A study of the effect of a platelet activating factor (PAF) receptor antagonist on antigen challenge of horses with chronic obstructive pulmonary disease

Antigen challenge involving exposure to straw and mouldy hay for 7 h produced lung function changes and neutrophil recruitment to the lungs in horses with chronic obstructive pulmonary disease (COPD). During the challenge, an increase in radiolabelled neutrophils in the lungs occurred, together with increased respiratory rate and pleural pressure. The role of platelet activating factor (PAF) in antigen-induced neutrophil accumulation, and increased pleural pressure and respiratory rate was investigated by administering the PAF receptor antagonist WEB 2086 to asymptomatic COPD horses prior to antigen challenge. WEB 2086 (3 mg/kg i.v.) did not affect antigen-induced changes in either neutrophil accumulation or respiratory function. These results suggest that PAF may not be an important mediator of the response to antigen in equine COPD.     

Phosphodiesterase activity in neutrophils from horses with chronic obstructive pulmonary disease

Neutrophils are recruited to the lungs of horses with chronic obstructive pulmonary disease (COPD) and exhibit increased activity after antigen challenge. Phosphodiesterase type4 (PDE4) inhibitors have been shown to attenuate human neutrophil activation. The aim of this study was to establish the PDE isoenzyme profile of equine neutrophils using isoenzyme selective inhibitors to determine if these compounds should be evaluated in horses with COPD. Total cAMP and cGMP dependent PDE activity was no different in neutrophils from normal (156.2+/-7.1 and 6.8+/-0.6 pmol/min/mg for cAMP and cGMP, respectively) and COPD susceptible horses (146.0+/-10.2 and 5.5+/-0.6 pmol/min/mg for cAMP and cGMP, respectively). The PDE4 inhibitors, CDP840 and rolipram, caused significant, concentration related and almost complete inhibition of PDE activity (IC(50) values=8.8+/-0.1 x 10(-9) and 7.3+/-0.2 x 10(-9)M for CDP840; 1.2+/-0.1 x 10(-6) and 1.1+/-0.1 x 10(-6)M for rolipram in normal and COPD susceptible horses, respectively). The inhibitory effects of the mixed PDE3/ PDE4 inhibitor, zardaverine were of similar magnitude and potency to rolipram. However, the limited inhibitory effects of the PDE3 inhibitor, siguazodan, suggest that zardaverine is acting primarily via PDE4 inhibition. These results indicate that PDE4 is the predominant isoenzyme present in the equine neutrophil and inhibition of PDE activity using selective PDE4 inhibitors may, therefore, modulate equine neutrophil activation in horses with COPD.     

Differential inhibition of equine neutrophil function by phosphodiesterase inhibitors

Neutrophils are recruited to the lungs of horses with chronic obstructive pulmonary disease (COPD) and exhibit increased activity after antigen challenge, which may contribute to inflammation and lung damage. Inhibition of phosphodiesterase isoenzymes (PDEs) has been shown to attenuate human neutrophil functions including superoxide production, leukotriene (LT)B4 biosynthesis, enzyme and chemokine release. As equine neutrophils contain predominantly the isoenzyme, PDE4, the present study was undertaken to investigate the effects of rolipram, a PDE4 inhibitor, on equine neutrophil function. For comparison, the effects of the nonselective PDE inhibitor, theophylline, were examined. Cells from both normal horses and COPD horses in remission were used. Superoxide production was significantly inhibited by both rolipram [32.2 +/- 2.6 vs. 10.1 +/- 1.1 nmol/10(6) cells and 49.8 +/- 6.8 vs. 22.7 +/- 2.2 nmol/10(6) cells for normal and COPD susceptible horses, respectively, in response to 10(-7) M human recombinant (hr) C5a] and theophylline (19.0 +/- 0.6 vs. 10.2 +/- 0.6 nmol/10(6) cells and 24.3 +/- 2.1 vs. 10.7 +/- 0.9 nmol/10(6) cells for normal and COPD susceptible horses, respectively, in response to 10(-7) M C5a). However, superoxide production induced by serum treated zymosan was inhibited only by theophylline (10(-3) M). Neither hrC5a- nor platelet activating factor (PAF)-induced neutrophil adherence to fibronectin coated plastic was reduced by rolipram (10(-5) M). These results demonstrate that the effects of PDE inhibitors on equine neutrophils are both stimulus and function dependent. The PDE4 inhibitors may reduce neutrophil activation in vivo in horses with COPD.     

