Many chronic heart failure (CHF) patients experience skeletal muscle wasting which has been shown to be associated in part with the elevated catecholamines (Anker et al. 1997). We have previously observed both myocyte necrosis and apoptosis in the heart and soleus muscle of the rat following a single injection of the synthetic catecholamine, isoprenaline (Ellison et al. 2002). This raises the possibility of catecholamine involvement in the progressive functional deterioration of the skeletal and cardiac musculature in CHF. Here we describe the regeneration of the soleus muscle, following damage inflicted by a single injection of isoprenaline.

Seven independent groups of male Wistar rats (Rattus norvegicus) (250 ± 7g) (mean ± S.E.M.) received 5 mg of isoprenaline kg^-1 (S.C.). All experimental procedures conformed to the UK Animals (Scientific procedures) Act 1986. Animals were killed by cervical dislocation at seven time points over a 28-day period and the soleus muscles were quickly isolated and snap frozen. Regenerating fibres were detected using an anti-embryonic/neonatal myosin heavy chain 1°Ab (Novacastra) on 5 mm cryo-sections. The 1°Ab was detected and visualised using a HRP-conjugated rabbit anti-mouse 2°Ab (Dako) and DAB. Image analysis was used to quantify the number of normal and regenerating fibres in the whole cross section of each soleus muscle. Three X one-way ANOVA were employed to analyse the data for total fibre number, normal and regenerating fibres, and Tukeys post hoc analysis to locate the differences.

No changes in total fibre number were observed in control animals over the 28-day experimental period. In contrast, 5 days after isoprenaline administration fibre number was reduced to 2196 ± 145 (17 % loss) (Fig. 1). By 28 days this had returned to 2544 ± 69. A significant (P < 0.05) increase in the number of regenerating fibres was observed at 5 days (6 ± 2.6 %) and 7 days (8 ± 2.6 %).

These data show that severely injured muscle fibres have the ability to regenerate, with complete restoration of fibres by 28 days following a single injection of isoprenaline. Whether, this process of regeneration is impaired by sustained high levels of catecholamines, as seen in CHF, remains to be ascertained.

This research was supported by the British Heart Foundation.