Comparison of 2 collection methods for cerebrospinal fluid analysis from standing, sedate adult horses.

BACKGROUND: Cerebrospinal fluid (CSF) analysis is an important component of the evaluation of horses with neurologic disease. Lumbosacral (LS) centesis is routine, but CSF is also collected from the space between the first and second cervical vertebrae (C1-C2). OBJECTIVES: To compare collection times, CSF cytology results, and equine protozoal myelitis (EPM) titers of CSF collected from the C1-C2 and LS sites. ANIMALS: Fifteen university-owned adult horses with no evidence of neurologic disease, and 9 horses with signs of neurologic disease: 3 university-owned and 6 client-owned. METHODS: Prospective study. Cerebrospinal fluid collection from the LS space and C1-C2 space of each horse was performed in randomized order. Continuous data were analyzed using mixed-effects linear models and count data using mixed-effects negative binomial regression. Statistical significance was set at P < .05. RESULTS: Cerebrospinal fluid collected from the C1-C2 site had a significantly lower mean protein concentration (49 [95% CI: 43-55.8] mg/dL C1-C2 versus 52.1 [95% CI: 45.7-59.3] mg/dL LS; P = .03) and red blood cell count (6 [95% CI: 2-16] cells/µL versus 33 [95% CI: 13-81] cells/µL; P = .02). Collection time, total nucleated cell count, EPM titers, and serum:CSF EPM titer ratios were not significantly different between collection sites. CONCLUSIONS AND CLINICAL IMPORTANCE: Cerebrospinal fluid from the C1-C2 space provides an acceptable alternative to LS CSF collection with decreased likelihood of clinically important blood contamination of samples.

Melarsomine hydrochloride (Cymelarsan®) fails to cure horses with Trypanosoma equiperdum OVI parasites in their cerebrospinal fluid.

The aim of this study was to evaluate the ability of melarsomine hydrochloride (Cymelarsan®) to cure horses suffering from a nervous form of dourine, a sexually-transmitted disease caused by Trypanosoma equiperdum. The recently described experimental model for assessing drug efficacy against horse trypanosomosis allowed us to obtain eight horses (Welsh pony mares) infected by T. equiperdum with parasites in their cerebrospinal fluid. The Cymelarsan® treatment evaluated consisted of the daily administration of 0.5 mg/kg of Cymelarsan® over 7 days. Two control horses remained untreated, three horses received the treatment 36 days p.i. and three horses received the treatment 16 days p.i. Following treatment, we observed parasite clearance in blood, stabilization of rectal temperature and a relative improvement in the mean packed cell volume levels for all treated horses. However, live parasites were later observed again in the CSF of all treated horses. Our results indicate the inability of Cymelarsan® to reach Trypanozoon located in the central nervous system of infected horses and thus discourage the use of Cymelarsan® to treat animals suffering from a nervous form of dourine.

Ultrasound-guided atlanto-occipital puncture for cerebrospinal fluid analysis on the standing horse.

The atlanto-occipital site (AO) is convenient for retrieving an adequate volume and quality of cerebrospinal fluid (CSF) in the diagnosis of neurological disease in horses. However, general anaesthesia is not always possible for horses displaying severe neurological signs, or for economical reasons. The objectives of the present work were to determine the feasibility and safety of ultrasound-guided CSF puncture at the AO site on the standing horse. Seven horses (six healthy and one mildly ataxic) were sedated with acepromazine (0.02 mg/kg bodyweight intravenously or 0.04 mg/kg bodyweight intramuscularly) and detomidine (0.01 mg/kg bodyweight intravenously), and placed in stocks or in a recovery stall with the head kept on a headstand. Puncture was performed by ultrasonographic guidance with a parasagittal technique, as previously described, using a 20 g, 3.5 inch spinal needle. In all horses, no adverse reaction was observed when crossing the dura mater and 20 ml of CSF was rapidly retrieved without any blood contamination. Ultrasound-guided CSF puncture can be performed easily at the AO site on a healthy standing horse. Regarding the potential risk of this procedure, safety measures and close observation are essential. Further studies on a larger amount of ataxic horses are also required before considering this technique as an alternative option for CSF puncture.