Characterization of a sterile soft-tissue inflammation model in Thoroughbred horses

This paper describes the use of subcutaneously-placed tissue chambers as a sterile soft-tissue inflammation model in Thoroughbred horses. Acute, nonimmune inflammation was initiated by injecting a sterile lambda carrageenan solution into a tissue chamber. This model was used to study the temporal changes in oxygen and carbon dioxide tensions, pH, bicarbonate, protein, albumin, prostaglandin E₂ (PGE₂) and leukotriene B₄ (LTB₄) concentrations, cell counts and differential counts in tissue fluid from inflamed tissue chambers and control chambers. Skin temperatures over control and inflamed chambers were also compared. Carrageenan-induced inflammation resulted in significant increases in tissue-fluid carbon dioxide tension, leucocyte count, albumin, and PGE₂ and LTB₄ concentrations. It also resulted in a significant decrease in tissue fluid pH and HCO₃- concentration. Inflammation did not result in significant changes in tissue-fluid protein concentration, differential cell counts or skin temperature over the chambers. The use of this type of tissue chamber is wellsuited for studying the pathophysiology of a self-contained, non-immune inflammatory process. The model described in this paper could prove to be very useful in studies of the distribution of anti-inflammatory drugs and the effects of such drugs on various aspects of the inflammatory process.     

Inhaled leukotrienes cause bronchoconstriction and neutrophil accumulation in horses

Leukotrienes have been shown to mimic many of the pathophysiological processes in allergic airway disease. In this study the bronchoconstrictor effect of inhaled LTB₄, and radiolabelled neutrophil accumulation in response to inhalation of LTB₄, have been examined in the horse. In separate studies, solutions of LTD₄ and LTB₄ were administered to the airways of normal animals by nebulisation. LTD₄, but not LTB₄, caused a dose-dependent increase in pleural pressure which was maximal at three to four minutes and had returned to baseline by 15 to 20 minutes. On a molar basis LTD₄ was 305 to 970 times more potent than methacholine. LTB₄ induced an early recruitment (15 minutes to 1 hour) to the lungs of radiolabelled neutrophils, which persisted for more than 5 hours in some animals. There was no effect on peripheral blood leucocyte counts or pleural pressure and neither LTB₄, nor LTD₄, affected respiratory rate. These results suggest that, if released during antigen challenge, LTB₄ and LTD₄ could contribute to the pathogenesis of equine COPD. In a small group of asymptomatic COPD horses these leukotrienes appeared to cause similar, but smaller, changes in lung function and neutrophil recruitment, which could suggest reduced responsiveness to these mediators.     

A Portable Blood Gas Analyzer for Equine Venous Blood

Evaluation of a portable blood gas analyzer, (StatPal II, Unifet, Inc, La Jolla, CA) was performed using tonometered solutions and equine blood. Samples were analyzed by the StatPal II and either an Instrument Laboratory IL1306 (Lexington, MA) or a Radiometer ABL50 blood gas analyzer (Radiometer America Inc., Westlake, OH). Comparison of the StatPal II and the IL1306 was done by analysis of 3 tonometered solutions (acidic, normal, and alkalotic) and 27 equine venous blood samples. Blood pH, Pco₂, Po₂, and [HCO₃^-] values were altered by IV infusion of 5% sodium bicarbonate or exercising the horses on a treadmill. Comparison of the StatPal II and the Radiometer was performed by analysis of 78 blood samples collected from Standard-bred horses before a race. Data were analyzed for the venous blood samples using a paired two-tailed Student's t test and Bland-Altman plots, with significance set at P < .05. The coefficients of variation for pH, Pco₂, Po₂, and [HCO₃^-] values of the tonometered solutions analyzed by the StatPal II ranged from 0.067% to 0.087%, 2% to 3.21 %, 1.21 % to 2.67%, and 0.267% to 0.828%, respectively. Comparison of the equine blood samples analyzed by the StatPal II and the IL1306 demonstrated statistically significant, but clinically irrelevant differences in pH, Pco₂, and Po₂, but not [HCO₃^-]. There were statistically significant, but clinically irrelevant differences between the StatPal II and the Radiometer for pH, Pco₂, and [HCO₃^-], but not for Po₂-It is concluded that the StatPal II provides reproducible and acceptable analysis of equine venous blood gas samples.     

