Blood plasma concentrations of oestradiol-17β, testosterone and testosterone/oestradiol ratio in dogs with neoplastic and degenerative testicular diseases

Oestradiol-17β and testosterone blood plasma concentrations were measured in dogs with Leydig-cell tumours (n=20), Sertoli-cell tumours (n=6), seminomas (n=9), unilateral inguinal cryptorchidism (n=7), abdominal cryptorchidism (n=9, one bilateral), degenerate scrotal testicles (n=6, two bilateral), and animals with normal scrotal testicles (n=20). The testosterone/oestradiol ratio (testosterone concentration [ng/mL] × 100/oestradiol concentration [pg/mL]) was calculated.A considerably higher oestradiol concentration was found in dogs with Sertoli-cell tumours (29.0, 14.4–48.3 pg/mL; median, minimum–maximum; P=0.0256, Mann–Whitney test) and lower oestradiol levels were found in animals with seminomas (12.0, 3.4–17.6 pg/mL; P=0.0025) compared to the healthy control group (18.0, 8.6–31.5 pg/mL). Testosterone concentration was decreased in dogs with Sertoli-cell tumours (0.08, 0.03–0.77 ng/mL) when compared to the control group (1.95, 0.05–3.70 ng/mL; P=0.0012). Testosterone/oestradiol ratios differed from the control (9.6, 0.58–35.8) only in dogs with Sertoli-cell tumours (0.32, 0.06–2.80; P=0.0005). Clinical signs of feminization were observed in five dogs with Sertoli-cell tumour and one dog with a Leydig-cell tumour, and were more often associated with decreased testosterone/oestradiol ratios than with an increased oestradiol-17β concentration.     

Evaluation of the pharmacokinetics of oral amitriptyline and its active metabolite nortriptyline in fed and fasted Greyhound dogs

This study reports the pharmacokinetics of oral amitriptyline and its active metabolite nortriptyline in Greyhound dogs. Five healthy Greyhound dogs were enrolled in a randomized crossover design. A single oral dose of amitriptyline hydrochloride (actual mean dose 8.1 per kg) was administered to fasted or fed dogs. Blood samples were collected at predetermined times from 0 to 24 h after administration, and plasma drug concentrations were measured by liquid chromatography with mass spectrometry. Noncompartmental pharmacokinetic analyses were performed. Two dogs in the fasted group vomited following amitriptyline administration and were excluded from analysis. The range of amitriptyline C_MAX for the remaining fasted dogs (n = 3) was 22.8–64.5 ng/mL compared to 30.6–127 ng/mL for the fed dogs (n = 5). The range of the amitriptyline AUC_INF for the three fasted dogs was 167–720 h·ng/mL compared to 287–1146 h·ng/mL for fed dogs. The relative bioavailability of amitriptyline in fasted dogs compared to fed dogs was 69–91% (n = 3). The exposure of the active metabolite nortriptyline was correlated to amitriptyline exposure (R² = 0.84). Due to pharmacokinetic variability and the small number of dogs completing this study, further studies are needed assessing the impact of feeding on oral amitriptyline pharmacokinetics. Amitriptyline may be more likely to cause vomiting in fasted dogs.     

Cardiac troponins as indicators of acute myocardial damage in dogs

Cardiac troponin I (cTnI) and T (cTnT) have a high sequence homology across phyla and are sensitive and specific markers of myocardial damage. The purpose of this study was to evaluate the Cardiac Reader, a human point-of-care system for the determination of cTnT and myoglobin, and the Abbott Axsym System for the determination of cTnI and creatine kinase isoenzyme MB (CK-MB) in healthy dogs and in dogs at risk for acute myocardial damage because of gastric dilatation-volvulus (GDV) and blunt chest trauma (BCT). In healthy dogs (n = 56), cTnI was below detection limits (<0.1 microg/L) in 35 of 56 dogs (reference range 0-0.7 microg/L), and cTnT was not measurable (<0.05 ng/mL) in all but 1 dog. At presentation, cTnI, CK-MB, myoglobin, and lactic acid were all significantly higher in dogs with GDV (n = 28) and BCT (n = 8) than in control dogs (P < .001), but cTnT was significantly higher only in dogs with BCT (P = .033). Increased cTnI or cTnT values were found in 26 of 28 (highest values 1.1-369 microg/L) and 16 of 28 dogs (0.1-1.7 ng/mL) with GDV, and in 6 of 8 (2.3-82.4 microg/L) and 3 of 8 dogs (0.1-0.29 ng/mL) with BCT, respectively. In dogs suffering from GDV, cTnI and cTnT increased further within the first 48 hours (P < .001). Increased cardiac troponins suggestive of myocardial damage occurred in 93% of dogs with GDV and 75% with BCT. cTnI appeared more sensitive, but cTnT may be a negative prognostic indicator in GDV. Both systems tested seemed applicable for the measurement of canine cardiac troponins, with the Cardiac Reader particularly suitable for use in emergency settings.     

