The effect of clenbuterol on lung function parameters in calves suffering from bronchopneumonia

Pulmonary function testing was performed in calves affected with bronchopneumonia. In these calves respiratory rate, viscous work per litre air and per minute, intrapleural pressure difference, mean inspiratory and expiratory flow rate and ventilation per minute were significantly increased. Total resistance of the lung was just not significantly increased. Dynamic compliance and tidal volume were significantly reduced.The main effect of clenbuterol was a significant increase in dynamic compliance. The reduction in the total resistance of the lung was just not significant. These results indicate that clenbuterol can antagonise, at least partly, the alterations caused by bronchopneumonia.     

The effect of clenbuterol on lung function parameters in calves suffering from bronchopneumonia

Pulmonary function testing was performed in calves affected with bronchopneumonia. In these calves respiratory rate, viscous work per litre air and per minute, intrapleural pressure difference, mean inspiratory and expiratory flow rate and ventilation per minute were significantly increased. Total resistance of the lung was just not significantly increased. Dynamic compliance and tidal volume were significantly reduced. The main effect of clenbuterol was a significant increase in dynamic compliance. The reduction in the total resistance of the lung was just not significant. These results indicate that clenbuterol can antagonise, at least partly, the alterations caused by bronchopneumonia.     

The influence of clenbuterol on prostaglandin F2 alpha-induced dyspnoea in calves

Pulmonary function tests were performed in six healthy calves. Prostaglandin F2 alpha causes severe narrowing of both upper and lower airways (total lung resistance increased, dynamic compliance decreased). Clenbuterol administered intravenously fifteen minutes prior to prostaglandin F2 alpha aerosol, and in increasing doses (0, 0.4, 0.8, 1.2 micrograms/kg), on days 1, 2, 4 and 6 of the experiment, effectively but not entirely suppressed these responses. These data indicate that beta-adrenergic receptors are present in the bovine airways and that the use of clenbuterol (0.8 micrograms/kg) may be effective in treating clinical respiratory disease such as bronchopneumonia in calves.     

Effect of clenbuterol on the incidence of abomasal ulcers in veal calves

The effect of clenbuterol on the incidence of abomasal lesions in veal calves was studied in two fattening units. Some of the calves in each unit were treated with 1.6 micrograms clenbuterol/kg bodyweight/day from the seventh until the 23rd week of the fattening period. In one unit the calves were fed milk replacer only and 176 of the 236 calves were treated with clenbuterol. In the other unit the calves were fed roughage pellets in addition to milk replacer and 92 of the 194 calves were treated with clenbuterol. Only in the second unit did the calves treated with clenbuterol have significantly fewer abomasal lesions.     

The effect of a β-agonist (clenbuterol) on the heart rate,nitrogen balance and some carcass characteristics of veal calves

Friesian bull calves were used to determine whether rapidly growing calves could be used to study the action of a β-adrenergic agonist (clenbuterol). At seventeen days of age calves were allocated to treatment (4 in initial slaughter group; 8 controls and two groups each of 5 calves given 0.1 or 1.0 mg clenbuterol kg⁻¹ milk replacer DM). Three digestibility/nitrogen balance trials were performed and calves were slaughtered between 150 and 170 kg live weight. Treatment with clenbuterol doubled heart rate for approximately 24 and 72 h in calves treated with 0.1 and 1.0 mg kg⁻¹ clenbuterol, respectively, thereafter heart rate was normal. N retention as a proportion of N intake was increased by treatment with clenbuterol, but differences were only significant in calves weighing 110 kg. At the same mean slaughter weight (160 kg) carcasses from clenbuterol-treated calves were heavier (96.3 and 100.1 kg for 0.1 and 1.0 mg kg⁻¹ clenbuterol-treated calves, respectively) compared with controls (92.2 kg). Results suggest that the proportion of muscle was higher and fat lower in the carcasses of treated compared with untreated calves.     

Observations on outbreaks of respiratory disease in housed calves--(2) Pathological and microbiological findings.

