Upregulation of major histocompatibility complex class II antigens in hepatocytes in Doberman hepatitis

Major histocompatibility complex (MHC) class II antigen expression in hepatocytes and its correlation with mononuclear cell infiltration into the liver were studied using immunohistochemical techniques in 38 Dobermans with Doberman hepatitis (DH). Liver biopsy samples were obtained from 18 dogs at the subclinical stage. Autopsy samples were taken from 6 DH dogs euthanized for a reason other than DH, from 14 dogs euthanized because of advanced liver failure and from 6 control Dobermans. Upon examination of the control liver samples, no expression of MHC class II antigens was detected in hepatocytes. By contrast, in 15 of the 18 DH biopsies (83%) and in all 20 DH autopsy liver samples, hepatocytes expressed MHC class II molecules. MHC class II expression was either cytoplasmic or membranous and occurred in conjunction with lymphocyte infiltration. A correlation between the inflammatory reaction and the expression of MHC class II in hepatocytes suggests that the aberrant expression of MHC class II in hepatocytes is induced by cytokines. Hepatocytes presenting a putative MHC class II molecule-associated autoantigen could thus become the target of an immune attack mediated by CD4+ T cells. In addition, corticosteroid treatment was observed to significantly decrease MHC class II expression in DH hepatocytes. Inappropriate MHC class II expression in hepatocytes and mononuclear cell infiltration are suggesting an autoimmune nature for chronic hepatitis in Dobermans.     

Cardiac Troponin I in Doberman Pinschers with Cardiomyopathy

Background: Cardiac troponin I (cTnI) is useful for detection of cardiac myocyte damage, but its efficacy in detecting various stages of dilated cardiomyopathy (DCM) in Doberman Pinschers is unclear. Objectives: To evaluate the diagnostic value of cTnI in various stages of DCM in Dobermans. Animals: Six hundred and fifty‐three cTnI measurements of 336 Doberman Pinschers. Methods: Using a longitudinal study design, staging of the disease was based upon 24‐hour‐ambulatory‐ECG (Holter) and echocardiography. A total of 447 cTnI measurements were performed in 264 healthy Dobermans, and 206 cTnI measurements in 75 Dobermans with cardiomyopathy. Eighty‐eight cTnI samples were from dogs with >100 ventricular premature contractions (VPCs)/24 hour, but without echocardiographic changes (“VPC group”). Additional 19 samples originated from dogs with only echocardiographic changes (“ECHO group”), and 56 samples from dogs with both VPCs and echocardiographic changes (“VPC plus ECHO group”). Twenty samples were from dogs with clinical signs (“clinical group”). The group “incipient” included 23 dogs, that were considered to be normal according to Holter and echocardiography at the time of the exam, but that developed DCM within 1.5 years. Results: cTnI values of dogs in all disease groups, including the “incipient” (0.30 ± 0.20) and “VPC group” (0.36 ± 0.34), were significantly (P= .04, P < .001) higher than the control group (0.07 ± 0.16). A cut‐off value of >0.22 ng/mL had a sensitivity of 79.5% and a specificity of 84.4% to detect all forms of cardiomyopathy. Conclusions and Clinical Importance: cTnI measurement is a valuable diagnostic test that can detect cardiomyopathy in dogs that are otherwise clinically normal.     

Force Plate Gait Analysis in Doberman Pinschers with and without Cervical Spondylomyelopathy

Background

The most accepted means of evaluating the response of a patient with cervical spondylomyelopathy (CSM) to treatment is subjective and based on the owner and clinician's perception of the gait.

Objective

To establish and compare kinetic parameters based on force plate gait analysis between normal and CSM‐affected Dobermans.

Animals

Nineteen Doberman Pinschers: 10 clinically normal and 9 with CSM.

Methods

Force plate analysis was prospectively performed in all dogs. At least 4 runs of ipsilateral limbs were collected from each dog. Eight force platform parameters were evaluated, including peak vertical force (PVF) and peak vertical impulse (PVI), peak mediolateral force (PMLF) and peak mediolateral impulse, peak braking force and peak braking impulse, and peak propulsive force (PPF) and peak propulsive impulse. In addition, the coefficient of variation (CV) for each limb was calculated for each parameter. Data analysis was performed by a repeated measures approach.