Serial determination of biomarkers of oxidative stress and antioxidant status in dogs with naturally occurring gastric dilatation-volvulus

Objective: To serially determine the biomarkers of oxidative stress and antioxidant status of dogs with gastric dilatation‐volvulus (GDV) over 48 hours. Design: Prospective study. Setting: Veterinary teaching hospital intensive care unit. Animals: Thirteen client‐owned dogs with GDV. Interventions: None. Measurement and main results: For all dogs, biomarkers of oxidative stress and antioxidant status were ascertained. Indicators of oxidative stress measured included F_2α‐isoprostanes (isoprostanes) and malondialdehyde (MDA). Vitamin C, vitamin E, glutathione peroxidase (GSHPx), and oxygen radical absorbance capacity (ORAC) were measured to assess antioxidant status. Oxidants and antioxidants were measured at the time of admission and at 24 and 48 hours post‐admission. There were significant decreases in vitamin E (P=0.002), vitamin C (P=0.001), ORAC (P=0.02), and MDA (P=0.001) during hospitalization. There was no significant change in GSHPx and isoprostane concentrations over time. Conclusion: Oxidative stress and antioxidant capacity in dogs with GDV change over time. Further studies measuring oxidative stress in more severely affected dogs and performing measurements earlier in the disease process may be beneficial in determining when oxidative stress is most severe during the course of GDV management.     

Assessment of a point‐of‐care cardiac troponin I test to differentiate cardiac from noncardiac causes of respiratory distress in dogs

Objectives – To (1) determine a reference interval for cardiac troponin I (cTnI) using a point‐of‐care device in normal dogs and compare the results with those published by the manufacturer and (2) determine if cTnI differs among dogs with cardiogenic and noncardiogenic respiratory distress. Design – Prospective observational study. Setting – Emergency and referral veterinary hospital. Animals – Twenty‐six clinically normal dogs and 67 dogs in respiratory distress. Interventions – All dogs underwent whole blood sampling for cTnI concentrations. Measurements and Results – Normal dogs had a median cTnI concentration of 0.03 ng/mL (range 0–0.11 ng/mL). Thirty‐six dogs were diagnosed with noncardiogenic respiratory distress with a median cTnI concentration of 0.14 ng/mL (range 0.01–4.31 ng/mL). Thirty‐one dogs were diagnosed with cardiogenic respiratory distress with a median cTnI concentration of 1.74 ng/mL (range 0.05–17.1 ng/mL). A significant difference between cTnI concentrations in normal dogs and dogs with noncardiogenic respiratory distress was not detected. Significant differences in cTnI concentrations were found between normals versus cardiogenic and cardiogenic versus noncardiogenic respiratory distress groups. Significant differences in cTnI concentrations were identified in >10 when compared with the <5 and the 5–10 years of age groups. Receiver operating curve analysis identified cTnI concentrations >1.5 ng/mL as the optimal “cut‐off point” having a sensitivity of 78% and specificity of 51.5%. The area under the receiver operating curve was 0.72. Overall test accuracy was 65%. Conclusions – cTnI concentrations were significantly increased in dogs with cardiogenic respiratory distress versus dogs with noncardiogenic respiratory distress and normal dogs. A significant difference between normal dogs and dogs with noncardiogenic causes of respiratory distress was detected. Although highly sensitive when cTnI concentrations exceed 1.5 ng/mL, the test has low specificity. Assessment of cTnI by the methodology used cannot be recommended as the sole diagnostic modality for evaluating the cause of respiratory distress in dogs.     

