Cardiopulmonary effects of dexmedetomidine in sevoflurane-anesthetized sheep with and without nitric oxide inhalation

OBJECTIVE: To determine whether inhaled nitric oxide (NO) prevents pulmonary hypertension and improves oxygenation after i.v. administration of a bolus of dexmedetomidine in anesthetized sheep. ANIMALS: 6 healthy adult sheep. PROCEDURE: In a crossover study, sevoflurane-anesthetized sheep received dexmedetomidine (2 microg/kg, i.v.) without NO (DEX treatment) or with inhaled NO (DEX-NO treatment). Cardiopulmonary variables, including respiratory mechanics, were measured before and for 120 minutes after bolus injection of dexmedetomidine. RESULTS: Dexmedetomidine induced a transient decrease in heart rate and cardiac output. A short-lived increase in mean arterial pressure (MAP) and systemic vascular resistance (SVR) was followed by a significant decrease in MAP and SVR for 90 minutes. Mean pulmonary arterial pressure (MPAP) and pulmonary vascular resistance increased transiently after dexmedetomidine injection. The Pao2 was significantly decreased 3 minutes after injection and reached a minimum of (mean +/- SEM) 13.3 +/- 78 kPa 10 minutes after injection. The decrease in Pao2 was accompanied by a sudden and prolonged decrease in dynamic compliance and a significant increase in airway resistance, shunt fraction, and alveolar dead space. Peak changes in MPAP did not differ between the 2 treatments. For the DEX-NO treatment, Pao2 was significantly lower and the shunt fraction significantly higher than for the DEX treatment. CONCLUSIONS AND CLINICAL RELEVANCE: Inhalation of NO did not prevent increases in pulmonary arterial pressures induced by i.v. administration of dexmedetomidine. Preemptive inhalation of NO intensified oxygenation impairment, probably through increases in intrapulmonary shunting.     

Dexmedetomidine-induced pulmonary alterations in sheep

Alpha(2) agonist-induced pulmonary oedema in sheep might be related to alterations in pulmonary haemodynamics and/or activation of inflammatory processes. In seven sevoflurane-anaesthetized sheep pulmonary haemodynamics, arterial oxygen tensions, nitric oxide and prostaglandin E(2) concentrations were determined before and after intravenous dexmedetomidine (2microg kg(-1)). In a second trial, lung tissue was sampled for histopathology and quantitative real-time PCR for IL-1beta and iNOS mRNA in a control sheep and 2, 10 and 30min after dexmedetomidine. Computer tomography of the lung under sevoflurane anaesthesia before and after dexmedetomidine was performed. Two minutes after dexmedetomidine mean pulmonary artery pressure, pulmonary arterial occlusion pressure and estimated capillary pressurewere significantly increased to 34.5mmHg, 22.2mmHg and 27.1mmHg, respectively. On computer tomography, lung density increased immediately after dexmedetomidine, with maximal density occurring between 9 and 12min. Histopathology was consistent with vascular congestion followed by protein and erythrocyte extravasation into alveoli. Increased iNOS mRNA levels were detected in sevoflurane anaesthetized animals only. An IL-1beta signal occurred after morphological changes had occurred in lung tissue. These findings support hydrostatic stress as the underlying cause of alpha(2) agonist-induced pulmonary oedema in sheep.     

Non-invasive measurement of the cardiovascular effects of chronic hypoxaemia on dogs living at moderately high altitude

Pulmonary hypertension is a well-recognised condition in dogs, and, among other mechanisms, is caused by hypoxia. In order to evaluate the effect of chronic hypobaric hypoxia on pulmonary arterial pressure in dogs, a colony of 19 clinically and biochemically healthy Greenland sled dogs living permanently at at least 2300 m above sea level (altitude dogs) and 10 clinically healthy Greenland sled dogs living at 700 to 900 m above sea level (control dogs) were examined. Investigations were made of the dogs' packed-cell volume, venous and arterial blood gases, electrocardiogram, blood pressure and echocardiograph, including the calculation of pulmonary arterial pressure by Doppler examination of tricuspid regurgitation. The altitude dogs had a marked arterial hypoxaemia with a mean (sd) oxygen partial pressure of 61.9 (7.4) mmHg and a significantly lower arterial oxygen saturation (90.7 [3.7] per cent) than the control dogs (96.7 [0.8] per cent). In eight of the altitude dogs, tricuspid regurgitation allowed calculation of the systolic pulmonary arterial pressure, which was 29.5 (10.4) mmHg. Eight of the control dogs had tricuspid insufficiency, and their derived systolic pulmonary arterial pressure was significantly lower (17.4 [3.9] mmHg).     

