Objective—To evaluate short-term cardiovascular effects after IV administration of boluses of fentanyl in rabbits.
Animals—6 healthy New Zealand White rabbits.
Procedures—Each rabbit was anesthetized with propofol (4.0 to 8.0 mg/kg, IV); anesthesia was maintained by administration of propofol (1.2 to 1.3 mg/kg/min, IV). Subsequently, 3 injections of fentanyl (0.0053 mg/kg) were administered. Before and for 10 minutes after injections, the following variables were measured: vessel diameter, peak systolic blood flow velocity, minimum diastolic blood flow velocity, end-diastolic blood flow velocity, time-average blood flow velocity, mean volumetric flow (VFmean), resistance index (RI), and pulsatility index for the left common carotid artery after the first injection and abdominal aorta after the third injection; mean arterial pressure (MAP); heart rate (HR); arterial oxygen saturation; end-tidal partial pressure of carbon dioxide; and body temperature. Echocardiography was performed after the second injection.
Results—Fentanyl injections caused a transient and significant decrease in diameter and VFmean of the abdominal aorta and end-diastolic blood flow velocity of the left common carotid artery and an increase in peak systolic blood flow velocity and RI of the left common carotid artery. Also, MAP, HR, and body temperature decreased significantly after injections.
Conclusions and Clinical Relevance—Fentanyl injections induced a short-term decrease of vessel diameter in the abdominal aorta and increased resistance in the distal distribution area of the left common carotid artery. Results revealed decreases in MAP, HR, and body temperature, with an increasing effect after the third bolus injection, which indicated a cumulative drug effect.
Objective—To evaluate the possible effect of melatonin implants on blood glutathione peroxidase (GSHPx) activity and in the prevention of selenium (Se)-responsive disorders in sheep from an Se-deficient region.
Design—Randomized controlled clinical trial.
Animals—100 Merino ewes.
Procedures—Ewes of the same age, parity, body weight, body condition, and reproductive and health history were randomly allotted to 1 of 2 groups (control and implanted) of 50 sheep each. Treatment consisted of implants of melatonin (18 g) administered SC in the pinna of the right ear 6 weeks prior to introduction of rams. The control group did not receive implants. Hematologic and serum biochemical analyses were performed at various points before and after treatment, in addition to determinations of erythrocyte mean corpuscular fragility (MCF) and blood GSHPx activity. The incidence of Se-responsive disorders in lambs was recorded in both groups.
Results—Hematologic and serum biochemical analyses yielded values within respective reference ranges for both groups. Significant differences between groups were evident in MCF at early mating (lower in the implanted group vs the control group) and in blood GSHPx activity at early mating, gestation, and early lambing (higher in the implanted group vs the control group). There were significantly fewer lambs with nutritional myodystrophy in the implanted versus the control group.
Conclusions and Clinical Relevance—Use of melatonin implants in sheep may improve reproductive performance and yield an earlier start of breeding season. The stimulating effect of melatonin on GSHPx activity may protect against oxidative damage during the first stage of gestation.
Objective—To investigate effects and mechanisms of ergotamine and ergovaline and effects of peramine on reticulum motility of sheep.
Sample Population—3 sheep with indwelling electrodes in the reticulum and samples of reticulum collected from 126 sheep at an abattoir.
Procedures—In conscious sheep, motility was recorded as integrated electromyograms from the reticulum. Ergotamine was administered IV alone or in combination with the cholinergic muscarinic receptor antagonist atropine to sheep, and motility of the reticulum was assessed. In vitro, whole wall strips of the reticulum, cut in a direction to record longitudinal muscle activity via force transducers, were placed in 10-mL organ baths and superfused with Tyrode Ringer's solution at 37°C and oxygenated with 95% oxygen and 5% carbon dioxide. Testing involved incubation of reticulum strips with ergotamine, ergovaline, and peramine and measurement of motility of the reticulum tissues.
