The bioenergetics of preservation of limbs before replantation. The rationale for intermediate hypothermia.

Sapega, Alexander A.; Heppenstall, R. Bruce; Sokolow, D; Graham, Thomas J. A.; Maris, J.; Ghosh, Arun K.; Chance, Britton; Osterman, A. Lee

doi:10.2106/00004623-198870100-00010

Cited by 88 publications

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“…According to Sapega et al [4], the rate of metabolic deterioration declined progres sively with decreasing tissue temperature down to 10 °C but it increased again at lower temperatures. This paradoxal response was explained by a severe inhibition of the cal cium pump of the sarcoplasmic reticulum at temperatures below 5°C.…”

Section: Discussionmentioning

confidence: 98%

“…A protective effect of cooling in an ice bath to 0-5 °C has been documented [1][2][3], Moderate hypother mia to between 10-15 °C has been claimed to give even better protection [4], In a pilot study we found that only a few degrees' changes in room temperature affected the postischemic muscle necrosis in rats. We therefore decided to study the effects of small differences in the ambient temperature.…”

Section: Introductionmentioning

confidence: 99%

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Protective Effect of Low-Grade Hypothermia in Experimental Skeletal Muscle Ischemia

Skjeldal

Grøgaard²,

Nordsletten³

et al. 1992

Eur Surg Res

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In the present study, a rat hindlimb tourniquet model was used to investigate the effect of moderate hypothermia on ischemic muscle necrosis. Complete circulatory arrest was maintained for 4.5 h. During the ischemic period the animals were kept in an infant incubator at different temperatures. After 72 h survival the percentage of necrosis in the anterior tibial muscle was measured morphometrically on histological slides. At an ambient temperature of 24 °C there was 80% necrosis in the anterior tibial muscle. At 22 ° C the necrosis was reduced to 29 %. This reduction corresponds to more than 30 min shortening of the ischemia time. Differences in tissue temperature may explain some of the discrepancies reported in tolerance limits for muscle ischemia. To achieve consistent results in experimental muscle ischemia, it is necessary to control the ambient temperature.

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Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Protective Effect of Low-Grade Hypothermia in Experimental Skeletal Muscle Ischemia

Skjeldal

Grøgaard²,

Nordsletten³

et al. 1992

Eur Surg Res

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“…These biochemical analysis are useful for evaluating the gross change in the muscle quantitatively. However, there are some reports [14,23] that deterioration of ATP level was not found in the muscle up to 4-h ischemia. Therefore, we concluded that these analysis including morphological, blood circulation and biochemical analysis may be less sensitive to detect the muscle damage up to 4-h ischemia and may not reflect certain levels of cell damage in the whole cell population compared to our method using RNA analysis.…”

Section: Discussionmentioning

confidence: 99%

Viability of ischemia/reperfused muscles in rat: a new evaluation method by RNA degradation

Akahane

Ono

Ohgushi

et al. 2001

Journal Orthopaedic Research

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The rat's skeletal muscle viability was evaluated using the muscle viability index (MVI) which reflects the mRNA degradation. To evaluate ischemic injury of the muscle, 24 hind limbs of Fischer rats (three subgroups of eight rats each) were preserved at normothermia for 1, 3 and 6 h and then tibialis anterior muscle was harvested. To investigate ischemia/reperfusion injury, another 48 limbs were transplanted to recipient Fischer rats after the ischemia at normothermia for 1, 3 and 6 h, respectively. The transplanted muscles were harvested on day 3 and day 7 after transplantation. Eight fresh muscles were also harvested and used as control. Total RNA isolated from each muscle was fractionated by electrophoresis and hybridized with 32P-labelled cDNA of GAPDH, and the radioactivity of intact and degraded GAPDH mRNA was measured. MVI was calculated as follows, MVI = { X / ( X + Y ) } x 100, where X and Y represent the radioactivities corresponding to intact GAPDH and degraded GAPDH mRNA band, respectively.In 1-h ischemia group, the MVI indices of both ischemic insult and ischemialreperfusion group were comparable to control, In the 3-h ischemia group, the index of ischemiaheperfused group was comparable to control although the index of ischemic insult group was significantly lower than control. However, in the 6-h ischemia group, both indices of ischemic insult and ischemia/ reperfusion group were significantly lower than control. These results show that the muscle damage was detected in ischemia at normothermia even after 3 h. However, this damage was overcome by reperfusion. There was no recovery from damage in muscles that had been preserved for more than 6 h which had resulted in irreversible degeneration. Therefore, in clinical muscle transplantation, one has to transplant the muscle at least within 3-h ischemia.

