Plasma levels of a methadone constant rate infusion and their corresponding effects on thermal and mechanical nociceptive thresholds in dogs.

BACKGROUND: The present study aimed to collect pharmacokinetic data of a methadone continuous rate infusion (CRI) and to investigate its effect on mechanical and thermal nociceptive thresholds. Seven, 47 to 54 months old beagle dogs, weighing 9.8 to 21.2 kg, were used in this experimental, randomized, blinded, placebo-controlled crossover study. Each dog was treated twice with either a methadone bolus of 0.2 mg kg- 1 followed by a 0.1 mg kg- 1 h- 1 methadone CRI (group M) or an equivalent volume of isotonic saline solution (group P) for 72 h. Mechanical and thermal thresholds, as well as vital parameters and sedation were measured during CRI and for further 24 h. Blood samples for methadone plasma concentrations were collected during this 96 h period. RESULTS: Percentage thermal excursion (%TE) increased significantly from baseline (BL) until 3 h after discontinuation of CRI in M. Within P and between treatment groups differences were not significant. Mechanical threshold (MT) increased in M until 2 h after CRI discontinuation. Bradycardia and hypothermia occurred in M during drug administration and dogs were mildly sedated for the first 47 h. Decreased food intake and regurgitation were observed in M in five and four dogs, respectively. For methadone a volume of distribution of 10.26 l kg- 1 and a terminal half-life of 2.4 h were detected and a clearance of 51.44 ml kg- 1 min- 1 was calculated. Effective methadone plasma concentrations for thermal and mechanical antinociception were above 17 ng ml- 1. CONCLUSION: A methadone CRI of 0.1 mg kg- 1 h- 1 for 3 days after a loading dose results in steady anti-nociceptive effects in an acute pain model in healthy dogs. Main side effects were related to gastrointestinal tract, hypothermia, bradycardia and sedation.

Effect of fentanyl on thermal and mechanical nociceptive thresholds in horses and estimation of anti-nociceptive plasma concentration.

There are few investigations relating anti-nociception to plasma concentrations of fentanyl in horses. The study objective was to evaluate analgesic efficacy and duration in horses and determine the minimum anti-nociceptive plasma concentrations. Eight horses were treated with saline (P) and fentanyl (F2.5=2.5µg/kg; F5=5µg/kg; F10=10µg/kg) given IV over 5min, with a wash-out period of 10 days. To evaluate thermal (°C) and mechanical (N) nociceptive threshold single stimulations were applied prior to (baseline) and 10, 30, 60, 90, 120, 180, 240, 300, 360, 420, 540min and 22.5h after treatment. Plasma fentanyl concentrations were measured at specific time points. Locomotor activity, heart rate, respiratory rate and gastrointestinal sounds were recorded. Two-way repeated measures ANOVA and pairwise comparisons were used for data analysis (P<0.05). With treatment F10, there was a significant increase in thermal threshold above baseline (47.2ö4.1°C) at t10 (53.7ö4.2°C) and t30 (52.1ö5.6°C), whereas mechanical threshold increased considerably above baseline (3.7ö1.3N) only at t10 (6.6ö3.6N). Estimated mean minimum anti-nociceptive plasma concentration determined by thermal stimulation was 6.1-6.8ng/mL. Dose-dependent increased locomotion occurred, but no significant changes in heart rate, respiratory rate and gastrointestinal sounds were observed. Fentanyl IV at 10µg/kg produced anti-nociception for 10-30min and fentanyl plasma concentrations of ≥6.1-6.8ng/mL appear necessary to induce thermal anti-nociception. Dose-dependent increased locomotion was the main side effect observed.

Development and clinical evaluation of a new sensor design for buccal pulse oximetry in horses.

