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1084 SECTION | XVI Feed and Water Contaminants

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FIGURE 78.7 Early necrotic focus in the left ventricle of a gelding
that died 20 h following gavage with 2.5 mg monensin/kg body weight.
Necrotic muscle fibers have sparse infiltration of neutrophils and lym-
phocytes. H&E. Original magnification 364.

FIGURE 78.6 Diffuse pallor in cross-sections of the heart from the
same mare described in Fig. 78.5 legend.

At necropsy, cutting the ventricular and thigh muscles
transversely often shows the diffuse pallor of myonecrosis
induced by toxic levels of ionophores. Skeletal muscle
lesions may be quite severe in sheep, pigs and dogs, moder-
ate in cattle and minimal to slight in horses. For this reason,
myoglobinuria, evidenced by red urine, has been observed
FIGURE 78.8 Larger foci of myofiber necrosis with contraction bands
in pigs, sheep and dogs but not in cattle or horses.
in the interventricular septum from a horse euthanized 72 h following a
single oral dose of 1.65 mg monensin/kg body weight given by gavage.
More cellular infiltrates with lymphocytes, macrophages, and few eosi-
Histopathologic Findings nophils are present. H&E. Original magnification 310.

Target organs damaged by toxic doses of monensin and
other ionophores were identified to include the heart and Focal swelling, fragmentation, loss of axons and formation
skeletal muscles in all species studied (Todd et al., 1984; of digestion chambers filled with macrophages were
Van Vleet et al., 1991; Dowling, 1992; Novilla, 2004). In observed in both sensory and motor nerves, and there was
addition, neurotoxic effects have been reported for lasalo- vacuolation with swelling, degeneration and fragmentation
cid (Shlosberg et al., 1985; Safran et al., 1993), narasin of myelin sheaths and axons in the spinal cord.
(Novilla et al., 1994) and salinomycin (Van der Linde- The most important change is a toxic myopathy char-
Sipman, 1999). The development of muscle lesions varies acterized by focal areas of degeneration, necrosis and
among species. The heart is primarily affected in horses, repair in cardiac and skeletal muscles with a variable
skeletal muscle in pigs and dogs, and there is about equal inflammatory component (Novilla, 1992; Van Vleet et al.,
tissue predilection in rats, chickens and cattle. Morphologic 1991). Muscle lesions are similar to those described for
effects include degeneration, necrosis and repair of cardiac compound A204, the first polyether antibiotic tested at
and skeletal muscle fibers with a variable inflammatory Lilly Research Laboratories (Todd et al., 1984). Doses
component and secondary lesions of CHF. Neuropathic and time factors influence the severity and distribution of
changes occurred in peripheral nerves and the spinal cord. lesions in ionophore toxicosis (Figs. 78.7 and 78.8).