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Effects of intra-articularly administered endotoxin on clinical signs of disease and synovial fluid tumor necrosis factor, interleukin 6, and prostaglanadin E2 values in horses
1993
Hawkins, D.L. | MacKay, R.J. | Gum, G.G. | Colahan, P.T. | Meyer, J.C.
In each of 4 horses, sterile synovitis was induced by intra-articular injection of 3 micrograms of Escherichia coli endotoxin (lipopolysaccharide, LPS) into one antebrachiocarpal joint; an equal volume (2 ml) of phosphate-buffered saline solution (PBSS) was injected into the opposite, control carpus. Blood and 1.5 ml of synovial fluid were obtained at postinjection hours (PIH) 0, 2, 4, 8, 12, 18, 42, 66, and 144. Synovial fluid sample collection was accomplished by use of an indwelling, intra-articular catheter through PIH 12, and by arthrocentesis subsequently. Joint fluid samples were analyzed for cell counts, protein concentration, cytologic variables, and tumor necrosis factor (TNF), interleukin 6 (IL-6), and prostaglandin E2 (PGE2) values. Tumor necrosis factor and IL-6 activities and WBC count were also measured in blood. To monitor local inflammation, skin temperature of each carpus was imaged, using a thermographic scanner prior to each sample collection time. Horses had minimal systemic effects. Mean (SEM) rectal temperature increased significantly to 39.02 +/- 0.15 C only at PIH 18 after intra-articular injection of LPS. One horse had signs of mild depression from PIH 7 to 18, but its vital signs did not change appreciably. Each horse had mild signs of discomfort in the LPS-injected limb from PIH 1 to 3 until PIH 8 to 10. Mean peak surface temperature of the LPS-injected carpi was significantly higher than that of control carpi from PIH 8 to 144 (P < 0.05). Mean synovial fluid WBC count in the LPS-injected and control carpi increased after injection and peaked by PIH 8 (193,125 +/- 8,528 cells/microliter, LPS-treated; 16,425 +/- 8,336 cells/microliter, controls). Mean values for LPS-treated (principal) joints were significantly greater than values for control joints from PIH 2 until after PIH 66 (P < 0.05). Mean synovial fluid protein concentration increased in the principal and control joints, with values for the principal joints remaining significantly greater than values for control joints from PIH to 144 (P < 0.05). Mean TNF activity in synovial fluid was maximal at PIH 2 (10,573 +/- 5,924 U/ml). Interleukin-6 activity increased more gradually and peaked at PIH 8 (1.78 +/- 0.71 X 10(6) U/ml). Tumor necrosis factor activity did not increase above the minimal detectable value of 6 U/ml in the control joints. Mean PGE2 concentration in the principal joints peaked by PIH 2 (3.6 +/- 0.37 ng/ml) and remained significantly (P < 0.05) greater than the value for control joints from PIH 2 through 66. These results indicate that a humane model of synovitis was created by intra-articular injection of LPS and can be used to establish the basic responses of synovial TNF, IL-6, and PGE, in horses with early inflammatory joint disease.
Показать больше [+] Меньше [-]Neuropeptidergic innervation of equine synovial joints
1993
Bowker, R.M. | Abhold, R.H. | Caron, J.P. | Sonea, I.M. | Vex, K.B. | Kotyk, R.
Immunocytochemical analysis of equine synovial membranes revealed presence of several neuropeptides, including substance P (SP), neurokinin A, and neuropeptide Y, in nerves of the radiocarpal, middle carpal, and metacarpophalangeal (fetlock) joints. Within the subsynovium, these neuropeptides were located perivascularly, whereas in the fronds, only neuropeptide Y was restricted to the vessels of the synovial membrane. Only SP and neurokinin A were found in the intimal layer. The intimal layer of the metacarpophalangeal joint contained more SP-immunoreactive fibers than were observed in the intimal layer of the radiocarpal joint. Substance P also was detected in the synovial fluid from all 3 joints, but mean +/- SD concentrations were significantly different only between the middle carpal joint (37.56 +/- 5.48 fmol/ml; n = 6) and the metacarpophalangeal joint (55.80 +/- 8.33 fmol/ml; n = 5) and between the middle carpal joint and the radiocarpal joint (52.43 +/- 14.60 fmol/ml; n = 7).
Показать больше [+] Меньше [-]Serum triiodothyronine, total thyroxine, and free thyroxine concentrations in horses
1993
Sojka, J.E. | Johnson, M.A. | Bottoms, G.D.