BACKGROUND: The use of pulse oximetry in horses is limited due to inadequate readings with conventional transmission sensor probes. OBJECTIVES: The objectives of this study were to 1) develop an improved sensor design for horses to be used at an appropriate anatomical site, and 2) evaluate this design in an experimental study. STUDY DESIGN: In vivo experiment. METHODS: A new sensor design for reflectance pulse oximetry at the buccal mucosa was developed. A conventional Nonin 2000SL sensor for transmission pulse oximetry was included into this design. Three different prototypes (N1, N2a, N2b) were constructed and used with the Nonin 2500A Vet pulse oximetry monitor. Thirteen anaesthetised warmblood horses were included into a desaturation protocol (100-70% SaO2 ). SpO2 and pulse frequency values were recorded, using SaO2 calculated from blood gas analysis and invasive pulse frequency measurements as reference methods. Bias and precision were evaluated by calculations of the root mean square deviation (Arms ). The agreement of the methods was tested with Bland-Altman analysis. RESULTS: The quality of the pulse frequency readings determined the quality of the SpO2 -readings. Good pulse signal strength resulted in a SpO2 -accuracy comparable to that of the original sensor (Nonin 2000SL: Arms = 3%; N1: Arms = 3.60%; N2b: Arms = 3.46%). Especially at heart rates ≤30 bpm, pulse rate readings that were about twice as high as the reference value occurred. Their exclusion from the dataset resulted in a pulse rate accuracy similar to that of the original sensor. Bland-Altman plots showed limits of agreement typical of pulse oximeters. MAIN LIMITATIONS: The pulse frequency accuracy requires further improvement. The usability in clinical cases needs to be tested. CONCLUSIONS: The new sensor design has been shown to be suitable for buccal pulse oximetry in horses.

Evaluation of intravenous regional anaesthesia and four-point nerve block efficacy in the distal hind limb of dairy cows.

BACKGROUND: Intravenous regional anaesthesia (IVRA) and hindfoot four-point nerve block anaesthesia (NBA) are recommended for local anaesthesia (LA) in the distal limb of dairy cows. Two studies were conducted to compare the efficacy, time until onset and stress responses to IVRA and NBA in dairy cows. In the first cross-over designed study, eight healthy unsedated German Holstein cows, restrained in lateral recumbency (LR) on a surgical tipping table, were treated with IVRA and NBA using procaine 2% as a local anaesthetic. Distal limb desensitization was tested by electrical (e-), mechanical (m-) and thermal (t-) nociceptive stimulation 10 min before and 15 and 30 min after LA. Hormonal-metabolic (blood concentrations of cortisol, lactate, non-esterified fatty acids, and glucose) and cardio-respiratory (heart and respiratory rate, mean arterial blood pressure) stress responses to treatment were assessed at predetermined intervals. In the second study, six healthy, unsedated German Holstein cows in LR were treated (crossover design) with IVRA and NBA. Short-interval e-stimulation was measured by the time until complete distal limb desensitization. RESULTS: In the first study, four of eight cows responded to e-stimulation 15 min after IVRA, while none of the cows treated with NBA responded until the safety cut-off level was reached. E-stimulation revealed complete desensitization of the distal limb 30 min after LA in all cows. Half of the cows did not respond to m- and t-stimulation before LA, so no further evaluation was performed. Stress reactions to IVRA and NBA treatment were similar, but differences may have been masked by stress response to LR restraint. In the second study, complete desensitization was achieved 12.5 min after NBA, while one of the six cows still responded to e-stimulation 20 min after IVRA. CONCLUSION: Hindfoot nerve block anaesthesia and intravenous regional anaesthesia induced complete desensitization of the distal hind limb in dairy cows. However, the anaesthesia onset after NBA was significantly faster than that of IVRA, which may be clinically relevant in the field, particularly when distal limb anaesthesia is required for major claw surgeries under time constraints.

Effects of positive end-expiratory pressure titration on intestinal oxygenation and perfusion in isoflurane anaesthetised horses.

