Accidental monensin sodium intoxication of feedlot cattle

Of 1,994 yearling and 2-year-old cattle in a winter feeding program, 117 died within 42 days of being fed toxic amounts of monensin sodium in a liquid protein supplement. Death losses commenced on the third day after ingestion of a toxic amount in the feed. Clinical signs in cattle that died in less than 9 days included anorexia, pica, diarrhea, depression, mild hindlimb ataxia, and dyspnea. Gross necropsy findings in cattle dying in the acute phase of the illness included hydrothorax, ascites, and pulmonary edema, as well as petechial hemorrhages, edema, and yellow streaking in skeletal and cardiac muscle. Cattle dying after 9 days had gray streaks in heart and skeletal muscle, generalized ventral edema, enlarged, firm, bluish discolored liver, and enlarged heart. Microscopic changes in cattle dying in the acute phase (less than 9 days) consisted of pulmonary edema, congestion, and hemorrhage. Cardiac and skeletal muscle had localized areas of edema, hemorrhage, and coagulative necrosis. In cattle dying after 9 days of illness, the changes included lymphocytic infiltration, sarcolemmal nuclear proliferation, and fibrosis in skeletal and cardiac muscle. Lungs contained increased alveolar macrophages and a few neutrophils. Centrilobular necrosis and mild fibrosis were found in the liver. Changes varied somewhat according to the area of heart or skeletal muscle that was affected. Active muscles, eg, those in the heart ventricles and diaphragm, were altered most severely. Intoxication appeared to be a result of sedimentation of monensin in the molasses carrier to give remarkable concentrations of the substance at the bottom of the holding tank.     

Pathologic changes associated with experimental lasalocid and monensin toxicosis in cattle

The acute toxicity of lasalocid and monensin was studied in 36 Holstein steers. The cattle were given (orally) a single dosage of lasalocid (1, 10, 50, or 100 mg/kg of body weight) or monensin (25 mg/kg of body weight) or rice hulls. Animals were observed once a day until they died or were euthanatized at 32 days after the dose was given. All cattle were necropsied. Heart, kidney, adrenal gland, liver, spleen, pancreas, lungs, brain, sciatic nerve, skeletal muscle, small intestine, large intestine, and rumen tissue sections, stained with hematoxylin and eosin, were studied microscopically. Lasalocid was lethal at dosages of 50 and 100 mg/kg, and monensin was lethal at the dosage given (25 mg/kg). Cattle dying of lasalocid and monensin toxicoses had gross and microscopic lesions consistent with cardiomyopathy. Dilated heart or petechial and ecchymotic hemorrhages were observed with both drugs. Microscopically, multifocal areas of myocyte necrosis were observed. Those cattle that died within 3 days of dosing with either drug had a marked degranulation of pancreatic acinar cells. Changes were not observed in any other tissues.     

Light and electron microscopic changes in cardiac and skeletal muscle of sheep with experimental monensin toxicosis

Monensin toxicosis was induced in lambs by either a single oral dose of 12 mg/kg or six daily doses of 8 mg/kg. Clinical signs of toxicosis consisted of depression, dyspnea, stiffness of gait, reluctance to move, and recumbency. Serum creatine phosphokinase activity was increased. Samples of skeletal and cardiac muscle were obtained over a six-day period and examined by light and electron microscopy. Light microscopic changes in cardiac and skeletal muscles consisted initially of vacuolation and intracellular edema of muscle cells followed by segmental necrosis. Interstitial fibrosis was present on days 5 and 6 postexposure. Muscle fiber necrosis was more severe in skeletal than cardiac muscles and most severe in sheep given 8 mg/kg of monensin daily. Macrophages were seen only in areas of severe necrosis. The earliest ultrastructural change was severe swelling of mitochondria. Secondary changes consisted of lipid accumulation and myofibrillar alterations. Myoblast proliferation was present as early as four days after initial exposure to monensin.     