Mass spectral measurements of the apoHDL in horse (Equus caballus) cerebrospinal fluid.

As a continuation of our proteogenomic studies of equine apolipoproteins, we have obtained molecular masses for several of the apolipoproteins associated with the HDL in horse cerebrospinal fluid (CSF). Using electrospray-ionization mass spectrometry (ESI-MS), we report on values for apolipoproteins, A-I and A-II, as well as acylated apoA-I. In comparison with our previously published data on equine plasma apolipoproteins, there appears to be a higher percentage of acylated apoA-I in the CSF than in plasma. As was the case in plasma, apoA-II circulates as a homodimer. These studies also revealed a protein with a mass of 34,468Da that we are speculating is the value for horse apoE.

Ultrasound-guided cervical centesis to obtain cerebrospinal fluid in the standing horse.

Horses with intracranial lesions and severe ataxia are not good anesthesia candidates; however, only one method to obtain cerebrospinal fluid (CSF) from the cervical region in a standing horse has been reported. This method is not performed routinely due to the difficulty for sample acquisition. Our hypothesis is that standing cervical centesis can be performed in horses without complication. Ultrasound-guided centesis of the CSF between C1 and C2 in 11 clinically normal horses and two horses with neurologic signs were performed. Horses were sedated and ultrasound was used to identify the subarachnoid space and spinal cord between C1 and C2. With ultrasound guidance, a needle was introduced into the dorsal aspect of the subarachnoid space using a lateral approach. Ten milliliters of CSF was obtained and analyzed. Two normal horses in this study had moderate red blood cell contamination in the CSF (940 and 612 RBC/microl). One horse had 11 RBC/microl and the remaining horses had < 4 RBC/microl. The total procedure time was approximately 2 min. No reaction was observed and no complications were detected up to 48 h after the procedure. Ultrasound-guided centesis between C1 and C2 is a rapid procedure that causes minimal to no reaction in standing, sedated horses used in this study. The use of ultrasound to guide a standing C1-2 centesis of the subarachnoid space provides an additional route to obtain CSF for analysis in the equine patient.

Pharmacokinetics and distribution of minocycline in mature horses after oral administration of multiple doses and comparison with minimum inhibitory concentrations.

REASONS FOR PERFORMING STUDY: Minocycline holds great potential for use in horses not only for its antimicrobial effects but also for its anti-inflammatory and neuroprotective properties. However, there are no pharmacokinetic or safety data available regarding the use of oral minocycline in horses. OBJECTIVES: To determine pharmacokinetics, safety and penetration into plasma, synovial fluid, aqueous humour (AH) and cerebral spinal fluid (CSF) of minocycline after oral administration of multiple doses in horses and to determine the minimum inhibitory concentrations (MIC) of minocycline for equine pathogenic bacteria. METHODS: Six horses received minocycline (4 mg/kg bwt q. 12 h for 5 doses). Thirty-three blood and 9 synovial fluid samples were collected over 96 h. Aqueous humour and CSF samples were collected 1 h after the final dose. Minocycline concentrations were measured using high pressure liquid chromatography. The MIC values of minocycline for equine bacterial isolates were determined. RESULTS: At steady state, the mean ± s.d. peak concentration of minocycline in the plasma was 0.67 ± 0.26 µg/ml and the mean half-life was 11.48 ± 3.23 h. The highest trough synovial fluid minocycline concentration was 0.33 ± 0.12 µg/ml. The AH concentration of minocycline was 0.09 ± 0.03 µg/ml in normal eyes and 0.11 ± 0.04 µg/ml in blood aqueous barrier-disrupted eyes. The mean CSF concentration of minocycline was 0.38 ± 0.09 µg/ml. The MIC values were determined for 301 isolates. Minocycline concentrations were above the MIC(50) and MIC(90) for many gram-positive equine pathogens. POTENTIAL RELEVANCE: This study supports the use of orally administered minocycline at a dose of 4 mg/kg bwt every 12 h for the treatment of nonocular infections caused by susceptible (MIC ≤ 0.25 µg/ml) organisms in horses. Further studies are required to determine the dose that would be effective for the treatment of ocular infections.