Results—Administration of ergotamine to sheep reduced the frequency of reticulum contractions and increased baseline electromyographic activity (tonus). Frequency was unaffected by atropine, whereas tonus was significantly reduced. In vitro, ergotamine and ergovaline increased tonic contractions and stimulated phasic contractions of reticulum tissues and potentiated electrically stimulated contractions. Atropine and tetrodotoxin re-duced tonic contractions, but stimulation of large-amplitude phasic contractions remained. Peramine had no effect on motility of reticulum tissues.
Conclusions and Clinical Relevance—Results of the study indicated that peripheral excitatory effects of the ergopeptides on motility of the reticulum appear to be mediated partly through myenteric neurons and muscarinic receptors and also through direct effects on the muscles.
Objective—To determine the diuretic effects and changes in plasma aldosterone concentration (PAC) following oral administration of a single dose of furosemide or azosemide in healthy dogs.
Animals—8 mixed-breed dogs.
Procedures—A single dose of furosemide (2 mg/kg), azosemide (1, 5, or 10 mg/kg), or placebo (bifidobacterium [1 mg/kg]) was administered orally (in random order at 7-day intervals) to each dog (5 treatments/dog). Urine and blood samples were collected before (2 hours after evacuation of the urinary bladder; baseline) and at intervals for 24 hours after drug treatment to assess urine volume and plasma and urine biochemical variables.
Results—Compared with baseline values, treatment with furosemide and azosemide (5 and 10 mg/kg) increased urine output for 1 to 2 hours and 2 to 4 hours, respectively. The 24-hour urine volume and urinary sodium excretion were significantly increased following furosemide and azosemide (5 and 10 mg/kg) treatments, compared with effects of pla-cebo; these increases were dose dependent for azosemide, and increases were similar for furosemide and the 5 mg/kg dose of azosemide. Compared with other treatments, 24-hour urinary potassium excretion was significantly increased with azosemide at 10 mg/kg. Azosemide (5 and 10 mg/kg) significantly increased plasma total protein concentration and decreased plasma potassium concentration, compared with baseline values. Compared with the effect of placebo, PAC was significantly increased by furosemide and the 10 mg/kg dose of azosemide.
Conclusions and Clinical Relevance—In healthy dogs, a moderate dose of azosemide caused sufficient diuretic action and increased PAC to a lesser extent than furosemide.
Objective—To investigate the effect of acute administration of caffeine on the athletic performance of Arabian horses.
Animals—12 healthy adult Arabian horses that were trained for exercise on a treadmill.
Procedures—By use of a crossover study design, horses received each of the following treatments: IV administration of caffeine (5 mg/kg) and IV administration of approximately the same volume of saline (0.9% NaCl) solution. Order of treatment was randomized, and there was a 10-day interval between treatments. Thirty minutes after treatments, horses underwent an incremental exercise test (IET) on a treadmill. Blood samples were collected 15 seconds before the end of each velocity step of the IET for determination of blood lactate, blood glucose, plasma cortisol, and plasma insulin concentrations. Heart rate and hematologic variables were also analyzed.
Results—Velocities achieved when heart rates were 180 and 200 beats/min increased significantly in caffeine-treated horses, compared with control horses. Velocities corresponding to blood lactate concentrations of 4 and 2 mmol/L decreased significantly in caffeine-treated horses, compared with control horses. In comparison between groups, insulinemia was greater in control horses and glycemia was greater in caffeine-treated horses. Plasma cortisol concentration was significantly lowered by treatment with caffeine.
Conclusions and Clinical Relevance—IV administration of caffeine at 5 mg/kg improved the performance of Arabian horses during intense exercise of short duration and diminished the oxidative metabolism of glucose.
Objective—To apply the principle of sodium dilution to calculate the changes in the extracellular fluid (ECF) volume (ECFV) and intracellular fluid volume (ICFV) that occur during dehydration and rehydration in horses.
Animals—8 healthy horses of various breeds.
