A dose-finding,long-term study on the use of calcium chloride in saline solution as a method of nonsurgical sterilization in dogs: evaluation of the most effective concentration with the lowest risk

Background

Canine overpopulation is a global issue with serious health and welfare implications. Nonsurgical methods of sterilization could yield positive impacts on this problem, but no long-term data on such methods are available. The objective of the current investigation was to determine the effects of intratesticular injections of calcium chloride dihydrate (CaCl₂) in saline in dogs over a one year period. Five concentrations (0%, 10%, 20%, 30%, 60%) of CaCl₂ in saline were administered via intratesticular injection to groups of 10 dogs each. Total sperm count and motility, blood levels of testosterone, and side effects were examined at 0, 2, 6, and 12 months post-injection (PI). Testicular size and semen volume were examined at 0 and 12 months PI.

Results

Total sperm count, semen volume and testosterone showed significant dose-dependent decreases upon treatment with 10%-60% CaCl₂ compared with either the control group (0% CaCl₂) or baseline for each treatment group. Azoospermia was achieved for at least 12 months PI in 60% and 80% of treated dogs after administration of a 10% and 20% CaCl₂, respectively. Treatment with 30% or 60% CaCl₂ resulted in azoospermia in 100% of dogs, but more side effects were observed, while no side effects were noticed at lower doses. For each treatment group, testosterone levels had decreased an average of 35%-70% at 6 months following treatment. However, testosterone levels rebounded by the 12-month time point in all groups except the highest dosage group (60% CaCl₂), which remained at the low end of physiological range throughout the study. Sperm motility dropped to zero or near zero in all dogs treated with CaCl₂. Testicular size was significantly smaller at 12 months PI for all groups when compared to baseline.

Conclusions

This first long-term study confirms reports of the efficacy of CaCl₂ sterilization. However, at dosages free of adverse events, calcium chloride in saline may not provide permanent sterilization as previously believed. Future work should explore optimized solvents to increase the permanence of the well-tolerated 20% formulation.     

Pharmacokinetics of Total Thyroxine after Repeated Oral Administration of Levothyroxine Solution and its Clinical Efficacy in Hypothyroid Dogs

Background

Oral levothyroxine (l‐T₄) supplementation is commonly used to treat hypothyroid dogs.

Objectives

Investigate the plasma profile and pharmacokinetics of total thyroxine (tT₄) after PO administration of a l‐T₄ solution and its clinical efficacy in hypothyroid dogs.

Animals

Ten dogs with naturally occurring hypothyroidism.

Methods

After hypothyroidism diagnosis and supplementation with l‐T₄ solution PO q24h at 20 μg/kg BW for minimum 4 weeks, the plasma profile and pharmacokinetics of tT₄ were determined over 34 hours and the clinical condition of the dogs was evaluated.

Results

Before dosing for pharmacokinetic evaluation, mean tT₄ concentration was 23 ± 9 nmol/L. l‐T₄ was absorbed rapidly (t _max, 5 hours), reaching a mean maximal tT₄ concentration of 56 ± 11 nmol/L. The apparent terminal half‐life was 11.8 hours. Clinical signs of hypothyroidism improved or resolved in all dogs after 4 weeks of treatment. The dosage of 20 μg/kg PO q24h was judged appropriate in 5 dogs, and 4 dogs required slight increases (9–16%). Twice daily treatment, with a 30% increase in dosage, was necessary for 1 dog.

Conclusions and Clinical Importance

The pharmacokinetics of l‐T₄ in hypothyroid dogs was similar to that reported in healthy euthyroid dogs. Clinical and hormonal responses to l‐T₄ solution were rapid in all dogs. The starting dosage of 20 μg/kg PO q24h was suitable for maintenance supplementation in 50% of the dogs, minor dosage modification was required in 4 other dogs, and treatment q12h was required in 1 dog.     

Assessment of Clinical and Laboratory Variables as a Guide to Packed Red Blood Cell Transfusion of Euvolemic Anemic Dogs

Background

There are no standardized guidelines for determining the likelihood that euvolemic anemic dogs will benefit from transfusion of packed red blood cells (pRBC).

Objectives

To report clinical and laboratory variables of dogs receiving pRBC transfusion, which could guide transfusion of other anemic dogs.

Animals

Twenty‐four client‐owned anemic dogs receiving pRBC transfusion.