Influence of a constant rate infusion of dexmedetomidine on cardiopulmonary function and recovery quality in isoflurane anaesthetized horses

ObjectiveTo investigate the influence of a dexmedetomidine constant rate infusion (CRI) in horses anaesthetized with isoflurane.Study designProspective, randomized, blinded, clinical study.AnimalsForty adult healthy horses (weight mean 491 ± SD 102 kg) undergoing elective surgery.MethodsAfter sedation [dexmedetomidine, 3.5 μg kg^?1 intravenously (IV)] and induction IV (midazolam 0.06 mg kg^?1, ketamine 2.2 mg kg^?1), anaesthesia was maintained with isoflurane in oxygen/air (FiO₂ 55–60%). Horses were ventilated and dobutamine was administered when hypoventilation [arterial partial pressure of CO₂ > 8.00 kPa (60 mmHg)] and hypotension [arterial pressure 70 mmHg] occurred respectively. During anaesthesia, horses were randomly allocated to receive a CRI of dexmedetomidine (1.75 μg kg^?1 hour^?1) (D) or saline (S). Monitoring included end-tidal isoflurane concentration, cardiopulmonary parameters, and need for dobutamine and additional ketamine. All horses received 0.875 μg kg^?1 dexmedetomidine IV for the recovery period. Age and weight of the horses, duration of anaesthesia, additional ketamine and dobutamine, cardiopulmonary data (anova), recovery scores (Wilcoxon Rank Sum Test), duration of recovery (t-test) and attempts to stand (Mann–Whitney test) were compared between groups. Significance was set at p < 0.05.ResultsHeart rate and arterial partial pressure of oxygen were significantly lower in group D compared to group S. An interaction between treatment and time was present for cardiac index, oxygen delivery index and systemic vascular resistance. End-tidal isoflurane concentration and heart rate significantly increased over time. Packed cell volume, systolic, diastolic and mean arterial pressure, arterial oxygen content, stroke volume index and systemic vascular resistance significantly decreased over time. Recovery scores were significantly better in group D, with fewer attempts to stand and significantly longer times to sternal position and first attempt to stand.Conclusions and clinical relevance A dexmedetomidine CRI produced limited cardiopulmonary effects, but significantly improved recovery quality.     

Cardiopulmonary effects of a tiletamine-zolazepam combination in sheep

To assess the effects on heart and lung function, a tiletamine-zolazepam (TZ) anesthetic combination was evaluated in 10 Dorset-type ewes. Ewes were randomly allotted to 2 equal groups. Ewes of groups 1 and 2 were given a single bolus of TZ (12 and 24 mg/kg of body weight, IV, respectively) at time zero. Hemodynamic, pulmonary, and ventilation variables were measured at 15-minute intervals to 120 minutes. Blood gas variables were evaluated at 5-minute intervals for the first 30 minutes, then at 15-minute intervals to 120 minutes. In all sheep, TZ administration induced rapid, smooth induction, with gradual and unremarkable recovery. Anesthesia duration was not significantly different between groups (mean +/- SD, 39 +/- 5 and 40 +/- 14 minutes for groups 1 and 2, respectively). Immediate drug effects included apnea, decreased mean arterial blood pressure, and arterial hypoxemia. Cardiac output was significantly decreased in both groups at all times after drug administration. Significant changes in group-1 ewes included increased pulmonary and systemic vascular resistances and decreased inspired minute ventilation, tidal volume, and respiratory airflow. Significant changes in group-2 ewes included increased systemic vascular resistance and decreased pulmonary arterial pressure, inspired minute ventilation, and respiratory airflow. Both drug dosages induced apneustic breathing patterns and caused significant changes in arterial and venous blood hemoglobin concentrations and PCV. Tiletamine-zolazepam is useful for intermediate-duration anesthesia in sheep.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of a constant‐rate infusion of dexmedetomidine on the minimal alveolar concentration of sevoflurane in ponies

