Objective—To validate the use of noninvasive pulmonary function testing in sedated and nonsedated llamas and establish reference range parameters of respiratory mechanical function.
Animals—10 healthy adult llamas.
Procedures—Pulmonary function testing in llamas included the following: measurement of functional residual capacity (FRC) via helium dilution, respiratory inductance plethysmography (RIP) to assess breathing pattern and flow limitations, esophageal-balloon pneumotachography, and a monofrequency forced oscillatory technique (FOT; 1 to 7 Hz) before and after IM administration of xylazine (0.2 mg/kg).
Results—The following mean ± SD measurements of respiratory function were obtained in nonsedated llamas: FRC (5.60 ± 1.24 L), tidal volume (1.03 ± 0.3 L), dynamic compliance (0.83 ± 0.4 L/cm H2O), pulmonary resistance (RL; 1.42 ± 0.54 cm H2O/L/s), and respiratory system resistance (2.4 ± 0.9, 2.3 ± 0.7, 2.2 ± 0.6, 2.7 ± 0.7, and 2.5 ± 0.5 cm H2O/L/s at 1, 2, 3, 5, and 7 Hz, respectively) by use of FOT. Measurements of flow limitations via RIP were comparable to other species. Sedation with xylazine induced significant increases in RL and maximum change in transpulmonary pressure. Following sedation, a mean 127% increase in RL and mean 116% increase in respiratory system resistance were observed across 1 to 7 Hz. The magnitude of change in respiratory system resistance increased with decreasing impulse frequency, suggesting bronchoconstriction.
Conclusions and Clinical Relevance—Noninvasive pulmonary function testing is well tolerated in untrained unsedated llamas. These techniques have clinical applications in the diagnosis and treatment of respiratory tract disease, although testing should not be performed after sedation with xylazine.
Objective—To characterize the cardiopulmonary effects of dobutamine and norepinephrine infusion in isoflurane-anesthetized healthy alpacas.
Animals—8 adult alpacas.
Procedures—Initial baseline cardiovascular, respiratory, and metabolic variables were obtained 30 minutes after induction of isoflurane anesthesia in 8 alpacas (3 females and 5 sexually intact males). Four treatments (dobutamine at 4 and 8 μg/kg/min and norepinephrine at 0.3 and 1 μg/kg/min) were administered in random order via constant rate infusion over 15 minutes, followed by repeat measurements of cardiopulmonary values and a 20-minute washout period. Subsequent baseline and posttreatment measurements were similarly repeated until both drugs and dosages were administered to each animal. Baseline data in awake alpacas were obtained 18 to 24 hours following recovery from anesthesia.
Results—Both dobutamine and norepinephrine significantly increased cardiac index and arterial blood pressure from baseline values. Similar increases in hemoglobin concentration, oxygen content, and oxygen delivery were observed following administration of each drug at either dosage. Only dobutamine, however, reduced relative oxygen consumption while improving overall tissue oxygenation. Furthermore, heart rate was selectively enhanced by dobutamine and systemic vascular resistance by norepinephrine. Norepinephrine infusion resulted in dose-dependent changes in cardiopulmonary variables.
Conclusions and Clinical Relevance—Results indicated that both dobutamine and norepinephrine were appropriate choices to improve cardiac index, mean arterial pressure, and overall oxygen delivery in alpacas with isoflurane-induced hypotension. Careful titration by use of low infusion rates of dobutamine and norepinephrine is recommended to avoid potential arrhythmogenic effects and excessive vasoconstriction, respectively.
Objective—To qualitatively describe lung CT images obtained from sedated healthy equine neonates (≤ 14 days of age), use quantitative analysis of CT images to characterize attenuation and distribution of gas and tissue volumes within the lungs, and identify differences between lung characteristics of foals ≤ 7 days of age and foals > 7 days of age.
Animals—10 Standardbred foals between 2.5 and 13 days of age.