Pharmacokinetics of a controlled‐release liposome‐encapsulated hydromorphone administered to healthy dogs

The purpose of the study was to assess the pharmacokinetics of liposome‐encapsulated (DPPC‐C) hydromorphone administered intravenously (IV) or subcutaneously (SC) to dogs. A total of eight healthy Beagles aged 12.13 ± 1.2 months and weighing 11.72 ± 1.10 kg were used. Dogs randomly received liposome encapsulated hydromorphone, 0.5 mg/kg IV (n = 6), 1.0 mg/kg (n = 6), 2.0 mg/kg (n = 6), or 3.0 mg/kg (n = 7) SC with a 14–28 day washout between trials. Blood was sampled at serial intervals after drug administration. Serum hydromorphone concentrations were measured using liquid chromatography with mass spectrometry. Serum concentrations of hydromorphone decreased rapidly after IV administration of the DPPC‐C formulation (half‐life = 0.52 h, volume of distribution = 12.47 L/kg, serum clearance = 128.97 mL/min/kg). The half‐life of hydromorphone after SC administration of DPPC‐C formulation at 1.0, 2.0, and 3.0 mg/kg was 5.22, 31.48, and 24.05 h, respectively. The maximum serum concentration normalized for dose (C_MAX/D) ranged between 19.41–24.96 ng/mL occurring at 0.18–0.27 h. Serum hydromorphone concentrations fluctuated around 4.0 ng/mL from 6–72 h after 2.0 mg/kg and mean concentrations remained above 4 ng/mL for 96 h after 3.0 mg/kg DPPC‐C hydromorphone. Liposome‐encapsulated hydromorphone (DPPC‐C) administered SC to healthy dogs provided a sustained duration of serum hydromorphone concentrations.     

Cardiac troponin I and C-reactive protein concentrations in dogs with severe pulmonic stenosis before and after balloon valvuloplasty

Objective

To report cardiac troponin I (cTnI) and C-reactive protein (CRP) concentrations in dogs with severe pulmonic stenosis (PS) before and after balloon valvuloplasty (BV).

Background

Increased morbidity and mortality have been reported with severe PS and histopathologic evidence of myocardial damage is demonstrated with BV. Severity of myocardial injury and inflammation associated with severe PS and BV, as assessed by cTnI and CRP, is unknown.

Animals, materials and methods

Serum cTnI and CRP concentrations were measured in dogs with severe PS (n = 23) and following BV (n = 16).

Results

Baseline cTnI and CRP were elevated in 7/23 (30.4%) and 8/23 (34.8%) dogs. Median cTnI at baseline and post-BV were 0.20 ng/mL (range, 0.20-1.29 ng/mL) and 2.85 ng/mL (range, 0.21-55.40 ng/mL), respectively. Median CRP at baseline and post-BV were 3.40 μg/mL (range, 0-14.70 μg/mL) and 11.70 μg/mL (range, 4.20-120 μg/mL), respectively. Post-BV concentrations were significantly increased compared to baseline for cTnI (p < 0.001) and CRP (p = 0.001).

Conclusions

Serum cTnI and CRP are increased in dogs with severe PS and following BV. Future studies should evaluate whether biomarkers correlate with severity and prognosis of PS or can be used to guide therapy.     

Effects of food intake on pharmacokinetics of mosapride in beagle dogs

This study was performed to determine the pharmacokinetic profile of mosapride in fasting and fed states. A single 5‐mg oral dose of mosapride was administered to fasted (n = 15) and fed (n = 12) beagle dogs, and the plasma concentrations of mosapride were measured by liquid chromatography–tandem mass spectrometry. The resultant data were analyzed by noncompartmental analysis (NCA). Mosapride was absorbed in fasted and fed dogs with similar T_max. Both C_max and AUC were significantly higher in the fasting group than in fed dogs, being four times (10.51 μg/mL vs. 2.76 μg/mL) and 3.5 times higher (38.53 h·μg/mL vs. 10.22 h·μg/mL), respectively. These findings suggest that food intake affects the pharmacokinetics of mosapride and that the dosage regimen for this drug need to be reconsidered.     

The curative and antioxidative efficiency of ivermectin and ivermectin + vitamin E-selenium treatment on canine <Emphasis Type="Italic">Sarcoptes scabiei</Emphasis> infestation

The objective of the present study was to investigate the curative and antioxidative efficacy of ivermectin and ivermectin + vitamin E-selenium, and the influence of these agents on oxidative stress parameters in canines infested by Sarcoptes scabiei. Twenty two sarcoptic mites infested dogs and nine healthy dogs of 6 months to 2 years of age were divided into three groups. Group I comprised of healthy dogs (n = 9) whereas animals in group II (n = 11) and III (n = 11) were positive for scabies. Group II animals were treated with only 1% ivermectin @ 0.2 mg/kg SC whereas group III were additionally treated with Vitamin E and selenium (tocopherol 50 mg + Se 1.5 mg/ml) @0.5 ml/20 kg IM at weekly intervals for three times. Blood samples were collected on day 0 and 28 post therapy. The values for hemato-biochemical parameters and activities of antioxidant enzymes were significantly decreased (P < 0.05) whereas level of lipid peroxidation was significantly increased in all the infested dogs in comparison to the healthy dogs on day 0 which approached normalcy by day 28 post therapy. The dogs of group III showed better clinical recovery in comparison to group II at the end of therapy. Thus, administration of vitamin E and selenium in addition to standard therapy can alleviate these alterations hastening the clinical recovery of diseased dogs and can be recommended as an adjunct therapy with miticides for canine sarcoptic mange.     

