Ultrastructural alterations in allylamine-induced cardiomyopathy. Early lesions

Ultrastructural studies were made of the early changes induced in left ventricular myocardium by allylamine given to rats either in drinking water (10.7 mM for 1 to 7 days) or by gavage (100 mg. per kg. per day for 1 or 2 days). Rats on the drinking water protocol developed myocardial alterations evident by light and electron microscopy within 2 days; those given allylamine by gavage developed lesions after 24 hours. The earliest alteration consisted of interstitial edema and 'activation' of interstitial cells possessing an oblong shape, abundant rough endoplasmic reticulum, occasional lysosomes, a prominent Golgi apparatus, few mitochondria, and large irregular nuclei (often with a typical nitschkow' morphology). Mitoses of these interstitial cells were frequent. Mitoses were also observed in endothelial cells. Acute myocardial necrosis, which developed after 6 days of the drinking water protocol or one gavage dose, was characterized by focal myofibrillar degeneration with lipid droplet accumulation and Z-line distortion and dissolution, especially prominent in areas of intercellular junctions. These focal lesions coalesced to involve whole myocytes with severe myofibrillar degeneration and contraction band necrosis. Mitochondria of severely altered cells were swollen and contained dense inclusions. Nuclei had prominent nucleoli and, in severely necrotic cells, clumped and irregular chromatin. Large areas of necrotic myocardium showed extravasated red blood cells and minimal intra- and extracellular deposition of fibrin. Vascular necrosis or thrombosis was not seen. A prompt inflammatory infiltrate was composed predominantly of macrophages invading necrotic myocytes, with occasional polymorphonuclear neutrophilic and eosinophilic leukocytes.