Results

PMLF (P = .0062), PVI (P = .0225), and PPF (P = .0408) were found to be lower in CSM‐affected dogs compared with normal dogs. Analysis by CV as the outcome indicated more variability in PVF in CSM‐affected dogs (P = 0.0045). The largest difference in the CV of PVF was seen in the thoracic limbs of affected dogs when compared with the thoracic limbs of normal dogs (P = 0.0019).

Conclusions and Clinical Importance

The CV of PVF in all 4 limbs, especially the thoracic limbs, distinguished clinically normal Dobermans from those with CSM. Other kinetic parameters less reliably distinguished CSM‐affected from clinically normal Dobermans.     

European Society of Veterinary Cardiology screening guidelines for dilated cardiomyopathy in Doberman Pinschers

Background

Dilated cardiomyopathy (DCM) is the most common cardiac disease in large breed dogs and is inherited in Doberman Pinschers with a high prevalence (58%).

Heart rate turbulence after ventricular premature beats in healthy Doberman pinschers and those with dilated cardiomyopathy

Objectives

To describe the measurement of heart rate turbulence (HRT) after ventricular premature beats and compare HRT in healthy Doberman pinschers and those with dilated cardiomyopathy (DCM), with and without congestive heart failure (CHF).

An in vitro investigation of predisposition to sulphonamide idiosyncratic toxicity in dogs

Sulphonamide idiosyncratic toxicosis has been reported in 28 dogs. Non-septic polyarthritis and fever occurring after 8 to 21 days therapy was the most common manifestation. Of 22 dogs with this syndrome, 7 were Doberman Pinschers. In humans, inherited decreased ability to detoxify sulphonamide hydroxylamine metabolites (as reflected in an in vitro mononuclear leukocyte (MNL) toxicity assay) has been associated with susceptibility to sulphonamide idiosyncratic toxicity. We have demonstrated that microsomes obtained from the liver of a dog were capable of metabolizing sulphamethoxazole to sulphamethoxazole hydroxylamine (SMX-HA). Production of SMX-HA was an NADPH dependent process and the yield was increased by the presence of 1 mmol/L ascorbic acid. SMX-HA was toxic to isolated MNL from mixed breed dogs (MBD) and Doberman Pinschers. The toxicity of SMX-HA to MNL from Dobermans was significantly different from that to MNL from MDB. MNL from 7 out of 15 Dobermans (including a dog with a history of an idiosyncratic reaction to a sulphonamide) had an LD-50 (concentration of SMX-HA required to produce 50% cytotoxicity in MNL) < 100 mol/L, while MNL from 0 out of 10 MBD had an LD-50 < 100 mol/L. These results suggest that the basis for the observed predisposition of Dobermans to sulphonamide idiosyncratic toxicity may be a limited capacity to detoxify the hydroxylamine metabolites of sulphonamides.     

Association between liver copper concentration and subclinical hepatitis in Doberman Pinschers

The prevalence of subclinical hepatitis was investigated in a group of 106 randomly selected 3-year-old Doberman Pinschers. Histopathologic examination of liver samples from 65 dogs (52 dogs with high bile acids, alkaline phosphatase activity, or alanine aminotransferase activity or with copper granules in hepatocytes in a liver aspirate and 13 normal dogs) revealed subclinical hepatitis in 22 dogs (19 females and 3 males). Liver copper concentrations measured by instrumental neutron activation analysis was significantly higher (mean +/- SD; 419 +/- 414 microg/g dry matter) in dogs with hepatitis than those without liver disease (197 +/- 113 microg/g; P = .0008). At 2.6 +/- 0.6 years hepatitis persisted in 5 of 16 dogs available for examination. One dog with a high copper concentration but normal liver subsequently developed subclinical hepatitis after 3 years. During the follow-up period, the average copper concentration of the 6 dogs with persistent subclinical hepatitis was 939 +/- 299 microg/g and had continued to rise significantly (P = .02). The hepatitis in these dogs was associated with apoptotic hepatocytes and copper-laden Kupffer cells in centrolobular regions. The results of this study suggest that there is a relationship among copper storage, hepatocellular damage, and hepatitis in Doberman Pinschers.     

