Oscillatory measurements,blood gas analysis and clinical observations after intravenous clenbuterol administration in healthy and acutely pneumonic calves

The effects of clenbuterol (Ventipulmin, Boehringer Ingelheim) on respiratory functions were investigated in 6 calves aged 4–6 weeks prior to and after experimental infection withPasteurella haemolytica A1. On days 1–3 (prior to infection) and on days 7–9 (after infection), blood gas analysis, monofrequency forced oscillation techniques and clinical examinations (heart rate, respiratory rate) were conducted for 135 min after the intravenous administration of clenbuterol (0.8 µg/kg body weight). In healthy calves prior toPasteurella infection, intravenous administration of clenbuterol induced a mild tachycardia and a reduction in the mean oscillatory respiratory resistance. Using the same dose of clenbuterol in diseased calves after infection, the statistically significant reduction in oscillatory respiratory resistance was more impressive and it was accompanied by a significant increase in the oxygen pressure of the arterialized blood. Heart rate and respiratory rate did not change significantly after the administration of clenbuterol in infected calves.Abbreviations HR heart rate - IV intravenous - MFOT monofrequency forced oscillation technique - PaO₂ arterial oxygen pressure - R_os oscillatory resistance - RR respiratory rate     

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.     

Side effects of clenbuterol as a repartitioning agent

Clenbuterol, a synthetic beta-adrenergic agonist drug, can be used to increase the ratio of protein to fat in the carcase of meat animals. During the first one to three days of its administration to sheep or calves clenbuterol increased their heart rate, and in sheep it decreased blood pressure. Continued administration had no further effect on heart rate or blood pressure but in sheep dose levels above 1.5 mg/day depressed appetite for up to five days; at all dose levels clenbuterol brought about a long term increase in metabolic rate.     

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.     

Subarachnoid butorphanol augments lidocaine sensory anaesthesia in calves

To determine the efficacy and safety of subarachnoid butorphanol combined with lidocaine, six calves were studied. Each calf underwent two treatments, at least one week apart, via subarachnoid injection: (1) butorphanol (0.03 mg/kg) plus 2% lidocaine (4 mg/kg) and (2) 2% lidocaine (4 mg/kg) alone. Subarachnoid injections were performed at the lumbosacral space. Analgesia, motor block, sedation, heart rate, arterial blood pressure, respiratory rate, arterial oxygen saturation as measured by pulse oximetry, and rectal temperature were compared before and after subarachnoid administration of drugs. Subarachnoid administration of the butorphanol-lidocaine combination induced bilateral prolonged analgesia extending from the coccygeal to the T11-T13 dermatomes in the calves, with minimal sedation and severe ataxia. Cardiovascular effects were significant in both treatments: heart rate was increased, and there was a minimal decrease in arterial pressure. It was concluded that adding a small dose of butorphanol to subarachnoid lidocaine in calves is effective and safe.     

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.     

Assessment of the effects of erythromycin, neostigmine, and metoclopramide on abomasal motility and emptying rate in calves

OBJECTIVE: To determine and compare the effects of erythromycin, neostigmine, and metoclopramide on abomasal motility and emptying rate in suckling calves. ANIMALS: 6 male Holstein calves (15 to 40 days of age). PROCEDURE: Calves were monitored for 1 hour before being fed milk replacer (60 mL/kg; time, 0 minutes) and then were monitored for another 3 hours. Calves received 6 treatments in randomized order: erythromycin (8.8 mg/kg, IM) at -30 minutes; low-dose erythromycin (0.88 mg/kg, IM) at -30 minutes; erythromycin (8.8 mg/kg, IM) at -30 minutes and neostigmine (0.02 mg/kg, SC) at -30 and 90 minutes; neostigmine (0.02 mg/kg, SC) at -30 and 90 minutes; metoclopramide (0.1 mg/kg, IM) at-30 and 90 minutes; and placebo (2 mL of saline [0.9% NaCl] solution, SC) at -30 minutes. Abomasal volume was calculated from ultrasonographic measurements of abomasal width, length, and height. Abomasal motility and emptying rate were assessed by measuring luminal pressure and change in abomasal volume over time. RESULTS: Administration of erythromycin (8.8 mg/kg) increased the frequency of abomasal luminal pressure waves and the mean abomasal luminal pressure and decreased the half-time of abomasal emptying by 37%. Administration of metoclopramide, neostigmine, and low-dose erythromycin (0.88 mg/kg) did not alter abomasal motility, mean luminal pressure, or emptying rate. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that administration of erythromycin at the labeled antimicrobial dose (8.8 mg/kg, IM) exerted an immediate, marked prokinetic effect in healthy suckling calves, whereas administration of metoclopramide or neostigmine did not alter abomasal motility or emptying rate.     