REASONS FOR PERFORMING STUDY: High airway pressures, necessary to keep equine lungs open, can have a detrimental impact on central and peripheral perfusion. OBJECTIVE: The aim of this study was to assess the effects of stepwise increasing airway pressure recruitment on central and intestinal perfusion and oxygenation during isoflurane anaesthesia in horses. STUDY DESIGN: In vivo experimental study. METHODS: Ten anaesthetised horses were ventilated using intermittent positive pressure ventilation immediately after induction. After 90 min, end-expiratory pressure (PEEP) was increased by steps of 5 cmH2 O every 10 min up to a PEEP of 30 cmH2 O and decreased back to zero maintaining a constant airway pressure difference of 20 cmH2 O. Mean arterial blood pressure (MAP), heart rate, central venous pressure, pulmonary artery pressure, expiratory isoflurane concentration and cardiac output (thermodilution method) were measured. Cardiac index (CI) was calculated. Arterial blood gases were taken to measure arterial partial oxygen pressure (PaO2 ) and calculate arterial oxygen saturation (SaO2 ). Intestinal microperfusion and oxygenation were measured by laser Doppler flowmetry and white-light spectrophotometry. After ventral median laparotomy, a probe was placed on the stomach, jejunum and pelvic flexion of the colon. An ANOVA for repeated measurements and Tukey's post hoc test were used for statistical analysis (α = 5%). RESULTS: Recruitment of the lungs resulted in a significant increase in PaO2 from 201 ± 58 mmHg (baseline) to a maximum of 495 ± 75 mmHg. The CI and MAP decreased continuously with increasing airway pressures. When CI and MAP were 37 ± 9 ml/kg/min and 52 ± 8 mmHg (at PEEP of 25 cmH2 O), respectively, a sudden decrease in intestinal perfusion followed by a delayed decrease in oxygenation occurred. CONCLUSIONS: There was linear correlation between airway pressures and CI and MAP but not between central and gastrointestinal perfusion. Despite improvement of arterial oxygenation the decrease in CI and, therefore, in oxygen delivery PEEP resulted in a decrease in gastrointestinal oxygenation.

Transcranial magnetic stimulation with acepromazine or dexmedetomidine in combination with levomethadone/fenpipramide in healthy Beagle dogs.

The aim of this study was to evaluate the influence of two sedation protocols on transcranial magnetic motor evoked potentials (TMMEPs) after transcranial magnetic stimulation in medium sized dogs. Onset latencies and peak-to-peak amplitudes, elicited in the extensor carpi radialis and cranial tibial muscles, were analysed in 10 healthy Beagles that received either acepromazine or dexmedetomidine in combination with levomethadone/fenpipramide, in a crossover design. Similar TMMEP recordings could be made using both sedation protocols at 80-90% stimulation intensity; however, there were significantly shorter onset latencies with the acepromazine-levomethadone/fenpipramide protocol at 100% stimulation intensity. Reference values were established and it was concluded that both drug combinations are feasible for measuring TMMEPs in medium sized dogs.

Histopathological changes and mRNA expression in lungs of horses after inhalation anaesthesia with different ventilation strategies.

Inappropriate mechanical ventilation can lead to ventilator-induced lung injury (VILI). Aim of this study was to evaluate the effects of inhalation anaesthesia and ventilation with and without recruitment (RM) and PEEP titration on alveolar integrity in horses. Twenty-three horses were divided into 4 groups (group OLC ventilated with OLC, group IPPV ventilated with intermittent positive pressure ventilation, group NV non-ventilated, and group C non-anaesthetized control group). After sedation with xylazine and induction with diazepam and ketamine anaesthetized horses were under isoflurane anaesthesia for 5.5h. The horses were euthanized and tissue samples of the dependent and non-dependent lung areas were collected. Histopathological examinations of the lung tissue as well as relative quantification of mRNA of IL-1ß, IL-6, iNOS, MMP1 and MMP9 by PCR were performed. Horses of group OLC had significantly less alveolar congestion and atelectasis but greater alveolar overdistension compared to groups NV and IPPV. In groups OLC and group IPPV an increase in IL-1ß/6 and MMP1/9 was detected compared to groups NV and C. In conclusion, in breathing spontaneously or IPPV-ventilated horses a higher degree of atelectasis was detected, whereas in OLC-ventilated horses a higher degree of overdistention was present. Elevated levels in IL and MMP might be early signs of VILI in ventilated horses.