Collection of peripheral blood CD34+ progenitor cells from healthy dogs and dogs diagnosed with lymphoproliferative diseases using a Baxter-Fenwal CS-3000 Plus blood cell separator

Background

Canine peripheral blood mononuclear cell (PBMC) apheresis using a Baxter‐Fenwal CS‐3000 Plus automated blood cell separator has not been reported.

Objective

To determine the feasibility and safety of using a CS‐3000 Plus blood cell separator with a small volume separation container holder (SVSCH) and small volume collection chamber (SVCC) to harvest canine PBMCs from dogs weighing <50 kg.

Animals

Eight healthy mongrel dogs and 11 client‐owned dogs in clinical remission for lymphoproliferative diseases (LPD).

Methods

In this prospective study, aphereses were performed using a Baxter‐Fenwal CS‐3000 Plus blood cell separator, with or without recombinant human granulocyte colony‐stimulating factor (rhG‐CSF) treatment.

Results

Aphereses from 6 healthy dogs given rhG‐CSF yielded an average of 1.1 × 10⁷ ± 8.2 × 10⁶ CD34+ cells/kg. Aphereses from LPD dogs given rhG‐CSF yielded an average of 5.4 × 10⁶ ± 3.25 × 10⁶ CD34+ cells/kg (P = .17). Higher hematocrit in both groups of dogs receiving rhG‐CSF correlated with an increased number of CD34+ cells/kg harvested (healthy, P = .04; LPD, P = .05). Apheresis was well tolerated by all dogs.

Conclusions and Clinical Importance

Canine PBMC apheresis using the Baxter‐Fenwal CS‐3000 Plus cell separator with an SVSCH and SVCC is a feasible and safe option for harvesting an adequate number of CD34+ peripheral blood progenitor cells from dogs weighing ≥17 kg for hematopoietic cell transplantation.     

Subclinical versus clinical hepatitis in the dobermann: evaluation of changes in blood parameters

Concentrations of the enzymes alanine aminotransferase (ALT) and alkaline phosphatase (AP) were determined in blood samples from 626 randomly selected clinically healthy dobermann. ALT levels greater than three times the normal upper value were detected in 55 dogs. These dogs were selected for further investigation; the owners of 23 of the dogs allowed a liver biopsy to be performed. Histopathological examination revealed various degrees of hepatitis and excessive amounts of copper in 21 of the dogs. These cases, referred to as subclinical dobermann hepatitis (DH), were selected for a follow-up investigation in which the clinical signs and serum parameters (ALT, AP and bilirubin) were studied for a period of three to 48 months. Serum parameters of those with subclinical DH were compared with blood samples collected from 22 dogs with clinical DH. Individual dogs showed great variation in the levels of ALT and AP between consecutive serum samples. These enzyme levels never, however, fell to the normal range. During the subclinical stage no statistically significant (P>0–05) change occurred in the concentrations of ALT or AP. When dogs with subclinical DH were compared with dogs with clinical DH, there was no statistically significant (P>0–05) difference in ALT levels, whereas AP concentrations were significantly (P<0001) higher among clinically affected dogs. Elevated levels of bilirubin were detected almost exclusively in dogs with clinical DH. After the onset of clinical signs there was a decrease in the ALT levels and an increase in AP concentrations as the disease progressed, but the changes were not statistically significant (P>0–05).     

Breed-specific pro-inflammatory cytokine production as a predisposing factor for susceptibility to sepsis in the dog

Objective: To determine whether 2 dog breeds with a high risk for parvoviral enteritis, a disease associated with sepsis, produce stronger pro‐inflammatory cytokine responses to a stimulus than dogs with a lower risk. Design: Blinded comparison. Setting: University outpatient clinic. Animals: Healthy, unrelated, purebred Doberman Pinschers (n=10) and Rottweilers (n=9) with age‐matched mixed‐breed dogs (n=7). Interventions: Heparinized, whole‐blood samples were collected from each dog and incubated for 6 hours with lipopolysaccharide. Plasma was collected, and bioassays were used to determine the concentrations of TNF‐α and IL‐6. The mean values obtained from the high‐risk breeds were compared with the mean obtained from the mixed‐breeds. Measurements and main results: The mean TNF‐α production from dogs with a high risk for parvoviral enteritis (1321±161 pg/mL; Doberman Pinscher and Rottweiler) was greater (P<0.05) than that from lower risk, mixed‐breed dogs (674±186 pg/mL). There were no differences in TNF‐α levels between Doberman (1128±247 pg/mL) and Rottweiler (1563±pg/mL) breeds or between any breeds with regard to IL‐6 production. Conclusions: The magnitude of TNF‐α production by peripheral blood monocytes was the greatest in the dogs with breed‐related risk for parvoviral enteritis. However, additional studies are needed to prove a causal relationship between high TNF and predilection for parvoviral enteritis. Regardless, breed appears to be a predisposing factor for variations in cytokine production that could impact the host response to infection and other inflammatory insults.     

