Ultrastructural alterations in skeletal muscle of pigs with acute monensin myotoxicosis.
Large doses of monensin, a Na+-selective carboxylic ionophore, produce polyfocal, monophasic necrosis of skeletal muscle, with Type I fiber selectivity, in swine. For a study of the sequential ultrastructural alterations in affected skeletal muscles, 14 weanling pigs were given 40 mg monensin/kg body weight and were euthanatized 1, 2, 4, 8, and 16 days later. Myotoxicosis and myoglobinuria were apparent clinically. At necropsy, white, dry areas of necrosis were present in the muscle masses of the anterior and posterior thigh, shoulder, and loin. Two patterns of skeletal muscle necrosis were observed on Day 1, especially in Type I fibers. In fibers exhibiting the first of these patterns, the contractile material was disrupted, forming dense amorphous and filamentous clumps scattered within the persistent sheaths of external lamina (sarcolemmal tubes); the mitochondria were swollen and contained flocculent matrix densities, and the nuclei were pyknotic. Fibers showing the second pattern were uniformly dense, but their sarcoplasm was not disrupted. Sublethally injured fibers were also observed and showed focal myofibrillar lysis. On Days 2 and 4, the necrotic muscle had marked infiltration of macrophages in the interstitium and within sarcolemmal tubes. Rapid resolution of the fiber necrosis occurred by phagocytosis of the sarcoplasmic debris. Regeneration of affected muscles developed early following injury and progressed rapidly to complete restoration of the necrotic muscles without residual fibrosis. Regeneration was initiated on Day 1 by activation of satellite cells to form presumptive myoblasts; on Days 4 and 8 these cells showed evidence of fusion, forming myotubes to restore the necrotic fibers.
D000208:Acute Disease; D000818:Animals; D005260:Female; D005663:Furans / Q000633:toxicity*; D008297:Male; D008931:Mitochondria, Muscle / Q000187:drug effects / Q000648:ultrastructure; D008985:Monensin / Q000633:toxicity*; D009119:Muscle Contraction / Q000187:drug effects; D009132:Muscles / Q000473:pathology / Q000502:physiology / Q000648:ultrastructure*; D009135:Muscular Diseases / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology; D009336:Necrosis; D012038:Regeneration; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000648:ultrastructure; D013552:Swine
D005663:Furans; D008985:Monensin