OBJECTIVE To compare ammonia concentrations in arterial blood, venous blood, and CSF samples of dogs with and without extrahepatic portosystemic shunts (EHPSS). ANIMALS 19 dogs with congenital EHPSS and 6 healthy control dogs. PROCEDURES All dogs underwent a physical examination and then were anesthetized for transsplenic portal scintigraphy to confirm the presence or absence of EHPSS. While dogs were anesthetized, arterial and venous blood samples and a CSF sample were simultaneously collected for determination of ammonia concentration, which was measured by use of a portable blood ammonia analyzer (device A) and a nonportable biochemical analyzer (device B). Results were compared between dogs with EHPSS and control dogs. RESULTS Arterial, venous, and CSF ammonia concentrations for dogs with EHPSS were significantly greater than those for control dogs. For dogs with EHPSS, ammonia concentrations in both arterial and venous blood samples were markedly increased from the reference range. There was a strong positive correlation between arterial and venous ammonia concentrations and between blood (arterial or venous) and CSF ammonia concentrations. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that blood and CSF ammonia concentrations in dogs with EHPSS were greater than those for healthy dogs and were strongly and positively correlated, albeit in a nonlinear manner. This suggested that the permeability of the blood-brain barrier to ammonia may be abnormally increased in dogs with EHPSS, but further investigation of the relationship between blood or CSF ammonia concentration and clinical signs of hepatic encephalopathy or the surgical outcome for dogs with EHPSS is warranted.

Objective—To image the spatial distribution of pulmonary blood flow by means of scintigraphy, evaluate ventilation-perfusion (VA/Q) matching and pulmonary blood shunting (Qs/Qt) by means of the multiple inert gas elimination technique (MIGET), and measure arterial oxygenation and plasma endothelin-1 concentrations before, during, and after pulse-delivered inhaled nitric oxide (PiNO) administration to isoflurane-anesthetized horses in dorsal recumbency. Animals—3 healthy adult Standardbreds. Procedures—Nitric oxide was pulsed into the inspired gases in dorsally recumbent isoflurane-anesthetized horses. Assessment of VA/Q matching, Qs/Qt, and Pao2 content was performed by use of the MIGET, and spatial distribution of pulmonary blood flow was measured by perfusion scintigraphy following IV injection of technetium Tc 99m–labeled macroaggregated human albumin before, during, and 30 minutes after cessation of PiNO administration. Results—During PiNO administration, significant redistribution of blood flow from the dependent regions to the nondependent regions of the lungs was found and was reflected by improvements in VA/Q matching, decreases in Qs/Qt, and increases in Pao2 content, all of which reverted to baseline values at 30 minutes after PiNO administration. Conclusions and Clinical Relevance—Administration of PiNO in anesthetized dorsally recumbent horses resulted in redistribution of pulmonary blood flow from dependent atelectatic lung regions to nondependent aerated lung regions. Because hypoxemia is commonly the result of atelectasis in anesthetized dorsally recumbent horses, the addition of nitric oxide to inhaled gases could be used clinically to alleviate hypoxemia in horses during anesthesia.

Objective: To compare estimation of glomerular filtration rate determined via conventional methods (ie, scintigraphy and plasma clearance of technetium Tc 99m pentetate) and dynamic single-slice computed tomography (CT). Animals: 8 healthy adult cats. Procedures: Scintigraphy, plasma clearance testing, and dynamic CT were performed on each cat on the same day; order of examinations was randomized. Separate observers performed GFR calculations for scintigraphy, plasma clearance testing, or dynamic CT. Methods were compared via Bland-Altman plots and considered interchangeable and acceptable when the 95% limits of agreement (mean difference between methods ± 1.96 SD of the differences) were ≤ 0.7 mL/min/kg. Results: Global GFR differed < 0.7 mL/min/kg in 5 of 8 cats when comparing plasma clearance testing and dynamic CT; the limits of agreement were 1.4 and −1.7 mL/min/kg. The mean ± SD difference was −0.2 ± 0.8 mL/min/kg, and the maximum difference was 1.6 mL/min/kg. The mean ± SD difference (absolute value) for percentage filtration by individual kidneys was 2.4 ± 10.5% when comparing scintigraphy and dynamic CT; the maximum difference was 20%, and the limits of agreement were 18% and 23% (absolute value). Conclusions and Clinical Relevance: GFR estimation via dynamic CT exceeded the definition for acceptable clinical use, compared with results for conventional methods, which was likely attributable to sample size and preventable technical complications. Because 5 of 8 cats had comparable values between methods, further investigation of dynamic CT in a larger sample population with a wide range of GFR values should be performed.

