ReviewThe impact of severe burns on skeletal muscle mitochondrial function
Introduction
The pathophysiological response to thermal trauma is multi-factorial with resulting perturbations in metabolism affecting nearly every physiological system [1], [2], [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16]. Like most forms of critical illness, severe burns result in an inflammatory and hypermetabolic stress response, but the extent and duration of these responses and their debilitating nature appear unique to burn trauma [1], [6], [7], [17], [18], [19], [20]. With recent advances in clinical practice such as early wound excision and closure, and robust infection management [21], severe burns are more survivable than ever before. Consequently, there is a real need for effective rehabilitative strategies that mitigate the pathophysiological response to burns and to restore normal physiological function in order to reduce morbidity and improve quality of life in patients recovering from severe burns. Central to the process of developing novel strategies that impact outcomes in burn patients is a comprehensive understanding of the pathophysiological response to severe burn trauma. While the stress response to burn trauma including but not limited to inflammation, the catecholamine surge, hypermetabolism and muscle wasting have been studied in human patients in great detail [1], [5], [6], [9], [10], [17], [19], [20], [22], [23], [24], [25], [26], [27], [28], [29], [30], [31], [32], [33], [34], [35], [36], [37], [38], [39], [40], [41], the impact of severe burns on skeletal muscle bioenergetics in human patients has been paid comparatively little attention [42], [43], [44], [45], [46]. This is perhaps surprising given the fact that supraphysiological rates of energy expenditure [1], [5], [18], [19], [23], [33], [47], [48], [49], insulin resistance [1], [4], [5], [29], [45], [50], [51] and muscle wasting [6], [14], [17], [19], [23], [25], [26], [28], [30], [31], [32], [34], [35], [36], [37], [38], [39], [40] are all considered as hallmarks of the pathophysiological response to severe burns. Moreover, mitochondria are sensitive to environmental and pharmacological stimuli [52], [53], [54], [55], meaning that these intriguing organelles make ideal candidates for interventions aimed at altering the pathophysiology of burn trauma. With this in mind, the purpose of this article is to review the current literature pertaining to skeletal muscle bioenergetics in patients with severe burns, with an aim to renewing interest in this field and wherever possible, offer direction to researchers interested in improving metabolic health and functional capacity in patients recovering from severe burns.
Section snippets
Hypermetabolism
Severe burns result in profound alterations in energy expenditure. Indeed, resting energy expenditure has been reported to be between 120 and 180% above normal values in the first one to two months post injury [1], [18], [19], [23]. Moreover, it has previously been reported that energy expenditure was significantly elevated for up to 24 months post injury in burned children and remained elevated, albeit not significantly, at 36 months post injury [1]. It is thought that heat loss through open
Skeletal muscle cachexia following severe burns
A hallmark of the adaptive response to thermal trauma is the catabolism of skeletal muscle, which is known to persist for at least 9 months post burn [6]. While excessive erosion of lean tissue impairs functional capacity and metabolic health, thus impeding rehabilitation post burn, it would seem the skeletal muscle is sacrificed to aid wound healing [62]. Indeed, acutely post burn, increasing protein intake does not further increase skeletal muscle protein synthesis. However, increasing
Skeletal muscle mitochondrial function in health
Mitochondria fulfill the role of the combustion engines of respiring cells. In essence these cellular organelles are able to catabolize nutrient derived substrates into a form (acetyl-CoA) which can participate in the tricarboxylic acid (TCA) cycle. In turn, the TCA cycle can generate NADH and succinate, which themselves feed protons (H+) and electrons (e−) to the electron transport chain (ETC) via NADH reductase (complex I) and succinate dehydrogenase (complex II) respectively. The subsequent
Summary and conclusions
Skeletal muscle mitochondrial function plays an obligatory role in the functional capacity and metabolic health of an individual. In patients with severe burns, there appears to be rapid and profound reductions in skeletal muscle mitochondrial content and function post injury, which are associated with poorer clinical outcomes. As such, strategies aimed at improving skeletal muscle oxidative capacity in severely burned individuals are likely to be efficacious with regards to aiding patient
Conflict of interest
The authors have no conflict of interest to disclose.
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2020, Present Knowledge in Nutrition: Clinical and Applied Topics in NutritionDeterminants of skeletal muscle protein turnover following severe burn trauma in children
2019, Clinical NutritionCitation Excerpt :Clearly then, increased muscle protein synthesis places a significant energetic demand on severely burned patients. Moreover, we have recently shown that the efficiency of mitochondrial ATP production in skeletal muscle declines post-burn [6,13]. Because muscle mitochondria produce the ATP required for muscle protein synthesis, our current data suggest that muscle protein turnover might make a greater contribution to burn-induced hypermetabolism than previously thought [37].
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