Reasons for performing study: Dexmedetomidine has been administered in the equine as a constant‐rate infusion (CRI) during inhalation anaesthesia, preserving optimal cardiopulmonary function with calm and coordinated recoveries. Inhalant anaesthetic sparing effects have been demonstrated in other species, but not in horses. Objectives: To determine the effects of a CRI of dexmedetomidine on the minimal alveolar concentration (MAC) of sevoflurane in ponies. Methods: Six healthy adult ponies were involved in this prospective, randomised, crossover, blinded, experimental study. Each pony was anaesthetised twice (3 weeks washout period). After induction with sevoflurane in oxygen (via nasotracheal tube), the ponies were positioned on a surgical table (T0), and anaesthesia was maintained with sevoflurane (expired sevoflurane fraction 2.5%) in 55% oxygen. The ponies were randomly allocated to treatment D (dexmedetomidine 3.5 µg/kg bwt i.v. [T10–T15] followed by a CRI of dexmedetomidine at 1.75 µg/kg bwt/h) or treatment S (bolus and CRI of saline at the same volume and rate as treatment D). After T60, MAC determination, using a classic bracketing technique, was initiated. Stimuli consisted of constant‐current electrical stimuli at the skin of the lateral pastern region. Triplicate MAC estimations were obtained and averaged in each pony. Monitoring included pulse oximetry, electrocardiography, anaesthetic gas monitoring, arterial blood pressure measurement and arterial blood gases. Normocapnia was maintained by mechanical ventilation. Analysis of variance (treatment and period as fixed factors) was used to detect differences between treatments (α= 0.05). Results: An intravenous (i.v.) dexmedetomidine CRI decreased mean ± s.d. sevoflurane MAC from 2.42 ± 0.55 to 1.07 ± 0.21% (mean MAC reduction 53 ± 15%). Conclusions and potential relevance: A dexmedetomidine CRI at the reported dose significantly reduces the MAC of sevoflurane.     

Effects of dopamine,norepinephrine or phenylephrine on the prevention of hypotension in isoflurane-anesthetized cats administered vatinoxan or vatinoxan and dexmedetomidine

ObjectiveTo determine the dose of phenylephrine, norepinephrine and dopamine necessary to maintain mean arterial pressure (MAP) within 70–80 mmHg during administration of isoflurane, isoflurane and vatinoxan and isoflurane, vatinoxan and dexmedetomidine at three plasma concentrations.Study designRandomized crossover experimental study.AnimalsA group of five adult healthy neutered male cats.MethodsInstrumentation occurred during anesthesia with isoflurane in oxygen. Isoflurane end-tidal concentration was set to 1.25 × minimum alveolar concentration (MAC). Phenylephrine, norepinephrine or dopamine was administered to maintain MAP 70–80 mmHg. A target-controlled infusion system was used to administer vatinoxan at a target plasma concentration of 1 μg mL^–1 and three dexmedetomidine concentrations (5, 10 and 20 ng mL^–1). Isoflurane concentration was altered to maintain an equivalent 1.25 MAC. Heart rate, arterial blood pressure, central venous pressure, pulmonary artery pressure, pulmonary artery occlusion pressure, body temperature, arterial and mixed venous blood gas, cardiac output and drug concentrations were measured at baseline (isoflurane alone), during vatinoxan administration, and during administration of vatinoxan and dexmedetomidine at the three target concentrations.ResultsMAP < 70 mmHg was observed with vatinoxan alone and in the dopamine treatment with dexmedetomidine concentrations ≤ 10 ng mL^–1. Norepinephrine and phenylephrine maintained MAP 70–80 mmHg during vatinoxan and dexmedetomidine ≤ 10 ng mL^–1. As the target dexmedetomidine concentration increased, the dose of norepinephrine and phenylephrine needed to maintain MAP 70–80 mmHg decreased; no treatment was necessary to maintain MAP > 70 mmHg at the 20 ng mL^–1 target dexmedetomidine concentration in most cats.Conclusions and clinical relevanceNorepinephrine and phenylephrine, but not dopamine, are effective to prevent hypotension in isoflurane-anesthetized cats administered dexmedetomidine and vatinoxan.     

Influence of modified open lung concept ventilation on the cardiovascular and pulmonary function of horses during total intravenous anaesthesia

