Effects of feeding aspirin and supplemental vitamin E on plasma concentrations of 3-methylindole, 3-methyleneindolenine-adduct concentrations in blood and pulmonary tissues,lung lesions,and growth performance in feedlot cattle

OBJECTIVE: To evaluate the effect of feeding aspirin and supplemental vitamin E on growth performance, lung lesions, plasma concentrations of 3-methylindole (3MI), and 3-methyleneindolenine (3MEIN)-adduct concentrations in blood and pulmonary tissues of feedlot cattle. ANIMALS: 256 crossbred steers; 64 cattle were used in experiment 1 and 192 cattle were used in experiment 2. PROCEDURES: A 2 X 2 factorial design was used for each experiment. Treatment factors were aspirin (0 or 3 g daily) and vitamin E (200 or 1,500 IU daily). Steers were housed in pens (8 steers/pen). Steers were slaughtered on days 59 and 138 for experiments 1 and 2, respectively. Lungs were grossly evaluated. 3MEIN-adduct concentrations were determined, and blood and pulmonary tissues. RESULTS: Treatment was not associated with improvement or adverse effects on weight gain, dry-matter intake, or feed efficiency in experiment 2. In experiment 1, 36 of 63 (57.1%) steers had lung lesions. Lesions were not associated with treatment or concentrations of 3MI and 3MEIN-adduct. Plasma 3MI concentration and concentrations of 3MEIN-adduct in blood and pulmonary tissues were 3.11 microg/mL, 0.51 U/microg of protein, and 0.49 U/microg of protein, respectively. Aspirin was associated with increased blood concentrations of 3MEIN-adduct for diets that did not contain supplemental vitamin E. CONCLUSIONS AND CLINICAL RELEVANCE: Differences n performance of feedlot steers were not associated with treatment diet. It is possible that concurrent exposure of feedlot cattle to other factors typically associated with development of respiratory tract disease would affect these findings.     

Ruminal and plasma concentrations of 3-methylindole associated with tryptophan-induced pulmonary edema and emphysema in cattle.

Five Hereford cows were given an intraruminal dose of L-tryptophan (0.35 g/kg of body weight), and 2 cows were used as controls. Of the 5 treated cows, 3 developed clinical signs of interstitial pul monary edema, and emphysema and severe pulmonary lesions were seen at necropsy after 96 hours. Another cow developed moderate clinical signs and pulmonary lesions, and the remaining cow had few clinical signs and mild pulmonary lesions. The severity of clinical signs in each cow was related to the severity of pulmonary lesions at necropsy. The 3-methylindole (3MI) was present in ruminal fluid and plasma within 6 hours after administration of tryptophan, and the concentrations increased to 3.0 and 9.0 mug/ml within 12 to 24 hours. Severity of pulmonary lesions was related to maximal concentration and duration of 3MI in the plasma. At necropsy, gross lesions were characterized by diffuse, pulmonary edema and interstital emphysema; and the lungs were dark red, firm, and heavier than normal. Predominant microscopic changes included accumulation of proteinaceous residue, hypertrophy and hyperplasia of alveolar lining epithelium, thickening of alveolar septums, and emphysematous thickening of interstitial tissues. These changes were similar to previously reported 3MI-induced pulmonary lesions. The presence of 3MI in ruminal fluid and plasma after administration of tryptophan and the relationship between concentration of 3MI and severity of clinical signs indicate that 3MI is the principal metabolite of ruminal fermentation which leads to the development of acute pulmonary edema and emphysema in cattle given tryptophan.     

Evaluation of the ability of orally administered aspirin to mitigate effects of 3-methylindole in feedlot cattle

OBJECTIVE: To evaluate the ability of orally administered aspirin to mitigate 3-methylindole (3MI)-induced respiratory tract disease and reduced rate of gain in feedlot cattle. ANIMALS: 244 beef cattle. PROCEDURE: In a masked, randomized, controlled field trial, calves were untreated (controls) or received a single orally administered dose of aspirin (31.2 g) on entry into a feedlot. Serum 3MI concentrations were measured on days 0, 3, and 6. Rumen 3MI concentration was measured on day 3. Cattle were observed daily for clinical signs of respiratory tract disease. Lungs were evaluated at slaughter for gross pulmonary lesions. RESULTS: Mean daily gain (MDG) in cattle treated with aspirin, compared with control cattle, was 0.06 kg greater in the backgrounding unit and 0.03 kg greater for the overall feeding period. Neither serum nor rumen 3MI concentrations appeared to modify this effect. Cattle treated with aspirin were more likely to be treated for respiratory tract disease. Mortality rate, gross pulmonary lesions, and serum and rumen 3MI concentrations were similar between groups. Increased rumen 3MI concentration was associated with a small difference in risk of lung fibrosis. CONCLUSIONS AND CLINICAL RELEVANCE: Cattle given a single orally administered dose of aspirin on feedlot entry had higher MDG in the backgrounding unit and for the overall feeding period, but this finding could not be attributed to mitigation of effects of 3MI. This may have been influenced by low peak 3MI production and slow rates of gain.     