Lithium dilution cardiac output and oxygen delivery in conscious dogs with systemic inflammatory response syndrome

Objective: Compare cardiac index (CI) and oxygen delivery index (DO₂I) in conscious, critically ill dogs to control dogs; evaluate the association of CI and DO₂I with outcome. Design: Prospective non‐randomized clinical study. Setting: Veterinary teaching hospital. Animals: Eighteen client‐owned dogs with systemic inflammatory response syndrome (SIRS) and 8 healthy control dogs. Measurements and Main Results: CI of dogs with SIRS was measured using lithium dilution at times 0, 4, 8, 16, and 24 hours. Data collected included physical exam, arterial blood gas (ABG) and hemoximetry. CI of control dogs was measured 3 times with 1 measurement of ABG. Mean CI ± SE in SIRS patients was 3.32 ± 0.95 L/min/m²; lower than controls at 4.18 ± 0.22 L/min/m² (P<0.001). Mean DO₂I ± SE in SIRS patients was 412.91 ± 156.67 mL O₂/min/m²; lower than controls at 785.24 ± 45.99 mL O₂/min/m² (P<0.001). There was no difference in CI (P=0.49) or DO₂I (P=0.51) for dogs that survived to discharge versus those that did not. There was no difference in mean CI (P=0.97) or DO₂I (P=0.50) of survivors versus non‐survivors for 28‐day survival. Survivors had lower blood glucose (P=0.03) and serum lactate concentrations (P=0.04) than non‐survivors. Conclusions: CI and DO₂I in conscious dogs with SIRS were lower than control dogs, which differs from theories that dogs with SIRS are in a high cardiac output state. CI and DO₂I were not significantly different between survivors and non‐survivors. Similar to previous studies, lactate and glucose concentrations of survivors were lower than non‐survivors.     

Cerebrospinal Fluid Myelin Basic Protein as a Prognostic Biomarker in Dogs with Thoracolumbar Intervertebral Disk Herniation

Background: Release of myelin basic protein (MBP) into the cerebrospinal fluid (CSF) is associated with active demyelination and correlates with outcome in various neurological diseases. Hypothesis/Objectives: To describe associations among CSF MBP concentration, initial neurological dysfunction, and long‐term ambulatory outcome in dogs with acute thoracolumbar intervertebral disk herniation (IVDH). Animals: Five hundred and seventy‐four dogs with acute thoracolumbar IVDH and 16 clinically normal dogs. Methods: Prospective case series clinical study. Signalment, initial neurological dysfunction as determined by a modified Frankel score (MFS), and ambulatory outcome at >3‐month follow‐up were recorded. Cisternal CSF MBP concentration was determined by an ELISA. Associations were estimated between CSF MBP concentration and various clinical parameters. Results: Dogs with thoracolumbar IVDH that did not ambulate at follow‐up had a higher CSF MBP concentration (median, 3.56 ng/mL; range, 0.59–51.2 ng/mL) compared with control dogs (median, 2.22 ng/mL; range, 0–3.82 ng/mL) (P= .032). A CSF MBP concentration of ≥3 ng/mL had a sensitivity of 78% and specificity of 76% to predict an unsuccessful outcome based on receiver‐operating characteristics curve analysis (area under the curve =0.688, P= .079). Affected dogs with a CSF MBP concentration ≥3 ng/mL had 0.09 times the odds of ambulation at follow‐up compared with affected dogs with CSF MBP concentration <3 ng/mL when adjusted for initial MFS (95% confidence interval 0.01–0.66, P= .018). Conclusions and Clinical Importance: These results would suggest that CSF MBP concentration may be useful as an independent prognostic indicator in dogs with thoracolumbar IVDH.     