Temporal and concentration effects of isoflurane anaesthesia on intestinal tissue oxygenation and perfusion in horses.

The aim of this study was to assess the effect of duration of anaesthesia and concentration of isoflurane on global perfusion as well as intestinal microperfusion and oxygenation. Nine Warmblood horses were premedicated with xylazine; anaesthesia was induced with midazolam and ketamine, and maintained with isoflurane. Horses were ventilated to normocapnia. During 7 h of anaesthesia, mean arterial blood pressures (MAP), heart rate, central venous pressure, pulmonary artery pressure, expiratory isoflurane concentration (ETIso) and cardiac output using lithium dilution were measured; cardiac index (CI) was calculated. Intestinal microperfusion and oxygenation were measured using laser Doppler flowmetry and white-light spectrophotometry. Surface probes were placed via median laparotomy on the serosal and mucosal site of the jejunum and the pelvic flexion of the colon. After 3 h of constant ETIso (1.4%), ETIso was increased in 0.2% increments up to 2.4%, followed by a decrease to 1.2% and an increase to 1.4%. The CI and MAP decreased continuously with increasing ETIso to 40 ± 5 mL/kg/min and 52 ± 8 mmHg, respectively. Microperfusion and oxygenation remained unchanged until an ETIso of 2.0% resulted in CI and MAP of 48 ± 5 mL/kg/min and 62 ± 6 mmHg, respectively, and then decreased rapidly. When ETIso decreased back to baseline, CI, MAP, microperfusion and oxygenation recovered to baseline. Isoflurane concentration but not duration of isoflurane anaesthesia influenced central and intestinal oxygenation and perfusion in healthy horses. Under isoflurane, intestinal perfusion appeared to be preserved until a threshold MAP or blood flow was reached.

[Evaluation of heart rate variability for monitoring the depth of anaesthesia in dogs. Investigations based on total intravenous anaesthesia using propofol alone or in combination with dexmedetomidine or remifentanil]. / Evaluation der Herzratenvariabilität als Narkosetiefenmonitoring beim Hund. Untersuchung anhand total intravenöser Propofolanästhesie allein sowie in Kombination mit Dexmedetomidin oder Remifentanil.

OBJECTIVE: Evaluation of heart-rate variability (HRV) as an indicator for autonomous activity to monitor anaesthesia in dogs during three different total intravenous anaesthetic protocols and three anaesthetic depth levels as well as before and after electrical nociceptive stimulation. MATERIAL AND METHODS: Seven beagle dogs (14.3±1.7 kg) were used in a randomised experimental trial with a complete cross-over design. Each dog went through all three anaesthetic protocols, which were propofol alone (group P) and propofol combined with dexmedetomidine (3 µg/kg/h, group PD) or remifentanil (18 µg/kg/h, group PR). Propofol was given using target-controlled infusion. Three anaesthetic depth levels (light, medium, deep) were defined by target concentrations for propofol in the blood and were adapted to the individual animal and treatment (mean of 7, 9 and 11 µg/ml, and in combination with dexmedetomidine or remifentanil, a mean of 3, 5 and 7 µg/ml). During each anaesthetic level, a standardised supramaximal nociceptive electric stimulus (50 Hz, 50 V, 10 ms) was applied medially to the right forearm. The bipolar-derived electrocardiogram (ECG) was recorded continuously. For each anaesthetic depth, the RR-intervals recorded 2 minutes before and after each stimulation were included in the statistical analysis. Using an HRV analytical program (Kubios HRV), the frequency domain HRV-parameters low (LF) and high (HF) frequency and the time-domain HRV-parameters RR-intervals, standard deviation of all RR-intervals (SDNN) and the square root of the mean of the sum of the squares of the differences between consecutive RR-intervals (RMSSD) were determined. RESULTS: Neither the RR-intervals nor the currently available HRV-parameters which were derived from the RR-intervals were able to discriminate between the different anaesthetic depths levels. Nociception could only be represented by the RR-intervals. CONCLUSION: Overall, the investigated standard HRV parameters offered no additional information for the monitoring of anaesthetic depths at the investigated, clinically used dose rates.

