aminomethane (THAM) has been used as an alkalizing agent for acidosis on brain injury and is reported to be effective. In the present study, we used a rat acute SDH model to assess the effect of mild (35 degrees C) hypothermia and THAM combined treatment on brain water content, brain ischemia, and blood-brain barrier (BBB) permeability at 4 h after hematoma induction. Mild hypothermia did not significantly reduce the brain water content beneath the hematoma (79.5 +/- 0.2%) compared to normothermia (80.2 +/- 0.2%), but mild hypothermia combined to THAM resulted in a significant reduction (78.7 +/- 0.0%; p < 0.01). Combined with mild hypothermia, THAM treatment significantly reduced the Evan's blue extravasation (35 +/- 7 ng/g wet tissue; p < 0.05) compared to normothermia (63 +/- 7 ng/g wet tissue). Furthermore, the volume of infarction at 24 h after the hematoma induction (54 +/- 3 mm(3); p < 0.01) was significantly smaller by the combined treatment compared with normothermia (70 +/- 2 mm(3)). The present findings indicate that mild hypothermia of 35 degrees C combined with THAM presents a potent cerebroprotective strategy. The protection of the BBB is one of the possible cerebroprotective mechanisms in this rat acute SDH model.
 ...
PMID:Effects of mild hypothermia and alkalizing agents on brain injuries in rats with acute subdural hematomas. 1216 34