C‐reactive protein concentration in dogs with primary immune‐mediated hemolytic anemia

Background: Canine primary immune-mediated hemolytic anemia (IMHA) is associated with a high-mortality rate. C-reactive protein (CRP) is the most important acute-phase protein in dogs and may have value as a marker of prognosis or response to treatment in IMHA. Objective: The objectives of this study were to evaluate serum CRP concentration in dogs with primary IMHA at presentation and during treatment, to assess potential differences based on survival time, and to compare CRP with other laboratory parameters of inflammation and prognosis. Methods: Inclusion criteria for primary IMHA were anemia (PCV<0.30 L/L), a positive Coombs' test or persistent autoagglutination of erythrocytes, and the exclusion of underlying diseases by other diagnostic tests. Dogs were divided into 2 groups based on survival: dogs that were still alive 14 days after start of treatment (group 1) and dogs that died or were euthanized before day 14 (group 2). Serum CRP concentration, a CBC, and a biochemistry profile were performed on days 0, 3, 8, and 14. Serum CRP also was determined in 25 clinically healthy dogs. Results: CRP concentration in the 25 clinically healthy dogs ranged from 0–8.9 μg/mL (median 2.2 μg/mL). Thirty dogs were diagnosed with primary IMHA, 24 in group 1 and 6 in group 2. On day 0, CRP concentration in dogs in both groups (median 224 μg/mL) was increased above the reference interval. In group 1 dogs, median CRP concentration was 242 μg/mL on day 0, 69 μg/mL on day 3, 35 μg/mL on day 8, and 2 μg/mL on day 14. In group 2 dogs, median CRP concentration was 194 μg/mL on day 0, 119 μg/mL on day 3, and 41 μg/mL on day 8; only 1 dog in group 2 survived to day 8. There was a significant correlation between CRP and total WBC concentrations on days 0 and 3 (r=−.598, P=.003). Conclusions: Serum CRP concentration was markedly increased in dogs with primary IMHA. CRP concentration did not differ based on patient survival, but might be a marker for long-term monitoring of these patients.     

Evaluation of cardiac performance of the dog after induction of portal hypertension and gastric ischemia

Objective: To determine changes in hemodynamic and cardiac energetic parameters in dogs after induction of portal hypertension and gastric ischemia. These blood flow alterations are similar to changes seen in splanchnic blood flow in dogs with gastric dilatation volvulus syndrome (GDV). Design: Original experimental study. Setting: Veterinary teaching hospital. Animals: Seven purpose‐bred, intact male dogs. Interventions: Standard midline laparotomy and median sternotomy were performed under general anesthesia. Dogs were instrumented to obtain arterial blood pressure, aortic flow, cardiac chamber pressures, central venous pressure, portal flow, and portal pressure. Colored microsphere technology was used for the determination of myocardial blood flow. Measurements and samples were obtained at baseline, following induction of portal hypertension, and after induction of portal hypertension and gastric ischemia. Measurements and main results: Left ventricular myocardial blood flow was increased from 81.8±20.1 mL/100 g/min at baseline to 127.7±57.2 mL/100 g/min (P=0.02) after induction of portal hypertension and gastric ischemia. Myocardial oxygen consumption increased from 142.2±27.4 J/min/100 g at baseline to 219.1±33.4 J/min/100 g (P=0.003) after induction of portal hypertension and gastric ischemia, but cardiac external work remained unchanged (13.67±6.2 to 13.27±9.6 J/min; P=0.78; power=0.79). Cardiac efficiency decreased from 11.6±6.1% at baseline to 7.6±5.1% (P=0.017) after induction of portal hypertension and gastric ischemia. Conclusions: Transfer of energy within the myocardium was less efficient after induction of portal hypertension and ischemia of the stomach wall. On the basis of these results, alterations in cardiac function associated with GDV may result from deterioration of cardiac efficiency.     

Altered Serum Thyrotropin Concentrations in Dogs with Primary Hypoadrenocorticism before and during Treatment

Background

Thyrotropin (TSH) can be increased in humans with primary hypoadrenocorticism (HA) before glucocorticoid treatment. Increase in TSH is a typical finding of primary hypothyroidism and both diseases can occur concurrently (Schmidt's syndrome); therefore, care must be taken in assessing thyroid function in untreated human patients with HA.

Objective

Evaluate whether alterations in cTSH can be observed in dogs with HA in absence of primary hypothyroidism.

Animals

Thirty dogs with newly diagnosed HA, and 30 dogs in which HA was suspected but excluded based on a normal ACTH stimulation test (controls) were prospectively enrolled.

Methods

cTSH and T4 concentrations were determined in all dogs and at selected time points during treatment (prednisolone, fludrocortisone, or DOCP) in dogs with HA.

