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.

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.

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.

Equivalence between invasive and oscillometric blood pressures at different anatomic locations in healthy normotensive anaesthetised horses.

REASONS FOR PERFORMING STUDY: Accurate blood pressure measurement is essential for effective clinical assessment and appropriate interventions in anaesthetised horses. Information on the accuracy of oscillometry for blood pressure measurement on the appendages of mature horses is limited. OBJECTIVES: To assess equivalence between invasive and oscillometric blood pressures at different anatomic locations in horses. STUDY DESIGN: Prospective experimental study using 6 healthy mature horses. METHODS: Blood pressure was measured invasively in the right transverse facial artery and noninvasively by oscillometry in nondependent limbs and tail of laterally recumbent sevoflurane- or desflurane-anaesthetised horses. Cuff widths of 5-12 cm were tested on the tail, metatarsus, metacarpus and distal radius/ulna. Equivalence between mean arterial pressure (MAP) oscillometric and MAP invasive was assessed using a linear mixed effects model with a significance level of P≤0.05. RESULTS: Twenty paired measurements were obtained for each cuff size in each of the locations, totalling 340 measurements. There was only one location (tail) and one cuff width (6 cm; cuff width-to-tail circumference ratio of 0.25) that resulted in equivalence between MAP measured with the oscillometric and the invasive methods (P = 0.8). All other locations (metacarpus, radius/ulna, metatarsus) and cuff widths were not equivalent (P≤0.01). CONCLUSIONS: A cuff width-to-tail circumference ratio of 0.25 is recommended for accurate oscillometric blood pressure measurement in mature, laterally recumbent anaesthetised normotensive horses. Studies with variable haemodynamics are warranted. Oscillometric measurements at other extremities and/or with other cuff sizes cannot be recommended for clinical use.

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.

Pharmacokinetics and physiological effects of repeated oral administrations of tramadol in horses.

This study evaluated the pharmacokinetics and physiological effects of tramadol during repeated oral administrations in horses. Nine adult healthy horses were administered tramadol at 5 and 10 mg/kg orally every 12 h for 5 days in a randomized, crossover design with a 3-week washout between treatments. Plasma concentrations of tramadol, O- and N-desmethyltramadol (M1 and M2) were measured using Liquid-Chromatography-Mass Spectrometry at predetermined time points following each tramadol administration. Cardiovascular, respiratory and gastrointestinal physiological variables were monitored and adverse events were recorded. Data were analysed with two-way repeated measures anova or Kruskal-Wallis one-way anova on ranks with P < 0.05 considered statistically significant. There were no significant effects of tramadol on the physiological variables. One horse receiving 10 mg/kg tramadol developed mild colic. Following tramadol at 5 and 10 mg/kg, respectively, maximum plasma concentrations (Cmax ) of tramadol ranged from 82-587 and 127-1280 ng/mL, nonconjugated M1 ranged from 2.51-26.7 and 4.88-34.3 ng/mL, and nonconjugated M2 from 12.5-356 and 35.4-486 ng/mL. Corresponding minimum plasma concentrations (Cmin ) of tramadol at 12 h following each dose ranged from 0.8-24 and 3-117 ng/mL. Tramadol accumulated considerably over time, more markedly when given at 10 mg/kg than at 5 mg/kg (accumulation indexes of 3.51 and 1.73 respectively). There was no accumulation of M1 but substantial accumulation of M2. In conclusion, there was accumulation and increase in exposure to tramadol and M2, but not M1, during repeated oral administrations in horses.

Pharmacokinetics of fentanyl, alfentanil, and sufentanil in isoflurane-anesthetized cats.