A retrospective study of heart disease in doberman pinscher dogs

The prevalence of gross and/or histological cardiac lesions was found to be much greater in Doberman pinscher dogs (16/26 or 62%) than in non-Doberman dogs (124/417 or 30%). At least some of the affected Dobermans were unrelated. Middle aged (mean age 4.7 yr) Dobermans of both sexes (11 M:5F) were affected. Four of the Dobermans with heart lesions had congestive cardiomyopathy; three of these four had congestive heart failure and the other one died suddenly. Prominent gross lesions were ventricular dilation and atrioventricular valvular endocardiosis. Histological lesions noted were prominent myocardial fibrosis, myofiber degeneration with fatty replacement, myofiber vacuolation and arterial intimal cushion formation. A spectrum of myocardial disease exists in Dobermans and clinically overt congestive cardiomyopathy represents one end of this spectrum.     

Renal resistive index in 55 dogs with degenerative mitral valve disease

Background

Azotemia occurs frequently in dogs with degenerative mitral valve disease (DMVD). It could indicate changes in renal hemodynamics.

Hypothesis/Objectives

To assess the renal resistive index (RI) in dogs with DMVD, and the statistical link between heart failure class, azotemia, echo‐Doppler parameters, several plasma variables, and RI.

Animals

Fifty‐five dogs with naturally occurring DVMD were used (ISACHC class 1 [n = 28], 2 [n = 19], and 3 [n = 8]).

Methods

Observational, blinded study, performed under standardized conditions. Physical examination, renal ultrasonography, and echo‐Doppler examinations were performed in awake dogs. The RI of the renal, interlobar, and arcuate arteries were measured. Plasma creatinine, urea, and N‐terminal pro‐B‐type natriuretic peptide concentrations (NT‐proBNP) were determined. Statistical links between variables and RI were tested by means of a general linear model.

Results

Although the RI of renal and arcuate arteries were unaffected by ISACHC class, the left interlobar RI increased (P < .001) from 0.62 ± 0.05 (mean ± SD) in class 1 to 0.76 ± 0.08 in class 3. It was also higher (P < .001) in azotemic (0.74 ± 0.08) than in non‐azotemic (0.62 ± 0.05) dogs. Similar findings were observed for right interlobar RI. Univariate analysis showed a positive statistical link between NT‐proBNP (P = .002), urea (P < .001), creatinine (P = .002), urea‐to‐creatinine ratio (P < .001), left atrium‐to‐aorta ratio (P < .001), regurgitation fraction (P < .001), systolic pulmonary arterial pressure (P < .001), shortening fraction (P = .035), and RI.

Conclusion and Clinical Importance

In dogs with DMVD, interlobar RI increases with heart failure severity and azotemia but a cause and effect relationship remains to be established.     

Effects of 6% Tetrastarch and Lactated Ringer's Solution on Extravascular Lung Water and Markers of Acute Renal Injury in Hemorrhaged,Isoflurane‐Anesthetized Healthy Dogs

Background

Tetrastarch can cause acute kidney injury (AKI) in humans with sepsis, but less likely to result in tissue edema than lactated Ringer's solution (LRS).

Objectives

Compare effects of volume replacement (VR) with LRS and 6% tetrastarch solution (TS) on extravascular lung water (EVLW) and markers of AKI in hemorrhaged dogs.

Animals

Six healthy English Pointer dogs (19.7–35.3 kg).

