Effects of muscarinic receptor antagonists on acetylcholine-induced contractions of jejunal smooth muscle in horses.

This study investigated the effects of a muscarinic type 1 (M(1)), 2 (M(2)), and 3 (M(3)) antagonists (4-DAMP, pirenzepine, and methoctramine, respectively) on acetylcholine (Ach)-induced contractions of longitudinal jejunal muscle strips of horses. Strips were irrigated with Krebs-Henseleit solution gassed with 95% O(2) and 5% CO(2), and the developed tension in response to Ach was recorded before and after incubation with increasing concentrations of 4-DAMP (10(-8)-10(-6) M), pirenzepine (10(-6)-10(-4) M), and methoctramine (10(-5)-10(-3) M). When competitive antagonism was characterized, the affinity constant (pA(2)) was calculated by Schild plots. A parallel rightward shift in the concentration-response curves was observed after 4-DAMP and pirenzepine. Methoctramine presented a dual effect on the concentration-response curves: lower concentrations induced a parallel rightward shift without altering the maximum intensity of contraction (E(max)), while the highest concentration increased slope of the concentration-response curve and increased E(max). The pA(2) for 4-DAMP and pirenzepine was 9.18 and 7.13, respectively. Acetylcholine-induced contractions of longitudinal jejunal smooth muscle are mediated mainly via M(3) receptors. The complex role of M(2) receptors in jejunal smooth muscle contractions was evident because methoctramine potentiated the contractile response to higher doses of Ach.

Comparison of aerobic capacity between racing standardbred horses.

A standardized treadmill test was used to compare metabolic and ventilatory measurements between 10 standardbred racehorses. The horses were divided into two groups: group A (n = 5) had mean racing speeds of 4.4 s faster than group B (n = 5) over a 1-mi. distance. Each horse was fitted with a venous catheter and connected to a valved gas-collection system. The exercise test consisted of 1-min incremental workloads ranging from 4.0 to 12.0 m/s at a treadmill incline of 3 degrees. Group A had significantly higher (P < 0.05) measurements of maximal O2 consumption (VO2max), O2 pulse, and tidal volume. Venous lactate concentration and respiratory exchange ratio measured at VO2max were also significantly higher (P < 0.05) in group A. Similar treadmill velocities were required to achieve a respiratory exchange ratio of > 1 and venous blood lactate concentration of > 4 mmol/l; however, group A was able to complete a significantly higher (P < 0.01) number of workloads before fatigue. The high aerobic and anaerobic capacity of group A horses may be a major contributor to a faster racing performance.

Comparative pulmonary mechanics in the horse and the cow.

Pulmonary mechanics and lung volumes were measured in horses and cows to determine if differences in breathing pattern between the two species were due to differences in the mechanical properties of the lungs. Tidal volume (VT) was larger in the horses, while the respiratory rate (fR) and minute ventilation (VE) were higher in the cows. The horses often had a double peak in airflow during inspiration and, or, expiration, while the cows had a single peak during expiration. Measured lung volumes were larger in the horses and they had a higher dynamic lung compliance (Cdyn,L), although the static compliance of the lung, chest wall and respiratory system (Cst,L,Cst,w and Cst,rs respectively) did not appear to differ between the two species. The cows had a greater change in maximum transpulmonary pressure (delta PLmax) and an increased nonelastic work of breathing (Wb). However, the pulmonary resistance (RL) did not differ between the two species, thus the higher delta PLmax and Wb in the cows were most likely a function of their higher flow rates. Calculations of the rate of work of breathing (W) indicate that both species breathed at an fR above the minimum W. The fR in the horses was close to the fR predicted for the average minimum muscle force, but the fR in the cows was higher. As the differences in the mechanical properties of the lung do not explain the differences in flow pattern, nor adequately account for the higher fR in the cows, it is suggested that the differences in breathing pattern between the two species is due to differences in the chest wall, particularly the size and shape of the abdomen.

Comparative ventilation and gas exchange in the horse and the cow.