Assessment of vitamin E concentrations in serum and cerebrospinal fluid of horses following oral administration of vitamin E.

OBJECTIVE: To determine concentrations of alpha-tocopherol in serum and CSF of healthy horses following administration of supplemental vitamin E in feed. ANIMALS: 10 healthy adult horses. PROCEDURES: Horses were allocated to receive supplemental d-alpha-tocopherol (1,000 U/d [group A; n=5] or 10,000 U/d [group B; 5]) in feed for 10 days. Blood samples were collected before (baseline), during, and at intervals for 10 days after discontinuation of vitamin E administration for assessment of serum alpha-tocopherol concentration. Cerebrospinal fluid samples were collected prior to and 24 hours after cessation of vitamin E administration. Alpha-tocopherol concentrations in serum and CSF samples were analyzed via high-performance liquid chromatography; changes in those values during the treatment period were compared between groups, and the relationship of serum and CSF alpha-tocopherol concentrations was evaluated. RESULTS: In both groups, serum alpha-tocopherol concentration increased significantly from baseline during vitamin E administration; values in group B were significantly greater than those in group A during and after treatment. At the end of vitamin E administration, CSF alpha-tocopherol concentration was not significantly greater than the baseline value in either group; however, the increase in CSF concentration was significant when the group data were combined and analyzed. Serum and CSF alpha-tocopherol concentrations were significantly correlated at baseline for all horses, but were not strongly correlated after 10 days of vitamin E administration. CONCLUSIONS AND CLINICAL RELEVANCE: In healthy horses, daily oral administration of supplemental vitamin E in feed resulted in increases in serum and CSF alpha-tocopherol concentrations.

Ultrasound-assisted collection of cerebrospinal fluid from the lumbosacral space in equids.

OBJECTIVE: To describe ultrasonographic landmarks for use in collection of CSF from the lumbosacral region in equids. DESIGN: Prospective study. ANIMALS: 37 equids (27 with neurologic disease and 10 with nonneurologic disease). PROCEDURES: Standing equids (n = 17) were sedated with detomidine hydrochloride (0.006 to 0.01 mg/kg [0.003 to 0.005 mg/lb], IV) followed by butorphanol tartrate (0.01 mg/kg, IV) and restrained with a nose twitch for collection of CSF. The CSF was collected from 20 laterally recumbent equids (10 sedated and 10 immediately after euthanasia). Anatomic landmarks were identified ultrasonographically. Height at the dorsal point of the shoulders, body weight, depth of the spinal needle, number of attempts to collect CSF, and cytologic evaluation of CSF were recorded. RESULTS: Lumbosacral puncture cranial to the cranial border of the most superficial location of both tuber sacrale along the midline was consistently successful for CSF collection (35/37 equids). Two horses had anatomic abnormalities that precluded CSF collection. Mean number of attempts to collect CSF per animal was 1.1. Height and body weight were strongly correlated with needle depth for CSF collection. Pelvic and sacral displacement was observed in several laterally recumbent animals, which resulted in discrepancies of the midline between the cranial and caudal aspects of the vertebral column. In most equids, the spinal needle was aligned on the midline of the caudal aspect of the vertebral column. CONCLUSIONS AND CLINICAL RELEVANCE: Ultrasonography was a useful aid for collection of CSF from the lumbosacral space and decreased the risk of repeated trauma and contamination in equids.

Evaluation of nephelometry for albumin measurement in serum and cerebrospinal fluid: experiences with an indwelling subarachnoidal catheter system for repetitive cerebrospinal fluid collection in horses.