Skeletal muscle lesions in turkeys associated with the feeding of monensin

The feeding of monensin as a coccidiostat in three separate flocks of turkeys was associated with increased mortality, posterior paresis, and a skeletal muscle myopathy. Mortality attributed to the disease was 1.65%, 1.86%, and 4.80% in the three flocks. Samples of monensin-supplemented feed fed to the flocks when showing clinical signs contained 88, 85, and 106 g/ton of complete feed, respectively. Clinically, the turkeys showed posterior paresis, inability to rise, incoordination, reluctance to move, and leg trembling and weakness. Necropsy findings included consistent lesions of pallor within the type I muscles of the legs, wings, and backs. Microscopic lesions included myofiber degeneration and necrosis with massive cellular proliferation interpreted as sarcolemmal nuclei proliferation. Occasional axonal degeneration with loss of axons was present in peripheral nerves embedded in the damaged musculature. In the youngest flock, multifocal areas of acute coagulation necrosis of the myocardium were also present. These outbreaks occurred following intake of monensin in the complete feed at levels considered therapeutic; however, no associated predisposing clinical condition, drug/toxin interaction, or excessive monensin levels in the feed could be demonstrated.     

Monensin toxicosis in water buffaloes (Bubalus bubalis).

The consumption of monensin-containing feed resulted in deaths of water buffaloes from a feedlot in which cattle and buffaloes were kept together. The monensin formulation was recommended only for use in cattle. Anorexia, muscular weakness, dyspnea, and recumbency were the major clinical findings. The most significant gross lesions were focal pale areas in semitendinosus and semimembranosus muscles, in which segmental necrosis of myofibers was seen microscopically. To compare susceptibilities of species to monensin, 3 bovine calves and 3 buffalo calves were orally dosed. At 5, 7.5, and 10 mg/kg of monensin, only the buffaloes became ill and died. Clinical signs initiated 18-20 h postdosing and were comparable to those from field cases. Gross changes consisted of ascites, hydrothorax, hydropericardium, hepatomegaly, and focal pale areas in the myocardium and to a lesser degree in semitendinosus and semimembranosus muscles. Histopathological changes also resembled those from the field cases, but were especially pronounced in the myocardial cells. The hypothesis that buffaloes could have a lower tolerance to monensin than cattle has been supported by experimental cases.     

Comparative toxicology of monensin sodium in laboratory animals

The toxicology of monensin has been studied in several laboratory animal species. There was considerable species variation in acute oral LD50 values. The consistent signs of acute toxicity were: anorexia, hypoactivity, skeletal muscle weakness, ataxia, diarrhea, decreased weight gain and delayed deaths. The 3-mo study in rats fed diets containing 0, 50, 150 or 500 ppm monensin resulted in no effects at the lowest dose level, slight reduction of body weight gain in the middle-dose group and severe depression in body weight gain, skeletal and cardiac lesions, and deaths in the highest dose group. The 3-mo study in dogs given daily oral doses of 0, 5, 15 or 50 mg/kg monensin resulted in no effects at the lowest dose level. Dogs in the 15 and 50 mg/kg groups developed, during test wk 1 to 4, anorexia, weakness, ataxia, labored respiration, body weight loss, increased serum muscle enzyme values, severe skeletal muscle degeneration and necrosis with less severe heart lesions and deaths. Mice fed diets containing 0, 37.5, 75, 150 or 300 ppm monensin for 3 mo had reduced body weight gain in all test groups but no other physical signs. Serum creatine phosphokinase (CPK) values were increased in mice in the two highest dose groups and minimal heart lesions were found in the highest dose group. Dogs given daily oral doses of 0, 1.25, 2.5, 5 or 7.5 mg/kg monensin for 1 yr survived with no evidence of toxicity in the two lowest dose groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of pretreatment with selenium-vitamin E on monensin toxicosis in cattle

Ten female beef calves weighing approximately 180 kg each were allotted to 2 groups of 5 each before they were given (orally) monensin (50 mg/kg of body weight). In group A, the calves were given (IM) a commercial selenium-vitamin E (Se-E) preparation (0.25 mg of Se and 17 IU of alpha-tocopherol/kg of body weight) at 72 and 24 hours before monensin was given. The calves in group B were injected at the 2 times with isotonic saline solution. Clinical signs of monensin toxicosis, including lethargy and recumbency, appeared on day 2 in the calves given the Se-E pretreatment, compared with the onset on day 1 in the saline solution-pretreated calves. All calves in the 2 groups died, but mean survival time was longer in group A (4.4 vs 2.2 days). Lesions of monensin toxicosis were myocardial necrosis, skeletal myonecrosis, pulmonary congestion, and rumenitis. The frequency and severity of the lesions were similar for both groups of calves. The results of the present study indicate that Se-E pretreatment modifies the development of monensin toxicosis in cattle.     