Ventilation and gas exchange were studied in healthy, adult horses and cows, two large species with different lung structures and different breathing patterns. The oxygen uptake (VO2), carbon dioxide output (VCO2), respiratory rate (fR), minute ventilation (VE), alveolar ventilation (VA), alveolar oxygen pressure (PAO2), and VE/VO2 ratio were higher in the cows, while the tidal volume (VT) and physiological dead space (VD) were larger in the horses. The arterial blood gases, alveolar-arterial oxygen pressure difference (PAO2-PaO2) and VD/VT ratio did not differ between the two species. The higher VO2 in the cows was most likely due to the energy cost of standing, and possibly to a higher cost of digestion. The higher VE, VA, VE/VO2 and PAO2 were most likely secondary to the increased VO2 and the slightly higher respiratory exchange ratio (R) in the cows. In contrast to hypotheses based on allometric equations, the PAO2 of horses and cows did not appear to differ from that of smaller mammals. The VD was larger than that predicted from allometric equations, and even though the VD/VT ratio (0.50) was lower than the previously reported values for horses and cows, it was significantly larger than the predicted weight-independent value of 0.36. Re-examination of the data used to derive the equation for VD raised questions as to the validity of this equation, and it is suggested that caution be exercised in the use of allometric equations for prediction.

Oxygen cost of ventilation in the resting horse.

The purpose of this study was to develop a technique to measure the oxygen cost of ventilation and the values of ventilatory parameters in seven normal horses rebreathing carbon dioxide (CO2). All the horses responded to increased inspiratory levels of CO2 by increasing their tidal volume (VT) and frequency of breathing (Vf). The mean (SE) oxygen cost litre-1 of ventilation, measured at rates of ventilation greater than 200 litres min-1 was 1.7 (0.04) ml litre-1, similar to that of normal human subjects ventilating submaximally. It was concluded that the CO2 rebreathing test is a practical, non-invasive means of measuring the oxygen cost of breathing and the ventilatory response to CO2 in horses.

Radiographic evidence of impaired pulmonary function in laterally recumbent anaesthetised horses.

Studies in conscious and anaesthetised ponies demonstrated that starvation, anaesthesia and changes in body position influence the radiographic appearance of the lungs in the lateral and dorsoventral views. Radiographic appearances could not be closely correlated with blood gas values, but they suggested that the volume of the lowermost lung of the laterally recumbent animal is greatly reduced.

The noxious effects of electroimmobilization in adult Holstein cows: a pilot study.

Ten adult Holstein cows were used in an experiment to determine whether the induction of electroimmobilization was a noxious event. The cows were halter trained and accustomed to being led into a set of stocks. The time taken for the cattle to walk the last ten metres into the stocks was recorded. The heart rate of the cow was recorded for a three minute period prior to a ten second exposure to a high pitched sound (the conditioning stimulus). Measurements were collected for three repetitions and then the cows were assigned to two groups of five. One group was immobilized for 30 seconds using a commercial electroimmobilizer, the other group was not treated. This procedure was repeated ten times over a period of eight days. The cows were then exposed to the conditioning stimulus and their response observed. The treated group took significantly (P less than 0.05) longer to get into the stocks and the regression slopes for heart rate were significantly different from the control group. The treated cows responded to the conditioning stimulus at five and nine months after the end of the conditioning period. Adult Holstein cows regarded electroimmobilization as a noxious event and were very strongly conditioned to this stimulus.

An evaluation of the multiple-breath nitrogen washout as a pulmonary function test in dairy cattle.

Multiple-breath nitrogen washouts (MBNW) were performed with 21 adult dairy cows (seven normal cows tested on two days each, four clinically normal cows tested on six days, and ten cows with respiratory disease tested on one day each). The functional residual capacity (FRC), lung clearance index (LCI), Becklake index (BI), mixing ratio (MR), pulmonary N2 clearance delay (PCD), index of distribution of inspiration (IDI) and ventilatory efficiency (EFF) were calculated for each MBNW. The LCI, MR, PCD, IDI and EFF were calculated at an end-tidal N2 concentration of 3% (FETN2,3%) and the end-tidal N2 concentration of the final breath of the MBNW (FETN2,fb), while BI was calculated and EFF was also calculated at FETN2 = 8% (i.e. after washout of 90% of the N2 in the lung). All of the MBNW were irregular due to breath-to-breath variability in the breathing pattern of cows and variability in FRC. The within day coefficients of variation for FRC, LCI, MR, IDI, EFF3% and EFFfb were less than 10%, but in the four cows tested on six days there was significant day-to-day variability for individuals for FRC, LCI, BI, MR, PCD and IDI. The shape of the MBNW curves differed between the normal cows and those with respiratory disease. The FRC, EFF3% and EFFfb were the most sensitive indices in detecting the cows with respiratory disease, and when EFF3%, EFFfb or FETN2fb, was used in conjunction with FRC it was possible to detect all of the cows with respiratory disease.

