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Objective-To evaluate the effects of endotoxin administered IV on glucose and insulin dynamics in horses. Animals-16 healthy adult mares. Procedures-Each week of a 2-week randomized crossover study, each horse received an IV injection (duration, 30 minutes) of Escherichia coli O55:B5 lipopolysaccharide (LPS) in 60 mL of sterile saline (0.9% NaCl) solution (20 ng/kg) or sterile saline solution alone (control treatment). Frequently sampled IV glucose tolerance test procedures were performed at 24 hours before (baseline) and 24 and 48 hours after injection; glucose and insulin dynamics were assessed via minimal model analysis. Results-13 of 16 horses had a clinical response to LPS, which was characterized by mild colic and leukopenia. Before treatment, mean +/- SD insulin sensitivity was 2.9 +/- 1.9 x 10(4) L.min(1).mU(1); this significantly decreased to 0.9 +/- 0.9 x 10(4) L.min(1).mU(1) 24 hours after treatment (69% reduction) and was 1.5 +/- 0.9 x 10(4) L.min(1).mU(1) 48 hours after treatment. At baseline, mean +/- SD acute insulin response to glucose was 520 +/- 196 mU.min.L(1); this significantly increased to 938 +/- 620 mU.min.L(1) (80% increase) and 755 +/- 400 mU.min.L(1) (45% increase) at 24 and 48 hours after LPS treatment, respectively. Conclusions and Clinical Relevance-Compared with baseline values, insulin sensitivity was decreased for 24 hours after IV injection of LPS, and affected horses had a compensatory pancreatic response. These disturbances in glucose and insulin dynamics may contribute to development of laminitis in horses.

Toth F　Frank N　Elliott SB　Geor RJ　Boston RC
Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996.
2008.69.1 no.10

Objective-To determine the effects of long-term oral administration of levothyroxine sodium (L-T(4)) on glucose dynamics in adult euthyroid horses. Animals-6 healthy adult mares. Procedures-Horses received L-T(4) (48 mg/d) orally for 48 weeks. Frequently sampled IV glucose tolerance test procedures were performed on 3 occasions (24-hour intervals) before and at 16, 32, and 48 weeks during the treatment period. Data were assessed via minimal model analysis. The repeatability of measurements was evaluated. Results-During treatment, body weight decreased significantly from the pretreatment value; mean +/- SD weight was 49 +/- 14 kg, 43 +/- 7 kg, and 25 +/- 18 kg less than the pretreatment value at weeks 16, 32, and 48, respectively. Compared with pretreatment findings, 1.8-, 2.4-, and 1.9-fold increases in mean insulin sensitivity (SI) were detected at weeks 16, 32, and 48, respectively; SI was negatively correlated with body weight (r = -0.42; P < 0.001). During treatment, glucose effectiveness increased and the acute insulin response to glucose decreased. Overall mean within-horse coefficients of variation were 5% and 29% for plasma glucose and serum insulin concentrations, respectively, and 33%, 26%, and 23% for SI, glucose effectiveness, and the acute insulin response to glucose, respectively. Conclusions and Clinical Relevance-Long-term administration of L-T(4) was associated with weight loss and increased SI in adult euthyroid horses, although other factors may have confounded results. Levothyroxine sodium may be useful for the treatment of obesity and insulin resistance in horses, but further studies are required.

Frank N　Elliott SB　Boston RC
Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996.

Objective-To determine whether abnormal laxity of hip joints of canine pups with genetic predisposition to hip dysplasia (HD+) is related to ingestion of milk-borne hormones. Animals-7 female Labrador Retrievers with HD+ and 8 with low predisposition to hip dysplasia (HD-) and their offspring. Procedures-Immunoactive relaxin, estrogen, and estrogen precursor concentrations in milk of HD+ lactating bitches and in serum of their pups were compared with those of HD- bitches and pups. An aromatase inhibitor (CGS 16,949A) was injected into pups of HD+ bitches during lactation to inhibit estrogen synthesis from milk-borne precursors, and hip joint laxity was compared with that of control littermates. Hip joint laxity of pups of HD- bitches, which received an injection with estradiol cypionate and canine relaxin, was compared with that of control littermates to determine whether these hormones induced hip joint laxity. Results-High concentrations of estrogens and relaxin were found in milk of HD+ and HD- bitches throughout lactation. Serum concentrations of milk-derived relaxin and total estrogens were similar in all pups, but estradiol-17B was detected only in pups of HD+ bitches. Hip joint laxity was reduced in pups that received CGS 16,949A. Hip joint laxity was increased in pups of HD- bitches that received estradiol cypionate and relaxin. Conclusions and Clinical Relevance-Milk-borne maternal hormones and precursors were absorbed into the circulation of canine neonates and may play a role in hip joint laxity in HD+ pups. Phenotypic expression of hip dysplasia may therefore be preventable by antihormone treatment.