Procedures—Horses were dehydrated over 4 hours by withholding water and administering furosemide. Saline (0.9% NaCl) solution was administered IV during the next 2 hours (20 mL/kg/h; total 40 mL/kg). Horses were monitored for an additional hour following IV fluid administration. Initial ECFV was determined by use of multifrequency bioelectrical impedance analysis, and serum sodium concentration was used to calculate total ECF sodium content. Sodium and fluid volume losses were monitored and calculated throughout the study and used to estimate changes in ECFV and ICFV during fluid balance alterations.
Results—Changes during dehydration and rehydration primarily occurred in the ECFV. The sodium dilution principle estimated an overexpansion of the ECFV beyond the volume of fluid administered, indicating a small contraction of the ICFV in response to fluid administration. Serum and urinary electrolyte changes were recorded and were consistent with those of previous reports.
Conclusions and Clinical Relevance—The sodium dilution principle provided a simple method that can be used to estimate the changes in ECFV and ICFV that occur during fluid administration. Results suggested an overexpansion of the ECFV in response to IV saline solution administration. The sodium dilution principle requires further validation in healthy and clinically ill horses, which could provide clinical applications similar to those in other species.
Objective—To determine whether platelet growth factors are preserved in supernatants obtained from rehydrated trehalose-stabilized, freeze-dried (lyophilized) equine platelets and whether those growth factors stimulate fibroblast proliferation and migration and enhance fibroblast-associated contraction in a collagen gel assay.
Animals—6 clinically normal adult horses.
Procedures—Blood samples were obtained from 6 horses, and washed platelets were prepared via differential centrifugation. Washed platelets were freeze-dried in a physiologic buffer with a mixture of trehalose and polyethylene glycol 4000. Rehydrated platelet supernatants and releasates prepared from fresh washed platelets stimulated with thrombin or platelet-activating factor were evaluated for transforming growth factor β1 and platelet-derived growth factor-BB by use of ELISAs. Effects of rehydrated freeze-dried platelet supernatants on fibroblast proliferation, migration, and collagen gel contraction were compared with effects of 1%, 2.5%, or 10% fetal bovine serum (FBS).
Results—Supernatants from freeze-dried platelets contained similar amounts of growth factors as thrombin- and platelet-activating factor–stimulated platelet releasates. The supernatants significantly enhanced fibroblast proliferation and migration in a scratch assay, compared with FBS-free control or low (1%) FBS conditions. Additionally, supernatants from freeze-dried platelets enhanced contraction of fibroblast-seeded collagen gels, compared with the effect of 1% FBS.
Conclusions and Clinical Relevance—The preparation technique preserved platelet growth factors, enhanced fibroblast proliferation and migration, and improved fibroblastseeded collagen gel contraction under conditions of low FBS concentration; these platelet supernatant preparations may prove useful as an aid to conventional wound management.
Objective—To determine pathophysiologic effects of phenylbutazone on the equine right dorsal colon (RDC).
Animals—12 healthy adult horses.
Procedures—A controlled crossover observational study was conducted. Clinical and serum variables, colonic inflammation (histologic grading), and measurement of myeloperoxidase (MPO) activity, malondialdehyde (MDA) and prostaglandin E2 (PGE2) concentrations, ingesta volatile fatty acid (VFA) content, and arterial blood flow in the RDC were evaluated for a 21-day period in horses administered phenylbutazone (8.8 mg/kg, PO, q 24 h) or a control substance.
Results—Data from 8 horses were analyzed. Plasma albumin concentrations decreased significantly from days 10 to 21 during phenylbutazone treatment, compared with results during the same days for the control treatment. Phenylbutazone treatment caused neutropenia (< 3.0 × 103 cells/μL). No other clinical or hematologic abnormalities were detected for phenylbutazone or control treatments. Two horses developed colitis while receiving phenylbutazone. No significant differences were detected in the RDC between phenylbutazone and control treatments for MPO activity, MDA and PGE2 concentrations, and histologic evidence of inflammation. Arterial blood flow in the RDC was significantly increased during phenylbutazone treatment, compared with values for the control treatment. Differences were identified in VFA production during phenylbutazone treatment, compared with the control treatment, with a decrease in acetic acid concentrations over time.