The measurement of albumin concentrations in cerebrospinal fluid (CSF) and serum for albumin quotient (AQ) calculations in normal horses was performed by 2 methods: 1) total protein measurement, followed by electrophoresis of the samples to obtain an albumin percentage; and 2) albumin immunoprecipitation quantitated by nephelometry. The results of both methods correlated well, and nephelometry was chosen to determine the albumin concentrations in CSF samples obtained from an indwelling subarachnoidal catheter for daily sampling. Because the use of an indwelling catheter to collect repetitive CSF samples is a novel technique, routine cytological CSF analysis was performed along with daily clinical evaluation to ascertain the well-being of the horses. The catheters were placed in 2 horses for periods of 14 and 17 days. One horse exhibited pleocytosis on cytological evaluation of CSF on 2 occasions for a 1-2-day duration; however, the AQ showed a significant increase on only 1 occasion. The other horse had a normal cell count in CSF but showed 2 sudden changes in the AQ value; however, these values remained within the 95% confidence interval for AQ in horses. Albumin quotient values of the second horse were consistently below the lower range of the confidence interval. Results from this study indicate that nephelometry can be used for albumin determination in serum and CSF samples from horses. Furthermore, an indwelling subarachnoidal catheter system can provide serial CSF samples in horses, thus obviating the need for repetitive centesis for serial CSF sampling.

Cutaneous analgesia, hemodynamic and respiratory effects, and beta-endorphin concentration in spinal fluid and plasma of horses after acupuncture and electroacupuncture.

OBJECTIVE: To determine cutaneous analgesia, hemodynamic and respiratory effects, and beta-endorphin concentration in spinal fluid and plasma of horses after acupuncture and electroacupuncture (EA). ANIMALS: 8 healthy 10- to 20-year-old mares that weighed between 470 and 600 kg. PROCEDURE: Each horse received 2 hours of acupuncture and 2 hours of PAES at acupoints Bladder 18, 23, 25, and 28 on both sides of the vertebral column as well as sham needle placement (control treatment). Each treatment was administered in a random order. At least 7 days elapsed between treatments. Nociceptive cutaneous pain threshold was measured by use of skin twitch reflex latency (STRL) and avoidance to radiant heat (< or = 50 degrees C) in the lumbar area. Skin temperature, cardiovascular and respiratory variables, and beta-endorphin concentration in spinal fluid (CSF-EN) and plasma (plasma-EN) were measured. RESULTS: Acupuncture and PAES significantly increased STRL and skin temperature. The CSF-EN was significantly increased from baseline values 30 to 120 minutes after onset of PAES, but it did not change after acupuncture and control treatments. Heart and respiratory rates, rectal temperature, arterial blood pressure, Hct, total solids and bicarbonate concentrations, base excess, plasma-EN, and results of blood gas analyses were not significantly different from baseline values after acupuncture, PAES, and control treatments. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of PAES was more effective than acupuncture for activating the spinal cord to release beta-endorphins into the CSF of horses. Acupuncture and PAES provided cutaneous analgesia in horses without adverse cardiovascular and respiratory effects.

Characterization of lipoproteins in cerebrospinal fluid of mares during pregnancy and lactation.

OBJECTIVE: To measure apolipoproteins in cerebrospinal fluid (CSF) from healthy mares and to determine whether CSF concentrations of apolipoproteins change during pregnancy and lactation. ANIMALS: 5 healthy pregnant mares. PROCEDURE: 2 sets of CSF samples were obtained; initial samples were obtained 10 to 30 days before parturition (mean, 18 days; median, 17 days), and second samples were obtained 19 to 26 days after parturition (mean, 23 days; median, 23 days). Cerebrospinal fluid was collected from the lumbosacral subarachnoid space of standing horses by use of routine collection techniques. Cerebrospinal fluid cholesterol concentrations were measured by use of a sensitive enzymatic assay. Ultracentrifugal fractions of CSF lipoproteins were characterized by determining the distribution of apolipoproteins, using polyacrylamide gel electrophoresis. RESULTS: Analyses of isolated ultracentrifugal fractions by polyacrylamide gel electrophoresis revealed 2 apolipoproteins, with the expected molecular weights for apolipoprotein E and apolipoprotein A-I. No significant differences were observed between pre- and postpartum values in mares. The concentration of cholesterol in CSF fluid of mares was comparable to values reported in other mammals. CONCLUSIONS AND CLINICAL RELEVANCE: Apolipoprotein E in CSF of horses is a major apolipoprotein associated with high-density lipoproteins, which is similar to findings in other mammals. Additional characterization of the role of apolipoproteins in mammalian CSF may provide critical insight into various degenerative neurologic disease processes.