Antigen challenge increases adherence of circulating neutrophils in horses with chronic obstructive pulmonary disease

Activation of circulating neutrophils has been observed following challenge of horses with chronic obstructive pulmonary disease (COPD) and may facilitate the accumulation of these cells in the airways. In this study, no significant difference was observed between adherence to protein coated plastic of blood neutrophils from asymptomatic COPD-susceptible and normal horses stimulated by the mediators PAF, human recombinant (hr)IL-8 and hrC5a. Twenty-four hours after the start of a 7 h antigen challenge, adherence of unstimulated neutrophils from COPD-susceptible horses increased from 2.5 (0.5-4.1)% and 3.4 (0.6-6.6)% to 19.6 (16.9-20.3)% and 21.8 (10.6-23.1)% adherence for cells in medium containing 0.1% or 0.2% BSA, respectively; (median [range]; n = 4). Adherence of cells from normal horses remained unchanged. Addition of an anti-CD18 monoclonal antibody, H20A, inhibited the increase in adherence at 24 h by 96 (45-100)%, n = 3. The percentage of neutrophils in bronchoalveolar lavage fluid at 24 h increased from 1 (0-2) to 80 (65-94), (median (range), n = 4). These results suggest that antigen challenge results in exposure of circulating equine neutrophils to one or more factors that prime, or activate, these cells, which may enhance their recruitment to the lungs. Inhibition of circulating neutrophil activation may therefore represent a therapeutic target.     

Effect of Hypercapnia or Xylazine on Lateral Ventricle and Lumbosacral Cerebrospinal Fluid Pressures in Pentobarbital-anesthetized Horses

Facial artery pressure, central venous pressure, heart rate, and lateral ventricle cerebrospinal fluid (CSF) pressure (LV-CSFP) were measured in 10 pentobarbital-anesthetized horses at arterial partial pressure of carbon dioxide (PaCO₂) values of 40,60, and 80 mm Hg, produced by varying the inspired carbon dioxide concentration. Variables were recorded at 5-minute intervals for 15 minutes at each level of PaCO₂. Arterial blood gas analysis was performed at the end of the 15-minute time period for each level of PaCO₂. Lateral ventricle CSF pressure was significantly increased (p < .05) at a PaCO₂ of 80 mm Hg. Cardiovascular variables were not significantly changed by changing PaCO₂. The PaCO₂ was returned to 40 mm Hg; 1.1 mg xylazine/kg body weight was injected intravenously in eight horses, and data were collected for 60 minutes. No significant changes were observed. No changes were observed in two control horses not receiving xylazine. Subsequently, placement of a lumbosacral subarachnoid catheter allowed simultaneous measurement of LV-CSFP and lumbosacral CSF pressure (LS-CSFP) at PaCO₂ values of 40,60, and 80 mm Hg. The Pearson Correlation Coefficient between LV-CSFP and LS-CSFP was 0.94 (p < .0001) It was concluded that changes in CSF pressure could be detected at the lateral ventricle and the lumbosacral space; increasing PaCO₂ to 80 mm Hg resulted in significant increases in LV-CSFP; xylazine does not increase LV-CSFP in pentobarbital-anesthetized, normocapnic horses; and under the conditions of this experiment, LV-CSFP and LS-CSFP were closely correlated.     

