Pharmacokinetics and pharmacodynamics of intravenous dexmedetomidine in the horse.

The aim of the study was to describe the pharmacokinetics and selected pharmacodynamics of intravenous dexmedetomidine in horses. Eight adult horses received 5 µg/kg dexmedetomidine IV. Blood samples were collected before and for 10 h after drug administration to determine dexmedetomidine plasma concentrations. Pharmacokinetic parameters were calculated using noncompartmental analysis. Data from one outlier were excluded from the statistical summary. Behavioral and physiological responses were recorded before and for 6 h after dexmedetomidine administration. Dexmedetomidine concentrations decreased rapidly (elimination half-life of 8.03 ± 0.84 min). Time of last detection varied from 30 to 60 min. Bradycardia was noted at 4 and 10 min after drug administration (26 ± 8 and 29 ± 8 beats/min respectively). Head height decreased by 70% at 4 and 10 min and gradually returned to baseline. Ability to ambulate was decreased for 60 min following drug administration, and mechanical nociceptive threshold was increased during 30 min. Blood glucose peaked at 30 min (134 ± 24 mg/dL) and borborygmi were decreased for the first hour after dexmedetomidine administration. Dexmedetomidine was quickly eliminated as indicated by the rapid decrease in plasma concentrations. Physiological, behavioral, and analgesic effects observed after dexmedetomidine administration were of short duration.

Preliminary pharmacokinetics of morphine and its major metabolites following intravenous administration of four doses to horses.

The objective of the current study was to describe the pharmacokinetics of morphine and its metabolites following intravenous administration to the horse. A total of eight horses (two per dose group) received a single intravenous dose of 0.05, 0.1, 0.2, or 0.5 mg/kg morphine. Blood samples were collected up to 72 h postdrug administration, analyzed using LC-MS/MS and pharmacokinetic parameters determined. Behavior, step counts, and gastrointestinal activity were also assessed. The beta and gamma half-life for morphine ranged from 0.675 to 2.09 and 6.70 to 18.1 h, respectively, following administration of the four different IV doses. The volume of distribution at steady-state and systemic clearance ranged from 6.95 to 15.8 L/kg and 28.3 to 35.7 mL · min/kg, respectively. The only metabolites identified in blood samples were the primary metabolites identified in other species, 3-morphine-glucuronide and 6-morphine-glucuronide. Muscle fasciculations were observed at 0.2 and 0.5 mg/kg and ataxia noted at 0.5 mg/kg. Gastrointestinal activity was decreased in all dose groups (for up to 8 h in 7/8 horses and 24 h in one horse). This study extends previous studies and is the first report describing the metabolites of morphine in the horse. Plasma concentrations of morphine-3-glucuronide, a metabolite with demonstrated neuro-excitatory activity in mice, far exceeded that of morphine-6-glucuronide. Further study is warranted to assess whether the high levels of the morphine-3-glucuronide contribute to the dose-dependent excitation observed at high morphine doses.

Pharmacokinetics and pharmacodynamics of three intravenous doses of yohimbine in the horse.

Yohimbine is an alpha 2 adrenergic receptor antagonist, which has been shown to counteract the CNS depressant effects of alpha 2 receptor agonists in a number of species. Recently, our laboratory identified yohimbine in the absence of detectable concentrations of an alpha 2 agonist in a regulatory sample collected from a horse racing in California. This coupled with anecdotal reports of CNS stimulation and documented reports of cardiovascular changes when administered in conjunction with an agonist led us to investigate the pharmacokinetics and pharmacodynamics of yohimbine when administered alone. Nine healthy adult horses received a single intravenous dose of 0.1, 0.2, and 0.4 mg/kg yohimbine. Blood samples were collected at time 0 (prior to drug administration) and at various times up to 24 h postdrug administration. Plasma samples were analyzed using liquid chromatography-mass spectrometry (LC-MS), and resulting data analyzed using both noncompartmental and compartmental analysis. Peak plasma concentrations were 106.0 ± 28.9, 156.7 ± 34.3, and 223.0 ± 44.5 ng/mL for doses of 0.1, 0.2, and 0.4 mg/kg, respectively. Immediately following administration, two horses showed signs of sedation, one horse appeared excited, while the other six appeared behaviorally unaffected. Episodes of tachycardia were noted within minutes of administration for all horses at all doses; however, there was no correlation between behavioral responses and episodes of increased heart rate. Sixty-three percent of the horses (8, 6, and 4 of the 9 horses in the 0.1, 0.2, and 0.4 mg/kg dose groups, respectively) exhibited second-degree atrial-ventricular conduction blocks and bradycardia prior to drug administration that transiently improved or disappeared upon administration of yohimbine. Gastrointestinal sounds were transiently increased following all doses.