Association of 3-methyleneindolenine, a toxic metabolite of 3-methylindole, with acute interstitial pneumonia in feedlot cattle

OBJECTIVE: To compare concentrations of 3-methyleneindolenine (3MEIN) in lung tissues obtained from feedlot cattle that died as a result of acute interstitial pneumonia (AIP) and cattle that died as a result of other causes and to compare blood concentrations of 3MEIN in healthy feedlot cattle and feedlot cattle with AIP. STUDY POPULATION: Blood samples and lung tissues collected from 186 cattle housed in 14 feedlots in the western United States. PROCEDURE: Samples of lung tissues were collected during routine postmortem examination and submitted for histologic, microbiologic, and toxicologic examination. Blood samples were collected from cattle with clinical manifestations of AIP and healthy penmates. Histologic diagnoses were categorized as AIP, bronchopneumonia (BP), control samples, and other disorders. Concentrations of 3MEIN were determined in lung tissues and blood samples, using an ELISA. RESULTS: Concentrations of 3MEIN in lung tissues were significantly greater in AIP and BP samples, compared with control samples. Absorbance per microgram of protein did not differ between BP and AIP samples. Blood concentrations of 3MEIN were significantly greater in cattle with AIP, compared with healthy cattle or cattle with BP. Odds of an animal with AIP being a heifer was 3.1 times greater than the odds of that animal being a steer. CONCLUSIONS AND CLINICAL RELEVANCE: Increased pulmonary production of 3MEIN may be an important etiologic factor in feedlot-associated AIP.     

Laminitis-like changes in the claws of feedlot cattle

The purpose of this study was to observe and quantitate changes in the claws of two groups of feedlot cattle (calves and backgrounded yearlings) fed diets that varied in energy (73.5 or 78.5% TDN) and crude protein (11, 13, 15, 16, 17, or 19%) content. At slaughter, the thickness of sole horn and the prevalence of toe and heel hemorrhages were greater in calves than in yearlings (p<0.02). Feeding the high-energy ration increased the prevalence of toe and heel hemorrhages in calves (p<0.02) and heel hemorrhages in yearlings (p<0.02). In yearlings, rotation of the distal phalanx and ridging of the dorsal wall of the claw were the most prominent pathological features. Osteopathy of the apex of the distal phalanx occurred more frequently in calves than in yearlings (p<0.01). This study suggests that intensive feeding of beef cattle before they reach 14 months of age has a deleterious effect on digital health.     

Impairment of sympathetic pulmonary vasoconstriction by 3-methylindole in cattle

Sixteen Holstein cattle allotted into 4 groups (4 cattle/group) were each given a single oral dosage of 0.2 g of 3-methylindole (3MI)/kg of body weight. The groups were killed at 12, 24, 48, and 72 hours, respectively, after 3MI administration. Comparison of clinical signs, pathologic pulmonary lesions, and in vitro pulmonary artery responses to pharmacologic stimuli was made between the 4 treated groups and 8 control Holstein cattle of similar age. Clinical signs of pulmonary distress first appeared 8 to 12 hours after 3MI administration. After 20 hours, clinical signs included dyspnea, moderate depression, and a marked expiratory grunt. A partial remission of these clinical signs was seen between 30 and 45 hours after 3MI administration. After remission, the cattle had clinical signs of severe dyspnea and depression and expiratory grunts were more pronounced. Pathologic pulmonary lesions, including heavy rubbery lungs, dilated interlobular septae, and subplural air bullae characteristic of pulmonary edema and interstitial emphysema were observed. The lungs of treated cattle did not collapse when the thorax was incised at necropsy. In vitro pulmonary artery strips contracted dose dependently to norepinephrine (NE). Group I tissues (12 hours after 3MI administration) responded similarly to control samples. Group II tissues (24 hours after 3MI administration) had a significant inhibition (P less than 0.05) in response to NE stimulation as compared with controls.     

Aflatoxicosis in feedlot cattle

Aflatoxicosis was diagnosed in lightweight feedlot cattle fed aflatoxin-contaminated cottonseed or gin trash. Clinical signs of hepatic damage and death were recorded for more than 200 of the 14,000 animals in a feedlot. Aflatoxin concentration in feedlot products fed to these cattle ranged from 96 to 1,700 ng/g. Diagnosis was based on the correlation of characteristic microscopic liver lesions, high concentration of aflatoxin in cottonseed feed products, and isolation and detection of aflatoxin B1 and aflatoxin M1 in urine and liver from affected calves. This report describes a large-scale outbreak of aflatoxicosis and demonstrates the need for careful quality control of feed products susceptible to aflatoxin contamination.     

