| A guinea pig model was used to assess the effect of cyclopiazonic acid (CPA) on skeletal muscle, characterize the lesion, determine the type of fiber predominantly involved, define the pathogenesis of the lesion, and determine whether or not the intoxication could be assessed using clinical pathology. Muscle from animals given CPA for 1, 2, 3 or 4 days was examined using light and electron microscopy. Serum levels of muscle specific enzymes began to increase within 2 days, and were greatly elevated by 4 days. Using histochemistry and electron microscopy techniques to identify muscle fibers, type IIa fibers were identified as being the primary fibers involved in the intoxication.;Mitochondria and sarcoplasmic reticulum were swollen in degenerate fibers. Sarcolemma was focally disrupted or absent in necrotic fibers. Myofiber hypercontraction and myofibril fragmentation were a significant component of this toxic myopathy. Many of the lesions were felt to be compatible with toxicity due to excess free calcium within the myofiber.;Vitamin E and selenium concentrations were determined in livers of guinea pigs given CPA. Although amounts of both compounds were increased in surviving guinea pigs, the difference was not significant compared to controls. One animal that died did have decreased amount of both vitamin E and selenium compared to treated animals, but not controls. |
