The objective of this prospective clinical study was to evaluate the accuracy of pulse oximetry and capnography in healthy and compromised horses during general anesthesia with spontaneous and controlled ventilation. Horses anesthetized in a dorsal recumbency position for arthroscopy (n = 20) or colic surgery (n = 16) were instrumented with an earlobe probe from the pulse oximeter positioned on the tip of the tongue and a sample line inserted at the Y-piece for capnography. The horses were allowed to breathe spontaneously (SV) for the first 20 min after induction, and thereafter ventilation was controlled (IPPV). Arterial blood, for blood gas analysis, was drawn 20 min after induction and 20 min after IPPV was started. Relationships between oxygen saturation as determined by pulse oximetry (SpO2), arterial oxygen saturation (SaO2), arterial carbon dioxide partial pressure (PaCO2), and end tidal carbon dioxide (P(et)CO2), several physiological variables, and the accuracy of pulse oximetry and capnography, were evaluated by Bland–Altman or regression analysis. In the present study, both SpO2 and P(et)CO2 provided a relatively poor indication of SaO2 and PaCO2, respectively, in both healthy and compromised horses, especially during SV. A difference in heart rate obtained by pulse oximetry, ECG, or palpation is significantly correlated with any pulse oximeter inaccuracy. If blood gas analysis is not available, ventilation to P(et)CO2 of 35 to 45 mmHg should maintain the PaCO2 within a normal range. However, especially in compromised horses, it should never substitute blood gas analysis.

Objective-To determine the effects of immersion in warm springwater (38° to 40°C) on autonomic nervous activity in horses. Animals-10 male Thoroughbreds. Procedure-Electrocardiograms were recorded from horses for 15 minutes during a warm springwater bath after being recorded for 15 minutes during stall rest. Variations in heart rate (HR) were evaluated from the power spectrum in terms of low frequency (LF, 0.01 to 0.07 Hz) power and high frequency (HF, 0.07 to 0.6 Hz) power as indices of autonomic nervous activity. Results-Mean (+/-SE) HR during stall rest and immersion in warm springwater was 31.1 +/- 1.7 and 30.3 +/- 1.0 beat/min, respectively. No significant difference was found between the HR recorded during stall rest and that recorded during immersion in warm springwater. The HF power significantly increased from 1,361 +/- 466 milliseconds2 during stall rest to 2,344 +/- 720 milliseconds2 during immersion in warm springwater. The LF power during stall rest and immersion in warm springwater was 3,847 +/- 663 and 5,120 +/- 1,094 milliseconds2, respectively, and were not significantly different from each other. Similarly, the LF:HF ratio did not change during immersion in warm springwater. The frequency of second-degree atrioventricular block, which was observed in 2 horses, increased during immersion in warm springwater, compared with during stall rest. Conclusions and Clinical Relevance-Increases in HF power indicates that the parasympathetic nervous activity in horses increases during immersion in warm springwater. Thus, immersion in warm springwater may provide a means of relaxation for horses.

To test the hypothesis that the pulmonary vascular pressures of Thoroughbred and Standardbred horses behave similarly during exertion. Measurements were made on 5 Thoroughbred and 5 Standardbred horses on a treadmill at rest and during 3-minute exercise intervals at speeds predicted to produce 75%, 90%, and 100% maximal heart rate. Left forelimb acceleration, heart rate, esophageal pressure, and pulmonary artery pressure were measured continuously. Pulmonary capillary and wedge pressures were measured during intermittent occlusion of the pulmonary artery. Breathing rate and gait frequency were the fundamental frequencies of the esophageal pressure and limb acceleration signals respectively. The ratio of speed:gait frequency gave stride length. The effects of exertion and breed were evaluated using two-way analysis of variance. Exertion produced significant increases in pulmonary artery (P = 0.001), capillary (P= 0.002), and wedge (P= 0.005) pressures. No significant effect of breed was detected on pulmonary artery pressure, but at exertion pulmonary capillary and wedge pressures were 15% (P= 0.03) and 23% (P= 0.04) greater in Thoroughbreds, respectively. Treadmill speed was ~12% greater (P= 0.04), stride length was ~25% greater (P= 0.0003), gait frequency was ~10% less (P= 0.006), breathing rate was ~10% less (P= 0.001), and heart rate was ~6% less (P= 0.06) for Thoroughbreds. There was no effect of breed on inspiratory or expiratory esophageal pressure although mean esophageal pressure was ~2 mmHg greater (P= 0.03) in exercising Standardbreds. In conclusion, pulmonary capillary and wedge pressures are greater in Thoroughbreds than in Standardbreds at similar fractions of maximal heart rate. This is compatible with the higher incidence of exercise-induced pulmonary hemorrhage observed in Thoroughbreds.