Methods

Prospective study; 30 transfusions assessed. Clinical findings (mucosal color, pulse quality, heart rate, respiratory rate, mentation/exercise tolerance) before and after transfusion were evaluated by the anemic dog clinical assessment score (ADCAS). Hemoglobin concentration, hematocrit, venous oxygen content (CvO₂), and lactate concentration were measured from blood samples taken before and after transfusion. These results were not used for case management.

Results

All ADCAS variables decreased significantly with transfusion (P < .001); the total score was ≥5/12 before transfusion, and ≤3/12 in all cases that were deemed to no longer require transfusion. Hematocrit and CvO₂ were <17% and <5 mL/dL, respectively, in 83% of cases before transfusion and hemoglobin concentration was <5.8 g/dL in 80%. Hemoglobin concentration, hematocrit, and CvO₂ increased significantly with transfusion (P < .001); lactate concentration decreased significantly (P = .006).

Conclusions and Clinical Importance

Clinical and laboratory variables improved significantly after transfusion of pRBC. By identifying how transfusion affected these variables, it was possible to recognize clinical (ADCAS) and laboratory (hemoglobin, CvO₂, lactate) variables, which could be useful in guiding the decision to transfuse dogs with similar presentations.     

Evaluation of the Effects of a Therapeutic Renal Diet to Control Proteinuria in Proteinuric Non‐Azotemic Dogs Treated with Benazepril

Background

Angiotensin‐converting enzyme inhibitors (ACEIs) are currently used to control proteinuria in dogs with chronic kidney disease. Renal diets (RDs) have beneficial effects in the management of azotemic dogs, but its role in proteinuric non‐azotemic (PNAz) dogs has been poorly documented.

Hypothesis

Administration of a RD to PNAz dogs treated with benazepril (Be) improves proteinuria control compared with the administration of a maintenance diet (MD).

Animals

Twenty‐two PNAz (urine protein/creatinine ratio [UPC] >1) dogs.

Methods

Randomized open label clinical trial design. Dogs were assigned to group‐MD (5.5 g protein/100 kcal ME)/Be or to group‐RD (3.7 g protein/100 kcal ME)/Be group during 60 days. Dogs with serum albumin (Alb) <2 g/dL received aspirin (1 mg/kg/12 hours). A physical examination, systolic blood pressure (SBP) measurement, complete blood count (CBC), biochemistry panel, urinalysis, and UPC were performed at day 0 (D0) and day 60 (D60).

Results

At D0, there were no significant differences between groups in the evaluated variables. During the study, logUPC (geometric mean (95% CI) and SBP (mean±SD mmHg) significantly decreased (paired t‐test, P = 0.001) in Group‐RD (logUPC_D0 = 3.16[1.9–5.25]; UPC_D60 = 1.20 [0.59–2.45]; SBP_D0 = 160 ± 17.2; SBP_D60 = 151 ± 15.8), but not in Group‐MD (UPC_D0 = 3.63[2.69–4.9]; UPC_D60 = 2.14 [0.76–6.17]; SBP_D0 = 158 ± 14.7; SBP_D60 = 153 ± 11.5). However, RM‐ANOVA test did not confirm that changes were consequence of dietary modification. Weight and Alb concentration did not change significantly in any group.

Conclusion and Clinical Relevance

The administration of a RD to PNAz dogs treated with Be might help to control proteinuria and SBP compared with the administration of a MD, without inducing clinically detectable malnutrition, but more studies are warranted.     

The Effect of Tramadol and Indomethacin Coadministration on Gastric Barrier Function in Dogs

Background

Tramadol is a centrally acting analgesic that is often used in conjunction with nonsteroidal anti‐inflammatory drugs (NSAIDs). The effect of coadministration of tramadol and indomethacin on gastric barrier function in dogs is unknown.

Hypothesis/Objectives

That coadministration of a nonselective NSAID (indomethacin) and tramadol would decrease recovery of barrier function as compared with acid‐injured, indomethacin‐treated, and tramadol‐treated mucosa.

Animals

Gastric mucosa of 10 humanely euthanized shelter dogs.

Methods

Ex vivo study. Mounted gastric mucosa was treated with indomethacin, tramadol, or both. Gastric barrier function, prostanoid production, and cyclooxygenase expression were quantified.