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 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).     

Effects of xylazine butorphanol on cecal arterial blood flow, cecal mechanical activity, and systemic hemodynamics in horses

A chronic model with an ultrasonic transit time blood flow probe and strain gauge force transducers implanted on the cecum was used to evaluate cecal mechanical activity and cecal arterial blood flow in 4 conscious adult horses. Intravenous administration of xylazine (1.1 mg/kg of body weight) significantly decreased heart rate and cardiac output, but significantly increased diastolic pulmonary arterial pressure, mean pulmonary arterial pressure, carotid arterial pressure, and central venous pressure. Lateral cecal arterial blood flow after xylazine administration was decreased substantially more than was cardiac output, suggesting that xylazine caused constriction of the cecal vasculature. This effect of xylazine may have resulted from either a direct effect of xylazine on the cecal vasculature or from reflex vasoconstriction attributable to reduced cardiac output. Intravenous administration of butorphanol tartrate (0.1 mg/kg) did not significantly alter the hemodynamic responses to xylazine. Cecal mechanical activity, as measured by the motility index, was decreased for 120 minutes after administration of xylazine and for 150 minutes after administration of xylazine/butorphanol.     

Effect of butorphanol administration on cardiovascular parameters in isoflurane-anesthetized horses - a retrospective clinical evaluation.

OBJECTIVE: To determine cardiovascular responses to administration of butorphanol in isoflurane-anesthetized horses. STUDY DESIGN: Retrospective evaluation of anesthetic records. ANIMALS: Seventy-six horses anesthetized for a variety of clinical surgical procedures. METHODS: Anesthetic records of clinical equine patients anesthetized between January 1999 and December 2003 were searched. The records were reviewed for horses in which anesthesia was induced with ketamine and a benzodiazepine and maintained with isoflurane, and horses that received butorphanol intraoperatively. Exclusion criteria included horses in which the rate of infusion of an inotrope or end-tidal isoflurane concentration was changed 10 minutes before or after the butorphanol bolus. The horses were separated into two groups: group 1 horses received butorphanol at intervals as part of a balanced protocol, group 2 horses had > or = 10% increase in heart rate (HR) or blood pressure within 10 minutes prior to butorphanol administration. RESULTS: Eighty-nine butorphanol administration events matched the criteria for inclusion, 49 in group 1 and 40 in group 2. There were no significant changes after butorphanol administration in systolic arterial pressure (SAP), mean arterial pressure (MAP), diastolic arterial pressure (DAP), and heart rate (HR) in group 1, or in end-tidal carbon dioxide concentration or hemoglobin oxygen saturation in either group. There were significant decreases in SAP (p < 0.0001), MAP (p < 0.0005), and DAP (p < 0.0008) after butorphanol administration in group 2. CONCLUSIONS AND CLINICAL RELEVANCE: The results presented here confirm that butorphanol can be administered to horses during isoflurane anesthesia without adverse effects on HR and arterial blood pressure. The results imply that butorphanol can deepen the plane of anesthesia and obtund sympathetic stimulation from a surgical procedure.     

Yohimbine/flumazenil antagonism of hemodynamic alterations induced by a combination of midazolam, xylazine, and butorphanol in dogs.

Reversal of hemodynamic alterations induced by midazolam maleate (1.0 mg/kg of body weight), xylazine hydrochloride (0.44 mg/kg), and butorphanol tartrate (0.1 mg/kg) with yohimbine (0.1 mg/kg) and flumazenil (0.25 mg/kg) was evaluated in 5 dogs. The dogs were anesthetized with isoflurane for instrumentation. With return to consciousness, baseline values were recorded, and the midazolam/xylazine/butorphanol mixture with glycopyrrolate was administered IV. Hemodynamic data were recorded for 60 minutes, and then a reversal mixture of yohimbine and flumazenil was administered IV. All variables were measured 1 minute from beginning of the reversal injection. Mean arterial pressure, pulmonary arterial pressure, systemic vascular resistance, and right ventricular stroke work index increased significantly (P < 0.05) above baseline at 60 minutes. Cardiac index and central venous pressure significantly decreased below baseline at 60 minutes. After reversal, mean arterial pressure and central venous pressure significantly decreased from baseline, whereas cardiac index, pulmonary arterial pressure, and right ventricular stroke work index increased significantly above baseline. Heart rate, cardiac index, and right ventricular stroke work index increased significantly above the 60-minute value after reversal. Mean arterial pressure and systemic vascular resistance decreased significantly (P < 0.05) below the 60-minute value after reversal. The hemodynamic alterations accompanying midazolam/xylazine/butorphanol sedation-anesthesia may be rapidly reversed with a combination of yohimbine and flumazenil.     