Reproducibility of pulmonary mechanics measurements in dairy cattle.

The reproducibility of pulmonary mechanics measurements in dairy cattle was examined using two study designs. In design A measurements were made with six cows on two days, and in design B measurements were made with four cows on six days. The mean coefficients of variation for within-day measurements for individuals ranged from 9.2 to 25.9% indicating considerable within-day variability. In design A there were no significant differences between days (P less than 0.05) for any measured variable for the group, but there were often significant differences between the two days for individuals. In design B there were significant cow-day interactions for all variables, again indicating significant differences between days for individuals. There were significant differences between days for the group for respiratory rate, and duration of inspiration and expiration. Both the interactions and differences between days appeared to be random. The high variability and limited reproducibility of pulmonary mechanics measurements, particularly in individual animals, indicate the need for caution in the interpretation of pulmonary mechanics measurements in dairy cattle.

An evaluation of the multiple-breath nitrogen washout as a pulmonary function test in horses.

Multiple-breath nitrogen washouts (MBNW) were performed with 29 light horses. Seven normal horses were used to examine the reproducibility, and 22, ranging from normal to severely diseased, were used to examine the changes in chronic obstructive pulmonary disease (COPD) and the effect of a bronchodilator, salbutamol, on the distribution of ventilation. The MBNW were analyzed using the functional residual capacity (FRC), end-tidal N2 concentration of the final breath of the MBNW (FETN2,fb), end-tidal N2 concentration when the cumulative expired volume was equal to body weight (FETN2,bw), lung clearance index (LCI), Becklake index (BI), mixing ratio (MR), index of distribution of inspiration (IDI), pulmonary N2 clearance delay (PCD) and ventilatory efficiency (EFF). The LCI, MR, IDI, PCD and EFF were calculated at end-tidal N2 concentrations (FETN2), equal to 3%, 2% and FETN2,fb. The EFF was also calculated at FETN2 = 8%, as was BI. The within day coefficient of variation for most indices of the MBNW was 10-15%. None of the indices varied significantly from day-to-day. The FETN2,fb, FETN2,bw, MR, IDI, PCD, and EFFfb, EFF3% and EFF2% differed between the horses with COPD and the normal horses, and all of the indices, except FRC, were correlated with a histopathological score of the small airways. The FETN2,bw appeared to be the most sensitive index in detecting the horses with COPD. In the horses with COPD, salbutamol caused a decrease in FRC and FETN2,fb indicating increased ventilation of the lung. However, LCI increased suggesting a less efficient distribution of ventilation.

Comparative hemodynamic effects of halothane and halothane-acepromazine at equipotent doses in dogs.

The purpose of this study was to compare the cardiovascular effects of halothane when used alone at increasing doses (1.2, 1.45 and 1.7 minimum alveolar concentration, MAC) to those produced with equipotent doses of halothane after potentiation of the anesthetic effect with acepromazine (ACP) sedation (45% reduction of halothane MAC). Six healthy mature dogs were used on three occasions. The treatments were halothane and intramuscular (IM) saline (1.0 mL), halothane and ACP (0.04 mg/kg IM), or halothane and ACP (0.2 mg/kg IM). Anesthesia was induced and maintained with halothane in oxygen and the dogs were prepared for the collection of arterial and mixed venous blood and for the determination of heart rate, systolic, diastolic and mean arterial pressure, mean pulmonary arterial pressure (PAP), central venous pressure and cardiac output. Following animal preparation the saline or ACP was administered and positive pressure ventilation instituted. Twenty-five minutes later the dogs were exposed to the first of three anesthetic levels, with random assignment of the sequence of administration. At each anesthetic level, measurements were obtained at 20 and 35 min. Calculated values included cardiac index, stroke index, left ventricular work, systemic vascular resistance, arterial oxygen content, mixed venous oxygen content, oxygen delivery and oxygen consumption. Heart rate was significantly higher with halothane alone than with both halothane-ACP combinations and was significantly higher with high dose ACP compared to low dose ACP. Systolic and mean blood pressures were lowest with halothane alone and highest with 0.2 mg/kg ACP, the differences being significant for each treatment. Oxygen uptake and PAP were significantly lower in dogs treated with ACP. It was concluded that ACP does not potentiate the cardiovascular depression that accompanies halothane anesthesia when the resultant lower dose requirements of halothane are taken into consideration.