Objective-To determine the influence of age on results of quantitative analysis of electromyographic (EMG) needle examination in the subclavian, triceps, and lateral vastus muscles of Dutch Warmblood horses. Animals-7 healthy young Dutch Warmblood horses (range, 13 to 18 months old), 7 healthy adult Dutch Warmblood horses (range, 4 to 10 years old), and 7 healthy elderly Dutch Warmblood horses (range, 18 to 21 years old). Procedure-An EMG needle examination was performed to evaluate insertional activity, spontaneous activity, and motor unit action potential (MUAP) variables. Although all horses were conscious, young horses were sedated prior to examination. Results-Mean insertional activity in young horses was significantly lower than in elderly horses. Pathologic spontaneous activity was rarely found in young and adult horses but was frequently evident in all muscles in all elderly horses. The MUAP duration and amplitude were significantly lower in all muscles of young horses, compared with values for adult and elderly horses. The MUAP duration and number of phases and turns were significantly lower in adult horses than in elderly horses. Group differences for percentages of polyphasic and complex MUAPs were also found. The 95% confidence intervals for MUAP duration, MUAP amplitude, and number of phases and turns for the subclavian, triceps, and lateral vastus muscles were significantly lower in young horses than in adult or elderly horses. Conclusion and Clinical Relevance-Age of the horse being examined should be considered when EMG examination is performed.

Objective-To quantitate dose- and time-related magnitudes of interactive effects of morphine (MOR) and isoflurane (ISO) in horses and to characterize pharmacokinetics of MOR in plasma and the ventilatory response to MOR during administration of ISO. Animals-6 adult horses. Procedure-Horses were anesthetized 3 times to determine the minimum alveolar concentration (MAC) of ISO in O2 and then to characterize the change in anesthetic requirement as defined by the alteration in ISO MAC following IV administration of saline (0.9% NaCl) solution and 2 doses of MOR (low dose, 0.25 mg/kg; high dose, 2.0 mg/kg). Arterial blood samples were obtained before and after MOR and analyzed. Results-Mean +/- SD baseline ISO MAC was 1.43 +/- 0.06%. The ISO MAC did not change with time after administration of saline solution. Effects of MOR on ISO MAC varied. Maximal change in MAC ranged from –20.2 to +28.3% and -18.9 to +56.2% after low and high doses of MOR, respectively. Typical half-life of MOR in plasma was 40 to 60 minutes and related to dose. Mean PaCO2 increased from 70 mm Hg before MOR to 88 to 102 mm Hg for 30 to 240 minutes after the high dose of MOR. Recovery from anesthesia after administration of the high dose of MOR was considered undesirable and dangerous. Conclusions and Clinical Relevance-Our results do not support routine clinical use of MOR administered IV at dosages of 0.25 or 2.0 mg/kg as an adjuvant to anesthesia in horses administered ISO.

Objective-To determine whether the nonsteroidal anti-inflammatory drugs (NSAIDs) carprofen, flunixin meglumine, and phenylbutazone have cyclooxygenase (COX)-independent effects that specifically inhibit activation of the proinflammatory transcription factor nuclear factor kappa B (NfκB). Study Population-Purified ovine COX-1 and -2 and cultures of RAW 264.7 murine macrophages. Procedure-The COX-1 and -2 inhibitory effects of the NSAIDs were tested in assays that used purified ovine COX-1 and -2. Prostaglandin production was analyzed by use of a radioimmunoassay. Inhibitory effects of these drugs on lipopolysaccharide (LPS)- induction of inducible nitric oxide synthase (iNOS) and LPS-stimulated translocation of NfκB were determined by use of RAW 264.7 murine macrophages. Results-Flunixin meglumine and phenylbutazone were selective inhibitors of COX-1. Carprofen and flunixin meglumine, but not phenylbutazone, inhibited LPS-induction of iNOS. Carprofen and, to a lesser degree, flunixin meglumine had inhibitory effects on NFκB activation. Conclusions and Clinical Relevance-The ability of drugs such as carprofen and flunixin meglumine to inhibit activation of NfκB-dependent genes such as iNOS, in addition to their effects on COX, suggests an additional mechanism for their anti-inflammatory effects and may explain the ability of flunixin meglumine to be an effective inhibitor of the effects of endotoxin in horses with endotoxemia.

Objective-To characterize insulin-sensitive glucose-transporter (GLUT-4) protein in equine tissues and determine effects of exercise and glucose administration on content of GLUT-4 protein in equine skeletal muscle. Sample Population-Tissue samples from 9 horses. Procedure-Western blot analyses were performed on crude membrane preparations of equine tissues to characterize GLUT-4. In a crossover, randomized study, horses were strenuously exercised for 3 consecutive days and then administered 13.5% glucose or isotonic saline (0.9% NaCl; control) solution, IV, at similar infusion rates for 12.1 hours. Samples were collected from the middle gluteal muscle before and after exercise and 10.1 hours after completion of an infusion and used for measurements of glycogen concentration and total content of GLUT-4 protein. Results-Immunoblot analyses detected specifically immunoreactive bands for GLUT-4 in insulin-sensitive tissues. Content of GLUT-4 protein in skeletal muscle increased significantly by 27.3 and 12.3% 22.2 hours after exercise for control and glucose groups, respectively. Intravenous infusion of glucose resulted in a significantly higher rate of glycogenesis, compared with results for the control group (mean +/- SD, 3.98 +/- 0.61 and 1.47 +/- 0.20 mmol/kg/h, respectively). Despite enhanced glycogenesis, we did not detect an increase in content of GLUT-4 protein after glucose infusion, compared with values after exercise. Conclusions and Clinical Relevance-GLUT-4 protein was expressed in equine skeletal and cardiac muscles. Exercise increased total content of GLUT-4 protein in skeletal muscle, and replenishment of muscle glycogen stores after glucose infusion attenuated the exercise-induced increase in the content of GLUT-4 protein in equine skeletal muscle.