The effects of clenbuterol hydrochloride on the pulmonary function of calves with subacute and chronic bronchopneumonia

The influence of clenbuterol on some pulmonary function tests in 11 calves with subacute and chronic bronchopneumonia has been investigated. Treatment with clenbuterol caused changes only in calves with subacute bronchopneumonia; in these animals it decreased the total pulmonary resistance, the viscous work per litre and the peak to peak changes in transpulmonary pressure.     

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.     

Visceral analgesia: effects of xylazine, butorphanol, meperidine, and pentazocine in horses

The visceral analgesic, cardiorespiratory, and behavioral effects induced by xylazine, butorphanol, meperidine, and pentazocine were determined in 9 adult horses with colic. Colic was produced by inflating a balloon in the horses' cecum. Heart rate, respiratory rate, mean arterial blood pressure, and cardiac output increased after cecal balloon inflation. Xylazine and butorphanol decreased the hemodynamic response to cecal balloon inflation. Meperidine and pentazocine had minimal effects on the cardiorespiratory changes induced by cecal balloon inflation. Xylazine produced the most pronounced visceral analgesia. The duration of visceral analgesia was longest with xylazine (approx 90 minutes) followed by butorphanol (approx 60 min) and then by meperidine and pentazocine (approx 30 to 35 min). Accurate assessment of the effects of visceral analgesics is dependent upon the use of objective tests to evaluate pain.     

Influence of ruminal insufflation on pulmonary function and diaphragmatic electromyography in cattle.

In 8 healthy, awake cows with permanent cannulated ruminal fistulas and carotid artery loops, respiratory mechanics, ventilation, and diaphragmatic electrical activity were studied before and during stepwise insufflation of the rumen with air pressure to 40 mm of Hg. We found that ruminal insufflation increased intraperitoneal, intrapleural, and transdiaphragmatic pressures and decreased lung volume and lung compliance. In individual cows with rumen insufflation there was an increase in pulmonary resistance, but this trend was not significant in the group. Peak expiratory flow rate was increased and peak inspiratory flow rate was unchanged. Inspiratory duration (Ti) decidal volume decreased slightly, breathing frequency decreased markedly, and minute volume decreased. When intraruminal pressure reached 40 mm of Hg, arterial partial pressure of carbon dioxide (PaCO2) increased (P less than 0.01) and that of oxygen (PaO2) decreased (P less than 0,01) and arterial blood pH decreased (P less than 0.02). Diaphragmatic electromyographic activity was increased, but mechanical effectiveness of the diaphragm was reduced at increased intraruminal pressures.     

The Hemodynamic Response of Calves to Tiletamine-Zolazepam Anesthesia

Six isoflurane-anesthetized calves were instrumented for hemodynamic studies and allowed to recover from anesthesia. When the mean arterial blood pressure rose to 100 mmHg or when vigorous movement occurred, a 1:1 tiletamine-zolazepam mixture (4 mg/kg) was administered intravenously (IV). Values for cardiac output, cardiac index, stroke index, central venous pressure, and right ventricular stroke work index did not change significantly. Systolic, mean, and diastolic arterial blood pressures and systemic vascular resistance were significantly decreased below baseline at 5 minutes; they were significantly increased above baseline at 20 minutes and remained so throughout the 60 minute study. Changes in left ventricular stroke work index and rate pressure product were similar to those of arterial blood pressure and systemic vascular resistance, although they were not significant. Heart rate and pulmonary capillary wedge pressure decreased significantly but gradually returned to baseline at 40 minutes and then increased significantly above baseline by the end of the study. Minor venous-arterial shunting or perhaps mismatching of ventilation and perfusion appeared to have developed in the later stages of the study. This was reflected in a minor increase in the arterial partial pressure of carbon dioxide (PaCO2) and a decrease in the arterial partial pressure of oxygen (PaO2) and arterial pH. At the dose administered, the hemodynamic changes induced by tiletamine-zolazepam were minimal and were compatible with safe anesthesia in calves.     