The influence of a modified open lung concept (mOLC) on pulmonary and cardiovascular function during total intravenous anaesthesia (TIVA) in horses was evaluated. Forty-two warmblood horses (American Society of Anesthesiologists class 1 to 2), scheduled for elective surgery (mean [sd] weight 526 [65] kg, age 6.4 [5.4] years) were randomly divided into three groups: ventilation with mOLC, intermittent positive-pressure ventilation (IPPV), and spontaneous breathing. Premedication (0.8 mg/kg xylazine), induction (2.2 mg/kg ketamine and 0.05 mg/kg diazepam) and maintenance of anaesthesia with TIVA (1.4 mg/kg/hour xylazine, 5.6 mg/kg/hour ketamine and 131.1 mg/kg/hour guaifenesin), with inhalation of 35 per cent oxygen in air, were identical in all horses. Heart rate, respiratory rate, mean arterial blood pressure (MAP), pH, and arterial partial pressure of oxygen (p(a)O(2)) and carbon dioxide (p(a)CO(2)) were evaluated. Data were collected every 10 minutes from 20 to 90 minutes anaesthesia time. Factorial analysis of variance and Tukey's post hoc test were used for statistical analysis (a=5 per cent). Horses in the mOLC-ventilated group had an overall significantly higher p(a)O(2) (16.9 [1.0] v 11.7 [1.34] v 10.5 [0.57] kPa) and lower MAP (93.1 [5.47] v 107.1 [6.99] v 101.2 [5.45] mmHg) than the IPPV and spontaneously breathing groups, respectively.     

Effects of Intermittent Positive Pressure Ventilation on Cardiopulmonary Function in Horses Anesthetized with Total Intravenous Anesthesia Using Combination of Medetomidine,Lidocaine, Butorphanol and Propofol (MLBP-TIVA)

Effects of intermittent positive pressure ventilation (IPPV) on cardiopulmonary function were evaluated in horses anesthetized with total intravenous anesthesia using constant rate infusions of medetomidine (3.5 µg/kg/hr), lidocaine (3 mg/kg/hr), butorphanol (24 µg/kg/hr) and propofol (0.1 mg/kg/min) (MLBP-TIVA). Five horses were anesthetized twice using MLBP-TIVA with or without IPPV at 4-week interval (crossover study). In each occasion, the horses breathed 100% oxygen with spontaneous ventilation (SB-group, n=5) or with IPPV (CV-group, n=5), and changes in cardiopulmonary parameters were observed for 120 min. In the SB-group, cardiovascular parameters were maintained within acceptable ranges (heart rate: 33–35 beats/min, cardiac output: 27–30 l/min, mean arterial blood pressure [MABP]: 114–123 mmHg, mean pulmonary arterial pressure [MPAP]: 28–29 mmHg and mean right atrial pressure [MRAP]: 19–21 mmHg), but severe hypercapnea and insufficient oxygenation were observed (arterial CO₂ pressure [PaCO₂]: 84–103 mmHg and arterial O₂ pressure [PaO₂]: 155–172 mmHg). In the CV-group, normocapnea (PaCO₂: 42–50 mmHg) and good oxygenation (PaO₂: 395–419 mmHg) were achieved by the IPPV without apparent cardiovascular depression (heart rate: 29–31 beats/min, cardiac output: 17–21 l /min, MABP: 111–123 mmHg, MPAP: 27–30 mmHg and MRAP: 15–16 mmHg). MLBP-TIVA preserved cardiovascular function even in horses artificially ventilated.     

The effect of moderate hypovolemia on cardiopulmonary function in dogs

Objective: To collate canine cardiopulmonary measurements from previously published and unpublished studies in instrumented, unsedated, normovolemic and moderately hypovolemic dogs. Design: Collation of data obtained from original investigations in our research laboratory. Setting: Research laboratory, School of Veterinary Medicine. Subjects: Sixty‐eight dogs. Interventions: Subjects were percutaneously instrumented with an arterial catheter and a thermodilution cardiac output catheter. A femoral artery catheter was percutaneously placed for blood removal. Measurements and main results: Body weight, arterial and mixed‐venous pH and blood gases, arterial, pulmonary arterial, pulmonary artery occlusion, and central venous blood pressure, cardiac output, and core body temperature were measured. Body surface area, bicarbonate concentration, standard base excess, cardiac index (CI), stroke volume, systemic and pulmonary vascular resistance, left and right ventricular work and stroke work indices, left and right rate‐pressure product, alveolar PO₂, alveolar–arterial PO₂ gradient, arterial and mixed‐venous and pulmonary capillary oxygen content, oxygen delivery, oxygen consumption, oxygen extraction, venous admixture, arterial and venous blood carbon dioxide content, arterial–venous carbon dioxide gradient, carbon dioxide production were calculated. In 68 dogs, hypovolemia sufficient to decrease mean arterial blood pressure (ABPm) to an average of 62 mmHg, was associated with the following changes: arterial partial pressure of carbon dioxide (PaCO₂) decreased from 40.0 to 32.9 mmHg; arterial base deficit (BDa) increased from ?2.2 to ?6.3 mEq/L; lactate increased from 0.85 to 10.7 mm /L, and arterial pH (pHa) did not change. Arterial partial pressure of oxygen (PaO₂) increased from 100.5 to 108.3 mmHg while mixed‐venous PO₂ (PmvO₂) decreased from 49.1 to 34.1 mmHg. Arterial and mixed‐venous oxygen content (CaO₂ and CmvO₂) decreased from 17.5 to 16.5 and 13.8 to 9.6 mL/dL, respectively. The alveolar–arterial PO₂ gradient (A‐a PO₂) increased from 5.5 to 8.9 mmHg while venous admixture decreased from 2.9% to 1.4%. The ABPm decreased from 100 to 62 mmHg; pulmonary arterial pressure (PAPm) decreased from 13.6 to 6.4 mmHg; and pulmonary arterial occlusion pressure (PAOP) decreased from 4.9 to 0.1 mmHg. CI decreased from 4.31 to 2.02 L/min/m². Systemic and pulmonary vascular resistance (SVRI and PVRI) increased from 1962 to 2753 and 189 to 269 dyn s/cm⁵, respectively. Oxygen delivery (DO₂) decreased from 787 to 340 mL/min/m² while oxygen consumption (VO₂) decreased from 172 to 141 mL/min/m². Oxygen extraction increased from 20.9% to 42.3%. Conclusions: Moderate hypovolemia caused CI and oxygen delivery to decrease to 47% and 42% of baseline. Oxygen extraction, however, doubled and, therefore, oxygen consumption decreased only to 82% of baseline.     