Pharmacokinetics of yohimbine following intravenous administration to horses.

Yohimbine is an alpha 2 adrenergic receptor antagonist used most commonly in veterinary medicine to reverse the effects of the alpha 2 receptor agonists, xylazine and detomidine. Most notably, yohimbine has been shown to counteract the CNS depressant effects of alpha 2 receptor agonists in a number of species. The recent identification of a yohimbine positive urine sample collected from a horse racing in California has led to the investigation of the pharmacokinetics of this compound. Eight healthy adult horses received a single intravenous dose of 0.12 mg/kg yohimbine. Blood samples were collected at time 0 (prior to drug administration) and at various times up to 72 h post drug administration. Plasma samples were analyzed using liquid chromatography-mass spectrometry (LC-MS) and data analyzed using both noncompartmental and compartmental analysis. Peak plasma concentration was 114.5 + 31.8 ng/mL and occurred at 0.09 + 0.03 h. Mean ± SD systemic clearance (Cls) and steady-state volume of distribution (Vdss) were 13.5 + 2.1 mL/min/kg and 3.3 + 1.3 L/kg following noncompartmental analysis. For compartmental analysis, plasma yohimbine vs. time data were best fitted to a two compartment model. Mean ± SD Cls and Vdss of yohimbine were 13.6 ± 2.0 mL/min/kg and 3.2 ± 1.1 L/kg, respectively. Mean ± SD terminal elimination half-life was 4.4 ± 0.9 h following noncompartmental analysis. Immediately following administration, two horses showed signs of sedation, while the other six appeared behaviorally unaffected. Gastrointestinal sounds were moderately increased compared to baseline while fecal consistency appeared normal.

Pharmacokinetic profile in relation to anaesthesia characteristics after a 5% micellar microemulsion of propofol in the horse.

BACKGROUND: To define the pharmacokinetic profile of propofol 5% microemulsion formulation in horses. METHODS: First, propofol was administered as bolus injection (2 mg kg(-1)) to six xylazine-sedated horses. Secondly, after sedation and bolus injection, propofol was maintained with continuous infusion for 3 h [8.1 (sd 3.2) mg kg(-1) h(-1)] to the same six horses. Thirdly, in two horses, a commercial propofol was used for comparison. Response to noxious stimulation was used to evaluate analgesia. Venous blood samples were obtained to measure propofol plasma concentration using liquid chromatography-mass spectrometry analysis. The plasma concentrations were related to the anaesthesia characteristics to determine the ED(50). RESULTS: The pharmacokinetic profile of propofol is best characterized by a non-compartmental model. The mean (confidence interval) for area under plasma concentration-time curve, elimination half-life, mean residence time, and clearance was 41 min microg ml(-1) (+/-7.7), 44.8 min (+/-21.3), 13.7 min (+/-3.2), and 45.8 ml min(-1) kg(-1) (+/-6.5), respectively. Linear regression analysis showed a correlation between plasma concentration and infusion rate (r(2)=0.47). Most propofol infusion rates did not inhibit the response to noxious stimulation and rates above 11.9 mg kg(-1) h(-1) caused involuntary muscle contractions. Better recoveries were associated with lower propofol plasma concentrations. Propofol plasma concentration frequently increased when horses woke from anaesthesia. CONCLUSIONS: Caution is warranted when propofol is used for continuous infusion due to variable kinetics, myoclonal activity, poor analgesia, and less desirable recovery quality.

Qualitative and quantitative characteristics of the electroencephalogram in normal horses during spontaneous drowsiness and sleep.

