Systemic effects of single hindlimb burn injury on skeletal muscle function and cyclic nucleotide levels in the murine model

Abstract

This study tested the hypothesis that a single hindlimb burn has both local and distant effects. Male CF 1 anaesthetized mice were given a full thickness scald burn of 3 per cent total body surface area (BSA) by immersion of their left hindlimb in water at 95°C for 5 s. Muscle tension was measured through twitch analysis. Levels of cyclic adenosine 3′–5′ monophosphate (cAMP) and cyclic guanosine 3′–5′ monophosphate (cGMP) were analysed by 125I-radioimmunoassay. Measurements were made in gastrocnemei of the ipsilateral burned and contralateral unburned limbs over a 28-day postburn period. Within 1 week the burned limb showed an increase in both tension and a 100-fold increase in levels of cAMP. However, by the end of the second week muscle tension in the burned limb dropped to one-seventh of control values despite persistence of high levels of cAMP. In contrast, the systemic effects were manifested in the unburned contralateral limb which showed tension to undergo a six-fold compensatory increase at the end of the second week with a 75-fold increase in cAMP. By the end of 4 weeks, tension levels of both burned and unburned limbs were attenuated to one-half control values indicating neuromuscular (NM) dysfunction. Nevertheless, cAMP levels remained elevated in both limbs. Levels of cGMP were reduced throughout the 4-week postburn period. Subsequent to the single hindlimb injury both ipsilateral and contralateral gastrocnemei muscles showed elevated levels of total protein content. Thus, in addition to the local effect of burn on the ipsilateral hindlimb, other systemic mediators are involved which influence contralateral limb tension and cyclic nucleotide metabolism. These findings are important to emerging pharmacological therapies undergoing development to combat NM dysfunction resulting from burn injury.