Results

Indomethacin decreased recovery of transepithelial electrical resistance after injury, although neither tramadol nor the coadministration of the two had an additional effect. Indomethacin inhibited production of gastroprotective prostanoids prostaglandin E₂ (acid‐injured PGE ₂: 509.3 ± 158.3 pg/mL, indomethacin + acid injury PGE ₂: 182.9 ± 93.8 pg/mL, P < .001) and thromboxane B₂ (acid‐injured TXB ₂: 233.2 ± 90.7 pg/mL, indomethacin + acid injury TXB ₂: 37.9 ± 16.8 pg/mL, P < .001), whereas tramadol had no significant effect (PGE ₂ P = .713, TXB ₂ P = .194). Neither drug had an effect on cyclooxygenase expression (COX‐1 P = .743, COX‐2 P = .705). Acid injury induced moderate to marked epithelial cell sloughing, which was unchanged by drug administration.

Conclusions and Clinical Importance

There was no apparent interaction of tramadol and a nonselective cyclooxygenase in this ex vivo model. These results suggest that if there is an adverse interaction of the 2 drugs in vivo, it is unlikely to be via prostanoid inhibition.     

Evaluation of total oxidant and antioxidant status in dogs under different CO2 pneumoperitoneum conditions

Background

The induction of the pneumoperitoneum increases intraabdominal pressure (IAP), causing splanchnic ischemia, whereas its deflation normalizes IAP and splanchnic blood flow. We investigated the oxidant-antioxidant status of dogs who underwent low pressure (7 mm Hg), standard pressure (12 mm Hg), and high pressure (15 mm Hg) pneumoperitoneum.

Results

Twenty-four beagle dogs (12 males and 12 females), 4–6 years old, weighing 8–11 kg were used. The animals were assigned to one of four groups (n = 6 dogs). Group 1 served as a control; these animals received only anaesthesia for 90 min. In groups 2, 3 and 4, intra-abdominal pressure was increased to 7, 12 and 15 mmHg, respectively, and maintained for 60 min. Total oxidant status (TOS) and total antioxidant status (TAS) were determined in venous blood samples. The percentage ratio of TOS to TAS provided an oxidative stress index (OSI).No significant difference in TOS levels was found among the groups. A significant decrease in TAS levels and an increase in OSI levels were observed at 90 min and 24 h of pneumoperitoneum deflation within group 4. No differences were found among the groups.

Conclusions

A high pressure pneumoperitoneum induced significant changes in TAS and OSI. In addition, TOS and TAS levels are useful markers for evaluating changes in the oxidative status caused by a pneumoperitoneum during laparoscopy. Furthermore, a low-pressure pneumoperitoneum could attenuate oxidative stress induced by CO₂ insufflation in dogs.     

Effect of Trilostane and Mitotane on Aldosterone Secretory Reserve in Dogs with Pituitary‐Dependent Hyperadrenocorticism

Background

Maximal aldosterone secretion in healthy dogs occurs 30 minutes postadrenocorticotropin (ACTH; 5 μg/kg IV) stimulation. The effect of trilostane and mitotane on aldosterone at that time is unknown.

Objectives

To assess the effect of trilostane and mitotane in dogs with pituitary‐dependent hyperadrenocorticism on aldosterone secretory reserve. To determine if aldosterone concentration correlates with electrolyte concentrations.

Animals

Serum collected from 79 client‐owned dogs and 33 stored samples.

Methods

Client‐owned dogs had ACTH stimulation tests with cortisol concentrations measured at 0 and 60 minutes and aldosterone concentrations measured at 0, 30, and 60 minutes. Stored samples had aldosterone concentrations measured at 0 and 60 minutes. Ten historical clinically healthy controls were included. All had basal sodium and potassium concentrations measured.

Results

The aldosterone concentrations in the mitotane‐ and trilostane‐treated dogs at 30 and 60 minutes post‐ACTH were significantly lower than in clinically healthy dogs; no significant difference was detected in aldosterone concentration between 30 and 60 minutes in treated dogs. However, a significantly higher percentage of dogs had decreased aldosterone secretory reserve detected at 30 minutes than at 60 minutes. At 30 minutes, decreased secretory reserve was detected in 49% and 78% of trilostane‐ and mitotane‐treated dogs, respectively. No correlation was detected between aldosterone and serum electrolyte concentrations.