Comparison of stroke volume and cardiac output as measured by a single observer using four different ultrasound techniques in six clinically healthy cats.

The aim of this study was to assess agreement and repeatability of four ultrasound methods for measuring stroke volume (SV) and cardiac output (CO) in cats. Measurement of SV and CO was performed by the Teichholz method, the Simpson's method (SM), the area length method (ALM) and a volumetric flow method across the aorta (Trace method). For each method, the coefficient of variation (CV) was calculated and agreement was determined by Bland-Altman analysis. The CV was acceptable (<20%) for all parameters, except for SV and CO obtained by SM (28.8% and 22.4%, respectively) and ALM (21.6% and 22.6%, respectively). Narrow limits of agreement were observed between both planimetric methods (SM and ALM). The Trace method was the most repeatable, followed by the Teichholz method. Despite excellent inter-method agreement, neither of the planimetric methods produced results with adequate repeatability. As the Teichholz and Trace methods were acceptably repeatable, and probably gave the most representative values, they appear to be the most useful methods for the measurement of SV and CO in cats. Further investigations are needed to compare the echocardiographic methods described here with a standard technique such as thermodilution.

Activation procedures in the electroencephalograms of healthy and epileptic cats under propofol anaesthesia.

The current study evaluated the diagnostic value of electroencephalographic recordings (EEG) in cats with epilepsy under special consideration of photic stimulation and hyperventilation. EEGs in six healthy cats were recorded under light (mean dose of 0.23 mg/kg/min) and deep (mean dose of 0.7 mg/kg/min) propofol anaesthesia, whereas EEGs in 13 diseased cats were recorded under a propofol anaesthesia which was kept as light as possible (mean dose of 0.39 mg/kg/min). Paroxysmal discharges were detected in six of 13 cats suffering from seizures (two cats with idiopathic epilepsy and four cats with symptomatic epilepsy). Activation techniques did not enhance the diagnostic value of the EEGs. Photic driving was detected in one of six healthy cats under light, in five of six healthy cats under deep propofol anaesthesia and in 11 of 13 cats with seizures. Systematic use of activation techniques does not seem to increase the diagnostic yield of the recorded EEGs and should not be used in a clinical setting until future studies indicate value. Further investigations into the origin of photic driving under propofol anaesthesia are needed and could lead to the development of a reliable animal model to research into drug effects on the EEG.

[Clinical usability and practicability of Alfaxalone for short-term anaesthesia in the cat after premedication with Buprenorphine]. / Klinische Anwendbarkeit und Praktikabilität von Alfaxalon zur Kurzanästhesie bei der Katze nach Prämedikation mit Buprenorphin.