Objective-To determine tracheal mucociliary clearance rate (TMCCR) by use of a standard protocol in healthy anesthetized cats and to determine the effect of theophylline on TMCCR in healthy anesthetized cats. Animals-6 healthy cats. Procedure-Cats were anesthetized with propofol, and a droplet of the radiopharmaceutical technetium Tc 99m macroaggregated albumin was placed endoscopically at the carina. Dynamic acquisition scintigraphic imaging was performed, using the larynx as the end point. The TMCCR was determined by measuring the distance the droplet traveled by frame rate. Each cat was imaged 6 times as follows: 3 times following placebo administration and 3 times following the administration of sustained release theophylline (25 mg/kg, PO). Serum theophylline concentrations were assessed during imaging to ensure therapeutic concentrations. Results-The TMCCR in healthy adult cats anesthetized with propofol was 22.2 +/- 2.8 mm/min. Tracheal mucociliary clearance rate in cats receiving theophylline was 21.8 +/- 3.5 mm/min. Theophylline administration did not significantly alter TMCCR. Conclusion and Clinical Relevance-Theophylline has been shown to increase TMCCR in humans and dogs. In our study, we determined TMCCR in healthy anesthetized cats and found that it was not accelerated by the administration of theophylline.

Technetium-99m sulfur colloid scintigraphy was used to study alterations of reticuloendothelial function in 7 dogs with experimentally induced biliary cirrhosis and portosystemic shunting. Scintigraphic studies were performed before and 6 weeks after common bile duct ligation. Radiocolloid plasma clearance rate was determined by measuring activity in plasma samples and by analyzing the rate of liver uptake on dynamic scintigraphic image sequences. Percentage of uptake in the liver, spleen, and lungs, as well as the ratio of hepatic-to-extrahepatic uptake, was determined from static equilibrium images. Relative to preoperative values, there were significant decreases in plasma clearance rate, percentage of liver uptake, and ratio of hepatic-to-extrahepatic uptake and significant increases in percentage of spleen and lung uptake on postoperative studies. The mechanism of technetium-99m-labeled sulfur colloid extraction by the liver is different from that of other radiocolloids; it does not require active phagocytosis or pinocytosis. Thus, liver uptake of this tracer principally reflects effective liver blood flow. Portosystemic shunting was documented in these dogs at the time of the postoperative radiocolloid scans, and we believed was responsible for the decrease in liver reticuloendothelial activity. Possible mechanisms for the increased splenic and pulmonary reticuloendothelial activities are discussed.

OBJECTIVE To evaluate agreement of 4 methods (Tikhonov gamma variate adaptive regularization of plasma concentration-time curve fitting applied to technetium Tc 99m diethylenetriamine pentaacetic acid [99mTc-DTPA] plasma clearance [Tk-GV], plasma clearance of exogenous creatinine [CrCL], Gates gamma camera-based measurement method with 99mTc-DTPA renal clearance and dynamic scintigraphy [GTS], and iohexol renal clearance assessed with dynamic CT with Patlak plotting [CT-Pp]) for measuring glomerular filtration rates (GFR) in healthy cats. ANIMALS 7 healthy, laboratory-raised cats. PROCEDURES Each method for measuring GFR was performed twice in 7 cats at 24-day intervals. The Wilcoxon signed-rank sum test was used to compare the results obtained from the 14 studies for each method. Results from the 4 methods were assessed for agreement and correlation. RESULTS The median GFR values were 2.75, 2.83, 3.14, and 4.26 mL/min/kg, for Tk-GV, CT-Pp, plasma CrCL, and GTS, respectively. Analysis with Wilcoxon signed-rank sum tests identified significant pairwise differences between results obtained with the Tk-GV versus the plasma CrCL method, the Tk-GV versus the GTS method, and the plasma CrCL versus the GTS method. The least variable method was Tk-GV, with an SD of 1.27 (mL/min/kg). CONCLUSIONS AND CLINICAL RELEVANCE Findings indicated that Tk-GV yielded GFR measurements comparable with those obtained with CT-Pp, plasma CrCL, and GTS; however, the Tk-GV method yielded the tightest range of results among the methods evaluated.

Objective-To determine expression of folate receptors (FRs) and folate uptake in multicentric lymphomas in dogs. Sample-10 dogs with histopathologically confirmed multicentric lymphoma and 20 archival lymph node biopsy specimens from dogs with multicentric lymphoma. Procedures-Multicentric lymphomas in 10 dogs were prospectively evaluated for FR expression by use of immunohistochemical analysis and for in vivo folate uptake by use of nuclear scintigraphy. Dogs with FR-expressing tumors were eligible for FR-targeted chemotherapy. Twenty archival lymphoma biopsy specimens were also evaluated with immunohistochemical analysis. Results-FRs were not detected with immunohistochemical analysis in lymph node samples obtained from the 10 dogs or in archival biopsy specimens. However, nuclear scintigraphy revealed uptake of radioactive tracer in 6 of 10 dogs. Five of these 6 dogs were treated with an FR-targeted chemotherapeutic agent; results of treatment were complete remission in 1 dog, stable disease in 2 dogs, and progressive disease in 2 dogs. Treatment-related toxicoses generally were mild. Conclusions and Clinical Relevance-This study provided strong evidence for folate uptake in a substantial portion of multicentric lymphomas of dogs and indicated the antitumor activity of FR-targeted chemotherapeutics for these cancers. Use of FR-targeted chemotherapeutics may be promising for the treatment of FR-expressing multicentric lymphomas in dogs. Further studies are needed to determine reasons for lack of immunoreactivity to currently identified anti-FR antibodies and to develop improved methods for detecting FRs in lymphomas of dogs.