Physiological changes and digestive capabilities of newly received feedlot cattle.

Newly arrived feedlot calves undergo numerous stressors that result in 1) transient endocrine responses, 2) altered products of energy and protein metabolism, 3) changes in appetite and growth rate, 4) possible limited compromise of digestive and rumen function, and 5) a challenged immune system. The most consistent endocrine and metabolic responses to marketing, transport, and feedlot adaptation are seen with cortisol and epinephrine. In contrast to earlier work done with indirect in vitro gas production measurements, recent research has shown that the ruminal microbial population is able to effectively digest available substrate immediately following a calfs weaning, trucking, and 24 h of feed and water deprivation. Additionally, a period of feed and water deprivation up to 72 h coupled with 8 h of trucking does not reduce the concentration or total numbers of either the viable cellulolytic or total bacteria present in the rumen of newly weaned or feedlot-adapted calves. However, ruminal volume, DM, total weight of ruminal contents, and total protozoal numbers decrease as duration of feed deprivation increases. To compensate for the reduced DMI that occurs in the first 2 wk after arrival at the feedlot, increased nutrient density is needed to meet an animal's requirements for nutrients. Limited data suggest that newly arrived calves prefer a diet that is similar in moisture and texture to feeds with which they are familiar. Additionally, modification of the stress-associated behavior using trainer animals may improve the feed intake of newly received calves and may reduce calf morbidity.     

Effects of 3-methylindole production and immunity against bovine respiratory syncytial virus on development of respiratory tract disease and rate of gain of feedlot cattle

OBJECTIVE: To determine whether immunity against bovine respiratory syncytial virus (BRSV) mitigates the effects of 3-methylindole (3MI) on occurrence of bovine respiratory tract disease (BRD) and rate of gain in feedlot cattle. ANIMALS: 254 mixed-breed beef cattle. PROCEDURE: Cattle were randomly assigned to 1 of 3 groups at the time of arrival at the feedlot. One group was vaccinated with an inactivated BRSV vaccine, another was vaccinated with a modified-live BRSV vaccine, and the third was maintained as unvaccinated control cattle. On days 0 and 28, serum BRSV antibody concentrations were measured, using serum neutralizing and ELISA techniques. Serum 3MI concentrations were measured at feedlot arrival and 3 days later. Cattle were monitored for development of BRD. At slaughter, lungs were evaluated grossly for chronic lesions. RESULTS: Higher serum 3MI concentrations early in the feeding period were associated with lower mean daily gain. Control cattle were more likely to be treated for BRD after day 3, compared with cattle vaccinated with the modified-live BRSV vaccine. Humoral immunity against BRSV did not appear to modify the effect of 3MI on development of BRD or mean daily gain. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that abrogating the effects of 3MI and BRSV infection may improve the health and growth performance of feedlot cattle. However, in this study, immunity against BRSV did not appear to protect against the potential synergism between 3MI and BRSV infection, possibly because of the slow rates of gain of cattle included in the study or timing of sample collection.     

Pulmonary function changes in goats given 3-methylindole orally

Six adult goats were given 0.2 g of 3-methylindole (3MI)/kg of body weight orally. Lung mechanics and ventilatory function were obtained before 3MI and 2, 4, 6, 24, 48, and 72 hours after 3MI administration. Clinical signs were also monitored. Lungs were removed for gross and microscopic examination and for morphometric analysis from goats that died spontaneously or were killed with an overdose of pentobarbital after 72 hours. The major pulmonary function changes observed included a marked decrease in dynamic lung compliance with a moderate increase in airway resistance, a concomitant hypoxemia, sustained increase in respiratory frequency, a progressive decrease in tidal volume and alveolar ventilation, and increased dead space to tidal volume ratio. A mild metabolic acidosis was also noticed.     

Acidosis in feedlot cattle.

Mortality from digestive diseases in feedlot cattle is second only to that from respiratory diseases. Acidosis is a major digestive disorder and is likely to continue because of ongoing attempts to improve the efficiency of beef production by feeding more grain and less roughage. Subacute acidosis is the most prevalent form of acidosis in feedlots but is difficult to diagnose because of the absence of overt clinical signs. Control of acidosis is achieved largely by sound nutritional management. No single strategy or solution exists; however, an effective management strategy should factor in dietary formulation, a consistent feeding program, prudent bunk management, use of nonstarch by-products, and feed additives to minimize pen-to-pen and animal-to-animal variations in feed intake.     