Conclusions and Clinical Importance

Decreased aldosterone secretory reserve is common in trilostane‐ and mitotane‐treated dogs; it cannot be predicted by measurement of serum electrolyte concentrations. Aldosterone concentration at 30 minutes post‐ACTH stimulation identifies more dogs with decreased aldosterone secretory reserve than conventional testing at 60 minutes.     

Plasma and Urine Neutrophil Gelatinase–Associated Lipocalin (NGAL) in Dogs with Acute Kidney Injury or Chronic Kidney Disease

Background

Neutrophil gelatinase–associated lipocalin (NGAL) is a protein that is used in human medicine as a real‐time indicator of acute kidney injury (AKI).

Hypothesis

Dogs with AKI have significantly higher plasma NGAL concentration and urine NGAL‐to‐creatinine ratio (UNCR) compared with healthy dogs and dogs with chronic kidney disease (CKD).

Animals

18 healthy control dogs, 17 dogs with CKD, and 48 dogs with AKI.

Methods

Over a period of 1 year, all dogs with renal azotemia were prospectively included. Urine and plasma samples were collected during the first 24 hours after presentation or after development of renal azotemia. Plasma and urine NGAL concentrations were measured with a commercially available canine NGAL Elisa Kit (Bioporto® Diagnostic) and UNCR was calculated. A single‐injection plasma inulin clearance was performed in the healthy dogs.

Results

Median (range) NGAL plasma concentration in healthy dogs, dogs with CKD, and AKI were 10.7 ng/mL (2.5–21.2), 22.0 ng/mL (7.7–62.3), and 48.3 ng/mL (5.7–469.0), respectively. UNCR was 2 × 10⁻⁸ (0–46), 1,424 × 10⁻⁸ (385–18,347), and 2,366 × 10⁻⁸ (36–994,669), respectively. Dogs with renal azotemia had significantly higher NGAL concentrations and UNCR than did healthy dogs (P < .0001 for both). Plasma NGAL concentration was significantly higher in dogs with AKI compared with dogs with CKD (P = .027).

Conclusions and Clinical Importance

Plasma NGAL could be helpful to differentiate AKI from CKD in dogs with renal azotemia.     

Levetiracetam Rectal Administration in Healthy Dogs

Background

Levetiracetam is used to manage status epilepticus (SE) and cluster seizures (CS) in humans. The drug might be absorbed after rectal administration and could offer a practical adjunct to rectal administration of diazepam in managing SE and CS.

Hypothesis

Levetiracetam is rapidly absorbed after rectal administration in dogs and maintains target serum concentrations for at least 9 hours.

Animals

Six healthy privately owned dogs between 2 and 6 years of age and weighing 10–20 kg.

Methods

Levetiracetam (40 mg/kg) was administered rectally and blood samples were obtained immediately before (time zero) and at 10, 20, 40, 60, 90, 180, 360, and 540 minutes after drug administration. Dogs were observed for signs of adverse effects over a 24‐hour period after drug administration.

Results

C _LEV at 10 minutes was 15.3 ± 5.5 μg/mL (mean, SD) with concentrations in the target range (5–40 μg/mL) for all dogs throughout the sampling period. C _max (36.0 ± 10.7 μg/mL) and T _max (103 ± 31 minutes) values were calculated and 2 disparate groups were appreciated. Dogs with feces in the rectum at the time of drug administration had lower mean C _max values (26.7 ± 3.4 μg/mL) compared with those without (45.2 ± 4.4 μg/mL). Mild sedation was observed between 60 and 90 minutes without other adverse effects noted.

Conclusions and Clinical Importance

This study supports the use of rectally administered levetiracetam in future studies of clinical effectiveness in the management of epileptic dogs.     

Cranial versus caudal thoracic epidural anesthesia using three volumes of lidocaine in conscious Beagle dogs

Objective

To compare the effects of epidural injection of three volumes of lidocaine injected at the third (T3) or eleventh thoracic vertebra (T11) in conscious dogs to induce thoracic epidural anesthesia (TEA) and to measure the epidural dispersion of iohexol under similar conditions.

Comparison of Adrenocorticotropic Hormone Stimulation Test Results Started 2 versus 4 Hours after Trilostane Administration in Dogs with Naturally Occurring Hyperadrenocorticism

Background

Trilostane medical treatment of naturally occurring hyperadrenocorticism (NOH) in dogs is common, as is use of the adrenocorticotropic hormone (ACTH) stimulation test (ACTHst) in monitoring response to treatment. There is uncertainty regarding when the ACTHst should be started relative to time of trilostane administration.

