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Abstract

Objective—To determine the pharmacokinetics and toxic effects associated with IV administration of lithium chloride (LiCl) to conscious healthy horses.

Animals—6 healthy Standardbred horses.

Procedure—Twenty 3-mmol boluses of LiCl (0.15 mmol/L) were injected IV at 3-minute intervals (total dose, 60 mmol) during a 1-hour period. Blood samples for measurement of serum lithium concentrations were collected before injection and up to 24 hours after injection. Behavioral and systemic toxic effects of LiCl were also assessed.

Results—Lithium elimination could best be described by a 3-compartment model for 5 of the 6 horses. Mean peak serum concentration was 0.561 mmol/L (range, 0.529 to 0.613 mmol/L), with actual measured mean serum value of 0.575 mmol/L (range, 0.52 to 0.67 mmol/L) at 2.5 minutes after administration of the last bolus. Half-life was 43.5 hours (range, 32 to 84 hours), and after 24 hours, mean serum lithium concentration was 0.13 ± 0.05 mmol/L (range, 0.07 to 0.21 mmol/L). The 60-mmol dose of LiCl did not produce significant differences in any measured hematologic or biochemical variables, gastrointestinal motility, or ECG variables evaluated during the study period.

Conclusions and Clinical Relevance—Distribution of lithium best fit a 3-compartment model, and clearance of the electrolyte was slow. Healthy horses remained unaffected by LiCl at doses that exceeded those required for determination of cardiac output. Peak serum concentrations were less than steadystate serum concentrations that reportedly cause toxic effects in other species. (Am J Vet Res 2001; 62:1387–1392)

Full access
in American Journal of Veterinary Research

Abstract

Objective—To evaluate cardiopulmonary effects of glycopyrrolate in horses anesthetized with halothane and xylazine.

Animals—6 horses.

Procedure—Horses were allocated to 2 treatment groups in a randomized complete block design. Anesthesia was maintained in mechanically ventilated horses by administration of halothane (1% end-tidal concentration) combined with a constant-rate infusion of xylazine hydrochloride (1 mg/kg/h, IV). Hemodynamic variables were monitored after induction of anesthesia and for 120 minutes after administration of glycopyrrolate or saline (0.9% NaCl) solution. Glycopyrrolate (2.5 µg/kg, IV) was administered at 10-minute intervals until heart rate (HR) increased at least 30% above baseline or a maximum cumulative dose of 7.5 µg/kg had been injected. Recovery characteristics and intestinal auscultation scores were evaluated for 24 hours after the end of anesthesia.

Results—Cumulative dose of glycopyrrolate administered to 5 horses was 5 µg/kg, whereas 1 horse received 7.5 µg/kg. The positive chronotropic effects of glycopyrrolate were accompanied by an increase in cardiac output, arterial blood pressure, and tissue oxygen delivery. Whereas HR increased by 53% above baseline values at 20 minutes after the last glycopyrrolate injection, cardiac output and mean arterial pressure increased by 38% and 31%, respectively. Glycopyrrolate administration was associated with impaction of the large colon in 1 horse and low intestinal auscultation scores lasting 24 hours in 3 horses.

Conclusions and Clinical Relevance—The positive chronotropic effects of glycopyrrolate resulted in improvement of hemodynamic function in horses anesthetized with halothane and xylazine. However, prolonged intestinal stasis and colic may limit its use during anesthesia. (Am J Vet Res 2004;65:456–463)

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in American Journal of Veterinary Research

Abstract

Objective—To evaluate the cardiorespiratory and intestinal effects of the muscarinic type-2 (M2) antagonist, methoctramine, in anesthetized horses.

Animals—6 horses.

Procedure—Horses were allocated to 2 treatments in a randomized complete block design. Anesthesia was maintained with halothane (1% end-tidal concentration) combined with a constant-rate infusion of xylazine hydrochloride (1 mg/kg/h, IV) and mechanical ventilation. Hemodynamic variables were monitored after induction of anesthesia and for 120 minutes after administration of methoctramine or saline (0.9% NaCl) solution (control treatment). Methoctramine was given at 10-minute intervals (10 µg/kg, IV) until heart rate (HR) increased at least 30% above baseline values or until a maximum cumulative dose of 30 µg/kg had been administered. Recovery characteristics, intestinal auscultation scores, and intestinal transit determined by use of chromium oxide were assessed during the postanesthetic period.

Results—Methoctramine was given at a total cumulative dose of 30 µg/kg to 4 horses, whereas 2 horses received 10 µg/kg. Administration of methoctramine resulted in increases in HR, cardiac output, arterial blood pressure, and tissue oxygen delivery. Intestinal auscultation scores and intestinal transit time (interval to first and last detection of chromium oxide in the feces) did not differ between treatment groups.