Effects of non-steroidal anti-inflammatory drugs on canine neutrophil chemotaxis

Strøm, H. & Krogsgaard Thomsen, M. Effects of non-steroidal anti-inflammatory drugs on canine neutrophil chemotaxis. J. vet. Pharmacol. Therap. 13, 186–191.
Non-steroidal anti-inflammatory drugs exhibit differences in their ability to suppress polymorphonuclear leucocyte (PMN) functions in different species. The present study investigated the in-vitro and ex-vivo effects of phenylbutazone and flunixin on leukotriene-B₄-directed migration of canine PMN. Furthermore, in-vitro comparison was made to indomethacin and the 5-lipoxygenase inhibitor, nordihydroguaiaretic acid (NDGA). In vitro , flunixin and NDGA were the most potent inhibitors, with IC ₅₀s of 13 and 7 μmol/l, respectively. Phenylbutazone had an IC ₅₀ of 42 μmol/l whereas indomethacin did not achieve 50% inhibition at concentrations less than 100 μmol/l. Ex vivo , flunixin almost completely abolished the LTB₄ response at 1h, and still possessed significant inhibitory activity 24 h after a dosage of 1mg/kg i.v. Phenylbutazone was less active ex vivo but did suppress chemotaxis by 23% (P<0.05) at 1h following an i.v. dose of 20mg/kg. It is suggested that part of the anti-inflammatory action of flunixin in dogs may be attributed to inhibition of PMN recruitment.
M. Krogsgaard Thomsen, Department of Pharmacology, Leo Pharmaceutical Products, DK-2750, Ballerup, Denmark.     

Reactivity of Equine Palmar Digital Arteries and Veins to Vasodilating Agents

Palmar digital arteries and veins removed surgically from healthy horses under general anesthesia were cut into 4 mm vascular rings, suspended in tissue baths, and attached to force displacement transducers for continuous measurement of vascular tension. In vitro vascular responses were determined for acetylcholine, acepromazine, isoxsuprine hydrochloride (isoxsuprine), prostaglandin E₂ (PGE₂), and prostaglandin I₂ (prostacyclin). After preconstriction with norepinephrine hydrochloride (norepinephrine), or prostaglandin F₂ alpha (PGF₂ alpha), the concentrations needed to produce 50% maximum relaxation (EC₅₀) and the maximum percentage of relaxation were determined for each drug.
Acetylcholine was the most potent arterial vasodilator (smallest EC₅₀ value) and PGE₂ was the least potent. Prostacyclin was the least potent venodilator (highest EC₅₀ value); there were no differences between acetylcholine, acepromazine, isoxsuprine, and PGE₂. Isoxsuprine produced greater arterial relaxation than all other agents. Isoxsuprine and acepromazine produced significantly greater venous relaxation than did acetylcholine and PGE₂. Prostacyclin produced minimal vasodilation of arteries or veins. Acepromazine and isoxsuprine relaxed the veins significantly more than the arteries. When PGF₂ alpha was used instead of norepinephrine to preconstrict the arteries and veins, the potency and effectiveness of acepromazine and isoxsuprine to produce vasodilation were significantly decreased. Results indicate that acepromazine and isoxsuprine can relax the equine digital vasculature but their effectiveness varies depending on the origin of the constriction.     

A study on the possible role of chymotrypsin in the aetiology of equine chronic obstructive pulmonary disease (COPD)

The chymotrypsin activity of seven batches of Micropolyspora faeni and of five batches of Aspergillus fumigatus culture extracts, prepared for inhalation challenge in horses, was assayed and was found to range between 0.29 and 1.45 units/mg protein and 0.02 and 0.20 units/mg protein respectively. Horses affected with chronic obstructive pulmonary disease (COPD) were challenged with two batches of each antigen which had different chymotrypsin activities and no significant correlations were found between the degree of response to challenge and the chymotrypsin activity of the antigens. Inhalation of two doses of nebulised, purified chymotrypsin over 4 days did not induce signs of respiratory disease in COPD-affected horses. However, repeated chymotrypsin inhalations after an interval of 3 weeks caused an exacerbation of signs of COPD in one horse. These studies suggest that, although repeated inhalation of purified chymotrypsin may induce respiratory hypersensitivity in horses, the chymotrypsin-like enzymes of M. faeni and A. fumigatus do not play a major role in the precipitation of clinical signs of equine COPD.     