Cerebrospinal fluid and serum concentrations of ponazuril in horses.

Ponazuril was administered orally to 10 adult horses at 5 mg/kg body weight, once a day for 28 days. Blood was collected once a week from each horse from Days 0 through 35, daily from Days 35 through 42, and on Day 49. Cerebrospinal fluid (CSF) was also collected once a week from Day 0 through Day 49. Concentrations of ponazuril in the serum and CSF were determined, and pharmacokinetic calculations were performed. Ponazuril was readily absorbed following oral administration; and after 7 days of dosing, the serum concentration was 4.33 +/- 1.10 mg/L, and the mean CSF concentration was 0.162 +/- 0.05 mg/L. Cerebrospinal fluid concentration did not vary during the 28 days of dosing and concentrations declined rapidly after cessation of administration on Day 28. The terminal elimination half-life ofponazuril in serum (using Day 28 to 42 results) was 4.3 +/- 0.6 days. Repeated CSF collections from the atlanto-occipital space did not induce changes in the immunoglobulin G index or albumin quotient. It was concluded that oral administration of ponazuril to healthy horses at 5 mg/kg provided concentrations of ponazuril in the CSF that are presumed to be adequate for the treatment of equine protozoal myeloencephalitis (EPM). These results indicate that this dosage rate should be investigated for efficacy against EPM.

Differences in total protein concentration, nucleated cell count, and red blood cell count among sequential samples of cerebrospinal fluid from horses.

OBJECTIVE: To examine total protein concentration and cell counts of sequentially collected samples of CSF to determine whether blood contamination decreases in subsequent samples and whether formulas used to correct nucleated cell count and total protein concentration are accurate. DESIGN: Case series. ANIMALS: 22 horses. PROCEDURE: For each horse, 3 or 4 sequential 2-ml samples of CSF were collected from the subarachnoid space in the lumbosacral region into separate syringes, and blood was obtained from the jugular vein. Total protein concentration, nucleated cell count, and RBC counts were determined in all samples. RESULTS: Among 3 sequential samples, total protein concentration and RBC count were significantly lower in samples 2 and 3, compared with sample 1. Nucleated cell count was significantly lower in sample 3, compared with sample 1. Among 4 sequential samples, total protein concentration and RBC count were significantly lower in samples 2, 3, and 4, compared with sample 1. Nucleated cell count was significantly lower in samples 3 and 4, compared with sample 1. For 3 correction formulas, significant differences in corrected values for nucleated cell count and total protein concentration were detected between sample 1 and sample 3 or 4. CONCLUSIONS AND CLINICAL RELEVANCE: Because iatrogenic blood contamination decreases in sequential CSF samples, a minimum of 3 samples should be collected before submitting the final sample for analysis. Formulas to correct nucleated cell count and total protein concentration are inaccurate and should not be used to correct for blood contamination in CSF samples.

Study of intragastric administration of doxycycline: pharmacokinetics including body fluid, endometrial and minimum inhibitory concentrations.