Methods

Prospective crossover study. Animals underwent anesthesia without hemorrhage (Control). Two weeks later, dogs hemorrhaged under anesthesia on 2 occasions (8‐week washout intervals) and randomly received VR with LRS or TS at 3 : 1 or 1 : 1 of shed blood, respectively. Anesthesia was maintained until 4 hour after VR for EVLW measurements derived from transpulmonary thermodilution cardiac output. Neutrophil gelatinase‐associated lipocalin (NGAL) and creatinine concentrations in plasma and urine were measured until 72 hour after VR.

Results

The EVLW index (mL/kg) was lower at 1 hour after TS (10.0 ± 1.9) in comparison with controls (11.9 ± 3.4, P = 0.04), and at 4 hour after TS (9.7 ± 1.9) in comparison with LRS (11.8 ± 2.7, P = 0.03). Arterial oxygen partial pressure‐to‐inspired oxygen fraction ratio did not differ among treatments from 0.5 to 4 hour after VR. Urine NGAL/creatinine ratio did not differ among treatments and remained below threshold for AKI (120,000 pg/mg).

Conclusions and Clinical Importance

Although TS causes less EVLW accumulation than LRS, neither fluid produced evidence of lung edema (impaired oxygenation). Both fluids appear not to cause AKI when used for VR after hemorrhage in healthy nonseptic dogs.     

Factor VIII activity in canine von Willebrand disease

This study was conducted to determine the relationship between factor VIII (FVIII) activity and von Willebrand factor antigen (vWf:Ag) concentration in canine von Willebrand Disease (vWD). In addition, the clinical utility of measuring FVIII activity in vWD was assessed. This was performed by the concurrent analysis of both FVIII activity and vWf:Ag concentration in three breeds of dogs, namely Dobermans (n=183), Scottish Terriers (n=169), and Labrador Retrievers (n=146). In the three breeds tested, linear regression analysis illustrated a positive relationship between FVIII activity and vWf:Ag concentration. This was reaffirmed in the Doberman and Scottish Terrier breeds, in which dogs with vWf:Ag concentrations < 50 CU/dL ("carriers") had lower median FVIII activities than dogs with vWf:Ag concentrations > 70 CU/dL ("normals"). The determination of various FVIII "cut-off" values was a poor test to separate Dobermans with and without clinical signs of hemorrhage attributable to vWD. In addition, the occurrence of hemorrhage in Dobermans with vWf:Ag concentrations < 50 CU/dL was not influenced by the FVIII activity. Various tests were performed to determine if the measurement of FVIII activity aided in the identification of "carriers" of the vWD gene in the Doberman and Scottish Terrier breeds. These included the use of optimal FVIII "cut-off" values for each breed and a FVIII "cut-off" value of 55 CU/dL; FVIII/vWf:Ag ratios and FVIII/vWf:Ag ratio "cut-off" values; and linear regression analysis of vWf:Ag concentration against FVIII activity. Of all these tests, only the determination of FVIII/vWf:Ag ratios appeared to have promise for "carrier" detection. The data in the present study indicated that routine FVIII assessment in vWD is not warranted; however, measurement of FVIII activity may be of use in confirming the "carrier" status of vWD.     

An eye on the Shih Tzu dog: Ophthalmic examination findings and ocular surface diagnostics

Objective

To characterize the ocular surface parameters and determine the prevalence of ocular pathology in Shih Tzu dogs.

Animal Studied

Fifty Shih Tzu dogs (28 male, 22 female).

Procedures

Each dog underwent a complete ophthalmic examination (recording any pathology) and a series of diagnostics, allowing for a 10 min-interval between tests: intraocular pressure (IOP), blink rate, palpebral fissure length (PFL), corneal tactile sensation (CTS), Schirmer tear test and nasolacrimal reflex without (STT-1, NL-STT1) and with topical anesthesia (STT-2, NL-STT2), tear ferning, strip meniscometry test (SMT), tear film breakup time (TFBUT), and punctate fluorescein staining (PFS) of the cornea.

