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

Hypothermia (4 degrees C) reversibly inhibits metabolism of prostaglandin A1 (PGA1) in the perfused rabbit lung and decreases the transit time of PGA1 through the lung. Co-perfusion of PGA1 (0.28 muM) and PGE1 (2.8 muM) resulted in 48% inhibition of PGA1 metabolism. Ouabain and phenoxybenzamine (10(-5) M) did not significantly affect PGA1 metabolism. We examined the effect of diphloretin phosphate (DPP; 6.0 mu/ml) on the metabolism of prostaglandin A1 (0.28-5.03 muM) and E1 (PGE1;0.28-11.56 muM). The metabolism of both prostaglandins appeared to be saturable processes and, in the case of PGE, the data conformed to Michaelis-Menten kinetics: the apparent Km (muM) and apparent Vmax (nmol/lung X min-1) in control lungs were 9.0 +/- 0.3 and 87.9 +/- 1.4, respectively, and in the DPP-treated lungs were 9.6 +/- 0.5 and 57.7 +/- 1.8. This suggests that DPP acts in a noncompetitive manner. The magnitude of inhibition of PGA1 and PGE1 metabolism (both at 0.28 muM) was linearly related to the DPP concentration, over the range of 0.06 to 25.0 mug/ml. The ID50 values of DPP inhibition of PGA1 and PGE1 metabolism were 2.2 and 8.4 mug/ml, respectively. Perfusion of PGA1 at 2.96 muM or higher concentrations caused reversible vasoconstriction which was significantly inhibited (P less than .05) by DPP (6.0 mug/ml) by an average of 77.2 +/- 5.8% (n = 7).
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PMID:Metabolism of prostaglandins A and E in the perfused rabbit lung and the effects of selected inhibitors. 97 71

The effect of temperature on myocardial protein synthesis was evaluated using L-[14C]phenylalanine incorporation into total protein of isolated rabbit right ventricular papillary muscles. Muscles were incubated in oxygenated Krebs-Ringer buffer containing tracer amino acid at temperatures of 25-43 degrees C or incubated without tracer at varying temperatures up to 120 min and then incubated at 37 degrees C for an additional 2 h with the tracer present for the final hour of incubation. Higher as well as lower than physiological temperatures depressed tracer amino acid incorporation. Recovery of myocardial protein synthesis from thermal injury was incomplete when the experimental temperature deviated by 6 degrees C or more from the control and exposure exceeded 60 min. In addition, tracer amino acid incorporation on reoxygenation and return to 37 degrees C in muscles exposed to anoxia at 25 degrees C did not differ from that in muscles exposed to anoxia at 37 degrees C. Specific activity of the intracellular amino acid pool was directly measured in appropriate experiments and variation of this parameter could not account for the depressed tracer amino acid incorporation. Likewise methylprednisolone (10-5 M), chloroquine phosphate (10-5 M), and glucose (15 mM), if present during hyperthemia, did not ameliorate thermal damage. It is concluded that hyperthermia as well as hypothermia can cause irreversible alterations rather than reversible inhibition of myocardial protein synthesis.
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PMID:Thermoregulation of myocardial protein synthesis. 111 53

Hypothermic arrest, potassium arrest, and ischemic arrest, either singly or in combination, with or without coronary perfusion were studied in an isolated perfused rat heart preparation. Procedures that permitted the maintenance of high cellular levels of adenosine triphosphate (ATP) and creatine phosphate during arrest, e.g., coronary perfusion with hypothermic solutions or solutions containing 16.0 mM potassium, produced a fully reversible arrest with complete cardiac recovery. Cardiac arrest and coronary flow were related to the degree of hypothermia and the concentration of potassium in the coronary perfusate, and the minimum conditions required to induce complete cardiac arrest were ascertained. The effects of hypothermia and potassium were additive; total cardiac arrest could be obtained by combining small evaluations of potassium with moderate hypothermia. Under these conditions, cellular high-energy phosphates were maintained, and complete recovery was possible. Under conditions in which arrest was obtained without maintaing coronary perfusion, e.g., ischemic arrest, cellular high-energy phosphates declined rapidly, and the hearts exhibited poor recoveries. Some protection could be afforded to the ischemic myocardium by topical hypothermia or by combining the ischemia with potassium arrest. In both instances, ATP and creatine phosphate were maintained at higher levels, and improved recoveries were observed.
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PMID:Hypothermic arrest and potassium arrest: metabolic and myocardial protection during elective cardiac arrest. 111 43