Monensin toxicosis in 2 sheep flocks

Several lambs in 2 sheep flocks died suddenly and others were examined for generalized weakness and dyspnea. Postmortem findings were suggestive of degenerative myocardial and skeletal muscle myopathy, which was confirmed histologically. Feed analysis revealed toxic levels of monensin and ionophore toxicosis was diagnosed.     

An outbreak of perirenal oedema syndrome in cattle associated with ingestion of pigweed (Amaranthus hybridus L.)

Forty seven of 150, 15-month-old long weaners died of an acute renal disease syndrome following introduction into an old maize field with a heavy stand of Amaranthus spp. The clinical syndrome was characterised by sudden onset neurological disease with ataxia and recumbency. Subcutaneous oedema, ascites and perirenal oedema with urine odour were the major gross necropsy findings. Renal histopathology revealed marked coagulative renal tubular necrosis of the proximal and distal straight tubules with intertubular haemorrhage. Acute renal failure and perirenal oedema has been described in cattle, pigs, horses and sheep associated with the ingestion of A. hybridus L. and A. retroflexus L. This perirenal oedema syndrome has been widely reported in the Americas, while in South Africa intoxication with the amaranths has only previously been associated with nitrate and possibly oxalate poisoning in cattle.     

Acute monensin toxicosis in sheep: light and electron microscopic changes

Monensin was administered orally to 3 sheep at dosages of 12 (the LD50), 16, and 24 mg/kg of body weight, respectively. Clinical signs of monensin toxicosis were observed in the sheep in 24 to 36 hours of administration. Clinical signs included CNS depression, anorexia, diarrhea, and stiffness. Increased serum creatine phosphokinase and aspartate aminotransferase activities identified possible muscle damage. Sheep were euthanatized at 54 hours after dosing; at necropsy, there were skeletal muscle hemorrhages, pale myocardium, and pulmonary edema. Ultrastructural lesions were in the liver, diaphragm, and myocardium; diaphragm and myocardium were most severely affected. Mitochondrial swelling and cristolysis, swollen sarcoplasmic reticulum, and disruption of myofibrillar architecture were prominent. These ultrastructural changes are consistent with the hypothesis that monensin causes muscle cell necrosis due to its ionophorous properties and disruption of cellular Na+:Ca2+ balance. It is proposed that this upset of normal ionic processes allows increased intracellular calcium, which directly leads to the functional and structural mitochondrial changes observed.     

一日龄大通牦牛和平原黄牛骨骼肌显微结构的比较

为了探讨1日龄大通牦牛骨骼肌组织学特点及对低氧的适应,以平原黄牛为对照,利用光镜和计算机图像分析系统测定骨骼肌肌纤维直径、表面积密度;通过透射电镜比较骨骼肌线粒体的面数密度、面积密度、体积密度、平均体积等结构参数。结果显示,1日龄大通牦牛骨骼肌肌纤维直径显著细于1日龄平原黄牛,表面积密度明显大于平原黄牛,差异极显著(P<0.01);1日龄大通牦牛骨骼肌细胞中线粒体平均体积小于1日龄平原黄牛,并具有极显著差异(P<0.01);而1日龄大通牦牛骨骼肌细胞中线粒体体积密度、面积密度、面数密度均大于1日龄平原黄牛,且差异极显著(P<0.01)。以上结果表明,大通牦牛通过增加骨骼肌线粒体面数密度、面积密度、体积密度,降低线粒体平均体积来提高其在低氧环境中对氧的利用,并且在长期进化中形成了肌纤维直径小,表面积密度大的组织学特点。     