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“…25 These observations have been supported by magnetic resonance spectroscopy which shows that cooling the limb preserves intracellular pH, slows depletion of muscle phosphocreatine and ATP and slows the accumulation of inorganic phosphate. 26 In experimental crush injury of muscle the severity of the resulting edema is reduced by a moderate degree of hypothermia (27-30°C). 27 Hypothermia also reduces the infarct size 28 and creatine kinase, lactate dehydrogenase and potassium release in muscle subjected to ischemia under experimental conditions.…”

Section: Discussionmentioning

confidence: 99%

Mild Hypothermia Preserves Contractile Function and Inhibits Prostaglandin E₂ Release from Metabolically Stressed Skeletal Muscle

Cwik

Majumdar

Brooke

1994

Can. J. Neurol. Sci

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An in vitro model of muscle damage was used to investigate the protective effect of mild hypothermia in muscle injury. Rat epitrochlearis muscles were dissected in their entirety and suspended in Krebs-Ringer solution and DNP, a mitochondrial uncoupler, was added. PGE, and lactate release and the contractile response to stimulation were measured and compared to untreated controls. Experiments were done at 37, 35, 33 and 27°C. At 37°C, DNP stimulated muscle releases large amounts of PGE 2 and lactate and is unable to contract. As the temperature is reduced, there is progressive preservation of contractile force, although high lactate levels at the lowest temperatures indicate that the metabolic stress is still present. In contrast, DNP stimulated PGE 2 release is completely inhibited at or below 35°C and may be related to a similar protective phenomenon seen in experimental ischemic neuronal death.Resume: L'hypothermie legere protege la fonction contractile et inhibe la liberation de prostaglandin E 2 par les muscles squelettiques soumis au stress. Nous avons utilise un modele in vitro de lesion musculaire pour investiguer l'effet protecteur d'une legere hypothermie dans le traumatisme musculaire. Des muscles 6pitrochl6ens de rat ont ete dissequ6s et suspendus dans une solution de Krebs-Ringer a laquelle du DNP, un dficoupleur mitochondrial, a ete ajoute. La liberation de PGE 2 et de lactate ainsi que la reponse contractile a la stimulation ont 6t6 mesurees et comparees a celles de controles non trait6s. Les essais etaient faits a 37, 35, 33 et 27°C. A 37°C, le muscle stimuld par le DNP libere de grandes quantites de PGE 2 et de lactate et il est incapable de se contracter. A mesure que la temperature est abaissee, on observe une preservation progressive de la force contractile, bien que de fortes concentrations de lactate aux temperatures les plus basses indiquent que le stress m£tabolique est encore present. Par contre, la stimulation de la liberation de PGE 2 par le DNP est completement inhibee a des temperatures de 35°C ou moins et peut etre reliee a un phenom^ne protecteur semblable a celui observe dans la mort neuronale experimental par ischemie.Can. J. Neurol. Sci. 1994; 21: 120-124 Mechanisms which can prevent cell damage are a major interest in neurology because of the possible implications for therapy. Even if the primary neurological event cannot be prevented, the ability to decrease subsequent cell death may offer a viable treatment. This concept of "damage control" is being explored in stroke, 1 " 4 Parkinson's disease, 5 motor neuron disease 6,7 and muscular dystrophy. 8 Mild hypothermia exerts a profound protective effect against cerebral ischemia, both experimentally 9 " 14 and clinically. 15 " 18 An in vitro muscle preparation for investigating damage uses the rat epitrochlearis muscle and permits simultaneous monitoring of biochemical parameters and muscle function.19 " 20 2,4-dinitrophenol (DNP) which reversibly binds to mitochondria and uncouples oxidative phosphorylation is used ...

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The bioenergetics of preservation of limbs before replantation. The rationale for intermediate hypothermia.

Cited by 88 publications

References 0 publications

Protective Effect of Low-Grade Hypothermia in Experimental Skeletal Muscle Ischemia

Protective Effect of Low-Grade Hypothermia in Experimental Skeletal Muscle Ischemia

Viability of ischemia/reperfused muscles in rat: a new evaluation method by RNA degradation

Mild Hypothermia Preserves Contractile Function and Inhibits Prostaglandin E₂ Release from Metabolically Stressed Skeletal Muscle

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The bioenergetics of preservation of limbs before replantation. The rationale for intermediate hypothermia.

Cited by 88 publications

References 0 publications

Protective Effect of Low-Grade Hypothermia in Experimental Skeletal Muscle Ischemia

Protective Effect of Low-Grade Hypothermia in Experimental Skeletal Muscle Ischemia

Viability of ischemia/reperfused muscles in rat: a new evaluation method by RNA degradation

Mild Hypothermia Preserves Contractile Function and Inhibits Prostaglandin E2 Release from Metabolically Stressed Skeletal Muscle

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Mild Hypothermia Preserves Contractile Function and Inhibits Prostaglandin E₂ Release from Metabolically Stressed Skeletal Muscle