1. The rise in blood glucose and the fall in body temperature which follows the injection of a glucose analogue, 2-deoxy-D-glucose (2-DG) into the lateral cerebral ventricle (I.C.V) of unanaesthetized rats were studied and found to be dose-dependent. These 2-DG induced responses are elicited by the impairment of glucose metabolism within central "glucoreceptors'. 2. 2DG induced hyperglycaemia and hypothermia were completely prevented and even the converse effects occurred when fivefold equimolar amounts of D-fructose were simultaneously injected I.C.V.; fructose, at equimolar doses, did not modify the effects of 2-DG. 3. D-xylose and D-ribose, even at high doses, did not influence 2-DG hyperglycaemia, but increased slightly the 2-DG induced hypothermia. This suggests that the pentose phosphate pathway is unable to support the metabolism within the glucoreceptors. 4. Pyruvate suppressed the 2-DG induced hyperglycaemia with a marked delay, while acetate (as ethyl ester) and a mixture of malate plus oxaloacetate did not prevent 2-DG induced effects. These results may be accounted for by the low dosage used. 5. Acetoacetate and 3-hydroxybutyrate did not prevent 2-DG hypothermia and hyperglycaemia. 6. An effective prevention of the 2-DG induced hyperglycaemia and hypothermia was achieved with fumarate and glutamate, indicating that the stimulation of the Krebs cycle within "glucoreceptors' removes the glucoprivic effects. 7. The results indicate that prevention of 2-DG induced effects occurred only with alternate source of metabolic fuel which can support high respiratory rates in brain tissue. It is concluded that central chemoreceptors are not specifically responsive to glucose, or hexoses, but to the rate of oxidative metabolism.
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PMID:Sensitivity of central chemoreceptors controlling blood glucose and body temperature during glucose deprivation. 115 83

Isolated perfused working rat hearts were subjected to elective cardiac arrest for 20 or 30 min. Various methods of arrest were studied, either singly or in combination and with or without coronary perfusion. The functional recovery of the heart following the termination of arrest was found to be related to the concentration of ATP and creatine phosphate in the myocardium at the end of the period of arrest. In turn, these concentrations were dependent upon the method used to induce arrest. Normothermic ischemic arrest led to a marked reduction in high energy phosphates and a poor functional recovery. In contrast, coronary perfusion with hypothermic solutions or solutions containing high concentrations of potassium, induced arrest without depleting ATP or creatine phosphate. These procedures conferred considerable protection on the myocardium and thus permitted good recoveries. The energy status and recovery associated with ischemic arrest could be improved by combining the ischemia with hypothermia or potassium arrest. The latter, while increasing recovery significantly, still failed to afford complete protection to the myocardium. Potassium chloride gave greater protection than potassium citrate. When topical hypothermia was combined with ischemia, a time and temperature relationship was demonstrated but effective protection could only be obtained with severe topical hypothermia over a relatively short time period. The results stress the importance of maintaining high energy phosphates during arrest, and this requires the provision of a continuous supply of oxygen and nutrient, which may perhaps be best achieved by ensuring continuous and adequate coronary perfusion.
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PMID:Ischemic damage and metabolism during elective cardiac arrest. 120 80

The ability of transient temperature variations for up to 120-min duration to affect myocardial protein synthesis (MPS) with return to normal temperatures was evaluated using 14C-phenylalanine incorporation into total protein of isolated rabbit right ventricular papillary muscles as in vitro model. Muscles were incubated in oxygenated Krebs-Ringer bicarbonate buffer containing tracer amino acid at temperatures of 28-43 degrees C or incubated without tracer at the same temperatures for up to 120 min and then incubated at 37 degrees C for an additional 2 hr with the tracer amino acid present for the final hour of incubation. Higher as well as lower than physiological temperatures depressed MPS. Recovery from thermal injury to MPS was significantly incomplete when the experimental temperature deviated by 6 degrees C or more from the control (28 and 43 degrees C, respectively) and exposure exceeded 60-min duration. Specific activity of the intracellular amino acid pool was directly measured, and variations in specific activity of the tracer pool were not responsible for the observed effects on MPS. Methylprednisolone (10(-5)M), chloroquine phosphate (10(-5) M), and glucose (15 mM) if present during hyperthermia did not ameliorate thermal damage. It is concluded that hypothermia causes inhibition as well as a degree of irreversible inactivation of the protein synthetic mechanism whereas hyperthermia causes predominant denaturation and irreversibile damage to MPS.
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PMID:Reversibility of thermal injury to myocardial protein synthesis. 121 32

Effects of 5 cold storage solution on hepatic high energy phosphate metabolism and metabolic function were examined using the isolated perfused rat liver. University of Wisconsin (UW), Euro-Collins (EC), and 2 cardioplegic solutions, Bretschneider's HTK and St. Thomas Hospital solution, were studied for their protective capacity. Krebs-Henseleit bicarbonate buffer (KHB) was used to point out the effect of simple hypothermia. Liver ATP, total adenine nucleotides and energy charge losses were significantly lower during 21 h of storage in UW-preserved livers. Also, only UW-protected livers were able to complete regeneration of ATP and total adenine nucleotides after 1 h of reperfusion, whereas EC, HTK, St. Thomas and KHB stored livers only showed minimal regeneration. Concerning metabolic function, UW protected livers liberated significantly less LDH and sGOT as well in the 21-hour storage solution as into the perfusate under reperfusion conditions. This study demonstrates the capability of UW solution in liver preservation by its ability to maintain and restore high energy phosphates.
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PMID:Hepatic energy metabolism during hypothermic storage and reperfusion using different protecting solutions. 129 38