BACKGROUND: The influence of sleep on the equine electroencephalogram (EEG) has not been well documented. HYPOTHESIS: The objectives were to develop a noninvasive method of electrode placement for recording the EEG in horses and to establish normal EEG parameters for the various states of vigilance. Findings are compared with previously published reports on equine sleep based on electrocorticography (ECoG). ANIMALS: Five neurologically normal horses. METHODS: Overnight EEGs were recorded digitally in association with simultaneous videotaping of the horses' behavior. Data were analyzed by visual inspection, states of vigilance were identified, and representative segments were quantitatively processed. Transient EEG events were examined. RESULTS: Slow wave sleep (SWS) was significantly different (P < .05) in frequency and power from drowsiness and rapid eye movement (REM) sleep. Second-degree heart block was associated with SWS as were transient events commonly recognized in EEGs of humans. Drowsiness and REM sleep were similar. In both, background activity was low-amplitude beta activity admixed with prominent activity of approximately 4 Hz. Standing REM sleep was associated with numerous partial collapses in 1 horse. CONCLUSIONS AND CLINICAL IMPORTANCE: Normative data for several states were described and probable benign variants identified. This information will serve as control data for sedative and anesthetic studies in this species. The sleep patterns observed during this study are those of horses removed from their usual surroundings, and thus may represent those encountered in a clinical environment.

Influence of general anaesthesia on the pharmacokinetics of intravenous fentanyl and its primary metabolite in horses.

REASONS FOR PERFORMING STUDY: In order to evaluate its potential as an adjunct to inhalant anaesthesia in horses, the pharmacokinetics of fentanyl must first be determined. OBJECTIVES: To describe the pharmacokinetics of fentanyl and its metabolite, N-[1-(2-phenethyl-4-piperidinyl)maloanilinic acid (PMA), after i.v. administration of a single dose to horses that were awake in Treatment 1 and anaesthetised with isoflurane in Treatment 2. METHODS: A balanced crossover design was used (n = 4/group). During Treatment 1, horses received a single dose of fentanyl (4 microg/kg bwt, i.v.) and during Treatment 2, they were anaesthetised with isoflurane and maintained at 1.2 x minimum alveolar anaesthetic concentration. After a 30 min equilibration period, a single dose of fentanyl (4 microg/kg bwt, i.v.) was administered to each horse. Plasma fentanyl and PMA concentrations were measured at various time points using liquid chromatography-mass spectrometry. RESULTS: Anaesthesia with isoflurane significantly decreased mean fentanyl clearance (P < 0.05). The fentanyl elimination half-life, in awake and anaesthetised horses, was 1 h and volume of distribution at steady state was 0.37 and 0.26 l/kg bwt, respectively. Anaesthesia with isoflurane also significantly decreased PMA apparent clearance and volume of distribution. The elimination half-life of PMA was 2 and 1.5 h in awake and anaesthetised horses, respectively. CONCLUSIONS AND POTENTIAL RELEVANCE: Pharmacokinetics of fentanyl and PMA in horses were substantially altered in horses anaesthetised with isoflurane. These pharmacokinetic parameters provide information necessary for determination of suitable fentanyl loading and infusion doses in awake and isoflurane-anaesthetised horses.

Effects of age on the pharmacokinetics of tramadol and its active metabolite, O-desmethyltramadol following intravenous administration to foals.

REASONS FOR PERFORMING STUDY: Tramadol is an analgesic agent used in man and a number of veterinary species. The pharmacokinetics and behavioural effects of tramadol and its active metabolite have been described in mature horses, but not in young foals. OBJECTIVES: To characterise the pharmacokinetics, metabolism and some induced behavioural and physiological responses following i.v. tramadol administration in the same group of foals on 4 different occasions, from a few days after birth to age 43 days. STUDY DESIGN: Experimental. METHODS: Tramadol was administered i.v. (3 mg/kg bwt) to a group of 8 foals on 4 separate occasions at ages 6­8, 13­15, 20­22 and 40­43 days. Blood samples were collected prior to administration and at multiple times until 48 h post administration. Blood samples were analysed for tramadol and metabolite concentrations and pharmacokinetics determined at each age. Behavioural and physiological effects were also assessed. RESULTS: The average volume of distribution was 5.10, 4.63, 4.02 and 3.84 l/kg bwt and clearance 3.44, 3.08, 3.14 and 2.69 l/h/kg bwt when foals were aged 6­8, 13­15, 20­22 and 40­43 days, respectively. There was not a significant difference in the elimination half-life between age groups (1.52, 1.73, 1.13 and 1.51 for ages 6­8, 13­15, 20­22 and 40­43 days, respectively). The metabolites produced were the same as in mature horses; however, glucuronidation capability, appeared to increase with increasing age. Tramadol administration was well tolerated at all ages studied with sedation noted in the 3 older age groups. CONCLUSIONS: Tramadol appears to be consistently well tolerated following i.v. administration of 3 mg/kg bwt to foals ranging in age from 1 to 6 weeks. Although analgesic concentrations in foals have yet to be established, the results of this study support further study of tramadol for clinical use in foals.