Results

cTSH concentrations ranged from 0.01 to 2.6 ng/mL (median 0.29) and were increased in 11/30 dogs with HA; values in controls were all within the reference interval (range: 0.01–0.2 ng/dL; median 0.06). There was no difference in T4 between dogs with increased cTSH (T4 range 1.0‐2.1; median 1.3 μg/dL) compared to those with normal cTSH (T4 range 0.5‐3.4, median 1.4 μg/dL; P=0.69) and controls (T4 range 0.3‐3.8, median 1.8 μg/dL; P=0.35). After starting treatment, cTSH normalized after 2–4 weeks in 9 dogs and after 3 and 4 months in 2 without thyroxine supplementation.

Conclusions and Clinical Relevance

Evaluation of thyroid function in untreated dogs with HA can lead to misdiagnosis of hypothyroidism; treatment with glucocorticoids for up to 4 months can be necessary to normalize cTSH.     

Indication,management, and outcome of brachycephalic dogs requiring mechanical ventilation

Objectives – To evaluate the frequency, and need for mechanical ventilation (MV) in a population of brachycephalic dogs (BD) compared with non‐BD. Also, to describe the pre‐MV abnormalities, ventilator settings used, the cardiovascular and pulmonary monitoring results and complications encountered in the same BD population. In addition, we sought to identify factors associated with successful weaning and describe outcomes of BD requiring MV. Design – Retrospective observational study (1990–2008). Setting – University Small Animal Teaching Hospital. Animals – Fifteen BD managed with MV. Interventions – None. Measurements and Main Results – Signalment, indication for MV, ventilator settings, arterial blood gas values, duration of MV, complications, and outcome were recorded for each patient enrolled in study. BD were more likely to receive MV than non‐BD (P=0.036). Out of the 15 dogs that fulfilled the inclusion criteria 7 (47%) underwent MV for impending respiratory fatigue, 6 (40%) for hypoxemia and 2 for hypercapnea. The most common underlying disease was aspiration pneumonia. Duration of MV ranged from 2 to 240 hours (median 15 hours). Seven patients were weaned (47%). Seven dogs had a temporary tracheostomy tube and 5 of them (71%) were weaned. Dogs that were weaned had a significantly greater preweaning trial PaO₂/FiO₂ ratio than those that were not (359 ± 92 versus 210 ± 57 mm Hg, P=0.025). No significant difference for weaning success between dogs with and those without a tracheostomy was detected (P=0.132). The discharge rate was 27% (all from the respiratory fatigue group). Conclusion – Among all dogs admitted to ICU, BD were more likely to receive MV than non‐BD. Aspiration pneumonia was frequently identified as the underlying cause of respiratory compromise. The survival rate for BD undergoing MV was not markedly different from previous studies. Weaning of BD from MV may be facilitated by employing preemptive strategies such as performing tracheostomy tube placements.     

Serum concentrations of leptin and adiponectin in dogs with chronic kidney disease

BackgroundAn imbalance in adipokines is associated with the progression of chronic kidney disease (CKD) in humans. However, alterations in adipokines in dogs with CKD remain unclear.ObjectivesTo examine whether adipokine concentrations in serum differ between healthy dogs and dogs with CKD and to determine the correlation between serum adipokine concentrations and CKD severity in dogs.AnimalsTwenty dogs with CKD and 10 healthy dogs.MethodsIn this cross‐sectional study, serum concentrations of leptin, adiponectin, interleukin (IL)‐6, IL‐10, IL‐18, and tumor necrosis factor (TNF)‐α were measured in healthy dogs and dogs with CKD, which were classified according to the International Renal Interest Society guidelines.ResultsSerum leptin concentrations were positively correlated with systolic arterial blood pressure (r = .41), creatinine concentrations (r = .39), and symmetric dimethylarginine concentrations (r = .73). Serum adiponectin concentrations (median [range]) in CKD dogs with borderline or non‐proteinuric (20.25 [14.9‐45.8] ng/mL) were significantly higher than those in proteinuric CKD dogs (13.95 [6.4‐22.1] ng/mL; P = .01). Serum IL‐6 (median [range]; 43.27 [24.30‐537.30] vs 25.63 [6.83‐61.03] pg/mL; P = .02), IL‐18 (median [range]; 25.98 [11.52‐280.55] vs 10.77 [3.53‐38.45] pg/mL; P = .01), and TNF‐α (median [range]) concentrations (11.44 [8.54‐38.45] vs 6.105 [3.97‐30.68] pg/mL; P = .02) were significantly different between proteinuric and borderline or non‐proteinuric CKD dogs.Conclusions and Clinical Importanceleptin and adiponectin concentrations in serum might be associated with severity of CKD and proteinuria in dogs with CKD, respectively.     