Clinical comparison of preanaesthetic intramuscular medetomidine and dexmedetomidine in domestic sheep.

Medetomidine and its active d-enantiomer, dexmedetomidine, are highly selective alpha-2 agonists with potent sedative, anaesthetic-sparing and analgesic effects. These properties make them an ideal pre-anaesthetic medication for noxious surgical procedures. However, sheep can develop adverse hypoxaemic effects after intravenous alpha-2 agonists. Objective of the present study was to compare intramuscular injection of medetomidine or dexmedetomidine at equipotent doses as preanaesthetic medication prior to isoflurane anaesthesia in sheep. Nineteen healthy, adult, non-pregnant, female sheep of various breeds were used. The study was carried out as a randomised, blind trial. Group A received 15 micrograms/kg bwt dexmedetomidine and group B received 30 micrograms/kg bwt medetomidine intramuscularly (i.m.) 30 minutes prior to induction of anaesthesia. Anaesthesia was induced with ketamine (2.0 mg/kg bwt i.v.) and maintained with isoflurane in 100% oxygen. End expired anaesthetic concentration (FEiso), respiratory frequency (fR), direct arterial blood pressures and heart rates (HR) were measured. Arterial blood samples were taken at intervals. Data were averaged over time (sum of measurements/number of measurements) and tested for differences between groups by independent t-tests, and ANOVA for repeated measures followed by Bonferroni corrected t-tests. There were no differences in demographic data between the groups. Duration of anaesthesia [A: 170 (42) minutes, B: 144 (33) minutes] and duration of surgery [A: 92 (32) minutes, B: 85 (31) minutes] were similar in both groups. Average FEiso concentrations required to maintain a surgical plane of anaesthesia were not significantly different between groups [A: 0.82 (0.14)%; B: 1.00 (0.25)%]. Mean average fR, did not differ between groups [A: 31 (14), B: 37 (15)]. Heart rates were significantly lower in group B over the course of the anaesthesia. Mean arterial blood pressures (MAP) were not significantly different between the groups. The PaO2 was less variable in group A than in group B. Individual minimum values were 19.1 kPa and 7.9 kPa in group A and B, respectively. There were no significant differences in PaCO2 and paH between the groups and over time. In conclusion, intramuscular application of dexmedetomidine at 15 micrograms/kg bwt and medetomidine at 30 micrograms/kg bwt prior to isoflurane anaesthesia induced similar changes in clinically monitored cardiorespiratory parameters. The observed differences (heart rates, PaO2) between dexmedetomidine and medetomidine at the chosen dose relationship can be considered clinically not significant. At the chosen dose rates individual animals responded with a transient drop in blood oxygenation, therefore careful monitoring is required. In addition, in compromised sheep medetomidine and dexmedetomidine should be used carefully.     