Effects of estradiol on uterine perfusion in anesthetized cyclic mares affected with uterine vascular elastosis.

Uterine vascular elastosis in mares is characterized by degeneration of uterine vasculature through thickening of the elastin layers. Factors commonly associated with this degeneration include age, parity, and chronic uterine endometritis. Affected mares have also been shown to exhibit decreases in uterine blood flow and perfusion of the uterus. Due to the increased thickness of the elastin layers, we hypothesize that vasodilatation of the uterine vasculature is also impaired. To test the functionality of these vessels, we evaluated the vasodilatory effects of estradiol on the uterine vascular bed in mares with normal vasculature and mares with severe elastosis. Both groups were tested in estrus and diestrus. Fluorescent microspheres were used to determine basal blood perfusion, followed by the intravenous administration of 1.0 µg/kg of 17ß-estradiol. After 90 min, perfusion was measured once again to determine the vascular response to estradiol. Control mares in estrus displayed a significant increase in total uterine blood flow after the administration of estradiol when compared to baseline levels. No other group had a significant increase in total blood flow and perfusion after estradiol administration. The administration of estradiol in control mares induced regional increases in perfusion in the uterine horns and uterine body during estrus and only in the uterine horns during diestrus. Mares affected by elastosis exhibited no regional differences in perfusion levels post-estradiol administration. The difference in the vasodilatory response induced by estradiol between reproductively healthy mares and mares affected with elastosis indicates that the functionality of the affected vessels is compromised.

Electroencephalogram of Healthy Horses During Inhaled Anesthesia.

BACKGROUND: Previous study of the diagnostic validity of electroencephalography (EEG) to detect abnormalities in equine cerebral cortical function relied on the administration of various drugs for sedation, induction, and maintenance of general anesthesia but used identical criteria to interpret recordings. OBJECTIVES: To determine the effects of 2 inhalation anesthetics on the EEG of healthy horses. ANIMALS: Six healthy horses. METHODS: Prospective study. After the sole administration of one of either isoflurane or halothane at 1.2, 1.4, and 1.6 times the minimum alveolar concentration, EEG was recorded during controlled ventilation, spontaneous ventilation, and nerve stimulation. RESULTS: Burst suppression was observed with isoflurane, along with EEG events that resembled epileptiform discharges. Halothane results were variable between horses, with epileptiform-like discharges and bursts of theta, alpha, and beta recorded intermittently. One horse died and 2 were euthanized as the result of anesthesia-related complications. CONCLUSIONS AND CLINICAL IMPORTANCE: The results of this study indicate that the effects of halothane and isoflurane on EEG activity in the normal horse can be quite variable, even when used in the absence of other drugs. It is recommended that equine EEG be performed without the use of these inhalation anesthetics and that general anesthesia be induced and maintained by other contemporary means.

Qualitative and Quantitative Characteristics of the Electroencephalogram in Normal Horses during Administration of Inhaled Anesthesia.

BACKGROUND: The effects of anesthesia on the equine electroencephalogram (EEG) after administration of various drugs for sedation, induction, and maintenance are known, but not that the effect of inhaled anesthetics alone for EEG recording. OBJECTIVE: To determine the effects of isoflurane and halothane, administered as single agents at multiple levels, on the EEG and quantitative EEG (qEEG) of normal horses. ANIMALS: Six healthy horses. METHODS: Prospective study. Digital EEG with video and quantitative EEG (qEEG) were recorded after the administration of one of the 2 anesthetics, isoflurane or halothane, at 3 alveolar doses (1.2, 1.4 and 1.6 MAC). Segments of EEG during controlled ventilation (CV), spontaneous ventilation (SV), and with peroneal nerve stimulation (ST) at each MAC multiple for each anesthetic were selected, analyzed, and compared. Multiple non-EEG measurements were also recorded. RESULTS: Specific raw EEG findings were indicative of changes in the depth of anesthesia. However, there was considerable variability in EEG between horses at identical MAC multiples/conditions and within individual horses over segments of a given epoch. Statistical significance for qEEG variables differed between anesthetics with bispectral index (BIS) CV MAC and 95% spectral edge frequency (SEF95) SV MAC differences in isoflurane only and median frequency (MED) differences in SV MAC with halothane only. CONCLUSIONS AND CLINICAL IMPORTANCE: Unprocessed EEG features (background and transients) appear to be beneficial for monitoring the depth of a particular anesthetic, but offer little advantage over the use of changes in mean arterial pressure for this purpose.

