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;
Objective—To evaluate cardiopulmonary effects of
glycopyrrolate in horses anesthetized with halothane
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)
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
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
Objective—To evaluate the cardiorespiratory and
intestinal effects of the muscarinic type-2 (M2) antagonist,
methoctramine, in anesthetized 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)
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
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
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.
Procedure—Mycobacterium 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)