Exeriences with isoprenaline induced myocardial necrosis in the rat

An attempt has been made to quantify myocardial lesions produced in the rat by isoprenaline for use as a model to assess possible incremental effects of environmental and dietary factors. This was initially made difficult by variation in the cardiotoxicity of different samples of isoprenaline. Investigation of these samples failed to reveal the basis for the differences. Active preparations have, however, produced profound changes both clinically and pathologically. The earliest light-microscopic changes both clinically and pathologically. The earliest light-microscopic change was loss of fuchsinophilia of fibres in sections stained by the picro-Mallory technique. By 24 hr obvious necrosis, fragmentation and lysis of the fibres had occurred. Treatment of frozen sections to demonstrate succinate dehydrogenase showed early changes in the character of formazan, suggesting the possibility of a transient alteration in the hydrogen transport system. By 48 hr, this is reversed except in those fibres undergoing necrosis where there is a complete loss of formazan. This contrast in staining between normal and necrotic fibres constitutes the basis for quantification which has been carried out by point counting. The results show some differences in the amount of myocardial necrosis between different batches of animals but relatively small differences within individual batches, suggesting that the introduction of additional variants into the system should be capable of producing clear cut results.