Objective: To determine the effects of exercise on the distribution and pharmacokinetics of technetium Tc 99m medronate (99mTc-MDP) following intra-articular (IA) injection in horses. Animals: 5 horses. Procedures: 1 antebrachiocarpal joint (ACJ)/horse was assigned to the exercised group (n = 5), and the contralateral ACJ was evaluated in the nonexercised group (5) after a minimum washout period of 7 days. Following IA injection of 99mTc-MDP (148 MBq), blood and scintigraphic images of the carpus were obtained at 5, 10, 15, 20, 25, 30, 45, 60, 90, 120, 240, 360, 480, 600, 720, and 1,440 minutes. Plasma and scintigraphic radioactivity were determined over time, and pharmacokinetic parameters were generated via noncompartmental and compartmental analyses. Each horse was monitored via physical and lameness examination and ACJ synovial fluid analysis before injection and at days 1, 2, 3, and 7. Results: Lameness was not observed. Mean ± SD synovial fluid WBC count increased at day 1 (exercised, 721 ± 234 cells/μL; nonexercised, 948 ± 223 cells/μL), but returned to baseline at days 3 and 7 Mean time to maximum plasma radioactivity was earlier in the exercised group (16.00 ± 2.35 minutes) than the nonexercised group (43.75 ± 3.64 minutes). Linear regression of the scintigraphic radioactivity-time curves revealed a greater negative slope in the exercised group within the first 25 minutes. There was no difference in absorption or elimination rate constants in a 2-compartment model. Conclusions and Clinical Relevance: IA injection of 99mTc-MDP was safe and effective for evaluating synovial solute distribution. Exercise significantly increased early transfer of 99mTc-MDP from the ACJ into plasma, although absorption and elimination rate constants were not affected. Exercise may affect synovial clearance and withdrawal times of medications administered IA.

Objective: To determine whether the reported drug-drug interaction between the flea medication spinosad and ivermectin is attributable to inhibition of P-glycoprotein by spinosad. Animals: 6 healthy adult dogs with the ABCB1 wildtype genotype. Procedures: The study was conducted as a prospective, masked, randomized crossover design. Six dogs were allocated to 2 groups; each dog served as its own control animal. Dogs in one of the groups received spinosad at the manufacturer's recommended dose; the other group received no treatment. Forty-eight hours later, scintigraphic imaging of the head and abdomen were performed with the radiolabeled P-glycoprotein substrate methoxy-isobutyl-isonitrile (sestamibi) in both groups of dogs. After a washout period of 60 days, the dogs in each group received the alternate treatment, and scintigraphic imaging again was performed 48 hours later. Gallbladder-to-liver and brain-to-neck musculature ratios of technetium Tc 99m sestamibi were calculated for each dog and compared between treatments. Results: No significant differences in gallbladder-to-liver or brain-to-neck musculature ratios were found between treatments. Conclusions and Clinical Relevance: Results provided evidence that spinosad did not inhibit P-glycoprotein function 48 hours after spinosad was administered at the manufacturer's recommended dose. Further investigations will be necessary to elucidate the mechanism of the reported toxic interaction between spinosad and ivermectin.

Objective: To evaluate use of a radiolabeled peptide nucleic acid–peptide conjugate (RaPP) targeting B-cell leukemia-lymphoma 2 (BCL2) mRNA for scintigraphic detection of neoplastic lymphocytes in dogs with B-cell lymphoma and to assess associations among RaPP uptake, time to tumor progression (TTP), and BCL2 mRNA expression. Animals: 11 dogs with B-cell lymphoma and 1 clinically normal dog. Procedures: Scintigraphic images were acquired 1 hour after IV injection of the RaPP. Regions of interest (ROIs) were drawn around lymph nodes, liver, and spleen; ROI intensity (relative to that of an equally sized region of muscle in the same image) was measured. Each ROI was also subjectively categorized as positive or negative for increased RaPP uptake. Expression of BCL2 mRNA was determined via quantitative reverse transcriptase PCR assay of a lymph node sample from dogs with lymphoma. Associations among imaging results, TTP, and BCL2 mRNA expression were evaluated. Results: Increased RaPP uptake was detected in affected tissues of dogs with lymphoma. Dogs with superficial cervical lymph node ROIs categorized as negative (n = 8) for increased RaPP uptake had a significantly longer TTP than did dogs for which this ROI was considered positive (2). Measured intensity of mandibular and superficial cervical lymph node ROIs was negatively associated with TTP. Associations among BCL2 mRNA and ROI intensity or TTP were not significant. Conclusions and Clinical Relevance: Increased RaPP uptake at mandibular or superficial cervical lymph node ROIs may be a negative prognostic indicator in dogs with lymphoma. A larger investigation is needed to determine clinical value of the RaPP for disease detection and prognostication.