Hypothermia was first applied therapeutically as a local anesthetic and later was used to achieve organ protection during procedures necessitating circulatory interruption. Profound whole-body hypothermia, typically carried out in conjunction with extracorporeal bypass, has long been employed during cardiac and neurosurgical operative procedures. More recently, studies in small-animal experimental models of cerebral ischemia have provided persuasive evidence that even small decreases in brain temperature confer striking protection against ischemic neuronal injury. By contrast, small elevations of brain temperature during ischemia accelerate and extend pathologic changes in the brain and promote early disruption of the blood-brain barrier. Hypothermia retards the rate of high-energy phosphate depletion during ischemia and promotes postischemic metabolic recovery. More importantly, mild intraischemic hypothermia markedly attenuates the release of glutamate into the brain's extracellular space and significantly diminishes the release of dopamine. Similarly, the inhibition of calcium-calmodulin-dependent protein kinase II triggered by normothermic ischemia is prevented by hypothermia, as is the ischemia-induced translocation and inhibition of the key regulatory enzyme protein kinase C. Hypothermia also appears to facilitate the resynthesis of ubiquitin following ischemia. Studies of potential clinical importance have shown that moderate hypothermia is capable of attenuating ischemic damage even if instituted early in the postischemic period. In the setting of focal cerebral ischemia, moderate brain hypothermia reduces the infarct size (particularly in the setting of reversible middle cerebral artery occlusion); conversely, hyperthermia markedly increases the infarct volume. These studies underscore the importance of monitoring and regulating the brain temperature during experimental studies of cerebral ischemia to insure a consistent pathologic outcome and to avoid the false attribution of "pharmacoprotection" to drugs that reduce the body temperature. The measurement of brain temperature is now practicable in neurosurgical patients requiring invasive monitoring, and human studies have shown that cortical and cerebroventricular temperatures may exceed systemic temperatures. Mild to moderate decreases in brain temperature are neuroprotective in cerebral ischemia, while mild elevations of brain temperature are markedly deleterious in the setting of ischemia or injury. It is anticipated that controlled clinical trials of therapeutic brain temperature modulation will be undertaken over the next several years.
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PMID:Therapeutic modulation of brain temperature: relevance to ischemic brain injury. 138 56

The impact of hypothermia on reperfusion-associated oxidative stress in postischemic skeletal muscle was evaluated in a small animal model of high-grade partial ischemia. The infrarenal aorta of heparinized Sprague-Dawley rats was clamped for 90 min, declamped, and then reperfused for 60 min. Previous characterization of this model with 51Cr-tagged microspheres revealed that hindlimb perfusion during aortic clamping continued at 16.6% of baseline values. Resting transmembrane potential difference (Em) and tissue malondialdehyde (MDA), lactate and high-energy phosphate content were determined in hindlimb skeletal muscle at baseline, during ischemia, and upon reperfusion. Four experimental groups (N = 7 in each group) were studied: control animals underwent aortic clamping and declamping; hypothermia animals underwent topical cooling of hindlimbs prior to aortic clamping, with muscle temperatures maintained between 5 and 15 degrees C during ischemia; sham animals underwent midline laparotomy only; and hypothermia-sham animals underwent cooling and midline laparotomy only. During ischemia, resting Em (-mV) was significantly depolarized (P < 0.05 versus baseline) in control (74.9 +/- 0.8 from 91.0 +/- 0.1), hypothermia (64.4 +/- 1.1 from 90.9 +/- 0.3), and hypothermia-sham (67.2 +/- 1.4 from 90.9 +/- 0.4) animals. Upon reperfusion, resting Em remained depolarized in control animals (74.7 +/- 1.6), while repolarization occurred in hypothermia (88.8 +/- 1.1) and hypothermia-sham (90.7 +/- 0.3) animals.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hypothermia relieves oxidative stress in reperfused skeletal muscle following partial ischemia. 140 21

Variations of the phosphate concentration in plasma were studied in two groups of 12 patients undergoing cardiac surgery with hypothermic cardiopulmonary bypass (CPB). Management of the acid-base status differed between the groups, according to whether or not carbon dioxide was added to the anesthetic gas mixture during hypothermia ('pH-stat' vs. 'alpha-stat' mode) following correction vs. no correction of pCO2 and pH for body temperature. Phosphate variations throughout the study were mostly within normal limits. From the start to the end of CPB, the mean rise in phosphate levels was 70% in the pH-stat group and 37% in the alpha-stat group (p < 0.001). During 3 hours after CPB, the phosphate values continued to rise by a mean of 25% in the alpha-stat patients, but fell by a mean of 3% in the pH-stat patients (p < 0.001). Such different phosphate patterns during and immediately after CPB may reflect profound metabolic disturbances and may be related to the altering effects of CO2 addition and respiratory acidosis on intracellular metabolic activity and phosphate homeostasis.
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PMID:Effect of acid-base management with or without carbon dioxide on plasma phosphate concentration during and after hypothermic cardiopulmonary bypass. 143 46


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