Haemodynamic, electrocardiographic, electrophysiologic and pharmacokinetic activity of 4'-hydroxypropranolol in dogs

We determined the haemodynamic, electrocardiographic and electrophysiologic effects, and the pharmacokinetic properties of 4′-hydroxypropranolol (4′-OHP) by conducting three different experiments in dogs. In experiment 1 the plasma concentrations of 4′-OHP (mg/kg, i.v.) in pentobarbital anaesthetized dogs were determined by HPLC and pharmacokinetic parameter values were estimated. The terminal elimination half-life (t1/2) for 4′-OHP was 69.4 min, the apparent volume of distribution (V_d) was 3.39 L/kg and the total clearance (Cl_t) was 53.6 mL/min·kg. These data were subsequently used to calculate the loading and maintenance doses of 4′-OHP required to produce targeted steady-state plasma concentrations for 4′-OHP of 30, 60, 120, 240 and 480 ng/mL. In experiment 2 the haemodynamic and electrocardiographic effects for target plasma concentrations of 4′-OHP were determined in two groups of pentobarbital anaesthetized dogs, and beta-blocking activity was assessed by infusion or bolus doses of isoproterenol. The haemodynamic and electrocardiographic effects of the target plasma concentrations (30, 60, 120 ng/mL) of 4′-OHP were first determined in seven pentobarbital anaesthetized dogs (Group 1). Beta blocking activity was assessed by the infusion of 0.1 μg/kg/min isoproterenol. The infusion of 4′-OHP produced dose dependent decreases in heart rate, cardiac output, dP/dt_max, mean arterial pressure and left ventricular diastolic pressure. The PR interval of the lead II electrocardiogram increased and the QT_c interval decreased. These haemodynamic and electrocardiographic changes became apparent at plasma 4′-OHP concentrations equal to or greater than 30 ng/mL. Plasma concentrations of 4′-OHP equal to or greater than 30 ng/mL prevented the haemodynamic and electrocardiographic effects of isoproterenol infusion. In group 2 dogs, (seven dogs) the haemodynamic and electrocardiographic effects of target plasma concentrations (30, 60, 120, 240, 480 ng/mL) of 4′-OHP were evaluated and beta-blocking activity was assessed by the i.v. bolus administration of 1 and 4 μg/kg of isoproterenol. The infusion of 4′-OHP produced haemodynamic and electrocardiographic changes similar to those in group 1 dogs. In addition, the QRS duration of the electrocardiogram increased at plasma concentrations of 4′-OHP equal to or greater than 240 ng/mL. The haemodynamic and electrocardiographic effects of i.v. bolus dose administrations of 1 and 4 μg/kg isoproterenol were abolished by plasma concentrations of 4′-OHP equal to or greater than 240 ng/mL. In experiment 3 we determined the electrophysiologic effects of 10^?9 to 10^?5 mmol/L 4′-OHP on Tyrodes superfused bundles of canine Purkinje fibres. Action potential duration and the effective refractory period decreased at superfusate concentrations of 4′-OHP equal to or greater than 10^?7 mmol/L. Action potential overshoot, action potential total amplitude, the rate of rise of phase O (dV/dt) and spontaneous rate decreased at superfusage concentrations of 4′-OHP equal to or greater than 800 ng/mL. These studies demonstrate that: 1) 4′-OHP produces haemodynamic, electrocardiographic and electrophysiologic effects similar to those of other beta-blocking drugs in pentobarbital anaesthetized dogs; 2) the haemodynamic and electrocardiographic effects produced by 4′-OHP are     

Effect of antivenin dose on outcome from crotalid envenomation: 218 dogs (1988–2006)