Objective-To determine effects of regional variation, interobserver variability, and vessel selection on quantitative vascular variables derived by dynamic contrast-enhanced computed tomography (DCE-CT) of the brain of clinically normal dogs. Animals-14 adult dogs with no evidence of CNS dysfunction. Procedures-Dogs were randomly assigned to 4 groups, and DCE-CT was performed at the level of the frontal lobe, rostral portion of the parietal-temporal lobes, caudal portions of the parietal-temporal lobes, or occipital lobe-cerebellum for groups 1 to 4, respectively. Cerebral blood flow (CBF), cerebral blood volume (CBV), and permeability in gray and white matter for both a large and small artery were calculated and compared. Values among 3 observers and 4 regions of the brain were calculated and compared. Results-Significant interobserver variability was detected for CBF and permeability in white matter. Values calculated for large and small arteries were correlated for CBV and CBF but not for permeability. Overall mean +/- SD for CBF, CBV, and permeability in gray matter was 53.5 +/- 27.7 mL/min/100 g, 2.9 +/- 1.4 mL/100 g, and 1.4 +/- 2.2 mL/min/100 g, respectively. Mean for CBF, CBV, and permeability in white matter was 44.2 +/- 28.5 mL/min/100 g, 2.5 +/- 1.5 mL/100 g, and 0.9 +/- 0.7 mL/min/100 g, respectively. Values did not differ significantly among brain regions. Conclusions and Clinical Relevance-Significant regional variations were not detected for quantitative vascular variables in the brain of clinically normal dogs. However, interobserver variability and vessel selection have an important role in variable estimation.

Peterson KL　Macleod AG　Wisner ER　Larson RF　Pollard RE
Veterinary Medical Teaching Hospital, School of Veterinary Medicine, University of California, Davis, CA 95616.

Objective-To describe the disposition of and pharmacodynamic response to atenolol when administered as a novel transdermal gel formulation to healthy cats. Animals-7 healthy neutered male client-owned cats. Procedures-Atenolol was administered either orally as a quarter of a 25-mg tablet or as an equal dose by transdermal gel. Following 1 week of treatment, an ECG and blood pressure measurements were performed and blood samples were collected for determination of plasma atenolol concentration at 2 and 12 hours after administration. Results-2 hours after oral administration, 6 of 7 cats reached therapeutic plasma atenolol concentrations with a mean peak concentration of 579 +/- 212 ng/mL. Two hours following transdermal administration, only 2 of 7 cats reached therapeutic plasma atenolol concentrations with a mean peak concentration of 177 +/- 123 ng/mL. The difference in concentration between treatments was significant. Trough plasma atenolol concentrations of 258 +/- 142 ng/mL and 62.4 +/- 17 ng/mL were achieved 12 hours after oral and transdermal administration, respectively. A negative correlation was found between heart rate and plasma atenolol concentration. Conclusions and Clinical Relevance-Oral administration of atenolol at a median dose of 1.1 mg/kg every 12 hours (range, 0.8 to 1.5 mg/kg) in cats induced effective plasma concentrations at 2 hours after treatment in most cats. Transdermal administration provided lower and inconsistent plasma atenolol concentrations. Further studies are needed to find an effective formulation and dosing scheme for transdermal administration of atenolol.

Macgregor JM　Rush JE　Rozanski EA　Boothe DM　Belmonte AA　Freeman LM
Department of Clinical Sciences, Cummings School of Veterinary Medicine, Tufts University, North Grafton, MA 01536.