UNLABELLED: Objective of this clinical study was to assess the anaesthetic quality (induction and recovery) and utility of short term alfaxalone anaesthesia in healthy and diseased cats. Cardiopulmonary effects and the influence on haematological and biochemical blood parameters were evaluated. MATERIAL AND METHODS: Twenty feline patients (ASA1-4) were anaesthetized with alfaxalone for various short surgical or diagnostic procedures. Heart rate, breathing rate, end-tidal CO2 partial pressure, arterial oxygen saturation, mean arterial blood pressure and the body temperature were measured and recorded every 10 minutes. Before, after and 6 hours after anaesthesia venous blood samples were taken and haematologic and blood chemistry parameters were determined. Recovery time and quality were assessed by a numerical rating scale. RESULTS: Anaesthetic induction was rapid and smooth in all cats. Spontaneous respiration was maintained in all cats. Cardiopulmonary parameters mostly remained within a clinically tolerable range. Noticeable was a high heart rate (mean >190 bpm) at the beginning of anaesthesia lasting up to 10 minutes. Statistically significant changes (p<0.05) occurred in some haematologic parameters (RBC, haemoglobin, haematocrit and MCV decreased), electrolytes and venous acid-base-status (bicarbonate, chloride and base excess increased, sodium and potassium decreased) and blood chemistry parameters (alanine aminotransferase, glutamate dehydrogenase and creatinine decreased). None of these changes appeared to have clinical relevance. Recovery was smooth in the majority of cats. Mild signs of hyperexcitability (muscle tremor, short term opisthotonus and hyperacusis) occurred in individual animals. The duration of recovery varied between 21 and 93 minutes. CONCLUSION AND CLINICAL RELEVANCE: Alfaxalone by repeated intravenous injection is suitable for short-term diagnostic and surgical procedures in cats. Because of its minor cardiovascular effects and slight respiratory depression, it is also well tolerated by patients with increased anaesthetic risk (ASA 3 and 4).

A small, silent, low friction, linear actuator for mechanical nociceptive testing in veterinary research.

Air pressure is commonly used to drive a mechanical stimulus for nociceptive threshold testing. This may be bulky, noisy, non-linear and suffer from friction, hence development of a better system is described. A novel, light (14 g) rolling diaphragm actuator was constructed, which supplied 20 N force via a constant actuation area irrespective of the pressure and position in the stroke. Three round-ended pins, 2.5 mm diameter, mounted in a triangle on the piston, provided the stimulus. Pressure was increased manually using a syringe with the rate of rise of force controlled at 0.8 N/s by warning lights. The pressure/force relationship was calibrated using a static force transducer and mercury column. Data were collected with the actuator attached to the antero-medial radius of 12 cats and four dogs. Mechanical threshold was recorded when the animal withdrew the limb and/or turned towards the actuator. Safety cut-off was 20 N. The pressure/force relationship was linear and independent of the start point in the actuator stroke. Baseline feline thresholds were 10.0 +/- 2.5 N (mean +/- SD), which increased significantly 30 min after butorphanol administration. Baseline canine thresholds were 5.5 +/- 1.4 N and increased significantly between 15 and 45 min after administration of fentanyl or butorphanol. The system overcame the problems of earlier devices and detected an opioid-induced increase in threshold. It has considerable advantages over previous systems for research in analgesia.

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.

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.

Cardiopulmonary effects of dexmedetomidine in goats and sheep anaesthetised with sevoflurane.

In sheep, alpha(2)-agonists can induce severe hypoxaemia. In goats, reports on changes in oxygenation are inconsistent. The aim of this study was to compare the cardiopulmonary effects of dexmedetomidine in six goats and four sheep anaesthetised with sevoflurane and maintained at approximately 1 minimal alveolar concentration. The animals were ventilated mechanically and held in an upright position to minimise the influence of positioning on pulmonary function. After baseline cardiopulmonary measures, 2 microg/kg dexmedetomidine was injected intravenously over one minute, and measurements were made for 120 minutes. In both species, respiratory resistance, alveolar dead space and shunt fraction increased and thoracic compliance decreased significantly; arterial, pulmonary arterial, pulmonary capillary wedge and central venous pressures increased and heart rate and cardiac output decreased significantly. Arterial oxygen tension decreased significantly, with no significant difference between the goats and sheep. Wide interindividual differences were observed in both the goats (mean [sd] 144 [149.1] mmHg, range 54.8 to 443.7 mmHg) and sheep (mean [sd] 129.8 [132.1] mmHg, range 33.7 to 352.8 mmHg), but the cardiovascular and respiratory changes were similar in the two species.

Mosaicplasty with photooxidized, mushroom shaped, bovine, osteochondral xenografts in experimental sheep.