Results

Mean ± SD test values were as follows: IOP (17.9 ± 3.7 mmHg), blink rate (2.4 ± 1.4 blinks/min), PFL (23.8 ± 1.8 mm), CTS (1.8 ± 0.7 cm), STT-1 (22.0 ± 5.5 mm/min), NL-STT1 (24.2 ± 4.7 mm/min), STT-2 (16.9 ± 6.5 mm/min), NL-STT2 (18.5 ± 7.5 mm/min), SMT (7.5 ± 3.5 mm/5 s), TFBUT (5.3 ± 2.4 s), tear ferning (1.3 ± 0.7), and PFS (1.6 ± 0.6). PFL was significantly greater in male vs. female Shih Tzus (p< .001). Age was negatively correlated with TFBUT results (r = −0.31, p = .027). Lagophthalmos was observed in 82% eyes. Ocular surface pathology was common, including adnexal abnormalities (100% eyes with caruncular trichiasis and medial lower lid entropion) and corneal opacification (27% pigmentation, 20% fibrosis, 12% neovascularization).

Conclusions

Qualitative tear film deficiency (low TFBUT), along with several anatomical abnormalities that promote ocular irritation and reduce globe protection, together help explain the concerningly high prevalence of ocular surface disease in the Shih Tzu breed. Prophylactic measures (e.g., medial canthoplasty, topical lubrication) could be considered to improve ocular health in Shih Tzus.     

Effect of oral trazodone on the minimum alveolar concentration of isoflurane in dogs

Objective

To determine the effect of oral trazodone on the minimum alveolar concentration (MAC) of isoflurane in dogs.

A Double‐blind,Placebo‐controlled,Multicenter, Prospective,Randomized Study of Beraprost Sodium Treatment for Cats with Chronic Kidney Disease

Background

Chronic kidney disease (CKD) is a common progressive and irreversible disease in cats. The efficacy and safety of beraprost sodium (BPS) in cats with CKD have not been evaluated.

Hypothesis/Objectives

To evaluate the efficacy and safety of BPS in the treatment of cats with CKD, as compared to placebo.

Animals

Seventy‐four client‐owned cats with naturally occurring CKD.

Methods

Double‐blind, placebo‐controlled, multicenter, prospective, randomized trial. The cats received BPS (55 μg/cat) or a placebo PO q12 h for 180 days. The primary endpoint was prospectively defined as a change in the serum creatinine (sCr), serum phosphorus‐to‐calcium ratio or urine specific gravity (USG).

Results

The sCr increased significantly (P = 0.0030) in the placebo group (mean ± SD: 2.8 ± 0.7 to 3.2 ± 1.3 mg/dL) but not in the BPS group (2.4 ± 0.7 to 2.5 ± 0.7 mg/dL). The difference between the groups at day 180 was significant (0.8 mg/dL, 95% CI: 0.2 to 1.3 mg/dL, P = 0.0071). The serum phosphorus‐to‐calcium ratio was significantly (P = 0.0037) increased in the placebo group (0.46 ± 0.10 to 0.52 ± 0.21 mg/dL) but not in the BPS group (0.50 ± 0.08 to 0.51 ± 0.11 mg/dL). There was no significant change in the USG in either group. An adverse event judged as being treatment‐related included vomiting that occurred in 1 case in the placebo group. No clinically relevant change was observed in the CBC and other blood chemistry tests.

Conclusions and Clinical Importance

Beraprost sodium treatment was well tolerated and safe in cats with CKD. BPS inhibited the reduction in renal filtration function as measured by sCr increase.     

Glutathione Peroxidase Activity,Plasma Total Antioxidant Capacity,and Urinary F2‐ Isoprostanes as Markers of Oxidative Stress in Anemic Dogs

Background

Oxidative stress plays a role in the pathophysiology of several diseases and has been documented as a contributor to disease in both the human and veterinary literature. One at‐risk cell is the erythrocyte, however, the role of oxidative stress in anemia in dogs has not been widely investigated.

Hypothesis/Objective

Anemic dogs will have an alteration in the activity of glutathione peroxidase (GPx), a decrease in of total antioxidant capacity (TAC), and an increased concentration of urinary 15‐F₂‐isoprostanes (F₂‐IsoP) when compared to healthy dogs.

Animals

40 client‐owned dogs with anemia (PCV <30%) age‐matched to 40 client‐owned healthy control dogs.

Methods

Prospective, cross‐sectional study. Whole blood GPx activity, plasma TAC, and urinary F₂‐isoprostane concentrations were evaluated in each dog and compared between groups.