The objectives of this experiment were to determine serum concentrations of triiodothyronine (T3), thyroxine (T4), and free thyroxine (fT4) at rest, following thyroid-stimulating hormone (TSH) administration, and following phenylbutazone administration in healthy horses. This was done to determine which available laboratory test can best be used for diagnosis of hypothyroid conditions in horses. Serum T3, T4, and fT4 concentrations in serum samples obtained before and after TSH stimulation and following phenylbutazone administration for 7 days were determined. Baseline values ranged from 0.21 to 0.80 ng of T3/ml, 6.2 to 25.1 ng of T4/ml, and 0.07 to 0.47 ng of fT3/dl. After 5 IU of TSH was administered IV, serum T3 values increased to 6 times baseline values in 2 hours. Thyroxine values increased to 3 times baseline values at 4 hours and remained high at 6 hours. Free T4 values increased to 4 times baseline values at 4 hours and remained high at 6 hours. Administration of 4.4 mg of phenylbutazone/kg, every 12 hours for 7 days significantly decreased T4 and fT4 values, but did not significantly affect serum T3 concentrations, It was concluded that a TSH stimulation test should be performed when hypothyroidism is suspected. Measurement of serum fT4 concentrations, by the single-stage radioimmunoassay, does not provide any additional information about thyroid gland function over that gained by measuring T4 concentrations. Phenylbutazone given at a dosage of 4.4 mg/kg every 24 hours, for 7 days did significantly decrease resting T4 and fT4 concentrations, but did not significantly affect T3 concentrations in horses.
Показать больше [+] Меньше [-]Critical tests of thiabendazole, oxibendazole, and oxfendazole for drug resistance of population-B equine small strongyles (1989 and 1990)
1993
Critical tests were conducted in horses (n = 11) with naturally acquired infections of benzimidazole (BZ)-resistant population-B small strongyles in 1989 and 1990. Anthelmintics administered were thiabendazole (44 mg/kg of body weight, n = 4), oxibendazole (10 mg/kg, n = 3), and oxfendazole (OFZ, 10 mg/kg; n = 4). All compounds were paste formulations administered orally except for 1 of the OFZ treatments, which was a suspension formulation given by stomach tube. Aggregate mean efficacy was calculated for all species of small strongyles, drug-resistant and nonresistant. The highest efficacy was for oxibendazole (98%) and OFZ 94%); efficacy for thiabendazole was 63%. Five genera and 16 species of small strongyles were recovered from the 11 horses, ranging from 7 to 13 species (mean, 11). Of these, 7 species were found to have resistance in variable degrees to most of the anthelmintics. These strongyles were Cyathostomum catinatum, Cyathostomum coronatum, Cylicocyclus nassatus, Cylicostephanus calicatus, Cylicostephanus goldi, Cylicostephanus longibursatus, and Cylicostephanus minutus. The large strongyle, Strongylus vulgaris, was present in afl 11 test horses, and efficacy was 100% for all drugs. Seven of the BZ-treated foals (at least 1 horse from each BZ-treatment group), were infected with S edentatus; removal was 100%.
Показать больше [+] Меньше [-]Ultrasonographically detected changes in equine superficial digital flexor tendons during the first months of race training
1993
Gillis, C.L. | Meagher, D.M. | Pool, R.R. | Stover, S.M. | Craychee, T.J. | Willits, N.
The forelimb superficial digital flexor (SDF) tendons of 6 Thoroughbreds were examined clinically and ultrasonographically during the first 4 months of race training. Sonograms were interpreted clinically and by use of computer-aided analysis. Tendon tissue from all horses was examined histologically at the end of the study. Computer-aided analysis of sonograms of the SDF tendons revealed trends toward an increase in mean cross-sectional area and a decrease in mean echogenicity over time with training. An inverse relation was found between increase in cross-sectional area and decrease in mean echogenicity over time in training. Two of the trained horses developed clinical signs of mild SDF tendonitis. Ultrasonography revealed an increase in cross-sectional area and decrease in mean echogenicity of clinically affected areas of the SDF tendons of 1 horse, compared with changes observed prior to the onset of tendonitis (these changes were not statistically significant). Blood vessels and lymphatics supplying the clinically and ultrasonographically affected tendon sites were large and thick-walled. These changes were not observed in the tendons of the other horses at the end of the study. The authors conclude that equine SDF tendons adapt to the early months of race training by increasing in size and decreasing in echogencity, as determined by ultrasonography.
