In chronic heart failure continuous activation of the sympathetic system leads to sustained high levels of circulating catecholamines (Anker et al. 1997). These hormones can cause cardiomyocyte death, thereby contributing to further progressive cardiac dysfunction. Although it is possible that similar catecholamine-induced injury may be manifest in skeletal muscles, to date this has been inadequately studied despite substantial losses in muscle mass in some patients. We have used an animal model in which myocyte-specific necrosis can be detected and quantified in cardiac and skeletal muscles of the rat in response to a single injection (S.C.) of the synthetic catecholamine, isoprenaline. Male Wistar rats (Rattus norvegicus) weighing 301 ± 4.1 g were used, with all experimental procedures carried out under the UK Animals (Scientific Procedures) Act, 1986. Rats were administered (I.P.) an anti-myosin antibody at 1 mg kg^-1 1 h before the single injection of isoprenaline, which ranged in dose from 0.0001 to 5 mg kg^-1. Myocyte necrosis in vivo can be studied in this way as the antibody is excluded from normal cells, but is admitted through the disrupted sarcolemmal membranes of necrotic myocytes. Rats were killed by cervical dislocation at either 12 h for the soleus muscle or 18 h for the heart. Muscles were quickly isolated and snap frozen. Necrotic myocytes were visualised on 5 mm cryo-sections using secondary immunoperoxidase with 3,3-diaminobenzidine (DAB). Image analysis was used to measure both the number (soleus) and area (ventricular subendocardium) of necrotic myocytes in randomly selected fields of view. Both muscle types were damaged by the isoprenaline, but with this occurring at lower doses in the skeletal muscle (Fig. 1).

Peak myocyte necrosis also occurred earlier (12 h) in the soleus, compared with the heart (18 h). Although damaging both types of myocytes through β-adrenergic (AR) pathways, this catecholamine acted via different receptor subtypes, i.e. β₁-ARs in the heart and β₂-ARs in the soleus. Clearly skeletal muscle, as well as the heart, can be severely damaged by elevated catecholamines. Indeed, the skeletal myocytes appear to be more sensitive than cardiomyocytes to the myotoxic effects. Although not a model of heart failure, our data support the concept of elevated catecholamines inducing a generalised, rather than cardiac-specific, myopathic process in heart failure (Opasich et al. 1999).

The research was supported by the BHF and NHRF.

All procedures accord with current UK legislation.