Cardiopulmonary effects of halothane anesthesia in cats

The cardiopulmonary effects of 2 planes of halothane anesthesia (halothane end-tidal concentrations of 1.78% [light anesthesia] and 2.75% [deep anesthesia]) and 2 ventilatory modes (spontaneous ventilation [SV] or mechanically controlled ventilation [CV]) were studied in 8 cats. Anesthesia was induced and maintained with halothane in O2 only, and each cat was administered each treatment according to a Latin square design. Cardiac output, arterial blood pressure, pulmonary arterial pressure, heart rate, respiratory frequency, and PaO2, PaCO2, and pH were measured during each treatment. Stroke volume, cardiac index, and total peripheral resistance were calculated. A probability value of less than 5% was accepted as significant. In the cats, cardiac output, cardiac index, and stroke volume were reduced by deep anesthesia and CV, although only the reduction attributable to CV was significant. Systemic arterial pressure was significantly reduced by use of deep anesthesia and CV. Respiratory frequency was significantly lower during CV than during SV. Arterial PO2 was significantly decreased at the deeper plan of anesthesia, compared with the lighter plane. At the deeper plane of anesthesia, arterial PCO2 and pulmonary arterial pressure were significantly lower during CV than during SV. The deeper plane of halothane anesthesia depressed cardiopulmonary function in these cats, resulting in hypotension and considerable hypercapnia. Compared with SV, CV significantly reduced circulatory variables and should be used with care in cats. Arterial blood pressure was judged to be more useful for assessing anesthetic depth than was heart rate or respiratory frequency.     

The effects of increasing doses of MK-467, a peripheral alpha(2)-adrenergic receptor antagonist, on the cardiopulmonary effects of intravenous dexmedetomidine in conscious dogs

Different doses of MK-467, a peripheral alpha(2)-adrenergic receptor antagonist, with or without dexmedetomidine were compared in conscious dogs. Eight animals received either dexmedetomidine (10 μg/kg [D]), MK-467 (250 μg/kg [M250] or dexmedetomidine (10 μg/kg) with increasing doses of MK-467 (250 μg/kg [DM250], 500 μg/kg [DM500] and 750 μg/kg [DM750], respectively). Treatments were given intravenously (i.v.) in a randomized, crossover design with a 14-day washout period. Systemic hemodynamics and arterial blood gas analyses were recorded at baseline and at intervals up to 90 min after drugs administration. Dexmedetomidine alone decreased heart rate, cardiac index and tissue oxygen delivery and increased mean arterial pressure and systemic vascular resistance 5 min after administration. DM250 did not completely prevent these early effects, while DM750 induced a decrease in mean arterial pressure. With DM500, systemic hemodynamics remained stable throughout the observational period. MK-467 alone increased cardiac index and tissue oxygen delivery and had no deleterious adverse effects. No differences in arterial blood gases were observed between treatments that included dexmedetomidine. It was concluded that MK-467 attenuated or prevented dexmedetomidine's systemic hemodynamic effects in a dose-dependent manner when given simultaneously i.v. but had no effect on the pulmonary outcome in conscious dogs. A 50:1 dose ratio (MK-467:dexmedetomidine) induced the least alterations in cardiovascular function.     

Comparative kinetic disposition of oxfendazole in sheep and goats before and during infection with Haemonchus contortus and Trich ostrongylus colubriformis

The kinetic disposition of [¹⁴C]-oxfendaEole (OFZ) and its metabolites, fenben-dazole (FBZ) and fenbendazole sulphone (FBZ.SO₂), in plasma and abomasal fluid were determined in Merino sheep and Angora goats before and during infection with Trichostrongylus colubriformis and Haemonchus contortus. The systemic availability (area under the plasma curve, AUC) of OFZ was significantly lower in goats (13.5 μg.h/ml) than in sheep (22.2 μg.h/ml) and was reduced with infection in goats (5.6 μg.h/ml) and sheep (15.1 μg.h/ml). The elimination of plasma [^l4C] was faster in goats than in sheep. The responses observed for [¹⁴C] were a reflection of the behaviour of OFZ. The concentration of OFZ and metabolites in abomasal fluid were similar in both species in the absence or presence of infection. However, as the mean flow rate of abomasal fluid was slower in goats (240 ml/h) than in sheep (488 ml/h), only 7% of the dose passed the pylorus in abomasal fluid of goats compared with 14% in sheep. The presence of gastrointestinal nematodes generally increased abomasal fluid flow rate but neither species nor infection had any effect on the rate or extent of [¹⁴C] excretion in urine or faeces. It is suggested that goats possess a faster hepatic metabolism than sheep resulting in more rapid elimination of OFZ.     