A new airway device for small laboratory animals.

There is a need for a device for improved management of the airway of small laboratory animals during general anaesthesia. This report introduces such a device, referred to here as the airway device (AD). The AD has some similarity to the laryngeal mask airway (LMA) developed for human patients, but the mask portion of the device is specifically designed for small laboratory animals. In addition, the device has an oesophageal extension and unlike the LMA does not have a cuff associated with the mask. This report also shares experience of tests of one prototype AD with six New Zealand white rabbits. The AD was used for administering isoflurane and its effectiveness was evaluated during conditions of spontaneous and controlled intermittent positive pressure ventilation. The results provide encouragement for further development of the AD for airway management of small laboratory animals.

Effects of vascular elastosis on uterine blood flow and perfusion in anesthetized mares.

In the uterus of the mare, data obtained using transrectal Doppler ultrasonography indicate that uterine blood flow (UBF) is dynamic and changes throughout the estrous cycle. Degenerative lesions in the uterus are associated with subfertility and infertility. Among these lesions, vascular elastosis has been reported in aged, multiparous, and infertile mares. Angiosis of the uterine vasculature could potentially compromise UBF. The objectives of this experiment are to determine levels of UBF and perfusion of reproductively healthy mares and compare them to levels of subfertile/infertile mares affected by uterine vascular elastosis. Twenty mares were classified on the basis of degree of vascular degeneration and stage of cycle. A fluorescent microsphere technique was used to measure reproductive organ perfusion, where microspheres were injected into the left ventricle of the heart and became trapped in capillary beds in proportion to blood flow and tissue perfusion. The reproductive tract was removed, sectioned, and the fluorescent intensity evaluated to measure blood flow and perfusion. Additionally, full-thickness samples of the uterine wall were examined postmortem to further assess the degree of vascular degeneration in all layers of uterine wall. The mean value of uterine perfusion for the control mares during estrus (n = 5) was higher (P < 0.01) than that during diestrus (n = 5); 17.6 and 11.9 mL/min/100g, respectively. For the subfertile/infertile mares, the mean value of tissue perfusion was not different (P > 0.05) during estrus (n = 5) and diestrus (n = 5); 5.9 and 7.2 mL/min/100g, respectively. Uterine perfusion in subfertile/infertile mares affected by elastosis was lower than that of control mares during both estrus (P < 0.01) and diestrus (P < 0.01). The differences in baseline levels of perfusion between the control and elastosis groups indicate that elastosis of the uterine vasculature is associated with decreased uterine perfusion during both phases of the estrous cycle. In the uterus, a compromise in UBF could have implications in endometrial glandular development, postbreeding endometritis, uterine clearance, development of the conceptus, and overall fertility.

Disposition, behavioural and physiological effects of escalating doses of intravenously administered fentanyl to young foals.

REASONS FOR PERFORMING STUDY: Foal responses to a broader range of plasma fentanyl concentrations than currently reported are desirable to support (or not) clinical use. OBJECTIVES: To describe fentanyl plasma concentrations following an escalating i.v. fentanyl dosing schedule in foals aged 5-13 days and describe selected, associated dose- and time-related behavioural and physiological responses to plasma fentanyl concentration. STUDY DESIGN: Experimental. METHODS: Fentanyl was administered i.v. in an escalating fashion (2, 4, 8, 16 and 32 µg/kg bwt) at 10-min intervals. Blood samples were collected before and at selected times until 24 h post administration. Blood samples were analysed for fentanyl and metabolite concentrations and correlated with behavioural and physiological observations and selected blood analytes. RESULTS: Foals mostly appeared to be unaffected following 2 µg/kg bwt (1.09 ± 0.41 µg/l; average maximal plasma concentration) of fentanyl, but 6 of the 8 foals appeared to be sedated following 4 µg/kg bwt (3.07 ± 1.11 µg/l). Ataxia with increased locomotor activity, muscle rigidity and head pressing posture was observed in many foals at 8 (7.24 ± 3.22 µg/l) and 16 µg/kg bwt (17.4 ± 5.67 µg/l). All foals were heavily sedated after 32 µg/kg bwt (34.5 ± 10.3 µg/l); 3 of the 8 foals became recumbent. The average (± s.d.) terminal half-life following administration of the final dose was 44.2 ± 9.85 min. CONCLUSIONS: Behavioural and physiological responses to i.v. fentanyl in young foals are dose related. As with mature horses, the window of fentanyl plasma concentrations related to possible clinically desirable actions appears relatively narrow.