The objectives of this study were to determine the pharmacokinetics and tissue concentrations of doxycycline after repeated intragastric administration, and to determine the minimum inhibitory concentrations (MIC) for equine pathogenic bacteria. In experiment 1, 2 mares received a single intragastric dose of doxycycline hyclate (3 mg/kg bwt). Mean peak serum concentration was 0.22 microg/ml 1 h postadministration. In experiment 2, 5 doses of doxycycline hyclate (10 mg/kg bwt), dissolved in water, were administered to each of 6 mares via nasogastric tube at 12 h intervals. The mean +/- s.e. peak serum doxycycline concentration was 0.32+/-0.16 microg/ml 1 h after the first dose and 0.42+/-0.05 microg/ml 2 h after the fifth dose. The mean trough serum concentrations were > 0.16 microg/ml. Highest mean synovial concentration was 0.46+/-0.13 microg/ml and highest mean peritoneal concentration was 0.43+/-0.07 microg/ml, both 2 h after the fifth dose. Highest urine concentration was mean +/- s.e. 145+/-25.4 microg/ml 2 h after the last dose. Highest endometrial concentration was mean +/- s.e. 1.30+/-0.36 microg/ml 3 h after the fifth dose. Doxycycline was not detected in any of the CSF samples. Mean +/- s.e. Vd(area) was 25.3+/-5.0 l/kg and mean t1/2 was 8.7+/-1.6 h. In experiment 3, minimum inhibitory concentrations of doxycycline were determined for 168 equine bacterial culture specimens. The MIC90 was < or = 1.0 microg/ml for Streptococcus zooepidemicus and 0.25 microg/ml for Staphylococcus aureus. Based on drug concentrations achieved in the serum, synovial and peritoneal fluids and endometrial tissues and MIC values determined in the present study, doxycycline at a dose of 10 mg/kg bwt per os every 12 h may be appropriate for the treatment of infections caused by susceptible (MIC < 0.25 microg/ml) gram-positive organisms in horses.

Cerebrospinal fluid and blood concentrations of toltrazuril 5% suspension in the horse after oral dosing.

Toltrazuril 5% suspension (Baycox, Bayer Canada, Ontario, Canada) was administered to six adult horses followed by blood collection and assay to determine the concentration of toltrazuril and its principal metabolites, toltrazuril sulfone and toltrazuril sulfoxide. From this data, the maximum concentration (C(max)), elimination half-life (T 1/2), and mean residence times of the plasma were determined from standard pharmacokinetic formulas. After a single oral dose of 10 mg/kg body weight a rapid absorption was found, with a mean peak serum concentration of 11.17 mg/L at 18 hours. Elimination was prolonged, with a mean T 1/2 for elimination of 61.4 hours. In addition, toltrazuril was administered to nine horses, and blood serum and cerebrospinal fluid (CSF) concentrations of toltrazuril and its principal metabolites were determined. Horses were randomly assigned to one of three treatment groups and received either 2.5 mg/kg body weight (Group A), 5.0 mg/kg body weight (Group B), or 7.5 mg/kg body weight (Group C) orally, once daily, for 10 days. Jugular venous blood was collected routinely on treatment days 2, 6, and 10, and CSF was collected on treatment day 10. Assay of toltrazuril and its metabolites revealed a dose-dependent effect within both the blood and CSF compartments. Mean concentrations within the CSF after 10 days of treatment were 0.146 mg/L in Group A, 0.190 mg/L in Group B, and 0.386 mg/L in Group C. Toltrazuril sulfone was the primary metabolite after 10 days of treatment, with concentrations that ranged from 39% to 116% of the parent drug in individual animals. Toltrazuril sulfone was also the predominant metabolite in the serum at treatment day 10; however, it did not always exceed the concentration of toltrazuril sulfoxide in the serum on treatment day 2. In the serum, drug concentrations at treatment day 2 were variable in the low-dose group (Group A), ranging from 4.0 to 11.61 mg/L; less variable in the high-dose group (Group C), ranging from 9.9 to 10.46 mg/L; and intermediate in Group B. This study confirms that toltrazuril is absorbed in the horse after oral administration and reaches effective in vitro concentrations within the CSF of the horse after once-daily dosing of 5 or 7.5 mg/kg. Although these data suggest that toltrazuril may have clinical value in the treatment of equine protozoal myeloencephalitis, clinical efficacy remains to be confirmed using appropriate methods. Effective in vitro concentrations are known; however, therapeutic concentrations in vivo have not been established. Further research in this area is needed to determine various drug values in the CSF (e.g., half-life, C(max), time to reach steady state).