Extensive pneumonic lesions were present in 42 out of 43 calves obtained for post mortem examination from 34 outbreaks of respiratory disease in Northern Ireland. Bronchiolitis and alveolitis with necrosis of bronchiolar mucosa which progressed to bronchiolitis obliterans and peribronchiolar fibrosis were prominent histopathological features in the lungs of calves obtained live. The majority of calves which died within the first two months of these outbreaks had severe exudative bronchopneumonia with marked vascular damage and necrosis of pulmonary parenchyma. Pasteurella spp, Mycoplasma spp and P13 virus were the organisms most frequently recovered from the pneumonic lungs.     

Clenbuterol hydrochloride in calves with a natural bovine respiratory syncytial virus infection

The effect of clenbuterol hydrochloride on the course of disease in calves with a natural bovine respiratory syncytial virus infection was examined. Six calves (three to nine months of age) originating from four herds with respiratory tract disease and serological evidence of a bovine respiratory syncytial virus infection were used in this study. The calves were injected intravenously with clenbuterol hydrochloride. The effect of clenbuterol on the course of disease was measured using the PO2 in blood taken from an indwelling canula inserted in the caudal auricular artery and by clinical signs. Clenbuterol did not improve clinical signs. After clenbuterol administration arterial PO2 values decreased significantly in five out of six patients. Six to eight hours after medication the mean arterial PO2 values were higher than initial values. The moderate positive effect of clenbuterol after six to eight hours may be caused by enhancing ciliary activity and by the secretolytic activity of clenbuterol.     

Acute Metabolic Effects of Clenbuterol in Calves

The acute metabolic effects of clenbuterol were studied in calves. Clenbuterol was given intravenously at a dose of 1 µg/kg body weight. Glucagon was used to increase insulin secretion. Pretreatment with clenbuterol did not change the glucagon-induced hyperglycaemia, but the serum levels of insulin were significantly higher. Clenbuterol showed a significant lipolytic effect. The post prandial increases in glucose and insulin were significantly higher in clenbuterol treated calves. The findings are in accordance with results from earlier studies where clenbuterol was given orally in much higher doses.     

Responses of calves to treadmill exercise during beta-adrenergic agonist administration.

Calves perorally administered the beta-adrenergic agonist (beta-A) clenbuterol for 28 d were studied before, during, and after a 12-min treadmill exercise. During exercise on d 1 of clenbuterol administration, respiratory rate, respiratory minute volume, and heart rate and blood glucose, lactate, and insulin concentrations increased more in beta-A-treated calves than in controls. Oxygen extraction rate and growth hormone concentrations were lower in clenbuterol-treated calves, whereas oxygen consumption, carbon dioxide production, and blood cortisol concentration increased similarly in the absence and presence of the beta-A. After 2 wk of daily clenbuterol administration, respiratory rate and respiratory minute volume during exercise were still higher and oxygen extraction was still lower, whereas all other measures were similar to those in controls. The increased heart rate in response to isoproterenol after 3 wk of clenbuterol administration was reduced markedly in resting but only slightly in exercising animals, whereas heart rate reduction by propranolol during exercise was similar to that in controls. Seven days after withdrawal of clenbuterol, newly administered clenbuterol evoked the same effects as on d 1. In conclusion, there were marked reactions to the first clenbuterol treatment that were in part enhanced during treadmill exercise. After 2 wk of beta-A administration, animals responded much less to the beta-A and changes were not different from those in controls. Resensitization to the beta-A was observed 7 d after its withdrawal.     

Naturally occurring Mycoplasma bovis-associated pneumonia and polyarthritis in feedlot beef calves.