Conclusions and Clinical Relevance—Methoctramine improved hemodynamic function in horses anesthetized by use of halothane and xylazine without causing a clinically detectable delay in the return to normal intestinal motility during the postanesthetic period. Because of their selective positive chronotropic effects, M2 antagonists may represent a safe alternative for treatment of horses with intraoperative bradycardia. (Am J Vet Res 2004;65:464–472)

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in American Journal of Veterinary Research

Abstract

Objective—To compare toxicokinetic variables and associated tissue drug concentrations with severity of articular lesions in weight-bearing joints of juvenile rabbits after oral administration of a fluoroquinolone.

Animals—Ten 6- to 7-week-old, 800- to 1,200-g, New Zealand White rabbits.

Procedures—Rabbits were gavaged daily with the fluoroquinolone PD 117596 at 500 mg/kg of body weight for 5 days. Blood samples were collected on day 4 at preestablished times, up to 24 hours after drug administration. On day 5 gross lesion severity and prevalence were evaluated in the major weight-bearing joints, and tissue specimens were collected (60 minutes after drug administration). Serum and tissue drug concentrations were determined by microbiologic plate assay.

Results—Macroscopically, treatment rabbits had a high prevalence of arthropathy with the distal portion of the femur having the highest prevalence and severity of lesions. Grossly, alterations to articular cartilage included 1 to 4 mm in diameter vesicles or erosions. Histologically, vesicles were identified in the midzone or close to the zone of calcified cartilage of treatment rabbits. Chondrocyte cellularity was reduced in affected areas, and perivesicular regions had reduced staining with Safranin O. Correlation analysis of area under the curve values with total scores for lesion severity had a significant positive relationship.

Conclusions—Our findings support the use of juvenile rabbits as a model for arthropathic changes induced by fluoroquinolone administration. (Am J Vet Res 2000;61:1396–1402)

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in American Journal of Veterinary Research

Abstract

Objective—To describe and compare the distribution of technetium Tc 99m (99mTc) pertechnate following intraosseous or IV injection (with or without use of a tourniquet) in the distal portion of the forelimb in standing horses.

Animals—4 horses.

Procedure—Each horse received 4 forelimb treatments in random sequence: intraosseous infusion with tourniquet application (IOT), intraosseous infusion without tourniquet application, IV infusion with tourniquet application (IVT), and IV infusion without tourniquet application. Dynamic nuclear scintigraphic imaging of the third metacarpal bone, proximal and middle phalanges, and distal phalanx was performed from the start of each treatment until 1 hour after infusion was completed. Radionuclide activity was compared within and between treatment groups.

Results—Tourniquet application was necessary to maintain high levels of radionuclide activity in the distal portion of the forelimb after intraosseous or IV infusion with 99mTc pertechnate; IVT and IOT treatments resulted in similar radionuclide activity in the proximal and middle phalanges and distal phalanx. Of the 4 treatments, there was significantly higher radionuclide activity in the distal aspect of the third metacarpal bone after the IOT treatment.

Conclusions and Clinical Relevance—By use of a tourniquet, radionuclide administration via the intraosseous or IV routes resulted in effective perfusion of the distal portion of the forelimb and similar distribution of the agent in the phalanges of horses. Further studies are required to ascertain whether these findings apply to delivery of therapeutic agents in infected tissues via IOT or IVT. (Am J Vet Res 2005;66:1267–1272)

Full access
in American Journal of Veterinary Research

Abstract

Objective—To assess phylogenetic relationships among Mycobacterium bovis isolates by use of random amplified polymorphic DNA polymerase chain reaction (RAPD-PCR) fingerprinting and to relate genetic profiles of isolates to epidemiologic characteristics.

Animals—400 cattle with tuberculosis.

ProcedureMycobacterium bovis was isolated from various organs of cattle slaughtered in 6 geographic regions of Mexico. Most cattle were adult Holsteins from large herds that did not participate in a tuberculosis control program. Four random primers and 2 selected primers were used in RAPD-PCR fingerprinting of 88 isolates. Pairwise genetic distance between isolates was obtained and subjected to cluster analysis with bootstrapping to test for levels of support.

Results—98 different fragments were obtained; there was broad genetic diversity among isolates, and each isolate had a unique RAPD-genotype, including those originating from the same herd. Clustering by geographic location, affected organ, or severity of lesion was not detected. Linkage disequilibrium analysis suggested that M bovis was highly clonal and that mutations develop at a rapid rate among isolates.

Conclusions and Clinical Relevance—Use of RAPDPCR could not differentiate M bovis isolates by epidemiologic characteristics or identify common sources of infection. (Am J Vet Res 2000;61:90–95)

Full access
in American Journal of Veterinary Research