The aim of this study was to compare the pharmacokinetics of fentanyl, alfentanil, and sufentanil in isoflurane-anesthetized cats. Six adult cats were used. Anesthesia was induced and maintained with isoflurane in oxygen. End-tidal isoflurane concentration was set at 2% and adjusted as required due to spontaneous movement. Fentanyl (10 µg/kg), alfentanil (100 µg/kg), or sufentanil (1 µg/kg) was administered intravenously as a bolus, on separate days. Blood samples were collected immediately before and for 8 h following drug administration. Plasma drug concentration was determined using liquid chromatography/mass spectrometry. Compartment models were fitted to concentration-time data. A 3-compartment model best fitted the concentration-time data for all drugs, except for 1 cat in the sufentanil group (excluded from analysis). The volume of the central compartment and the volume of distribution at steady-state (L/kg) [mean ± SEM (range)], the clearance (mL/min/kg) [harmonic mean ± pseudo-SD (range)], and the terminal half-life (min) [median (range)] were 0.25 ± 0.04 (0.09-0.34), 2.18 ± 0.16 (1.79-2.83), 18.6 ± 5.0 (15-29.8), and 151 (115-211) for fentanyl; 0.10 ± 0.01 (0.07-0.14), 0.89 ± 0.16 (0.68-1.83), 11.6 ± 2.6 (9.2-15.8), and 144 (118-501) for alfentanil; and 0.06 ± 0.01 (0.04-0.10), 0.77 ± 0.07 (0.63-0.99), 17.6 ± 4.3 (13.9-24.3), and 54 (46-76) for sufentanil. Differences in clearance and volume of distribution result in similar terminal half-lives for fentanyl and alfentanil, longer than for sufentanil.

Sensory nerve conduction and somatosensory evoked potentials of the trigeminal nerve in horses with idiopathic headshaking.

BACKGROUND: Idiopathic headshaking (HSK) in horses is a distressing disorder in which the etiology and pathophysiology are unknown. HYPOTHESIS: Differences in sensory function of the trigeminal nerve exist between healthy and affected horses. ANIMALS: Six healthy mature geldings and 6 mature geldings with idiopathic HSK. METHODS: Prospective study. Sensory nerve action and somatosensory evoked potentials studies were performed. The stimulus site comprised the gingival mucosa dorsal to the maxillary canine. A pair of recording electrodes was placed along the sensory pathway of the trigeminal complex at the infraorbital nerve (R1), maxillary nerve (R2), spinal tract of trigeminal (R3), and somatosensory cortex (R4). Sensory nerve action potential latency (ms), amplitude (µV), duration (ms), area under the curve (µVms), and conduction velocity (m/s) were calculated. RESULTS: Threshold for activation of the infraorbital branch of the trigeminal nerve was significantly different between 5 affected (≤ 5 mA) and 6 control horses (≥ 10 mA). After initiation of an action potential, there were no differences in all parameters measured and no differences between left and right sides. A horse with seasonal HSK tested during a time of no clinical manifestations showed a threshold for activation similar to control horses. CONCLUSIONS AND CLINICAL IMPORTANCE: This study confirms involvement of the trigeminal nerve hyperexcitability in the pathophysiology of disease. Further, results might support a functional rather than a structural alteration in the sensory pathway of the trigeminal complex that can be seasonal. The horse could serve as a natural animal model for humans with idiopathic trigeminal neuralgia.

Scintigraphic evaluation of intra-arterial and intravenous regional limb perfusion of allogeneic bone marrow-derived mesenchymal stem cells in the normal equine distal limb using (99m) Tc-HMPAO.

REASONS FOR PERFORMING STUDY: Mesenchymal stem cells (MSCs) are commonly injected intralesionally for treatment of soft tissue injuries in the horse. Alternative routes of administration would be beneficial for treatment of lesions that cannot be accessed directly or to limit needle-induced iatrogenic damage to the surrounding tissue. OBJECTIVES: The purpose of our study was to evaluate MSC distribution after intra-arterial (IA) and intravenous (IV) regional limb perfusions (RLP) using scintigraphy. We hypothesised that MSCs would persist in the distal limb after tourniquet removal and that both techniques would lead to diffuse MSC distribution. METHODS: Six horses were used in the study. MSCs were labelled with hexamethyl propylene amine oxime (HMPAO) and technetium-99m. RLP was performed through the median artery of one forelimb and the cephalic vein of the opposite limb under general anaesthesia. The tourniquet was left in place for 45 min. Scintigraphic images were obtained at 0, 45, 75 min, 6 h and 24 h post injection. RESULTS: Distribution of labelled MSCs through the entire distal limb was achieved with all 6 IA RLP, but 3 out of 6 IV RLP showed poor or absent uptake distal to the metacarpus. Mesenchymal stem cell persistence was 39% (30-60%) and 28% (14-50%) (median [minimum-maximum]) at 6 h for IA and IV RLP, respectively. Severe arterial thrombosis occurred in one horse after IA RLP. CONCLUSIONS: Both IA and IV RLP of the distal limb result in MSC persistence in perfused tissues. The IA perfusion resulted in more reliable cell distribution to the pastern and foot area. POTENTIAL RELEVANCE: Regional limb perfusion of MSCs might be used in cases where intralesional injection is not possible or in order to avoid iatrogenic needle damage. Further work is needed to assess the safety of IA RLP before its clinical use.