Correlation of Serum Cardiac Troponin I and Myocardial Damage in Cattle with Monensin Toxicosis

Background: Cardiac troponin I (cTnI) is used as a biomarker of myocardial injury in people and small animals. Little is known about the diagnostic use of cTnI in cattle.
Hypothesis: Serum cTnI correlates to myocardial function and histopathologic lesions in cattle with monensin-induced myocardial injury.
Animals: Ten healthy cows.
Methods: Experimental study. Animals received 1 dose of monensin PO; 30 mg/kg (n = 1) or 40 mg/kg (n = 1) (Group A) or 50 mg/kg monensin (n = 8) (Group B) of body weight. Repeated measurements were performed of serum cTnI, biochemistry, and ECG and echocardiography until study termination at 80 (Group A) and 144 hours (Group B) after dosing. Semiquantitative histopathologic examinations of the heart were performed in each cow. A scoring system with regard to the magnitude of myocardial injury was established and a total heart score was compared with maximum cTnI concentration measured after monensin administration. Five hearts from healthy cows served as controls.
Results: Increased cTnI (>0.07 ng/mL) was found in 9/10 cows. cTnI was significantly associated with left ventricular shortening fraction ( r ²= 0.51; P = .02) and myocardial histopathologic lesion score ( r ²= 0.49; P = .021). All cows (n = 7) with evidence of myocardial necrosis had a cTnI concentration ≥ 1.04 ng/mL.
Conclusion and Clinical Importance: cTnI is related to myocardial necrosis and severity of myocardial damage in cattle with monensin toxicosis. cTnI could become a useful diagnostic tool in the noninvasive assessment of myocardial injury in cattle with naturally occurring cardiac disease.     

Myocardial toxicity in a group of greyhounds administered ractopamine

Ractopamine, a synthetic β(2)-adrenoceptor agonist, is widely used as a feed additive in the United States to promote a reduction in body fat and enhance muscle growth in cattle, pigs, and turkeys. It has the potential for illegal use in show and racing animals because it may affect performance via its β-adrenergic agonist properties or anabolic activities. Nine greyhounds were orally administered 1 mg/kg of ractopamine to investigate the ability to detect the drug in urine. Postdosing, 7 of 9 dogs developed cardiac arrhythmias and had elevated troponin levels indicating myocardial damage. One dog necropsied 4 days postdosing had massive myocardial necrosis, mild to focally moderate skeletal muscle necrosis, and widespread segmental arterial mediolysis. A second dog necropsied 17 days postdosing had mild myocardial necrosis and fibrosis. Scattered arteries exhibited segmental medial and perimedial fibromuscular dysplasia. This is the first reported case of arterial, cardiac, and skeletal muscle damage associated with ractopamine.     

大通牦牛骨骼肌胶原纤维含量增龄性变化特点

为探讨高原牦牛随着年龄的增长,骨骼肌中胶原纤维含量的变化规律及其对高原低氧环境的适应性。本研究以不同生长期大通牦牛作为研究对象,并以平原黄牛作对照,对生长发育过程骨骼肌中胶原纤维含量变化进行测量。结果表明,大通牦牛骨骼肌中胶原纤维含量从1日龄的一个相对低点,到30日龄迅速增长至一个峰值,然后再逐渐下降,至成年时,胶原纤维含量降至最低。平原黄牛骨骼肌中胶原纤维含量1日龄处于峰值,与其他年龄组差异显著(P<0.05),而随着年龄的增长,胶原纤维含量下降,30日龄、180日龄和成年组差异不显著(P>0.05);相同发育阶段大通牦牛骨骼肌中胶原纤维含量均高于平原黄牛胶原纤维含量,且差异显著(P<0.05)。结果提示,大通牦牛骨骼肌中胶原纤维具有适应高原环境的组织学特点,但也在个体发育过程中,不断发生改变,以满足机体生长发育的需要和对外界环境的适应。     