Показать больше [+] Меньше [-]Recovery of horses from inhalation anesthesia
1993
Whitehair, K.J. | Steffey, E.P. | Willitis, N.H. | Woliner, M.J.
To study behavioral and cardiopulmonary characteristics of horses recovering from inhalation anesthesia, 6 nonmedicated horses were anesthetized under laboratory conditions on 3 different days, with either halothane or isoflurane in O2. Anesthesia was maintained at constant dose (1.5 times the minimum alveolar concentration [MAC]) of halothane in O2 for 1 hour (H1), halothane in O2 for 3 hours (H3), or isoflurane in O2 for 3 hours (13). The order of exposure was set up as a pair of Latin squares to account for horse and trial effects. Circulatory (arterial blood pressure and heart rate) and respiratory (frequency, PaCO2, PaO, pHa) variables were monitored during anesthesia and for as long as possible during the recovery period. End-tidal percentage of the inhaled agent was measured every 15 seconds by automated mass spectrometry, then by hand-sampling after horses started moving. Times of recovery events, including movement of the eyelids, ears, head, and limbs, head lift, chewing, swallowing, first sternal posture and stand attempts, and the number of sternal posture and stand attempts, were recorded. The washout curve or the ET ratio (end-tidal percentage of the inhaled agent at time t to end-tidal percentage of the inhaled agent at the time the anesthesia circuit was disconnected from the tracheal tube) plotted against time was similar for HI and H3. The slower, then faster (compared with halothane groups) washout curve of isoflurane was explainable by changes in respiratory frequency as horses awakened and by lower blood/gas solubility of isoflurane. The respiratory depressant effects of isoflurane were marked and were more progressive than those for halothane at the same 1.5 MAC dose. During the first 15 minutes of recovery, respiratory frequency for group-13 horses increased significantly (P < 0.05), compared with that for the halothane groups. For all groups, arterial blood pressure increased throughout the early recovery period and heart rate remained constant. Preanesthesia temperament of horses and the inhalation agent used did not influence the time of the early recovery events (movement of eyelids, ears, head, and limbs), except for head lift. For events that occurred at anesthetic end-tidal percentage < 0.20, or when horses were awake, temperament was the only factor that significantly influenced the nature of the recovery (chewing P = 0.04, extubation P = 0.001, first stand attempt P = 0.008, and standing P = 0.005). The quality of the recoveries did not differ significantly among groups (H1, H3, I3) or horses; however 5 of 6 horses recovering from the H1 exposure had ideal recovery. During recovery, the anesthetic end-tidal percentage did not differ significantly among groups. However, when concentrations were compared on the basis of anesthetic potency (ie, MAC multiple) a significantly (P < 0.05) lower MAC multiple of isoflurane was measured for the events ear movement, limb movement, head lift, and first attempt to sternal posture, compared with that for horses given halothane, indicating that isoflurane may be a more-potent sedative than halothane in these horses.
Показать больше [+] Меньше [-]Effects of atropine on the arrhythmogenic dose of dobutamine in xylazine-thiamylal-halothane-anesthetized horses
1993
Light, G.S. | Hellyer, P.W.
We investigated the influence of parasympathetic tone on the arrhythmogenic dose of dobutamine in horses premedicated with xylazine, anesthetized with guaifenesin and thiamylal, and maintained on halothane in oxygen. Six horses were used in 12 randomized trials. In each trial, after end-tidal halothane concentration was stabilized at 1.1% (1.25 times minimum alveolar concentration [MAC]) in oxygen, either saline solution (0.02 ml/kg of body weight) or atropine (0.04 mg/kg) was administered IV. Five minutes later, dobutamine infusion was started at dosage of 2.5 micrograms/kg/min, IV. The dobutamine infusion was continued for 10 minutes, or until 4 or more premature ventricular complexes occurred within 15 seconds, or sustained narrow-complex tachyarrhythmia clearly not sinus in nature occurred. If the criteria for termination were not met, dobutamine infusion was increased by 2.5 micrograms/kg/min, after the hemodynamic variables had returned to baseline. The horses were allowed to recover, and were rested for at least 1 week before the second trial. The arrhythmogenic dose of dobutamine was calculated by multiplying the infusion rate by the elapsed time into infusion when arrhythmia occurred. There was significant difference between the arrhythmogenic dose of dobutamine (ADD) in saline-treated horses (mean +/- SEM, ADD 105.6 +/- 16.3 micrograms/kg) and atropinized horses (ADD 36.2 +/- 8.7 micrograms/kg). There were no differences in the prearrhythmia or immediate postarrhythmia ventricular heart rate (HR) or systolic (SAP), diastolic (DAP), or mean (MAP) arterial pressures between treated and control groups. The change in hemodynamic variables from prearrhythmia to immediate postarrhythmia formation was not different between the 2 groups. Ventricular beats were clearly evident in 8 of the 12 arrhythmias meeting the criteria for establishing the ADD. These results indicate that atropine may lower the arrhythmogenic threshold for dobutamine in halothane-anesthetized horses.