Diclazuril in the horse: its identification and detection and preliminary pharmacokinetics.

Diclazuril (4-chlorophenyl [2,6-dichloro-4-(4,5-dihydro-3H-3,5-dioxo-1,2,4-triazin-2-yl)pheny l] acetonitrile), is a benzeneacetonitrile antiprotozoal agent (Janssen Research Compound R 64433) marketed as Clinacox . Diclazuril may have clinical application in the treatment of Equine Protozoal Myeloencephalitis (EPM). To evaluate its bioavailability and preliminary pharmacokinetics in the horse we developed a sensitive quantitative high-pressure liquid chromatography (HPLC) method for diclazuril in equine biological fluids. MS/MS analysis of diclazuril in our HPLC solvent yielded mass spectral data consistent with the presence of diclazuril. After a single oral dose of diclazuril at 2.5 g/450 kg (as 500 g Clinacox), plasma samples from four horses showed good plasma concentrations of diclazuril which peaked at 1.077 +/- 0.174 microg/mL (mean +/- SEM) with an apparent plasma half-life of about 43 h. When this dose of Clinacox was administered daily for 21 days to two horses, mean steady state plasma concentrations of 7-9 microg/mL were attained. Steady-state levels in the CSF ranged between 100 and 250 ng/mL. There was no detectable parent diclazuril in the urine samples of dosed horses by HPLC or by routine postrace thin layer chromatography (TLC). These results show that diclazuril is absorbed after oral administration and attains steady-state concentrations in plasma and CSF. The steady state concentrations attained in CSF are more than sufficient to interfere with Sarcocystis neurona, whose proliferation is reportedly 95% inhibited by concentrations of diclazuril as low as 1 ng/mL. These results are therefore entirely consistent with and support the reported clinical efficacy of diclazuril in the treatment of clinical cases of EPM.

The effects of equivalent doses of tromethamine or sodium bicarbonate in healthy horses.

OBJECTIVE: To describe the effects of tromethamine, a putative treatment for metabolic acidosis, and to compare its biochemical effects with those of sodium bicarbonate. DESIGN: Randomized intervention study with repeated measures. ANIMALS: 16 healthy horses, 3 to 17 years old, weighing 391 to 684 kg. METHODS: Ten horses received 3 mEq/kg tromethamine and six received 3 mEq/kg sodium bicarbonate. Samples of venous blood and cerebrospinal fluid (CSF) were collected at intervals before and after drug administration. Heart rate and breathing rate were also recorded at intervals. RESULTS: Median standard base excess increased significantly (P < .05) from baseline immediately after both bicarbonate and tromethamine. These increases were not significantly different between treatments. Standard base excess returned toward baseline but remained significantly increased 3 hours after infusion of either treatment. After tromethamine, there was a significant decrease in plasma sodium concentration that lasted for at least 90 minutes. After sodium bicarbonate, no change in plasma sodium concentration was detected. Both sodium bicarbonate and tromethamine increased carbon dioxide tension in venous blood and CSF. Despite venous alkalemia, the pH of CSF decreased after both treatments. CONCLUSIONS: Tromethamine and sodium bicarbonate have similar alkalinizing ability. Tromethamine causes hyponatremia, whereas both tromethamine and sodium bicarbonate increase carbon dioxide tension in venous blood and CSF. CLINICAL RELEVANCE: If hyponatremia, hypercarbia, and acidosis of the CSF occur after tromethamine is given to horses with existing metabolic acidosis, some of the potential advantages of tromethamine may prove theoretical rather than practical.