Pathology of experimentally-induced, acute toxoplasmosis in macropods

SUMMARY Thirteen Tammar wallabies (Macropus eugenii) were dosed orally with 500, 1000 or 10 000 oocysts of Toxoplasma gondii, as part of a vaccination trial. Eleven animals died of acute toxoplasmosis 9 to 15 days after challenge. The lesions were similar in all animals, consisting of foci of necrosis and inflammation in the intestines, lymphoid tissue, adrenal cortex, heart, skeletal muscle and brain, and severe generalised pulmonary congestion and oedema. Free and intracellular tachyzoites of Toxoplasma were associated with the lesions. The remaining 2 animals had shown no signs of disease when euthanased four months after challenge. Small, focal, non-suppurative inflammatory lesions were seen in brain, heart and skeletal muscle of these animals and chronic Toxoplasma infection was confirmed by mouse inoculation.     

Effect of monensin on the performance of cattle on pasture or fed harvested forages in confinement

Three series of trials were conducted to evaluate the effect of monensin on the growth performance of cattle. Twenty-four trials were conducted to evaluate the addition of monensin at 200 mg/d to limited quantities of supplemental concentrate for growing cattle grazing pastures. The pastures ranged from dormant end-of-the-season grasses and crop residues to lush green pastures, and were located in several different states. Pasture plus supplement supported gains of control cattle (without monensin) of .24 to .96 kg, with an average of .56 kg/d. The addition of 200 mg monensin to the supplement increased daily gain in all 24 trials by an average of .09 kg daily (+16.3%). Eleven trials were conducted with monensin and energy supplements fed at .907 kg.- head-1 X d-1 to growing cattle grazing growing, nondormant pastures for an average period of 117 d. Each trial was designed to compare the performance of unsupplemented cattle, cattle fed a supplement and cattle fed a supplement with monensin. Cattle on pasture gained .50 kg daily. Supplement feeding increased average daily gain by .09 kg and the addition of monensin to the supplement further increased gain by .09 kg, for a total increase of .18 kg (34.2%). The efficiencies with which supplemental feed was converted to extra gain (kg supplement/kg gain) for the supplement-only and the monensin treatment groups were 10.1:1 and 5.0:1, respectively. In a series of 12 trials, monensin was added at a level of 33 mg/kg air-dry diet to limited quantities of supplemental feed for cattle fed harvested forages in confinement. All trials compared monensin feeding with a nonmedicated control treatment. Hay was fed in 8 of the 12 trials, fresh-cut green-chop in two trials and ensiled corn stover and ensiled milo stover in one trial each. Monensin reduced feed intake by -3.1%, improved average daily gain by .09 kg (+14.4%) and improved feed efficiency by 15.3%.     

Monensin toxicity in cattle

Monensin has been tested to determine its toxicity and safety in cattle. Single dose acute toxicity and signs associated with toxicity were determined by oral gavage, 7-d oral gavage and feeding experiments with high concentrations of monensin in feed. Oral feeding studies indicated a near complete anorexia resulting from intake of sublethal amounts of monensin. In these cases, cattle recovered from the insulting dose and resumed growth and feed intake. In long-term chronic feedlot, pasture supplement, and reproduction safety studies conducted with monensin administered in the feed, the high concentrations caused cattle to show signs of mild monensin intoxication. Mortality resulted from feeding groups of cattle large quantities of monensin in small quantities of feed. Furthermore, these studies have demonstrated no detrimental effects upon reproduction. Collectively, these studies indicate that the greatest risk of intoxication occurs when cattle first receive a feed containing monensin. Mixing errors and misuse situations under actual use conditions have resulted in cases of cattle mortality. In most cases the mortality was predictable based upon the exposure in controlled studies.     