Conclusions and Clinical Relevance—Prolonged phenylbutazone administration caused hypoalbuminemia, neutropenia, changes in RDC arterial blood flow, and changes in VFA production. Veterinarians should monitor serum albumin concentrations and neutrophil counts and be cautious when making dosing recommendations for phenylbutazone treatment of horses.
Objective—To compare the effects of administration of 2 volumes of a calcium solution (calcium oxide and calcium gluconate) on plasma ionized calcium concentration (PICaC) and clinical recovery from naturally occurring hypocalcemia (NOHC; milk fever) in lactating dairy cows.
Animals—123 cows with NOHC (PICaC < 0.95 mmol/L [3.81 mg/dL]) and 20 clinically normal control cows.
Procedures—Affected cows were treated IV once or repeatedly with 450 (n = 56) or 750 mL (67) of calcium solution (1.65 g of calcium/100 mL) until clinical recovery was achieved. The PICaC was assessed 48 hours after the first treatment or after the treatment that achieved clinical recovery. Biochemical recovery was defined as PICaC ≥ 0.95 mmol/L. Plasma from control cows was used for PICaC reference range determination. Plasma samples from both groups were assessed after storage for 20 days at 20°C.
Results—The PICaC reference range derived from blood collected in tubes containing lithium heparin was 1.02 to 1.29 mmol/L (4.09 to 5.17 mg/dL). Following storage, plasma samples were suitable for PICaC assessment. All cows treated with ≥ 1 volume of 450 and 750 mL of calcium solution recovered clinically; however, 31 of 83 (37%) evaluated cows were not biochemically recovered at 48 hours following treatment. Only cows with PICaC < 0.48 mmol/L (1.92 mg/dL) before the first treatment had to be treated ≥ 3 times.
Conclusions and Clinical Relevance—Results did not support the need to increase the administered volume of calcium solution from 450 to 750 mL for treatment of NOHC in dairy cows.
Objective—To evaluate the in vivo effects of firocoxib, meloxicam, and tepoxalin on prostaglandin (PG) and leukotriene production in duodenal mucosa and other target tissues in dogs with chronic osteoarthritis (OA).
Animals—8 dogs with chronic, unilateral OA of the stifle joint.
Procedures—In a crossover design, each dog received placebo (no treatment), firocoxib, meloxicam, or tepoxalin for 7 days, followed by a 21-day washout period. On the first day of treatment (day 0; baseline) and days 2, 4, and 7, samples of whole blood, synovial fluid, and gastric and duodenal mucosae were collected. Prostaglandin E2 concentrations were measured in synovial fluid of the stifle joint and after ex vivo stimulation of whole blood samples. Synthesis of PGE1 and PGE2 was measured in samples of gastric and duodenal mucosae. Concentrations of thromboxane B2 (TxB2) were measured in whole blood samples. Leukotriene B4 (LTB4) concentrations were measured in samples of whole blood (ex vivo stimulation) and gastric and duodenal mucosae.
Results—Firocoxib, meloxicam, and tepoxalin significantly suppressed whole blood concentrations of PGE2, compared with baseline and placebo concentrations, at days 2, 4, and 7. Tepoxalin significantly suppressed serum TxB2 concentrations, compared with baseline, firocoxib, meloxicam, and placebo, at all 3 time points. Production of PGE1 and PGE2 was significantly lower in duodenal versus gastric mucosa. Tepoxalin significantly decreased rates of PGE1 and PGE2 in duodenal and gastric mucosae, compared with baseline rates.
Conclusions and Clinical Relevance—PG production was lower in the duodenum than in the stomach. Firocoxib had a COX-1–sparing effect in vivo.