Procedures—Foals were sedated with butorphanol, midazolam, and propofol and positioned in sternal recumbency for thoracic CT. Image analysis software was used to exclude lung from nonlung structures. Lung attenuation was measured in Hounsfield units (HU) for analysis of whole lung and regional changes in attenuation and lung gas and tissue components. Degree of lung attenuation was classified as follows: hyperinflated or emphysema, −1,000 to −901 HU; well aerated, −900 to −501 HU; poorly aerated, −500 to −101 HU; and nonaerated, > −100 HU.
Results—Qualitative evidence of an increase in lung attenuation and patchy alveolar patterns in the ventral lung region were more pronounced in foals ≤ 7 days of age than in older foals. Quantitative analysis revealed that mean ± SD lung attenuation was greater in foals ≤ 7 days of age (−442 ± 28 HU) than in foals > 7 days of age (−521 ± 24 HU). Lung aeration and gas volumes were lower than in other regions ventrally and in the mid lung region caudal to the heart.
Conclusions and Clinical Relevance—Identified radiographic patterns and changes in attenuation were most consistent with atelectasis and appeared more severe in foals ≤ 7 days of age than in older neonatal foals. Recognition of these changes may have implications for accurate CT interpretation in sedated neonatal foals with pulmonary disease.
To characterize the pharmacokinetics of a clinically relevant dose of misoprostol administered PO or per rectum (PR) to horses.
8 healthy adult horses.
In a randomized 3-way crossover design, horses received a single dose of misoprostol (5 μg/kg) administered PO (with horses fed and unfed) and PR, with a minimum 3-week washout period separating the experimental conditions. Blood samples were obtained before and at various points after drug administration (total, 24 hours), and plasma concentrations of misoprostol free acid were measured.
Mean maximum plasma concentration of misoprostol was significantly higher in the PR condition (mean ± SD, 967 ± 492 pg/mL) and unfed PO condition (655 ± 259 pg/mL) than in the fed PO condition (352 ± 109 pg/mL). Mean area under the concentration-versus-time curve was significantly lower in the PR condition (219 ± 131 pg•h/mL) than in the unfed (1,072 ± 360 pg•h/mL) and fed (518 ± 301 pg•h/mL) PO conditions. Mean time to maximum concentration was ≤ 30 minutes for all conditions. Mean disappearance half-life was shortest in the PR condition (21 ± 29 minutes), compared with values for the unfed (170 ± 129 minutes) and fed (119 ± 51 minutes) PO conditions. No adverse effects were noted.
CONCLUSIONS AND CLINICAL RELEVANCE
Misoprostol was rapidly absorbed and eliminated regardless of whether administered PO or PR to horses. Rectal administration may be a viable alternative for horses that cannot receive misoprostol PO, but this route may require more frequent administration to maintain therapeutic drug concentrations.
To compare measurements of left ventricular volume and function derived from 2-D transthoracic echocardiography (2DE), transesophageal echocardiography (TEE), and the ultrasound velocity dilution cardiac output method (UDCO) with those derived from cardiac MRI (cMRI) in healthy neonatal foals.
6 healthy 1-week-old Standardbred foals.
Foals were anesthetized and underwent 2DE, TEE, and cMRI; UDCO was performed simultaneously with 2DE. Images acquired by 2DE included the right parasternal 4-chamber (R4CH), left apical 4- and 2-chamber (biplane), and right parasternal short-axis M-mode (M-mode) views. The longitudinal 4-chamber view was obtained by TEE. Measurements assessed included left ventricular end-diastolic volume (LVEDV), end-systolic volume (LVESV), ejection fraction, stroke volume (LVSV), cardiac output (CO), and cardiac index (CI). Bland-Altman analyses were used to compare measurements derived from biplane, R4CH, and M-mode images and UDCO with cMRI-derived measurements. Repeatability of measurements calculated by 3 independent reviewers was assessed by the intraclass correlation coefficient.
Compared with cMRI, all 2DE and TEE modalities underestimated LVEDV and LVESV and overestimated ejection fraction, CO, and CI. The LVSV was underestimated by the biplane, R4CH, and TEE modalities and overestimated by UDCO and M-mode methods. However, the R4CH-derived LVSV, CO, and CI were clinically comparable to cMRI-derived measures. Repeatability was good to excellent for measures derived from the biplane, R4CH, M-mode, UDCO, and cMRI methods and poor for TEE-derived measures.