PHYSIOLOGY OF THE RESPIRATORY SYSTEM, SIGNIFICANT SPECIES DIFFERENCES, MEASUREMENTS OF PULMONARY FUNCTION, NORMAL VALUES AND SIGNIFICANCE OF VARIATIONS FROM NORMAL

The respiratory system of animals can be divided for evaluation into pulmonary system and circulatory system. The pulmonary system is involved in external respiration whereas the circulatory system is involved in internal respiration. External respiration is the exchange of oxygen (O₂) and carbon dioxide (CO₂) between the environment and circulating blood by way of the lungs and internal respiration is the transport of O₂ and CO₂ between the lungs and the metabolic machinery of the body cells.     

The actions of medetomidine may not be mediated exclusively by α2-adrenoceptors in the equine saphenous vein

Spirals of endothelially denuded equine saphenous vein were used to study the pre- and post-junctional effects of medetomidine in vitro . The pD₂ values were calculated for noradrenaline (6.7 /pm 0.1), phenylephrine (5.6 /pm 0.1), BHT 920 (6.2 /pm 0.2) and UK 14304 (5.7 /pm 0.2). Medetomidine produced a biphasic response, with a pD₂1 of 8.2 /pm 0.1 and a pD₂2 of 5.7 /pm 0.1 in the equine saphenous vein ( n = 6 ). Prazosin (10⁻⁷ m) significantly shifted the second phase of the medetomidine concentration-response curve to the right (pD₂1 was 8.1 /pm 0.2 and pD₂2 was 5.0 /pm 0.2, P < 0.05). Rings of equine saphenous vein were electrically stimulated to investigate the pre-junctional effects of medetomidine. Increasing concentrations of the α₂-adrenoceptor agonist BHT 920 reduced the response to electrical stimulation in a concentration dependent manner to a maximum of 40 /pm 5%. whereas medetomidine (0.1-100 nm) caused a concentration dependent enhancement to a maximum of 490 /pm 150%. These results suggest α₁- and α₂-adrenoceptors are functional in the equine saphenous vein, but that medetomidine is not acting exclusively as an α₂-adrenoceptor agonist.     

Relaxation of equine tracheal muscle in vitro by different adrenoceptor drugs

Strips of tracheal smooth muscle from 12 horses were contracted by carbachol in tissue baths under isometric conditions. This contraction (≅50% of maximum: EC₅₀) was relaxed completely with adrenoceptor drugs. The only exception was clenbuterol, where the degree of relaxation was ≅90%. In all horses the EC₅₀-value for isoprenaline (mean 1.6 × 10⁻⁸M) was less than that for adrenaline (mean 9.6 × 10^{− 8}M) and noradrenaline (mean 1. 8 × 10_{- 6}M). The potency ratio was 1 < 6 < 110 which indicates that the β₂-subtype dominates among the β-adrenoceptors of equine airways. All preparations were also very sensitive to the specific and potent β₂-receptor agonists clenbuterol (mean 5.7 × 10^{− 9}M) and procaterol (mean 3.6 × 10⁻¹⁰M). No differences in EC₅₀-values due to age, sex and breed were observed in this material. The standard deviation of the mean EC₅₀-values seems to be larger for the specific β₂-adrenoceptor agonists than for the unspecific. A reason for this could be differences in the pattern of the β-adrenoceptor population.     