Results

Anemic dogs had significantly lower GPx activity (43.1 × 10³ +/‐ 1.6 × 10³ U/L) than did dogs in the control group (75.8 × 10³ +/‐ 2.0 × 10³ U/L; P < 0.0001). The GPx activity in dogs with hemolysis (10³ +/‐ 0.8 × 10³ U/L) was not significantly different (P = 0.57) than in dogs with nonhemolytic anemia (43.5 × 10³ +/‐ 1.1 × 10³ U/L). The TAC concentrations (P = 0.15) and urinary F₂‐isoprostanes (P = 0.73) did not significantly differ between groups.

Conclusions and Clinical Importance

Glutathione peroxidase activity was significantly decreased in anemic dogs indicating oxidative stress. Additional studies are warranted to determine if antioxidant supplementation would improve survival and overall outcome as part of a therapeutic regimen for anemic dogs.     

Pharmacokinetics of cyclophosphamide after oral and intravenous administration to dogs with lymphoma

Background: Cyclophosphamide is an alkylating chemotherapeutic drug administered IV or PO. It is currently assumed that exposure to the active metabolite, 4‐hydroxycyclophosphamide (4‐OHCP), is the same with either route of administration.

Objectives:

To characterize the pharmacokinetics of cyclophosphamide and 4‐OHCP in dogs with lymphoma when administered PO or IV. Animals: Sixteen client‐owned dogs with substage A lymphoma were enrolled in the study. Eight dogs received cyclophosphamide IV and 8 received it PO. Methods: Prospective randomized clinical trial was performed. Blood was collected from each dog at specific time points after administration of cyclophosphamide. The serum was evaluated for the concentration of cyclophosphamide and 4‐OHCP with mass spectrometry and liquid chromatography. Results: Drug exposure to cyclophosphamide measured by area under the curve (AUC)_0–inf is significantly higher after intravenous administration (7.14 ± 3.77 μg/h/mL) compared with exposure after oral administration (P‐value < .05). No difference in drug exposure to 4‐OHCP was detected after IV (1.66 ± 0.36 μg/h/mL) or PO (1.42 ± 0.64 μg/h/mL) administered cyclophosphamide. Conclusions and Clinical Importance: Drug exposure to the active metabolite 4‐OHCP is equivalent after administration of cyclophosphamide either PO or IV.     

Thromboelastographic results and hypercoagulability in dogs with surgically treated hepatocellular adenoma and carcinoma: A Veterinary Society of Surgical Oncology prospective study

Background

The most common haemostatic abnormality in dogs with cancer is hypercoagulability. A transient hypercoagulability has been documented in people with hepatocellular carcinoma (HCC) that resolves within weeks following hepatic tumour resection.

Objective

The objective was to compare the haemostatic status of dogs with liver tumours and healthy control dogs, by comparing coagulation and thromboelastography (TEG) measurements at three time points.

Methods

Liver tumour and healthy control dogs receiving surgery for liver lobectomy and ovariohysterectomy, respectively, were prospectively enrolled. All dogs had blood collected at three time points: pre-operative, 24 h post-operative and ~2 weeks post-operative. Haematological and haemostatic values were compared across time points in each group using repeated measures ANOVA tests.

Results

Ten and eight dogs were enrolled for the liver and control groups, respectively. Platelet count was significantly higher in the liver group than the control group at all time points, but within the normal range (pre-operative: 438.7 vs. 300.9 × 10⁹/L, p = .0078; 24 h post-operative: 416.2 vs. 283.9 × 10⁹/L, p = .0123; 10–14 days post-operative: 524.6 vs. 317.3 × 10⁹/L, p = .0072). The measure of the overall coagulant state (G-value) was significantly increased for the liver group compared to the control group at all time points (pre-operative: 15.6 vs. 8.6 d/sc, p = .0003; 24 h post-operative: 18.3 vs. 11.2 d/sc, p = .039; 10–14 days post-operative: 15.1 vs. 9.6 d/sc, p = .015).

Conclusion

The liver group was hypercoagulable based on elevated G-values at all time points compared to the control group. This hypercoagulability was attributed to the effect of hepatic tumours alone, and not secondary to surgery and anaesthesia.