Open canalicular system of platelets in porcine stress syndrome.

A study was undertaken to test whether a previously reported alteration in platelet morphology could be of predictive value for the detection of stress-susceptibility in pigs. Platelets from 20 normal pigs, nine pigs classified as stress-susceptible on the basis of their response to halothane challenge, and 11 siblings of halothane reactors belonging to two different breeds were subjected to electron microscopic examination. A quantitative analysis of electron micrographs, based on the extent of dilatation of the open canalicular system in platelets and the percentage of affected platelets, revealed that halothane reactor pigs could be distinguished from normal animals on the basis of their open canalicular system score. The discrete nature of the score categories in siblings indicates that platelet alteration may be an inherent component of the porcine stress syndrome and suggests that some of the false negatives in the halothane test may be identified as stress-susceptible on this criterion. Further studies involving a larger number of halothane reactors and siblings are needed to ascertain the consistency of the open canalicular system features and eventually, to develop a simple test system based on platelet alterations for the detection of stress-susceptibility in pigs.

Pulmonary structure and function in adult dairy cows with an expanded lung field.

Pulmonary function tests were performed on seven adult dairy cows with an expanded lung field (ExLF) and the results were compared to the values from seven cows with normal lung fields. The cows with ExLF had an increased functional residual capacity (FRC) and end-tidal N2 concentration of the final breath of the multiple-breath N2 washout (FETN2,fb), and an abnormal distribution of ventilation. The measurements of ventilation and gas exchange and pulmonary mechanics did not differ between the two groups. Postmortem examination of the lungs of five of the cows in each group indicated the cows with ExLF had a bronchiolitis with varying degrees of goblet cell hyperplasia, epithelial cell hyperplasia and metaplasia, smooth muscle hypertrophy, inflammatory cell infiltrate, vascular thickening, peribronchiolar fibrosis, and a mild overinflation of the lung. A histopathological score, based on the preceding indices and bronchus-associated lymphoid tissue, was correlated with FRC, FETN2,fb, the lung clearance index and pulmonary resistance. There were no correlations between the histopathological score and any of the measures of ventilation and gas exchange.

Modification of cardiopulmonary and intestinal motility effects of xylazine with glycopyrrolate in horses.

Xylazine (XYL) administration in horses is accompanied by significant cardiovascular depression characterized by a 25-35% decrease in cardiac output (CO) which is likely to compromise tissue oxygen delivery (DO2), and usually vagally mediated bradycardia is an important cause of this reduced cardiovascular performance. To examine the possible benefit of preventing the bradycardiac response, 6 healthy horses were treated with intravenous (IV) saline (SAL) or 2.5 micrograms/kg glycopyrrolate (GLY) in a blinded, randomized, crossover trial. Fifteen minutes later, 1 mg/kg XYL was administered IV and systolic, diastolic and mean blood pressures (SBP, DBP, and MBP, respectively), central venous pressure (CVP), mean pulmonary artery pressure, heart rate (HR), CO, and arterial and mixed venous blood gases were measured at the following times: baseline, 2, 5, and 10 min post-SAL or GLY; and 2, 5, 10, 15, 30, 45 and 60 min post-XYL. Determination of cardiac index (CI), stroke index (SI), left ventricular work, systemic vascular resistance (SVR), DO2, oxygen uptake, and oxygen extraction ratio were made at the same time. Gastrointestinal (GI) motility was evaluated by four-quadrant auscultation for 24 h post-XYL. Statistical analysis of continuous variables was carried out using ANOVA for repeated measures and Wilcoxon's rank-sum test for non-parametric data. In GLY treated horses, HR, SBP, MBP, DBP, CI, DO2 and mixed venous oxygen tension were significantly higher up to 30 min after XYL (P < or = 0.02) while CVP and SI were significantly lower 2 and 5 min post-XYL, respectively. In both groups, GI motility as assessed by auscultation was virtually abolished for an hour, with a non-significant tendency for the decrease in motility to last longer in the GLY/XYL group. None of the treated horses developed abdominal discomfort. No significant difference was observed in the other variables. The study shows that 2.5 micrograms/kg GLY premedication reduces the cardiovascular depression caused by 1 mg/kg XYL, without adversely affecting GI motility.