马疱疹病毒1型感染马疾病模型的建立及评价

试验旨在建立马疱疹病毒1型（Equine herpesvirus type1,EHV-1）人工发病模型,确定EHV-1感染马的半数感染量（ID₅₀）及感染发病的判定标准,为该病的预防与治疗药物的研发奠定基础。以新疆伊犁地区某发病马场流产胎儿中分离的EHV-1 XJ2015株为研究对象,设立4组不同病毒剂量感染组及对照组,经鼻内喷雾感染马,5 mL/匹,每天观察试验马的临床症状和发病情况,14 d后进行剖检,观察各组织脏器病理变化并应用实时荧光定量PCR方法检测鼻腔排毒及病毒分布情况。结果显示,EHV-1 XJ2015株感染马的ID₅₀为10^-6.67/5 mL,其病毒含量为10^4.33 TCID₅₀/mL。与对照组相比,1×10⁶和1×10⁵ TCID₅₀/mL感染组马临床评分显著升高,主要表现为体温升高（高达39.5 ℃,一般持续2~6 d）、食欲不振、流浆液性鼻液和下颌淋巴结肿大;且1×10⁶和1×10⁵ TCID₅₀/mL感染组试验马均表现出不同程度的排毒,肺脏及脑组织中可检测出大量病毒,与对照组相比极显著或显著升高（P<0.01;P<0.05）;病理学检查发现,患马脑组织出现非化脓性脑炎及神经元水肿,肺脏组织出现间质性肺炎、嗜中性粒细胞、炎性细胞浸润、出血和肺泡间隔增厚。以上结果表明,EHV-1 XJ2015株对马具有较强的致病性,患病马临床症状典型,病毒主要随鼻液排出,并富集在肺脏及脑组织,通过上述指标确定EHV-1感染马发病的判定标准,本试验成功建立EHV-1感染本体动物疾病模型。     

Pharmacokinetic interactions between repeated dose phenylbutazone and gentamicin in the horse

This study examined the pharmacokinetics of steady-state phenylbutazone and single bolus intravenous gentamicin when administered together in the horse. The trial design was completed as a cross-over with seven thoroughbred horses. In the first phase each horse received 2.2 mg/kg gentamicin intravenously. After a 2-week washout, each horse received 4.4 mg/kg phenylbutazone intravenously every 24 h for 5 days. On the fourth day each horse received gentamicin as before. Plasma was harvested for gentamicin concentration determination by fluorescence polarization immunoassay and for phenylbutazone concentration determination by high-performance liquid chromatography. All gentamicin data were best approximated by a two-compartment open model using sequential, weighted non-linear regression. Pharmacokinetic parameters were calculated using model-dependent formulae. Phenylbutazone data were analysed by non-compartmental methods. Phenylbutazone induced a 49% increase in the rate of gentamicin return to the central compartment from peripheral tissues (k₂₁) (P<0.05) and there was a trend to a 24% increase in k₁₂ (P = 0.052). The gentamicin elimination half-life was decreased 23% and the V_d(area) was reduced by 26%. No induction by gentamicin of changes in phenylbutazone pharmacokinetics were detected. In summary, phenylbutazone induced changes to the rate and extent of distribution and elimination of gentamicin. Therefore, care should be exercised in the use of aminoglycosides in equine patients concurrently maintained on phenylbutazone.     

Pharmacokinetics of the injectable formulation of methadone hydrochloride administered orally in horses

Methadone hydrochloride is a synthetic μ-opioid receptor agonist with potent analgesic properties. Oral methadone has been successfully used in human medicine and may overcome some limitations of other analgesics in equine species for producing analgesia with minimal adverse effects. However, there are no studies describing the pharmacokinetics (PK) of oral opioids in horses. The aim of this study was to describe the PK of orally administered methadone (0.1, 0.2 and 0.4 mg/kg) and physical effects in 12 healthy adult horses. Serum methadone concentrations were measured by gas chromatography/mass spectrometry at predetermined time points for 24 h, and PK parameters were estimated using a noncompartmental model. Physical effects were observed and recorded by experienced clinicians. No drug toxicity, behavioural or adverse effects were observed in the horses. The disposition of methadone followed first order elimination and a biphasic serum profile with rapid absorption and elimination phases. The PK profile of methadone was characterized by high clearance ( Cl / F ), small volume of distribution (V_d/ F ) and short elimination half-life ( t _1/2). The mean of the estimated t _1/2 (SD) for each dose (0.1, 0.2 and 0.4 mg/kg) was 2.2 (35.6), 1.3 (46.1) and 1.5 (40.8), and the mean for the estimated C _max (SD) was 33.9 (6.7), 127.9 (36.0) and 193.5 (65.8) respectively.     