Effects of age on the pharmacokinetics and selected pharmacodynamics of intravenously administered fentanyl in foals.

REASONS FOR PERFORMING STUDY: The use of fentanyl is limited in adult horses, in part due to potential for central nervous system excitation. The pharmacokinetics and the plasma concentration-related behavioural actions of fentanyl have not been described for young foals. OBJECTIVES: The goal of the present study was to describe the pharmacokinetics and behavioural effects of fentanyl following administration to the same group of foals at 3 different ages. STUDY DESIGN: Experimental study in healthy foals. METHODS: Fentanyl was administered i.v. (4 µg/kg bwt) to a group of 9 foals on 3 separate occasions at 6­8, 20­22 and 41­42 days of age. Blood samples were collected prior to administration and at multiple times until 24 h post administration. Blood samples were analysed for fentanyl concentrations and pharmacokinetics determined at each age. Behavioural and physiological effects were also assessed. RESULTS: The average volume of distribution was 3.55, 1.53 and 1.82 l/kg bwt and clearance 50.2, 40.7 and 35.7 ml/min/kg bwt when foals were 6­8, 20­22 and 41­42 days of age, respectively. The elimination half-life was slightly prolonged (49.3 min) at 6­8 days relative to 20­22 and 41­42 days of age (25.8 and 33.7 min, respectively). The primary metabolite detected in blood samples was the same as for adult horses. While the onset and duration varied widely between foals, sedation was observed at all ages studied. CONCLUSIONS: Fentanyl appears to be consistently well tolerated following i.v. administration of 4 µg/kg bwt to foals ranging in age from 1 to 6 weeks. The results of this study support further study of fentanyl for clinical use in foals.

Cardiopulmonary function during 7 h of constant-dose halothane and methoxyflurane.

Cardiopulmonary effects of prolonged, constant-alveolar-dose halothane (HAL) and methoxyflurane (MOF) in O2 anesthesia on spontaneously breathing dogs were determined. One hour after anesthetic induction, end-tidal concentration was set at 1.04% HAL or 0.28% MOF [each representing 1.2 minimum alveolar concentration (MAC) for dogs] and maintained for 7 h. No time-related changes were associated with MOF. However, HAL significantly (P less than 0.05) elevated cardiac output (Q) from 2 to 7 h by increasing stroke volume; mean aortic pressure (MAP) also increased with time (P less than 0.05 beginning at 5 h). Four of these dogs were studied again at least 3 wk later at a constant end-tidal dose of 1.48% HAL in O2 (1.7 MAC). Q and MAP were lower initially during 1.7 MAC than during 1.2 MAC but not after 2 h of anesthesia. The greater HAL dose initially depressed ventilation and elevated arterial partial pressure of CO2 (PaCO2) compared with the lower dose. PaCO2 continued to increase with duration of 1.7 MAC HAL, as did results of ventilatory gas volume and flow measurements.

Pulmonary blood flow distribution in anesthetized ponies.

Results of recent investigations in humans and dogs indicate that gravity-independent factors may be important in determining the distribution of pulmonary blood flow. To further evaluate the role of gravity-independent factors, pulmonary blood flow distribution was examined using 15-microns radionuclide-labeled microspheres in five prone ponies over 5 h of pentobarbital sodium anesthesia. The ponies were killed, and the lungs were excised and dried by air inflation (pressure 45 cmH2O). The dry lungs were cut into transverse slices 1-2 cm thick along the dorsal-ventral axis, parallel to gravity. Radioactivity of pieces cut from alternate slices was measured with a gamma well counter. The main finding was a preferential distribution of pulmonary blood flow to dorsal-caudal regions and higher flow in the center of each lung slice when compared with the slice periphery. Flow was lowest in cranial and ventral areas. Differences of +/- 2 SD were observed between core and peripheral blood flow. No medial-lateral differences were found. Pulmonary blood flow distribution did not change over 5 h of anesthesia, and the basic flow pattern was not different in the left vs. right lung. These results suggest that in the intact prone mechanically ventilated pony (inspired O2 fraction greater than or equal to 0.95) factors other than gravity are primary determinants of pulmonary blood flow.