Simple nonrebreathing valves for use with large mammals.

Two simple nonrebreathing valves suitable for use with large mammals are described. These valves can be constructed in a reasonably well equipped workshop using materials that are readily available. The resistive pressure of both valves is less than 0.1 kPa at flow rates up to 15 L.s-1. Their main limitation is a relatively large dead space, although the dead space of valve B (290 mL) is less than the dead space of some commercially available valves. Healthy adult horses and cows compensate for the increased dead space by an increase in tidal volume.

An evaluation of the influence of medetomidine hydrochloride and atipamezole hydrochloride on the arrhythmogenic dose of epinephrine in dogs during halothane anesthesia.

Alterations in the arrhythmogenic dose of epinephrine (ADE) were determined following administration of medetomidine hydrochloride (750 micrograms/M2) and a saline placebo, or medetomidine hydrochloride (750 micrograms/M2), followed by specific medetomidine reversal agent, atipamezole hydrochloride (50 micrograms/kg) 20 min later, in halothane-anesthetized dogs (n = 6). ADE determinations were made prior to the administration of either treatment, 20 min and 4 h following medetomidine/saline or medetomidine/atipamezole administration. Epinephrine was infused for 3 min at increasing dose rates (2.5 and 5.0 micrograms/kg/min) until the arrhythmia criterion (4 or more intermittent or continuous premature ventricular contractions) was reached. The interinfusion interval was 20 min. There were no significant differences in the amount of epinephrine required to reach the arrhythmia criterion following the administration of either treatment. In addition, the ADE at each determination was not different between treatment groups. In this study, the administration of medetomidine to halothane-anesthetized dogs did not alter their arrhythmogenic response to infused epinephrine.

Evaluation of a commercial creatine kinase screening test for malignant hyperthermia (porcine stress syndrome).

Two hundred and seven boars entering a Record of Performance Test Station at New Hamburg, Ontario were screened for susceptibility to malignant hyperthermia or the porcine stress syndrome. Screening tests included the determination of whole blood creatine kinase levels by a commercially available test using the method of bioluminescence and a halothane challenge. The validity of the bioluminescent or whole blood creatine kinase test as a screening mechanism for malignant hyperthermia was evaluated in boars in a field trial. The susceptibility of these animals to malignant hyperthermia or the porcine stress syndrome was unknown at the time of the study. It was determined in the initial field trial that 76.3% or 158 of the 207 boars tested by the bioluminescent creatine kinase screening test were stress susceptible. In contrast, only one boar (0.5%) reacted to a standard five minute halothane challenge. After further examination of the commercial screening test, little correlation was found to exist between the bioluminescent and Rosalki methods of creatine kinase determination. The coefficient of analytical variation for the bioluminescent method of creatine kinase determination ranged from 17.6% at a mean of 359 LU to 21.9% at a mean of 318 LU. Similarly, the coefficient for the Rosalki technique ranged from 7.1% at a mean of 324 U/L to 14.0% at a mean of 64 U/L. In addition, little correlation was found to exist between creatine kinase levels as determined by the bioluminescent method and outcome to the halothane or halothane/succinylcholine challenge, age of boars in weeks or percentage gain in weight.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiopulmonary effects of xylazine and yohimbine in laterally recumbent sheep.

The effects of yohimbine (0.125 mg/kg) on cardiopulmonary parameters in six adult, xylazine treated (0.15 mg/kg), laterally recumbent sheep were studied. Following collection of baseline data, xylazine was administered intravenously and data were collected five and fifteen minutes later. At twenty minutes post-xylazine either yohimbine (0.125 mg/kg) or saline was given and further collection of data occurred at 25, 30, 40 and 50 minutes. Xylazine administration resulted in significant (P less than 0.05) respiratory depression, as reflected by a decrease in arterial oxygen partial pressure (PaO2). No significant changes in haemodynamic variables were observed. Yohimbine produced a significant improvement in PaO2 at the 50 minute period and abolished the paradoxical respiratory pattern when present. The results indicated that yohimbine can be used as an antagonist to control the duration of xylazine induced respiratory depression, although the degree of reversal was less than is clinically desirable.