Mycoplasma bovis is perceived as an emerging cause of mortality in feedlot beef cattle. This study examined the lesions and infectious agents in naturally occurring M. bovis-associated bronchopneumonia and arthritis and the relationship of this condition with bovine viral diarrhea virus (BVDV) infection. Standardized pathologic, immunohistochemical, and microbiologic investigations were conducted on 99 calves that died or were euthanized within 60 days after arrival in 72 feedlots. Cranioventral bronchopneumonia with multiple foci of caseous necrosis was identified in 54 of 99 calves, including 30 with concurrent fibrinosuppurative bronchopneumonia typical of pneumonic pasteurellosis. Mycoplasma bovis was consistently identified in these lesions by culture and immunohistochemistry, but also commonly in healthy lungs and those with pneumonia of other causes. Focal lesions of coagulation necrosis, typical of pneumonic pasteurellosis, were often infected with both Mannheimia haemolytica and M. bovis. Arthritis was present in 25 of 54 (46%) calves with M. bovis pneumonia, and all calves with arthritis had pneumonia. BVDV infection was more common in calves with lesions of bacterial pneumonia than in those dying of other causes, but BVDV infection was not more common in calves with caseonecrotic bronchopneumonia than those with fibrinosuppurative bronchopneumonia. Retrospective analysis identified cases of M. bovis pneumonia in the early 1980s that had milder lesions than the current cases. The findings suggest that, in at least some calves, M. bovis induces caseonecrotic bronchopneumonia within the lesions of pneumonic pasteurellosis.     

Effects of metoclopramide, clenbuterol and butorphanol on ruminoreticular motility of calves

Rate and amplitude of contractions of the rumen dorsal sac and reticulum of 6 male Holstein calves ages 12 to 20 weeks were monitored with electromyography, strain gauges and an intraruminal pressure catheter. Heart rate and mean arterial pressure were measured with ultrasound. The effects of metoclopramide, a dopamine antagonist, clenbuterol, a beta-2 adrenergic agonist, and butorphanol, a narcotic agonist/antagonist, were observed utilizing dosages bracketing those employed clinically. Metoclopramide significantly decreased the intraruminal pressure peaks associated with cyclical contractions without changing their rate. Clenbuterol had no measurable effect on the ruminoreticulum. Butorphanol totally inhibited ruminoreticular contractions for periods of 6 to greater than 40 min depending on dosage. Only clenbuterol significantly affected cardiovascular function; it increased heart rate and decreased mean arterial pressure. Both metoclopramide and butorphanol produced behavioral changes in the calves.     

Cardiopulmonary effects of clenbuterol in the horse

Clenbuterol, a bronchospasmolytic agent (β₂ agonist) was studied in terms of its hemodynamic and airflow response in eight, healthy horses. Four animals were instrumented to record intrapleural pressure and air flow, these were used to compute pulmonary resistance, peak flow rates, and tidal volumes. Four animals were instrumented to record pulmonary arterial pressure, carotid arterial pressure, cardiac output, and arterial gas tensions. After control values were recorded, clenbuterol (0.8 μg/kg) was intravenously administered to each horse in each experiment group.
Following clenbuterol administration, non-elastic resistance of the lung or pulmonary resistance significantly decreased, 33.6% reduction at 10 min post-clenbuterol. Pulmonary resistance remained lowered during the entire procedure and showed no tendency of returning toward control values by 3 h post-clenbuterol. Within 30 sec following clenbuterol injection carotid arterial pressure decreased (mean pressure decrease 28.2%). Accompanying the change in arterial pressure, the heart rate drastically increased, 99.0%. Both changes were transient and returned to control ranges within 2 min.
Clenbuterol appears to be effective in reducing non-elastic resistance of the lung, however intravenous administration to an animal with pre-existing cardiovascular or cardiopulmonary disease should be avoided.     

Ultrasonographic evaluation of thymus in Holstein calves and Heifers and its diagnostic application

This study was performed to evaluate the cross section of the thymus in 46 clinically healthy Holstein calves and heifers from birth to 100 weeks of age and 8 age-matched affected animals with chronic bronchopneumonia by ultrasonography. The cross sectional area of the thymus increased in healthy calves and heifers from birth to 31 weeks of age, peaked around 35 weeks of age, and then decreased until 100 weeks after birth. A positive correlation (r = 0.74, P < 0.05) was found between the area in cross section and the weight of the whole thymus in calves and heifers with chronic bronchopneumonia. The cross- sectional areas of the thymus were significantly (P < 0.05) lowered in animals with chronic bronchopneumonia. The cross sections of thymus in clinically healthy calves at 2 weeks of age and heifers at 34 weeks and 87 weeks of age were hypoechoic, moderately hyperechoic and hyperechoic, respectively. The observation of thymus by ultrasonography seems to be an effective tool for estimating the size of the thymus objectively in Holstein calves and heifers from birth to 100 weeks of age. The results of this study prove the approach to be useful and applicable to monitor the growth of thymus in Holstein calves and heifers and their association with chronic pneumonia.     