CONCLUSIONS AND CLINICAL RELEVANCE
All assessed modalities yielded clinically acceptable measurements of LVEDV, LVESV, and function, but those measurements should not be used interchangeably when monitoring patient progress.
OBJECTIVE To determine pharmacokinetics and pulmonary disposition of minocycline in horses after IV and intragastric administration.
ANIMALS 7 healthy adult horses.
PROCEDURES For experiment 1 of the study, minocycline was administered IV (2.2 mg/kg) or intragastrically (4 mg/kg) to 6 horses by use of a randomized crossover design. Plasma samples were obtained before and 16 times within 36 hours after minocycline administration. Bronchoalveolar lavage (BAL) was performed 4 times within 24 hours after minocycline administration for collection of pulmonary epithelial lining fluid (PELF) and BAL cells. For experiment 2, minocycline was administered intragastrically (4 mg/kg, q 12 h, for 5 doses) to 6 horses. Plasma samples were obtained before and 20 times within 96 hours after minocycline administration. A BAL was performed 6 times within 72 hours after minocycline administration for collection of PELF samples and BAL cells.
RESULTS Mean bioavailability of minocycline was 48% (range, 35% to 75%). At steady state, mean ± SD maximum concentration (Cmax) of minocycline in plasma was 2.3 ± 1.3 μg/mL, and terminal half-life was 11.8 ± 0.5 hours. Median time to Cmax (Tmax) was 1.3 hours (interquartile range [IQR], 1.0 to 1.5 hours). The Cmax and Tmax of minocycline in the PELF were 10.5 ± 12.8 μg/mL and 9.0 hours (IQR, 5.5 to 12.0 hours), respectively. The Cmax and Tmax for BAL cells were 0.24 ± 0.1 μg/mL and 6.0 hours (IQR, 0 to 6.0 hours), respectively.
CONCLUSIONS AND CLINICAL RELEVANCE Minocycline was distributed into the PELF and BAL cells of adult horses.
OBJECTIVE To evaluate use of single manual alveolar recruitment maneuvers (ARMs) to eliminate atelectasis during CT of anesthetized foals.
ANIMALS 6 neonatal Standardbred foals.
PROCEDURES Thoracic CT was performed on spontaneously breathing anesthetized foals positioned in sternal (n = 3) or dorsal (3) recumbency when foals were 24 to 36 hours old (time 1), 4 days old (time 2), 7 days old (time 3), and 10 days old (time 4). The CT images were collected without ARMs (all times) and during ARMs with an internal airway pressure of 10, 20, and 30 cm H2O (times 2 and 3). Quantitative analysis of CT images measured whole lung and regional changes in attenuation or volume with ARMs.
RESULTS Increased attenuation and an alveolar pattern were most prominent in the dependent portion of the lungs. Subjectively, ARMs did not eliminate atelectasis; however, they did incrementally reduce attenuation, particularly in the nondependent portion of the lungs. Quantitative differences in lung attenuation attributable to position of foal were not identified. Lung attenuation decreased significantly (times 2 and 3) and lung volume increased significantly (times 2 and 3) after ARMs. Changes in attenuation and volume were most pronounced in the nondependent portion of the lungs and at ARMs of 20 and 30 cm H2O.
CONCLUSIONS AND CLINICAL RELEVANCE Manual ARMs did not eliminate atelectasis but reduced attenuation in nondependent portions of the lungs. Positioning of foals in dorsal recumbency for CT may be appropriate when pathological changes in the ventral portion of the lungs are suspected.
To describe misoprostol pharmacokinetics and anti-inflammatory efficacy when administered orally or per rectum in endotoxin-challenged horses.
6 healthy geldings.