Objective – To determine whether the dose of antivenin administered is associated with a difference in survival of crotalid‐envenomated dogs. A secondary objective was to determine whether other covariables affect survival. Design – Retrospective study (1988–2006). Setting – Private referral center and university small animal teaching hospital. Animals – Two hundred and eighteen dogs with evidence of crotalid envenomation and treatment with equine‐derived antivenin. Interventions – Administration of antivenin. Measurements and Main Results – Patient signalment, physical and clinicopathologic data at time of presentation, treatments, complications of antivenin therapy, length and cost of hospitalization, and outcome were recorded. Confidence intervals were determined for the difference in median number of vials administered and for median dosage for patients that lived versus died. Penalized logistic regression was performed to evaluate the effect of other covariables on survival. The median age of affected dogs was 3 years (range 6 w–12 y) with a median weight of 25.7 kg (range 1.95–86.4 kg). The median number of antivenin vials administered was 1.0 (range 1.0–10.0). Acute and chronic reactions were reported in 7% (16/218) and 0.9% (2/218) of dogs, respectively. Nine of 218 dogs (4.1%) died. The median number of vials administered to the nonsurvivors and survivors were 2.0 (range 1–5 vials) and 1.0 (range 1–10 vials), respectively. The median number of vials received was significantly different in dogs that died versus those that lived (P<0.05). Increased heart rate (P=0.02) and petechiation (P=0.04) were associated with decreased likelihood of survival, while diphenhydramine (P=0.02) and fluoroquinolone (P=0.046) administration was associated with increased likelihood of survival. The median duration of hospitalization was 1.0 day (range 2 h–22 d). The median cost of hospitalization was US$1592.00 (range US$267.20–US$6738.00). Conclusion – The administration of more vials of antivenin is potentially associated with negative outcome; however, a causal relationship has not been established. Controlled, prospective studies are needed to optimize antivenin administration.     

Single and multiple dose pharmacokinetics of a novel mirtazapine transdermal ointment in cats

Single and multiple dose pharmacokinetics (PK) of mirtazapine transdermal ointment applied to the inner ear pinna of cats were assessed. Study 1 was a randomized, cross‐over single dose study (n = 8). Cats were treated once with 0.5 mg/kg of mirtazapine transdermal ointment applied topically to the inner ear pinna (treatment) or administered orally (control) and then crossed over after washout. Plasma was collected predose and at specified intervals over 96 hr following dosing. Study 2 was a multiple dose study (n = 8). Cats were treated daily for 14 days with 0.5 mg/kg of mirtazapine transdermal ointment applied topically to the inner pinna. Plasma was collected on Day 13 predose and at specified intervals over 96 hr following the final dose. In Study 1, single transdermal administration of mirtazapine resulted in mean T_max = 15.9 hr, C_max = 21.5 ng/mL, AUC_0‐24 = 100 ng*hr/mL, AUC_0‐∞ = 260 ng*hr/mL and calculated half‐life = 26.8 hr. Single oral administration of mirtazapine resulted in mean T_max = 1.1 hr, C_max = 83.1 ng/mL, AUC_0‐24 = 377 ng*hr/mL, AUC_0‐∞ = 434 ng*hr/mL and calculated half‐life = 10.1 hr. Mean relative bioavailability (F) of transdermal to oral dosing was 64.9%. In Study 2, daily application of mirtazapine for 14 days resulted in mean T_max = 2.1 hr, C_max = 39.6 ng/mL, AUC_0‐24 = 400 ng*hr/mL, AUC_0‐∞ = 647 ng*hr/mL and calculated half‐life = 20.7 hr. Single and repeat topical doses of a novel mirtazapine transdermal ointment achieve measurable plasma concentrations in cats.     

Clinical pharmacokinetics and outcomes of oral fluconazole therapy in dogs and cats with naturally occurring fungal disease

This multi-institutional study was designed to determine the clinical pharmacokinetics of fluconazole and outcomes in client-owned dogs (n = 37) and cats (n = 35) with fungal disease. Fluconazole serum concentrations were measured. Pharmacokinetic analysis was limited to animals at steady state (≥72 hr of treatment). The mean (range) body weight in 31 dogs was 25.6 (2.8–58.2) kg and in 31 cats was 3.9 (2.4–6.1) kg included in pharmacokinetic analyses. The dose, average steady-state serum concentrations (C_SS), and oral clearance in dogs were 14.2 (4.5–21.3) mg/kg/d, 26.8 (3.8–61.5) µg/mL, and 0.63 ml min⁻¹ kg⁻¹, respectively, and in cats were 18.6 (8.2–40.0) mg/kg/d, 32.1 (1.9–103.5) µg/mL, and 0.61 ml min⁻¹ kg⁻¹, respectively. Random inter-animal pharmacokinetic variability was high in both species. Two dogs had near twofold increases in serum fluconazole when generic formulations were changed, suggesting lack of bioequivalence. Median C_SS for dogs and cats achieving clinical remission was 19.4 and 35.8 µg/ml, respectively. Starting oral doses of 10 mg/kg q12h in dogs and 50–100 mg total daily dose in cats are recommended to achieve median C_SS associated with clinical remission. Due to the large pharmacokinetic variability, individualized dose adjustments based on C_SS (therapeutic drug monitoring) and treatment failure should be considered.