Multiple oral dosing of valacyclovir in horses and ponies

The aim of the current study was to investigate whether multiple oral dosing of valacyclovir could result in plasma concentrations exceeding the EC₅₀-value of acyclovir against equine herpesvirus 1 (EHV1) during the majority of the treatment period. Additionally, we wanted to determine the concentration of acyclovir in nasal mucus and cerebrospinal fluid (CSF). Valacyclovir was administered to four horses and two ponies, three times daily, at a dosage of 40 mg/kg, for four consecutive days. Blood was collected prior to each administration and 1 h after dosing. Nasal mucus samples and CSF were collected once during treatment; 1 h after the last administration. This dosage regimen resulted in plasma concentrations that were higher than the EC₅₀-value of 1.7 μg/mL, i.e. EC₅₀ of an isolate highly susceptible to acyclovir, for 80% of the treatment period; and higher than the EC₅₀-value of 3.0 μg/mL, i.e. EC₅₀ of an isolate less susceptible to acyclovir, for 60% of the treatment period. Concentration in nasal mucus samples and CSF was 0.36–1.17 μg/mL and 0.11–0.23 μg/mL, respectively. This study illustrates that multiple dosing of valacyclovir may result in a therapeutic benefit as plasma concentrations could be maintained above the EC₅₀-value of acyclovir against EHV1 for more than 50% of the treatment period. Acyclovir could be detected in both nasal mucus samples and CSF. However, these concentrations were lower than the EC₅₀.     

RADIOGRAPHIC AND MYELOGRAPHIC EXAMINATION OF THE CERVICAL VERTEBRAL COLUMN IN 306 ATAXIC HORSES

This study consists of a review of 306 ataxic horses subjected to survey radiography and myelography of the cervical vertebral column. Fifty-eight percent of horses had evidence of compressive spinal cord lesion on myelography. Sixty-six percent of horses were less than 3 years old. Age had no effect on the distribution of spinal cord compressive lesions. No conclusion could be drawn from sex and breed distribution. The most common sites of cord compression on myelography in order of decreasing frequency were C_3–4, C_6–7, C_5–6, and C_4–5. Twenty-nine percent of horses with myelographic evidence of cord compression had multiple compressive sites. Survey radiographs were not reliable to diagnose compressive spinal cord lesions. Myelography was a safe and more accurate procedure. Several factors may result in misinterpretation of the myelographic examination.     

PRACTICALITY, USEFULNESS, AND LIMITS OF END-TIDAL CARBON DIOXIDE MONITORING IN CRITICAL SMALL ANIMAL PATIENTS

End-tidal monitors for measuring carbon dioxide (CO₂) have become widely available for clinical use in the last two decades. This non-invasive technology has been previously evaluated in anesthetized veterinary patients, but its accuracy has not been assessed in critical patients. We investigated the usefulness and limits of end-tidal CO₂ monitoring in two populations of critical small animal patients: spontaneously breathing dogs and mechanically ventilated patients with healthy and damaged lungs. In analyzing samples from 43 spontaneously breathing dogs and 34 ventilated patients (28 dogs and six cats), the end-tidal CO₂ was generally lower than pCO₂. The predictive value for hypoventilation was excellent in both populations (100%). The linear correlation of the end-tidal CO₂ and arterial pCO₂ in non-panting dogs with healthy lungs was 0.84 (p<0.0001), and the 95% confidence interval (CI) of the difference was ± 3.2 mm Hg. However, the measures were uncorrelated in panting dogs (r=0.37, p=0.27), and the 95% CI was ± 13.37 mm Hg. Furthermore, where multiple samples could be obtained in individual patients, the r values and differences of end-tidal compared to arterial pCO₂ varied unpredictably. These variations did not appear to be predicted by patient factors such as lung disease. We conclude that the end-tidal CO₂ monitor is clinically useful for detecting hypoventilation and monitoring apnea, but it should be supplemented with arterial pCO₂ determinations if it is important to obtain accurate pCO₂ measures.