Influence of monensin on the performance of cattle

Performance data on nearly 16,000 head of cattle that were used in trials to document effects of monensin on feedlot cattle were summarized. Cattle fed monensin-containing diets gained 1.6% faster, consumed 6.4% less feed and required 7.5% less feed/100 kg gain than cattle fed control diets. Monensin resulted in the greatest improvement in feed/gain at 2.9 Mcal metabolizable energy (ME)/kg diet dry matter (DM). Within the range of monensin concentrations used in the trials that were summarized (31.8 +/- 7.5 mg/kg DM), high monensin concentrations did not improve feed/gain over that obtained with lower concentrations. Carcass characteristics were not significantly influenced by monensin. Responses of cattle to monensin and implants were additive. Energy metabolism data suggested that monensin improved digestibility of DM, reduced fasting heat production and increased dietary net energy maintenance (NEm) values more than it increased net energy gain (NEg) values. Data showing the response of cattle to monensin when fed various dietary protein concentrations or sources of supplemental N suggested that monensin had a protein sparing effect. Monensin has also been shown to reduce lactic acid production, aid in the control of coccidia and bloat and to be toxic to face and horn fly larva in feces of monensin-fed cattle. In pasture trials, monensin improved daily gains. When fed to beef cows, monensin reduced amounts of feed required to maintain cow weight.     

Field observations during the bluetongue serotype 8 epidemic in 2006. I. Detection of first outbreaks and clinical signs in sheep and cattle in Belgium, France and the Netherlands

Starting August 2006, a major epidemic of bluetongue (BT) was identified in North-West Europe, affecting The Netherlands, Belgium, Germany, Luxemburg and the North of France. It was caused by BT virus serotype 8 (BTV-8), a serotype previously unknown to the European Union (EU). In this outbreak, the virus caused clinical disease in a few individual animals within cattle herds, whereas overt clinical disease was usually restricted to sheep. Investigations in Belgium suggested that the first clinical signs of BTV-8 appeared mid July 2006 in a cattle herd, while the first suspicion of a BT-outbreak in Belgium was reported on 17 August 2006. In the first 10 BTV-8 outbreaks in the Netherlands, the owners indicated that the first clinical signs started approximately 12-17 days before a suspicion was reported to the veterinary authorities via a veterinary practitioner. In BTV-8 affected sheep flocks, erosions of the oral mucosa, fever, salivation, facial and mandibular oedema, apathy and tiredness, mortality, oedema of the lips, lameness, and dysphagia were among the most frequent clinical signs recorded. The most prominent clinical signs in BTV-8 affected cattle herds were: crusts/lesions of the nasal mucosa, erosions of lips/crusts in or around the nostrils, erosions of the oral mucosa, salivation, fever, conjunctivitis, coronitis, muscle necrosis, and stiffness of the limbs. Crusts/lesions of nasal mucosa, conjunctivitis, hyperaemic/purple coloration and lesions of the teats, and redness/hypersensitivity of the skin were relatively more seen on outbreak farms with cattle compared to sheep. Mortality, oedema of the head and ears, coronitis, redness of the oral mucosa, erosions/ulceration of tongue mucosa, purple coloration of the tongue and tongue protrusion and dyspneu were relatively more seen on outbreak farms with sheep compared to cattle.     

Review of monensin toxicosis in horses

Results of experimental studiesindicate that horses are much more sensitive to monensin toxicity than cattle. Single dose studies by gavage with mycelial monensin resulted in an estimated LD₅₀ of 1.38 mg/kg of body weight. Subacute feeding studies indicate that horses will tolerate the highest use level for cattle of 33 ppm without any evidence of toxicity. Evidence of intoxication was apparent with the highest use level for chickens of 121 ppm.In pasture supplement studies, horses ate supplement containing high levels of nonensin upon initial exposure which resulted in toxicity and/or death. Following initial exposure to sublethal levels, consumption of monensin containing supplements was negligible.The clinical signs of toxicity includedpartial to complete anorexia, colicky pain, sweating and tachycardia, uneasiness, polyuria, progressive ataxia, recumbency with frequent attempts to rise and thrashing of the limbs followed by death. Examination at necropsy of animals that die soon after initial exposure to monensin may show no significant lesions, otherwise hemorrhage and pale areas in the heart with transudation into body cavities may be seen. Evidence of degenerative cardiomyopathy and congestive heart failure may be observed on histopathologic examination. Increased activities of muscle origin enzymes may also be found.The results of controlled studiesand evidence from field reports indicated that the greatest risk of intoxication was upon initial exposure to feed or supplement containing monensin. Feed mistakes and mixing errors were the two most common causes of monensin toxicity in field cases.