Показать больше [+] Меньше [-]Evaluation of the microcirculation of the equine jejunum and ascending colon after ischemia and reperfusion
1993
Dabareiner, R.M. | Snyder, J.R. | Sullins, K.E. | White, N.A. II. | Gardner, I.A.
Intramural vascular patterns of the jejunum and colon were evaluated during ischemic strangulation obstruction (ISO, 70 minutes) and subsequent reperfusion (60 minutes) in 7 adult anesthetized horses. Microvasculature of experimental and control segments was described by comparison of results from microangiography, light microscopy, and scanning electron microscopy of vascular replicas. Experimental and control segments with isolated vascular arcades were removed either immediately after the experimental period or after 60 minutes of reperfusion. Blood was flushed from the vascular system by use of isotonic NaCl, and the segments were divided. Half of each segment was perfused with a modified radiopaque medium for microangiographic evaluation, and half was perfused with dilute methylmethacrylate to create a vascular replica to be studied by scanning electron microscopy. Microangiographic section also were evaluated for histologic changes. Microvasculature of jejunal control segments and all colon segments was similar to described normal microvasculature of the equine jejunum and ascending colon. In jejunal ISO segments, intramural perfusion was redistributed away from the mucosa. In the villi, the central arteriole was short and convoluted and the subepithelial capillaries were not filled. The submucosal vessels and crypt capillaries were congested, compared with those of controls, and the serosal vessels were not filled in the ischemic segments. Histologic grade II-III mucosal lesion was seen in jejunal ISO segments. Reperfused jejunal segments had a transmural hyperemic response, and previously unfilled capillaries were observed in all intestinal layers. After reperfusion, the mucosal lesion progressed to grade III-IV and a cellular infiltrate and edema formation were observed in the serosa. The intramural vasculature of the ischemic and reperfused colon remain unchanged. Minimal histologic damage was observed in the colon after 70 minutes of ISO or after 60 minutes of reperfusion.
Показать больше [+] Меньше [-]Pharmacokinetics of metronidazole after rectal administration in horses
1993
Garber, J.L. | Brown, M.P. | Gronwall, R.R. | Merritt, K.
Five healthy adult mares and 1 gelding were given a single dose (15 mg/kg of body weight) of metronidazole per rectum. After manual evacuation of feces from the rectum, a suspension of crushed tablets and water (40 ml) was administered via a 28-F catheter advanced 30 cm into the rectum. Blood samples were obtained by jugular venipuncture, and metronidazole concentration was measured serially for the 14 hours after drug administration. Mean serum concentration of metronidazole peaked at 4.5 micrograms/ml, 0.83 hour after administration, and decreased to 0.38 micrograms/ml, 14 hours after administration. Mean elimination rate constant was 0.23/h, and the harmonic mean elimination half-life was 3.04 hours. Further study is necessary to determine a therapeutic dose regimen for metronidazole administered per rectum.
Показать больше [+] Меньше [-]Capacitation-like membrane changes and prolonged viability in vitro of equine spermatozoa cultured with uterine tube epithelial cells
1993
Ellington, J.E. | Ball, B.A. | Blue, B.J. | Wilker, C.E.
Reliable capacitation of equine spermatozoa has been a major obstacle in the development of equine in vitro fertilization. Experiments were done to compare in vitro capacitation of equine spermatozoa by use of heparin/caffeine, calcium ionophore, uterine tube epithelial cell (UTEC)-conditioned medium, and direct culturing of spermatozoa with UTEC (coculturing). Capacitation-like changes, as determined by chlortetracycline membrane staining patterns, developed with UTEC-conditioned medium and coculturing, equivalent to that with calcium ionophore. Both of these treatments induced more (P < 0.05) capacitation-like changes than did the control, a modified Tyrode's medium. More (P < 0.05) spermatozoa were viable after 24 hours of UTEC coculturing than in the control incubation.
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