Hypovitaminosis A in feedlot cattle

Hypovitaminosis A was diagnosed in a group of feedlot cattle that had been fed a diet low in carotene for 18 months. The primary signs of disease in the cattle were poor weight gain, ataxia, convulsions, night blindness, and total blindness. Serum vitamin A concentrations were used to confirm the diagnosis. The cattle were treated orally and intramuscularly with vitamin A, and the less severely affected herd members recovered rapidly.     

Lameness in feedlot cattle.

This article examines the various causes of lameness in feedlot cattle, with an emphasis on clinical signs, treatment, and prevention. Specific conditions are discussed, including interdigital necrobacillosis, laminitis, feedlot injuries, and feedlot lameness associated with Mycoplasma bovis. Immune management of the foot is also reviewed.     

Net absorption of 3-methylindole and indole in cattle after oral administration of L-tryptophan

The time course and quantity of 3-methylindole (3MI) and indole absorbed after oral administration of L-tryptophan (TRP) was determined in 2 steers. The relationship between the appearance of 3MI and indole in the rumen and blood plasma to absorption of 3MI and indole was also studied. Two Hereford X Angus steers with portal vein, mesenteric vein, and femoral (steer 1) or iliac (steer 2) artery catheters were used. Absorption rates from the portal drained viscera (net absorption) of 3MI and indole were determined by the product of portal and arterial concentration difference and blood flow. Blood flow was determined by primed continuous infusion of p-aminohippuric acid into a mesenteric vein. Three absorption measurements 30 minutes apart were taken at midpoint times of 0, 12, 24, 36, and 48 hours after oral administration of 0.4 g of TRP/kg of body weight. Steer 1 was dosed twice resulting in a total of 45 absorption measurements. Net absorption of 3MI and indole peaked at an average of 1.05 and 0.81 g/hr, respectively. By 48 hours, 29.2% and 15.3% of the TRP dose were accounted for by 3MI and indole absorption, respectively. Closed system in vitro incubations of TRP with ruminal fluid from the same 2 steers resulted in a TRP to 3MI conversion of 23.2% and a TRP to indole conversion of 10.7%. Net absorption of 3MI and indole closely followed and was correlated with concentration of 3MI and indole in ruminal fluid and blood plasma.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of turn-out to pasture on blood plasma iron concentrations in beef cattle

Beef cows, bred to calve in the spring, were housed indoors over the winter. On May 25, 48 of the cows, and their calves, were put out to pasture while the other 24 cows and calves remained confined.Plasma iron concentrations in the pasture cows were higher (P<0.01) than the levels of the barn cows for several weeks after turn-out, but in September there was no difference (P>0.05). In contrast, the pasture calves showed significantly lower (P<0.01) levels than did the barn calves during the first two weeks, however, there was no difference (P>0.05) in September. No difference in plasma iron levels between male and female calves was found.     

Pulmonary edema and emphysema in cattle after intraruminal and intravenous administration of 3-methylindole.

Intraruminal and intravenous administration of 3-methylindole (3MI; skatole) caused interstitial pulmonary edema and emphysema in cattle. In 3 adult heifers given the intraruminal dose of 0.2 g of 3 MI per kilogram of body weight, clinical signs of respiratory disease appeared between 6 and 12 hours after dosing, and death due to pulmonary edema and emphysema occurred at 33, 69, and 72 hours. The mean plasma concentration of 3MI became maximal (18.5 mug/ml) at 3 hours and then decreased to low concentrations by 48 hours. In 2 heifers given an intraruminal dose of 0.1 g of 3MI/kg, clinical signs developed, but they did not die during the 96-hour experiment. The mean plasma concentration of 3 MI became maximal (16.8 mug/ml) at 3 hours and decreased to 1.6 and 0.4 mug/ml at 12 and 36 hours, respectively. At necropsy of the heifers, the lung were large, firm, dark red, and heavier than normal. Diffuse pulmonary edema was the predominant change in cattle which died early, and interstitial emphysema was more severe at later stages of the disease. During the early stages, alveoli were overdistended, and a few more ruptured. Most alveolar spaces were filled with proteinaceous residue, but the alveolar septums were smooth and of normal thickness. At later stages, proliferation of alveolar cells was observed, and alveolar septums were thickened. In 3 cows given 0.06 g of 3MI/kg by jugular infusion, clinical signs appeared in all cows, and 1 cow died of pulmonary edema and emphysema 56 hours after the infusion was started. Severe pulmonary lesions seen in all of the cows given a 3MI infusion were similar to those in the cows given an intraruminal dose of 3MI. The mean plasma concentration of 3MI increased to 10.7 mug/ml at 9 hours after starting the infusion and decreased to 0.5 mug/ml at 18 hours. The results indicate that 3MI, a product of ruminal tryptophan fermentation, can cause pulmonary edema and interstitial emphysema in cattle and support the hypothesis that 3MI is the causative agent in tryptophan-induced pulmonary disease.