Objective-To evaluate a modified digital imaging technique for quantitative assessment of the grade of osteoarthritis across the proximal articular surface of the first phalanx in horses. Sample Population-6 metacarpophalangeal (fetlock) joint specimens from 6 horses with various stages of osteoarthritis. Procedure-First phalanx specimens, together with 4 gray scale reference calibration targets, were positioned in a bath with the proximal articular cartilage surface submerged in saline (0.9% NaCl) solution. Digital images were obtained from the articular surface before and after staining with Indian ink. Computer-controlled gray level analysis of the nonstained and Indian ink-stained cartilage surfaces and gray scale reference calibration targets was performed by use of the mean pixel value (based on 255-gray scale). An increase in the mean pixel value after staining was used to calculate the cartilage degeneration index (CDI). Results-The CDI of the proximal articular cartilage surface of the first phalanx specimens ranged from 9.2 +/- 5.7 (early stage osteoarthritis) to 41.5 +/- 3.6% (late stage osteoarthritis). The effect of repeating the measurement 6 times in nonstained (including repositioning) and stained specimens (including repositioning and restaining) was not significant. Up to 10 measurements of nonstained specimens could be made without refreshing the bath solution. In stained specimens, mean gray level increased significantly after the sixth measurement. Conclusion and Clinical Relevance-The modified digital imaging technique allowed quantitative assessment of cartilage degeneration across the articular cartilage surface. The CDI is the first quantitative measure for osteoarthritis-induced cartilage degeneration over an entire joint surface in horses.

Objective-To evaluate effects of sedation on stability of resistance of the respiratory system (RRS) and measures of resting energy expenditure (REE) by use of open-flow indirect calorimetry (IC) and treatment with aerosolized albuterol on REE in horses with recurrent airway obstruction (RAO). Animals-9 clinically normal horses and 8 horses with RAO. Procedure-In phase 1, RRS was measured by using forced oscillometry (FOT) in 5 clinically normal horses before and after sedation with xylazine. In phase 2, REE was measured in 4 clinically normal horses between 20 and 25 minutes and again 35 to 40 minutes after sedation with xylazine. In phase 3, IC was performed between 20 and 25 minutes and FOT was performed between 30 and 35 minutes after xylazine administration in 8 horses with RAO; after administration of 450 µg of albuterol, IC and FOT were repeated. Results-In phase 1, RRS values were significantly lower 5 and 10 minutes after sedation. In phase 2, diminishing sedation did not significantly affect REE. In phase 3, there was a significant decrease in mean RRS (1.15 +/- 0.25 vs 0.84 +/- 0.14 cm H20/L/s) and REE (30.68 +/- 17.89 vs 27.46 +/- 16.54 kcal/kg/d) after albuterol administration. Conclusions and Clinical Relevance-FOT and IC are useful in obtaining repeatable measurements of RRS and REE, respectively, in sedated horses. Concurrent bronchodilation and decreased REE after albuterol administration suggest that increased work of breathing as a result of airway obstruction may contribute to increased energy demands in horses with RAO.

Objective-To determine the presence of adenosine receptor subtypes A1 and A2a in equine forebrain tissues and to characterize the interactions of caffeine and its metabolites with adenosine receptors in the CNS of horses. Sample Population-Brain tissue specimens obtained during necropsy from 5 adult male research Procedures-Membrane-enriched homogenates from cerebral cortex and striatum were evaluated by radioligand binding assays with the A1-selective ligand [3H]DPCPX and the A2a-selective ligand [3H]ZM241385. Functional responses to adenosine receptor agonists and antagonists were determined by a nucleotide exchange assay using [35S]-guanosine 5'-(γ-thio) triphosphate [35S]GTPγS). Results-Saturable high affinity [3H]DPCPX binding (A1) sites were detected in cerebral cortex and striatum, whereas high-affinity [3H]ZM241385 binding (A2a) sites were detected only in striatum. Caffeine and related methylxanthines had similar binding affinities at A1 and A2a sites with rank orders of drug binding affinities (theophylline > paraxanthine ≥ caffeine >> theobromine) similar to other species. [35S]GTPγS exchange revealed that caffeine and its metabolites act as pure adenosine receptor antagonists at concentrations that correspond to A1 and A2a receptor binding affinities. Conclusions and Clinical Relevance-Results of our study affirm the presence of guanine nucleotide binding protein linked adenosine receptors (ie, high-affinity A1 and A2a adenosine receptors) in equine forebrain tissues and reveal the antagonistic actions by caffeine and several biologically active caffeine metabolites. Antagonism of adenosine actions in the equine CNS by these stimulants may be responsible for some central actions of methylxanthine drugs, including motor stimulation and enhanced racing performance.