Surgical treatment of severe pulmonic stenosis under cardiopulmonary bypass in small dogs

Objectives : The aim of this study was to report the long‐term outcome of the surgical palliation of pulmonic stenosis in dogs. Methods : The subjects comprised three female and six male dogs, mean (±sd) age: 23 (±25) months, mean (±sd) weight: 3·4 (±2·1) kg, diagnosed with severe pulmonic stenosis and right ventricular hypertrophy, with an average preoperative pressure gradient of 153 (±43) mmHg on echocardiography. Results : The pressure overload with severe pulmonic stenosis was reduced by valvotomy, i.e., open pulmonary valve commissurotomy, with/without biomembrane patch grafting, under cardiopulmonary bypass. The postoperative pressure gradient at 1 to 7 days was significantly decreased to 65 (±39) mmHg (P<0·05). The reduced pressure gradient was maintained at 58 (±38) mmHg at final follow‐up. Clinical Significance : Open valvotomy, pulmonary valve commissurotomy and biomembrane patch grafting were effective in reducing obstruction in severe pulmonic stenosis in dogs.     

Effects of epidural administration of dexmedetomidine on the minimum alveolar concentration of isoflurane in dogs

Objective-To evaluate the effects of epidural administration of 3 doses of dexmedetomidine on isoflurane minimum alveolar concentration (MAC) and characterize changes in bispectral index (BIS) induced by nociceptive stimulation used for MAC determination in dogs. Animals-6 adult dogs. Procedures-Isoflurane-anesthetized dogs received physiologic saline (0.9% NaCl) solution (control treatment) or dexmedetomidine (1.5 [DEX1.5], 3.0 [DEX3], or 6.0 [DEX6] mug/kg) epidurally in a crossover study. Isoflurane MAC (determined by use of electrical nociceptive stimulation of the hind limb) was targeted to be accomplished at 2 and 4.5 hours. Changes in BIS attributable to nociceptive stimulation and cardiopulmonary data were recorded at each MAC determination. Results-With the control treatment, mean +/- SD MAC values did not change over time (1.57 +/- 0.23% and 1.55 +/- 0.25% at 2 and 4.5 hours, respectively). Compared with the control treatment, MAC was significantly lower at 2 hours (13% reduction) but not at 4.5 hours (7% reduction) in DEX1.5-treated dogs and significantly lower at 2 hours (29% reduction) and 4.5 hours (13% reduction) in DEX3-treated dogs. The DEX6 treatment yielded the greatest MAC reduction (31% and 22% at 2 and 4.5 hours, respectively). During all treatments, noxious stimulation increased BIS; but changes in BIS were correlated with increases in electromyographic activity. Conclusions and Clinical Relevance-In dogs, epidural administration of dexmedetomidine resulted in dose-dependent decreases in isoflurane MAC and that effect decreased over time. Changes in BIS during MAC determinations may not represent increased awareness because of the possible interference of electromyographic activity.     

Effect of inhaled nitric oxide on the hypoxic pulmonary vasoconstrictor response in anaesthetised calves

The effect of inhaling nitric oxide in the hypoxic pulmonary vascular response was measured in five calves anaesthetised with a combination of guaiacol, ketamine and xylazine. Alveolar hypoxia was induced by means of the inhalation of a gas mixture with an inspiratory oxygen fraction of 14–18 per cent. This alveolar hypoxia resulted in a pronounced pulmonary hypertension (mean pulmonary artery pressure in hypoxic animals : 30·2 mmHg). Inhalation of 20 and 40 ppm of nitric oxide significantly attenuated the hypoxia induced pulmonary hypertension. The effect ceased once nitric oxide administration was stopped. A concentration of 40 ppm of nitric oxide fully abolished the hypoxia induced pulmonary hypertension (mean pulmonary artery pressure during inhalation of 40 ppm nitric oxide : 22·8 mmHg). Inhalation of nitric oxide had no effect on systemic arterial blood pressure nor on systemic vascular resistance. It was concluded that inhalation of 20 or 40 ppm of nitric oxide prevented a selective pulmonary vasoconstriction during alveolar hypoxia in calves, which may be helpful in the treatment of acute respiratory disorders in calves.     

