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

Abstract

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 ...

Temperature dependency of force loss and Ca2+homeostasis in mouse EDL muscle after eccentric contractions

“…The general aim of this study was to manipulate muscle temperature during the eccentric contractions in hope of further elucidating the mechanisms underlying the reduction in strength. For example, numerous studies have shown hypothermia to provide protection against skeletal muscle injury induced by the Ca 2ϩ paradox, ischemia-reperfusion, and metabolic overload (4,8,22,27,34). Even small reductions in muscle temperature (from 37°C to 32-35°C) provide protection against these injuries as assessed histologically, biochemically, and/or functionally (8,22,34).…”

“…For example, numerous studies have shown hypothermia to provide protection against skeletal muscle injury induced by the Ca 2ϩ paradox, ischemia-reperfusion, and metabolic overload (4,8,22,27,34). Even small reductions in muscle temperature (from 37°C to 32-35°C) provide protection against these injuries as assessed histologically, biochemically, and/or functionally (8,22,34). The protective effect at lower muscle temperatures may be due to better maintenance of plasmalemmal and/or t-tubular integrity, and as a consequence, improved intracellular Ca 2ϩ homeostasis (27).…”