Biochemical and haematological changes following prolonged halothane anaesthesia in horses.

Six healthy horses were anaesthetised with halothane (1.2 times the horse minimal alveolar concentration) in oxygen for more than 12 hours. Serum bilirubin, aspartate aminotransferase, alkaline phosphatase and L-iditol dehydrogenase values were significantly (P < 0.05) increased for up to nine days after anaesthesia. These changes suggest an anaesthesia related liver dysfunction. Creatine kinase increased to an average of more than 1400 IU litre-1 24 hours after anaesthesia and this change is indicative of muscle cell disruption. Renal-associated biochemical results, (that is serum creatinine and inorganic phosphate concentrations) were significantly increased transiently and are indicative of reduced renal function during and immediately after anaesthesia. Plasma concentrations of eicosanoids (6-keto-PGF1a, PGF2a, PGE and thromboxane) following anaesthesia were not different from preanaesthetic values. The magnitude of liver and muscle cell related increases in serum enzyme activities resulting from prolonged halothane anaesthesia was in excess of that previously reported for anaesthesia of shorter duration.

Effects of five hours of constant 1.2 MAC halothane in sternally recumbent, spontaneously breathing horses.

Circulatory and respiratory effects of five h of constant 1.06 per cent alveolar halothane in oxygen were identified in eight healthy horses, which breathed spontaneously, were otherwise unmedicated and positioned in sternal recumbency. Only a few important significant (P less than 0.05) changes occurred with time. Total peripheral resistance was about 15 per cent lower after two hours of constant dose halothane than after 30 mins of constant dose (P less than 0.05) and accounted for the significant 10 per cent reduction in mean carotid arterial blood pressure. By 5 h, the reduction in resistance and arterial blood pressure was 20 and 25 per cent respectively. Heart rate increased progressively with time and the increase became significant at 5 h (15 per cent increase). However, the heart rate change was not large enough to alter cardiac output. There were no major time-related changes in PaO2 or PaCO2. Three of four horses recovered from anaesthesia had markedly elevated serum creatine kinase levels and clinical signs of severe post anaesthetic myopathy.

Arterial blood PO2 and PCO2 in horses during early halothane-oxygen anaesthesia.

Arterial blood was collected from 25 clinically normal horses immediately before and serially throughout the first hour of halothane oxygen anaesthesia. Blood was analysed for oxygen and carbon dioxide partial pressure (PaO2, PaCO2). Measurements of inspired oxygen concentration during anaesthesia permitted direct correlation with blood gases. Horses were divided arbitrarily into two groups based on their age: two to seven years, n = 15; over seven years, n = 10. Average (+/- sd) PaO2 and PaCO2 was 14.1 +/- 1.5 kPa (106 +/- 11 mmHg) and 5.9 +/- 0.6 kPa (44.4 +/- 4.4 mmHg) respectively in conscious, young horses and 14.0 +/- 0.7 and 5.8 +/- 0.5 kPa (105 +/- 5 and 43.3 +/- 3.8 mmHg) respectively in conscious older horses. Arterial oxygen tension decreased to 9.3 +/- 1.0 and 8.5 +/- 1.4 kPa (69.6 +/- 7.8 and 63.7 +/- 10.4 mmHg) in young and older air breathing horses respectively immediately following intravenous anaesthetic induction, recumbency and orotracheal intubation. At this time, PaCO2 was 6.5 +/- 0.5 and 6.0 +/- 0.7 kPa (48.7 +/- 3.5 and 45.1 +/- 4.9 mmHg) respectively. By 30 mins after the start of halothane in oxygen (6 litres/min) anaesthesia PaO2 increased to a maximum in both study groups. Arterial PCO2 increased steadily during anaesthesia and 60 mins after induction PaCO2 was 10.5 +/- 2.4 kPa (78.5 +/- 17.8 mmHg) in the younger horses and 9.2 +/- 1.6 kPa (68.8 +/- 11.8 mmHg) in the older horses. During inhalation anaesthesia PaO2 tended to be greater at comparable time periods in the younger horses despite a slightly greater degree of hypoventilation.