Cardiopulmonary side-effects and pharmacokinetics of an emulsion of propofol (Disoprivan) in comparison to propofol solved in polysorbate 80 in goats

The aim of this study was to determine whether any pharmacokinetic or pharmacodynamic differences exist in goats between propofol in its currently licensed form (Disoprivan) and a new 1% solution of propofol (NSP) containing polysorbate 80. Nine goats received, on two different occasions in a randomized double-blinded order, 4 mg/kg propofol intravenously (i.v.; Disoprivan or NSP). To detect differences in cardiopulmonary effects and pharmacokinetics, the Wilcoxon signed rank test for paired data was used. In the NSP group the duration of initial apnoea was significantly longer, and 6 and 12 min after drug application PaO2 levels were significantly lower than in the Disoprivan group. Mean cardiovascular parameters did not differ significantly between the groups but in the NSP group in six goats marked changes in blood pressure occurred: systolic arterial pressures fell to a minimum of 40-60 mmHg within the first 10 min. This was followed by a marked increase in blood pressure, with maxima exceeding 300 mmHg. In the NSP group the half-life of propofol was significantly longer, the clearance rate was smaller and the areas under the drug concentration-time curves were larger than in the Disoprivan group. The cardiopulmonary side-effects of NSP suggest that propofol dissolved in polysorbate 80 is not a suitable alternative to the current formulation of propofol.     

Use of the monofrequency forced oscillation technique to measure changes in upper airway resistance in Friesian and blue Belgian calves

Monofrequency forced oscillometry ( ) using a sinusoidal test signal of one frequency (10 Hz) was compared with the classical pulmonary function technique (using an oesophageal balloon with airflow measurements) in two breeds of cattle which differ in their respiratory physiology, particularly to assess changes in upper airway resistance. Six healthy male Friesian calves (mean [ ] bodyweight 131 [12] kg) and six healthy male blue Belgian calves (mean [ ] bodyweight 137 [13] kg) were examined successively with their heads either in a normal position or held vertically, using a cross-over study design. In the normal position, higher resistances, a higher respiratory impedance, and lower values of the dynamic lung compliance (Cdyn) were measured in the blue Belgian than in the Friesian calves. In the vertical head position, total pulmonary resistance (RL) increased and Cdyn decreased significantly (P<0·05). The changes in -derived parameters were in accordance with the changes in classical parameters, and for both methods, the percentage changes were markedly higher in the blue Belgian calves.     

The cardiovascular effects of dexmedetomidine given by continuous infusion during isoflurane anesthesia in dogs

In a previous study we showed that the MAC of isoflurane was decreased by 18 ± 12% and 59 ± 7% by constant rate infusions of dexmedetomidine at 0.5 and 3 μg kg^–1 hour^–1. The purpose of this study was to document the cardiovascular changes associated with these infusions of dexmedetomidine at 1.3 MAC isoflurane/ dexmedetomidine. Dogs were anesthetized with isoflurane in oxygen given by mask. A cephalic venous catheter, a dorsal pedal arterial catheter and a balloon tipped, Swan–Ganz, pulmonary arterial catheter were placed percutaneously. After instrumentation the dogs were maintained at 1.3 MAC isoflurane for 60 minutes. At this time a set of measurements was made including, heart rate, respiratory rate, core body temperature, pulmonary and systemic arterial blood pressures (SAP, MAP, DAP, CVP, SPAP, MPAP, DPAP and PAOP), cardiac output and arterial and mixed venous blood samples were collected for the measurement of blood gases, pH, hemoglobin concentration, PCV and total protein. Calculated variables included base excess (BE), (HCO₃^?), cardiac index, systemic and pulmonary vascular resistance indices, oxygen delivery, oxygen consumption, oxygen utilization ratio and shunt fraction. After these measurements to dogs were randomly assigned to receive a loading dose of 0.5 or 3 μg kg^–1 of dexmedetomidine given over 6 minutes followed by an infusion of 0.5 (LD) or 3 μg kg^–1 hour^–1 (HD), respectively. The concentration of isoflurane was reduced by the above percentages, respectively, to maintain 1.3 MAC. Full sets of measurements were repeated at 10, 30, 60, 90, 120, 150 and 180 minutes after the start of the loading dose. Measured and calculated variables were compared with baseline using an anova and a post‐hoc Tukey's test. Significance was set at p = 0.05 and results are given as mean ± SD. The initial concentration of isoflurane was 1.73 ± 0.02% and was reduced to 1.41 ± 0.02 and 0.72 ± 0.09% for the LD and HD, respectively. Heart rate decreased with both doses but no other parameter changed significantly with the LD. With the HD there were significant changes in SAP, MAP, DAP, CVP, MPAP, PAOP, CI, SVRI, PCV, DO₂ and shunt fraction. The LD appeared to have minimal effect on the cardiopulmonary values measured, whereas the HD caused typical changes expected with an alpha‐2 agonist.