Received February 18, 2004
Revised March 22, 2004
Accepted after revision April 20, 2004

¹ Liverpool John Moores University
² Michael Reese Hospital and Medical Center
³ University of Leeds

^* To whom correspondence should be addressed. E-mail: d.goldspink{at}livjm.ac.uk.

	Abstract

High levels of catecholamines are myotoxic but the relative amounts of apoptosis and necrosis have not been established in vivo in cardiac and skeletal muscles. Immunohistochemistry was used to detect and quantify myocyte-specific necrosis (myosin antibody in vivo) and apoptosis (caspase-3 antibody in vitro) in the heart and soleus muscles of male Wistar rats that had received single subcutaneous injections of isoprenaline over the range 1 µg to 5 mg kg^-1 BW. Peak myocyte apoptosis occurred 3-6 h after, and necrosis 18 h after, a single injection of 5 mg kg^-1 BW isoprenaline in vivo. In the heart myocyte death was mediated through the ₁-adrenergic receptor whereas myocyte death in the soleus muscle was mediated through the ₂-adrenergic receptor. Cardiomyocyte death was heterogeneously distributed throughout the heart, being greatest in the LV subendocardium and peaking close to the apex, but with significantly more necrosis than apoptosis. Extensive co-localization of caspase-3 and myosin labeling was found in the myocytes of both the heart and slow-twitch soleus muscle. This, together with similar spatial distributions and responses to catecholamine doses suggests that, either caspase-3 activation occurs in necrotic as well as apoptotic myocytes, or that a large proportion of apoptotic myocytes progress to secondary necrosis in vivo.

Key Words: Histochemistry, Isoprenaline, Myocyte

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