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)

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.
...
PMID:The bioenergetics of preservation of limbs before replantation. The rationale for intermediate hypothermia. 319 76

Two recently completed studies in our laboratory have evaluated the relationship between myocardial temperature during cardioplegic preservation and calcium accumulation within the cell. In the large animal model, the pig, we investigated the influence of normothermic versus hypothermic blood cardioplegic preservation on sarcoplasmic reticulum calcium ATPase activity and calcium uptake following 2-hour cardioplegic arrest and 1 hour of normothermic reperfusion. The second investigation in the small animal model, the rat, measured intracellular calcium concentration in hearts subjected to cardioplegic arrest by continuous administration of cardioplegia at temperatures from 4 degrees to 37 degrees C. In the pig heart, global left ventricular function and coronary blood flow were improved, while creatine kinase release was reduced in the warm preserved heart. The rate of sarcoplasmic reticulum calcium uptake and calcium ATPase activity were impaired only in the presence of hypothermic preservation, and the higher calcium ATPase activity corresponded to the higher rate of sarcoplasmic reticulum calcium uptake observed in the warm preserved heart. Measurements of intracellular calcium concentration accomplished with a spectrofluorimeter documented a significant increase in free calcium in the 4 degrees C and 20 degrees C preserved rat heart during normothermic reperfusion. At both 28 degrees and 37 degrees C preservation, the free calcium level did not increase. It is concluded that intracellular calcium accumulation is associated with hypothermic preservation. Hypothermia appears to jeopardize the control of calcium homeostasis, which then is manifested as a more rapid increase of intracellular calcium during reperfusion. This would be associated with increased myocardial stunning in the hypothermic heart.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Myocardial stunning: a temperature dependent phenomenon. 806 42