Pathophysiologic study of 3-methylindole-induced pulmonary toxicosis in immature cattle

In 5 Friesian calves given 3-methylindole (3-MI) (100 mg/kg once a week for 8 weeks, except calf 4, given a 50 mg/kg dose on weeks 3 to 8), pulmonary function (PF) values and arterial blood gas tensions (PaO2 and PaCO2) were measured 24 hours after dosing was done and were correlated with clinical, biochemical, and pathologic changes. Three of the calves (No. 1, 2, and 3) showed acute respiratory distress syndrome 24 hours after the first 3-MI treatment, with a large increase in respiratory frequency, minute viscous work, and PaCO2 and a large decrease in tidal volume, dynamic lung compliance, and PaCO2. They died 36, 38, and 84 hours after dosing. Pulmonary function changes were compatible with the severe pulmonary edema and alveolar damage observed at necropsy. The 2 other calves, after they were given the 1st dose, showed only subacute respiratory distress syndrome with less severe changes in PF values recorded at 24 hours. Furthermore, they became progressively more tolerant to the 2nd, 3rd, and 4th weekly treatments, and showed base-line PF values after the 5th weekly treatment. Pathologic changes were not observed in lung biopsy material from these 2 animals at 2 and at 12 weeks after the 8th (or last) 3-MI treatment.     

Use of a beta 2-adrenergic stimulant (clenbuterol) for eliminating night-time calving.

To determine whether beta 2-adrenergic stimulant (clenbuterol) would exhibit beneficial effects upon the elimination of night-time calving, 42 Holstein Friesian cows and heifers at the first stage of labour were injected intramuscularly twice with clenbuterol; 300 micrograms at 18:00 and 210 micrograms at 22:00. Other 26 cows and heifers of the same breed at the first stage of labour at 18:00 were not treated and served as controls. All of the treated animals, but one, calved after 5:00 in the next morning, showing a peak of parturition between 5:00 and 10:00. In contrast to this, 42% of the control animals calved at night between 22:00 and 5:00. Thus, the double administrations of clenbuterol were shown to be effective for eliminating night-time calving. The cows treated with clenbuterol tended to show lower incidences of dystocia and retained placenta and a higher first insemination conception rate than the control animals. No adverse effects of the treatment on the viability of newborn calves and milk yields were observed.     

Pathology and residues in veal calves treated experimentally with clenbuterol

Six veal calves were medicated with clenbuterol at 20 μg kg bodyweight⁻¹ day⁻¹ for 42 days before they were slaughtered, to evaluate the lesions and residues in target organs. Compared with six unmedicated calves the most noticeable changes were tracheal dilatation, decreased uterine weight, slight mucous hypersecretion in the uterus and vagina and depletion of liver glycogen. The highest concentrations of clenbuterol (62 to 128 ng/g⁻¹) were recorded in the choroid/retina, and the aqueous humour had the lowest concentration (0·5 to 2·4 ng ml⁻¹). The residue concentrations were higher than the maximum residue level set for clenbuterol (0·5 ng g⁻¹)     

The pharmacokinetics and residues of clenbuterol in veal calves.