Cardiopulmonary effects of hypercapnia during controlled intermittent positive pressure ventilation in the horse.

The cardiopulmonary effects of eucapnia (arterial CO2 tension [PaCO2] 40.4 +/- 2.9 mm Hg, mean +/- SD), mild hypercapnia (PaCO2, 59.1 +/- 3.5 mm Hg), moderate hypercapnia (PaCO2, 82.6 +/- 4.9 mm Hg), and severe hypercapnia (PaCO2, 110.3 +/- 12.2 mm Hg) were studied in 8 horses during isoflurane anesthesia with volume controlled intermittent positive pressure ventilation (IPPV) and neuromuscular blockade. The sequence of changes in PaCO2 was randomized. Mild hypercapnia produced bradycardia resulting in a significant (P < 0.05) decrease in cardiac index (CI) and oxygen delivery (DO2), while hemoglobin concentration (Hb), the hematocrit (Hct), systolic blood pressure (SBP), mean blood pressure (MBP), systemic vascular resistance (SVR), and venous admixture (QS/QT) increased significantly. Moderate hypercapnia resulted in a significant rise in CI, stroke index (SI), SBP, MBP, mean pulmonary artery pressure (PAP), Hct, Hb, arterial oxygen content (CaO2), mixed venous oxygen content (CvO2), and DO2, with heart rate (HR) staying below eucapnic levels. Severe hypercapnia resulted in a marked rise in HR, CI, SI, SBP, PAP, Hct, Hb, CaO2, CvO2, and DO2. Systemic vascular resistance was significantly decreased, while MBP levels were not different from those during moderate hypercapnia. No cardiac arrhythmias were recorded with any of the ranges of PaCO2. Norepinephrine levels increased progressively with each increase in PaCO2, whereas plasma cortisol levels remained unchanged. It was concluded that hypercapnia in isoflurane-anesthetized horses elicits a biphasic cardiopulmonary response, with mild hypercapnia producing a fall in CI and DO2 despite an increase in MBP, while moderate and severe hypercapnia produce an augmentation of the cardiopulmonary performance and DO2.

Cardiorespiratory effects of a 5HT2 antagonist (R51703) in awake and anesthetized dogs.

To investigate cardiorespiratory effects of an experimental 5-hydroxytryptamine receptor antagonist (R51703) with sedative properties, intramuscular doses of the drug were studied in 6 awake dogs of mixed breed, and in 6 anesthetized beagles. Two doses (0.2 and 0.4 mg/kg) of R51703 and a saline control were studied in the awake dogs using a randomized crossover trial. Subsequently, the higher dose of R51703 was included as a component of halothane anesthesia to determine whether the halothane sparing effect of R51703 produced a beneficial alteration of hemodynamic function. Data were obtained at equipotent halothane/R51703 (H/R) and halothane/saline (H/S) doses equivalent to 1.0, 1.5 and 2.0 MAC. In awake dogs, heart rates tended to be lower in dogs sedated with R51703, significantly so at 30 min for both doses, and at 90 and 120 min for the 0.2 and 0.4 mg/kg doses, respectively (P < 0.05). The cardiac index (CI) was lower at 60 min with both doses compared to the saline control group. Both doses of R51703 reduced mean blood pressure at 30, 90 and 120 min, and diastolic pressure at 30 and 90 min after administration; however, systolic blood pressure (SBP) was not altered. Overall, the cardiovascular alterations were minimal in conscious dogs and there was no evidence of respiratory depression. In the anesthetized dogs, at equipotent MAC, CI tended to be lower with H/R than with H/S, though the difference was not significant. Heart rate and stroke volume index also tended to be lower in the dogs treated with R51703, while systemic vascular resistance tended to be higher: these changes were not significant. Mean and SBP were higher at each MAC multiple in the H/R group. It was concluded that the halothane sparing effect of R51703 did not substantially improve hemodynamic function compared to the use of halothane alone at equipotent doses.