Cardiovascular effects of sevoflurane in Holstein calves

Objective The purpose of this study was to determine the cardiovascular effects of sevoflurane in calves. Study design Prospective experimental study. Animals Six, healthy, 8–12‐week‐old Holstein calves weighing 80 ± 4.5 (mean ± SEM) kg were studied. Methods Anesthesia was induced by face‐mask administration of 7% sevoflurane in O₂. Calves tracheae were intubated, placed in right lateral recumbency, and maintained with 3.7% end‐tidal concentration sevoflurane for 30 minutes to allow catheterization of the auricular artery and placement of a Swan‐Ganz thermodilution catheter into the pulmonary artery. After instrumentation, administration of sevoflurane was temporarily discontinued until mean arterial pressure was > 100 mm Hg. Baseline values were recorded and the vaporizer output increased to administer 3.7% end‐tidal sevoflurane concentration. Ventilation was controlled to maintain normocapnia. The following were recorded at 5, 10, 15, 30 and 45 minutes after collection of baseline data and expressed as the mean value (± SEM): direct systolic, diastolic, and mean arterial blood pressures; cardiac output; mean pulmonary arterial pressure; pulmonary arterial occlusion pressure, heart rate; and pulmonary arterial temperature. Cardiac index and systemic and pulmonary vascular resistance values were calculated using standard formulae. Arterial blood gases were analyzed at baseline, and at 15 and 45 minutes. Differences from baseline values were determined using one‐way analysis of variance for repeated measures with post‐hoc differences between mean values identified using Dunnet's test (p < 0.05). Results Mean time from beginning sevoflurane administration to intubation of the trachea was 224 ± 9 seconds. The mean end‐tidal sevoflurane concentration at baseline was 0.7 (± 0.11)%. Sevoflurane anesthesia was associated with decreased arterial blood pressure at all sampling times. Mean arterial blood pressure decreased from a baseline value of 112 ± 7 mm Hg to a minimum value of 88 ± 4 mm Hg at 5 minutes. Compared with baseline, arterial pH was decreased at 15 minutes. Pulmonary arterial blood temperature was decreased at 15, 30 and 45 minutes. Arterial CO₂ tension increased from a baseline value of 43 ± 3 to 54 ± 4 mm Hg (5.7 ± 0.4 to 7.2 ± 0.3 kPa) at 15 minutes. Mean pulmonary arterial pressure was increased at 30 and 45 minutes. Pulmonary arterial occlusion pressure increased from a baseline value of 18 ± 2 to 23 ± 2 mm Hg at 45 minutes. There were no significant changes in other measured variables. All calves recovered from anesthesia uneventfully. Conclusion We conclude that sevoflurane for induction and maintenance of anesthesia was effective and reliable in these calves and that neither hypotension nor decreased cardiac output was a clinical concern. Clinical relevance Use of sevoflurane for mask induction and maintenance of anesthesia in young calves is a suitable alternative to injectable and other inhalant anesthetics.     

Hemodynamics, plasma eicosanoid concentrations, and plasma biochemical changes in calves given multiple injections of Escherichia coli endotoxin

Twelve male neonatal calves (39 to 50 kg) were allotted to 3 groups of 4 calves each. All calves were anesthetized with halothane, and then Escherichia coli endotoxin was given intravenously (3 times) and intraperitoneally (3 times) during a 6-hour period. Group-1 calves were untreated, group-2 calves were pretreated with a low dose of flunixin meglumine (1.1 mg/kg of body weight), and group-3 calves were pretreated with a high dose of flunixin meglumine (4.4 mg/kg). In calves of group 1, the mean systemic arterial blood pressure (MABP) and cardiac output (CO) decreased, but pulmonary arterial pressure increased after the initial intravenous and intraperitoneal injections of endotoxin. In calves of this group, these changes were accompanied by increased plasma thromboxane B2 (TxB2) concentration. During this period, increased plasma TxB2 concentration or hemodynamic changes were not detected in calves of groups 2 and 3. Only calves of group 1 had altered hemodynamics early in the experiment; however, after 6 hours, calves of all 3 groups had similarly decreased CO and MABP. In calves of the untreated group, plasma 6-keto-prostaglandin (PG)F1 alpha concentration increased steadily from the beginning of the experiment until 3 hours later. The CO and MABP were low at the time when serum 6-keto-PGF1 alpha concentration was high; however, these 2 measurements also were low in treated calves who did not have correspondingly high plasma 6-keto-PGF1 alpha concentration. Regional blood flow analysis did not reveal correlations between prostanoid concentrations and altered blood flow to selected tissues.(ABSTRACT TRUNCATED AT 250 WORDS)