Seven female Brown Swiss calves were used to study the pharmacokinetics of clenbuterol after an effective anabolic dosage of 5 micrograms/kg of BW was given twice daily for 3 wk. Analyses of clenbuterol concentrations in different tissues was done by enzyme immunoassay (EIA). Tissue samples were taken from three calves on the last day of administration and from two more after 3.5 or 14 d of clenbuterol withdrawal. The rate of clenbuterol elimination was dependent on time and tissue. Clenbuterol concentrations in the lung dropped from a mean of 76 ng/g to a level of less than .08 ng/g after 14 d, whereas in the liver the clenbuterol concentrations decreased from 46 ng/g to .6 ng/g within 14 d of withdrawal. Highest levels were always found in the eye: 118 ng/g, 57.5 ng/g, and 15.1 ng/g after 0, 3.5, and 14 d of withdrawal, respectively. These data reveal that different compartments contribute to the elimination of clenbuterol; therefore, concentrations in urine do not follow first order kinetics. An initial rapid decline in the concentration of clenbuterol in urine with a half-life of 10 h is followed by a slower elimination with a half-life of about 2.5 d. Treatments using the anabolic dose of 5 micrograms/kg of BW require longer withdrawal times than the therapeutic dose (.8 micrograms/kg BW).     

Experimental production of bovine respiratory tract disease with bovine viral diarrhea virus

Five 6-month-old calves were inoculated with bovine viral diarrhea (BVD) virus (n = 3) or Pasteurella haemolytica (n = 2) endobronchially with a fiberoptic bronchoscope. Five additional calves were inoculated sequentially with BVD virus followed by P haemolytica at a 5-day interval. Blood samples were collected daily from the calves for bacterial isolation. Clinical signs of respiratory tract disease in calves were recorded daily. If the calves survived, they were killed for necropsy 3 or 4 days after inoculation with P haemolytica (or 8 days after inoculation with BVD virus). The extent and nature of pulmonary lesions in the calves were determined, and the lower portion of the respiratory tract (lungs and trachea) was examined for both these organisms. The 3 calves, inoculated with BVD virus only, developed mild clinical signs mainly manifested as fever, nasal discharge, and occasional cough. Approximately 2% to 7% of the total lung capacity of these calves was pneumonic. Mild clinical signs and localized lesions involving about 15% of the lung volume developed in the 2 calves exposed to P haemolytica only. However, severe fibrinopurulent bronchopneumonia and pleuritis involving 40% to 75% of lung volume developed in the 5 calves inoculated sequentially with BVD virus and P haemolytica. The possible role BVD virus may have in bovine respiratory tract disease is discussed.     

Longitudinal study of the effects of lungworm infection on bovine pulmonary function

Clinical and physiologic investigations were done weekly in 5 nonsedated Friesian calves before, during, and after an induced infection with Dictyocaulus viviparus infective larvae. Clinical, hematologic, serologic, and parasitologic findings were all compatible with the classic picture of moderate subacute verminous bronchitis. Most pulmonary function values revealed significant (P less than or equal to 0.05) changes in the 2nd or 3rd week after inoculation and maximal changes at 5 weeks after inoculation. Most marked changes included a decrease in tidal volume, dynamic lung compliance, and arterial oxygen tension, and an increase in minute ventilation, minute viscous work of breathing, and alveolar-arterial oxygen difference. Minute ventilation, dynamic lung compliance, minute viscous work of breathing, and PaO2 revealed the most homogeneous change. Conversely, maximal change of intrapleural pressure, total pulmonary resistance, and viscous work of breathing had higher variability from week to week.     

Profiles of serum amino acids to screen for catabolic and inflammation status in calves with Mycoplasma bronchopneumonia

The aim of the present study was to investigate the relationships between serum amino acid profiles in normal and calves with Mycoplasma bronchopneumonia. Serum free amino acid concentrations in serum obtained from 34 calves with or without Mycoplasma bronchopneumonia were determined by high-performance liquid chromatography. The calves with Mycoplasma were characterized by significantly lower total amino acid and total essential amino acid concentrations and molar ratios of branched-chain amino acid (BCAA) to aromatic amino acid (BCAA/AAA) and BCAA to tyrosine (BTR), and by a significantly higher molar ratio of serine phosphorylation (SPR). The proposed diagnostic cutoffs for BCAA/AAA, BTR and SPR in serum based on ROC analysis for detection of catabolic states associated with Mycoplasma bronchopneumonia were set at <1.75, <2.86 and >0.85, respectively. Our results suggest that determining the profiles of amino acids, especially BTR and SPR, could provide useful diagnostic information in terms of predicting protein catabolism in Mycoplasma bronchopneumonia.