A randomized 3-treatment crossover design was performed with a minimum washout period of 28 days between treatment arms. Prior to endotoxin challenge (lipopolysaccharide, 30 ng/kg IV over 30 minutes), horses received misoprostol (5 µg/kg once) per os (M-PO) or per rectum (M-PR) or water as control (CON). Clinical parameters were evaluated and blood samples obtained to measure plasma misoprostol free acid concentration, leukocyte counts, and tumor necrosis factor-α (TNFα) and interleukin 6 (IL-6) leukocyte gene expression and serum concentrations.
In the M-PO treatment arm, maximum plasma concentration and area under the concentration-versus-time curve (mean ± SD) were higher (5,209 ± 3,487 pg/mL and 17,998,254 ± 13,194,420 h·pg/mL, respectively) and median (interquartile range) time to maximum concentration (25 min [18 to 34 min]) was longer than in the M-PR treatment arm (854 ± 855 pg/mL; 644,960 ± 558,866 h·pg/mL; 3 min [3 to 3.5 min]). Significant differences in clinical parameters, leukocyte counts, and TNFα or IL-6 gene expression or serum protein concentration were not detected. Downregulation of relative gene expression was appreciated for individual horses in the M-PO and M-PR treatment arms at select time points.
Considerable variability in measured parameters was detected among horses within and between treatment arms. Misoprostol absorption and systemic exposure after PO administration differed from previous reports in horses not administered LPS. Investigation of multidose administration of misoprostol is warranted to better evaluate efficacy as an anti-inflammatory therapeutic.
To compare the pharmacokinetics between repeated doses and to characterize changes in the fecal microbiome after oral and rectal multidose misoprostol administration.
6 healthy university-owned geldings.
In a randomized, crossover study, misoprostol (5 μg/kg) was administered orally or rectally every 8 hours for 10 doses, or not administered (control), with a 21-day washout between treatments. Concentration-versus-time data for dose 1 and dose 10 were subject to noncompartmental analysis. For microbiota analysis using 16S rRNA amplicon sequencing, manure was collected 7 days before study onset, immediately before dose 1, and 6 hours, 7 days, and 14 days after dose 10, with time-matched points in controls.
Repeated dosing-related differences in pharmacokinetic parameters were not detected for either administration route. The area under the concentration-versus-time curve was greater (P < .04) after oral versus rectal administration. The relative bioavailability of rectal administration was 4 to 86% of that of oral administration. Microbial composition, richness, and β-diversity differed among subjects (P < .001 all) while only composition differed between treatments (P ≤ .01). Richness was decreased 6 hours after dose 10 and at the control-matched time point (P = .0109) in all subjects. No other differences for time points, treatments, or their interactions were observed.
Differences in systemic exposure were associated with the route of administration but were not detected after repeated administration of misoprostol. Differences in microbiota parameters were primarily associated with interindividual variation and management rather than misoprostol administration.
OBJECTIVE To compare CT and radiographic images of the lungs in sedated healthy foals positioned in sternal recumbency and to investigate whether a relationship exists between CT-derived measurements of lung attenuation and Paco2 and Pao2.
ANIMALS 6 healthy Standardbred foals < 14 days of age.
PROCEDURES Thoracic CT images were acquired followed by radiographic views with each foal sedated and positioned in sternal recumbency. For each foal, both CT and radiographic images were evaluated for severity and extent of changes by lung regions on the basis of a subjective scoring system by 3 investigators. Quantitative analysis of CT images was also performed. Assessments of Pao2 and Paco2 were performed before sedation, following sedation prior to CT, and after CT prior to radiography.
RESULTS Interobserver agreement for CT and radiographic image scoring was strong (0.73) and fair (0.65), respectively; intraobserver agreement was near perfect for CT (0.97) and radiographic (0.94) image scoring. Increased CT attenuation and radiographic changes were identified for all foals and were preferentially distributed in the caudoventral portion of the lungs. Radiographic scores were significantly lower than CT image scores. A positive correlation (r = 0.872) between lung attenuation and CT image score was identified. A significant increase in Paco2 was not considered clinically relevant. Significant changes in Pao2 were not observed.
CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that interpretation of CT images may be less subjective, compared with interpretation of radiographic images. These findings may aid in the evaluation of CT and radiographic images of neonatal foals with respiratory tract disease.