Abstract
This study investigates alterations in rat skeletal muscle after burn trauma (30% body surface area, full-thickness scald injury) with or without concomitant burn wound infection (immediate postburn inoculation with Pseudomonas aeruginosa), an injury model previously described by the authors.1 The study design allowed evaluation of sequential changes in skeletal muscle membrane integrity after burn or burn-infection injury and whether these occur coordinately with changes in muscle protein mass, specific protein transcription, intracellular amino acid and electrolyte concentrations, and indices of cellular energy status. Four groups of rats were compared: animals subjected to burn injury alone (Burn), burn injury plus wound infection (BI), freely fed, unburned control animals (FF), and unburned animals pair-fed to BI (PF: to control for anorexia in the BI group). Skeletal muscle myofibrillar protein transcription (relative abundance of messenger RNA for actin and myosin heavy chain); indices of muscle mass (protein RNA and DNA concentrations), muscle transmembrane potential (Em)2; intracellular sodium, potassium, and amino acid (AA) concentrations; and high-energy phosphate content in muscle (ATP and creatinine phosphate [CrP]) were determined 12 hours and 3, 7, and 10 days after injury in BI animals. These endpoints were also determined 3, 7, and 10 days after sham burn in PF-control rats, and 3 and 7 days postinjury in the Burn group and in FF rats.
Burn injury alone produced a transient (3-day) decline in food intake and body weight; these indices then returned to the levels seen in FF rats. In contrast, BI caused a marked (50% to 75%) reduction in food intake and a progressive decrease in body weight, such that by 10 days, postinjury weight had fallen approximately 35%. Body weight in PF animals fell only about 10% (significantly less than in BI), demonstrating the accelerated loss of body mass due to infection and burn injury coupled with anorexia. Skeletal muscle transmembrane potentials in Burn animals at 3 and 7 days were not different from FF values; however, with simultaneous burn wounding and infection, membrane potential fell significantly by 12 hours (BI 85.2 ± 2.3 mV vs FF 92.1 ± 0.3 mV; p < .05, mean ± SEM); membrane potential continued to fall progressively over time in this group. Muscle membrane potential in the BI group was significantly less than corresponding values over time in Burn and PF rats. Membrane potential values in PF rats were similar to those of FF animals; thus, membrane changes in BI animals were not due to reduced food intake alone. At 10 days postinjury, intracellular sodium content was significantly greater and potassium content significantly less in BI than in FF and PF values; no other significant changes in muscle electrolyte content were seen. Muscle ATP and CrP contents were unchanged in all groups until 7 days postinjury; thus, a cellular energy deficit could not explain the early (12 hours to 3 days) membrane potential changes in BI. However, by day 7 the ATP content in the BI group was significantly less than the corresponding Burn value and the CrP content was significantly less than in FF. By 10 days, ATP and CrP concentrations in BI were significantly less than in PF and FF (eg, ATP: BI 4.5 ± 0.4 μmol/g adductor muscle us PF 7.3 ± 0.2 us FF 6.6 ± 0.4; p < .05 for BI us PF and FF). Thus, either thermal injury or poor nutrient intake alone was insufficient to cause depletion of these measures of high-energy phosphate content in muscle.
Intracellular amino acid levels were altered only in BI; by 7 days postinjury, total AA, essential AA, and branched-chain AA concentrations were higher in this group than in FF, Burn, and PF. In contrast, glutamine (Gln) levels in BI fell markedly within 12 hours after injury (BI 3.6 ± 1.1 mM us FF 6.0 ± 0.2 mM; p < .05) and remained in this low range at 10 days: Gln and AA levels in the Burn and PF groups were not significantly altered. Gastrocnemius muscle weight, RNA, and protein content fell when compared with FF by 3 days with burn injury alone, but these parameters were returning toward normal by 7 days after injury. However, burn plus infection caused a more marked and progressive decrease in these indices of muscle mass. By 7 days, muscle weight, RNA, and protein content were significantly lower than values in the other three groups and fell further by 10 days post-BI. Reduced food intake alone (the PF group) or burn injury alone resulted in a moderate reduction in muscle weight, protein, and RNA content compared with FF. Northern analysis utilizing cDNA probes for actin and myosin heavy chain demonstrated a decline in mRNA levels for both myofibillar proteins by day 3 in the Burn group. However, this effect was transient because mRNA levels returned to the FF levels by 7 days. PF mRNA values decreased slightly over time. In contrast, beginning 3 days after injury, BI rats demonstrated a progressive decrease in mRNA expression for actin and myosin heavy chain over time.
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