Repetitive stimulation of the common peroneal nerve as a diagnostic aid for botulism in foals.

BACKGROUND: Botulism is a potentially fatal paralytic disorder for which definitive diagnosis is difficult. OBJECTIVES: To determine if repetitive stimulation of the common peroneal nerve will aid in the diagnosis of botulism in foals. ANIMALS: Four control and 3 affected foals. METHODS: Validation of the test in healthy foals for its comparison in foals with suspected botulism. Controls were anesthetized and affected foals were sedated to avoid risks of anesthesia. The common peroneal nerve was chosen for its superficial location and easy access. Stimulating electrodes were placed along the common peroneal nerve. For recording, the active and reference electrodes were positioned over the midpoint and distal end of the extensor digitorum longus muscle, respectively. Repeated supramaximal stimulation of the nerve was performed utilizing a range of frequencies (1-50 Hz). Data analysis consisted of measuring the amplitude and area under the curve for each M wave and converting these values into percentages of decrement or increment based on the comparison of subsequent potentials to the initial one (baseline) within each set. RESULTS: A decremental response was seen at all frequencies in control foals. Decremental responses also were observed in affected foals at low frequencies. An incremental response was seen in all affected foals at 50 Hz. CONCLUSIONS AND CLINICAL IMPORTANCE: Decreased baseline M wave amplitudes with incremental responses at high rates are supportive of botulism. Repetitive nerve stimulation is a safe, simple, fast, and noninvasive technique that can aid in the diagnosis of suspected botulism in foals.

Carbon dioxide negatively modulates N-methyl-D-aspartate receptors.

BACKGROUND: Carbon dioxide (CO2) dose-dependently decreases minimum alveolar concentration (MAC) of anaesthetics in rats. CO2 also dose-dependently decreases cerebrospinal fluid pH. N-methyl-D-aspartate (NMDA) channels exhibit pH sensitivity and are putative targets for inhaled anaesthetics. We hypothesized that CO2 dose-dependently decreases rat NMDA channel current via an acidifying effect at concentrations relevant to CO2 MAC. METHODS: To test this hypothesis, we studied rat NR1/NR2A glutamate receptors expressed in voltage-clamped Xenopus oocytes. To measure pH effects, we used perfusates adjusted between 7.3 and 5.3 with HCl. To measure CO2 effects, we used equimolar sodium perfusates containing either 0 or 24 mM NaHCO3 and CO2 between 0% and 87% atm. Solution compositions were measured using a blood gas analyser with values corrected using a calibrated pH meter and gas chromatograph with solutions at 37 degrees C. RESULTS: We found that decreasing pH decreased NMDA current. Moreover, pH effects produced by adding CO2 to NaHCO3-containing perfusates were identical to those produced by adding HCl to normal perfusates. The pH inhibiting 50% of NMDA current was 6.52. The CO2 concentration inhibiting 50% of rat NMDA current was 63% for solutions with 24 mM NaHCO3. CO2 exhibited a linear dose-dependent NMDA response analogous to that observed for in vivo CO2 anaesthetic potency in rats. CONCLUSIONS: CO2 and hydrogen ions act via the same mechanism to inhibit NMDA receptors. Moreover, CO2 inhibits rat NMDA receptors in a manner that is consistent with CO2 MAC-sparing effects in rats.