Skeletal muscle amino acid and myofibrillar protein mRNA response to thermal injury and infection

Skeletal muscle changes associated with severe injury were investigated in male Wistar rats subjected to 30% full thickness scald injury (burn) and thermal injury followed by immediate colonization with 10⁸ colony-forming units of Pseudomonas aeruginosa (BI). Freely fed animals (FF) and animals pair fed to the BI animals (PF) served as controls. Thermal injury in conjunction with infection produced a rapid and sustained muscle cellular membrane depolarization (transmembrane potential difference at 12 h after injury: FF 92.1 ± 0.3 and BI 85.2 ± 2.3 mV; P < 0.05). This was followed by body weight loss and skeletal muscle protein wasting (gastrocnemius protein at 7 days: FF 0.35 ± 0.01 and BI 0.16 ± 0.03 g; P < 0.05) and intracellular high-energy phosphate depletion (ATP at 10 days: FF 6.6 ± 0.4 and BI 4.5 ± 0.4 μmol/g tissue; P < 0.05). These body and cellular changes were not accounted for by the anorexia alone. Marked alterations in intracellular free amino acids were also noted in the BI group characterized by increases in levels of all amino acids (total intracellular free amino acids at 7 days: FF 51 ± 7 and BI 91 ± 12 mM; P < 0.05) except intracellular glutamine (at 7 days: FF 6.0 ± 0.2 and BI 2.4 ± 0.6 mM; P < 0.05). A significant decline in total cellular RNA content (RNA at 7 days: FF 4.7 ± 0.6 and BI 2.2 ± 0.2 mg; P < 0.05), as well as a coordinate decrease in mRNA for α-actin and myosin heavy chain were noted in the BI animals. We conclude from our data that 1) early alterations in membrane ionic gradient after burn-infection injury are not due to a cellular energy deficit; 2) infected burn injury produced a muscle protein wasting and intracellular high-energy phosphate depletion not explainable by anorexia alone; and 3) decrease in muscle protein mass is in part due to decrease in myofibrillar protein transcription.