The goal was to study the performance of mushroom shaped, photooxidized, osteochondral grafts in mosaicplasty focusing on graft stability and survival. Mushroom shaped, photooxidized grafts (6 mm for the cartilaginous head of the mushroom, 3 mm for the stem) were implanted in the medial femoral condyle of 10 sheep. Four transplants were inserted per condyle in an overlapping fashion using the pressfit technique (n=40 grafts in 10 condyles). The grafts were followed for 6 and 12 months. Semi-quantitative evaluation of graft performance was performed using a validated score system. All grafts were mechanically stable at 6 and 12 months with one exception, where the mushroom head broke off. The formation of cystic lesions in the subchondral bone area was minimal. Repopulation of the old photooxidized cartilage was noticed with cells invading the matrix from the subchondral bone area and also from the pannus on the surface. Fusion between host and graft cartilage was observed in some of the grafts at 12 months, while remodeling of the calcified cartilage zone and tidemark was noticed in all grafts. Results scored significantly better for the 6 months compared to the 12 months group if cartilage surface integrity was compared (p<0.05). In all other variables no significant differences were found between groups. Despite moderate graft recession in the 12 months group partial fusion of grafts and functional results were satisfactory. The photooxidized mushroom shaped osteochondral transplants may be a suitable type of graft for functional results in cartilage resurfacing if stable anchorage of the grafts can be achieved.

The effects of automated plasmapheresis on clinical, haematological, biochemical and coagulation variables in horses.

The goal of this study was to determine the effects of plasmapheresis on the behaviour, general condition, haematological, biochemical and coagulation variables of donor horses for 32 days following the procedure. Twenty millilitres of plasma/kg body weight were collected via plasmapheresis in six clinically healthy horses. The general behaviour and condition of the horses was not affected by the procedure. During plasmapheresis, there was a mild increase in the haematocrit, haemoglobin concentration and total erythrocyte and leucocyte counts (P < 0.01). The mean concentrations of total protein and albumin decreased significantly (P < 0.01) and total protein did not normalise for about three weeks. Several other biochemical variables also decreased significantly during plasmapheresis, but mostly remained within reference ranges. After plasmapheresis, the mean value of the activated partial thromboplastin time and the thrombin time were mildly but significantly increased (P < 0.01), and the mean activities of factor V, factor VIII and antithrombin decreased significantly (P < 0.01), although all coagulation values remained within reference ranges. Our results indicate that, in horses, the collection of 20 mL of plasma/kg body weight via plasmapheresis results in mild changes in several haematological, biochemical and coagulation variables, although these were of no clinical relevance for the donors.

Pharmacokinetics of recombinant hirudin in healthy horses.

REASONS FOR PERFORMING STUDY: Recombinant (r)-hirudin is a specific inhibitor of thrombin that is independent of the activity of antithrombin. OBJECTIVES: To evaluate pharmacokinetic properties and coagulatory changes of r-hirudin in healthy horses. METHODS: Two clinically healthy horses received a single i.v. bolus of 0.4 mg/kg bwt r-hirudin and 6 clinically healthy horses received the same dose subcutaneously (subcut.) q. 12 h for 3 days. Coagulation times and r-hirudin plasma concentration were determined over 720 mins and 3 days after i.v. and subcut. administration, respectively. RESULTS: In all horses, treatment with r-hirudin was not associated with systemic or local side effects. After i.v. injection, the 2 horses showed an elimination half-life of 58 and 80 mins, respectively. After subcut. administration, maximum plasma concentration of r-hirudin occurred at 128 +/- 55 mins and declined with a terminal half-life of 561 +/- 364 mins. Maximum response of activated partial thromboplastin time (aPTT) occurred 1.5 h after administration of r-hirudin. A prolongation of 1.9 +/- 0.2 times the pretreatment value was noted. CONCLUSIONS: Pharmacokinetics of r-hirudin in healthy horses were similar to those in man and other animal species. POTENTIAL RELEVANCE: The results of this study indicate that r-hirudin can be used in horses, but further studies should be performed in order to prove its effectiveness in diseased horses.