Objective

To compare ACTHst results in dogs being treated for NOH with trilostane when the test is begun 2 versus 4 hours after trilostane administration.

Animals

Twenty‐one privately owned dogs with NOH, each treated with trilostane for at least 30 days.

Methods

Each dog had 2 ACTHst completed, 1 started 2 hours and the other 4 hours after trilostane administration. The second test was started no sooner than 46 hours and no later than 74 hours after the first.

Results

For all 21 dogs, the mean post‐ACTH serum cortisol concentration from tests started 2 hours after trilostane administration (5.4 ± 3.7 μg/dL) was significantly lower (P = .03) as compared with results from the tests started 4 hours after administration (6.5 ± 4.5 μg/dL).

Conclusions

Results of ACTHst started at different times yield significantly different results. Dogs with NOH, treated with trilostane, and monitored with ACTHst results should have all of their subsequent ACTHst tests begun at or about the same time after trilostane administration.     

Long‐Term Outcome in Dogs with Patent Ductus Arteriosus: 520 Cases (1994–2009)

Background

Published information regarding survival and long‐term cardiac remodeling after patent ductus arteriosus (PDA) closure in dogs is limited.

Objectives

To report outcome and identify prognostic variables in dogs with PDA, and to identify risk factors for persistent remodeling in dogs with a minimum of 12 months of follow‐up after closure.

Animals

Five hundred and twenty client‐owned dogs.

Methods

Retrospective review of medical records of 520 dogs with PDA. Outcome was determined by contacting owners and veterinarians. Dogs with PDA closure and ≥ 12 months of follow‐up were asked to return for a re‐evaluation.

Results

In multivariable analysis of 506 dogs not euthanized at the time of diagnosis, not having a PDA closure procedure negatively affected survival (HzR = 16.9, P < .001). In 444 dogs undergoing successful PDA closure, clinical signs at presentation (HzR = 17, P = .02), concurrent congenital heart disease (HD) (HzR = 4.8, P = .038), and severe mitral regurgitation (MR) documented within 24 hours of closure (HzR = 4.5, P = .028) negatively affected survival. Seventy‐one dogs with ≥ 12 months follow‐up demonstrated a significant reduction in radiographic and echocardiographic measures of heart size (P = 0) and increased incidence of acquired HD (P = .001) at re‐evaluation. Dogs with increased left ventricular size and low fractional shortening at baseline were more likely to have persistent remodeling at re‐evaluation.

Conclusions and Clinical Importance

Patent ductus arteriosus closure confers important survival benefits and results in long‐term reverse remodeling in most dogs. Clinical signs at presentation, concurrent congenital HD, and severe MR negatively affect survival. Increased left ventricular systolic dimensions and systolic dysfunction at baseline correlated significantly with persistent remodeling.     

Intratesticular lidocaine reduces the response to surgical castration in dogs

ObjectiveTo investigate whether intratesticular injection of lidocaine pre-surgery would reduce the intraoperative responses to elective castration in dogs.Study designDouble-blinded, randomized, controlled, prospective clinical study.AnimalsForty-two client-owned dogs weighing 2.2–38.4 kg and aged between 4.5 and 56 months.MethodsGroup L dogs received an intratesticular injection of 2% lidocaine (2 mg kg^?1) and Group S an identical volume of saline prior to surgery. Premedication was with acepromazine and morphine intramuscularly. Anaesthesia was induced with propofol intravenously and maintained with isoflurane vaporized in oxygen. Heart rate (HR), mean arterial pressure (MAP), respiratory rate (f_R), end-tidal isoflurane (Fe′ISO) and carbon dioxide concentrations, oxygen saturation and ECG were monitored during surgery. Fe′ISO was maintained at 1.0 ± 0.1%. Supplemental propofol was given in response to gross movement.ResultsGroup L had significantly lower maximum values for both HR and MAP. Group L displayed significantly smaller increases in HR during exteriorization of the first testis than Group S. There was an overall significant difference in MAP between groups during all surgical events (p = 0.041) and time points (p = 0.002). In univariate analysis, Group L showed significantly less changes in MAP during skin incision, exteriorization of the first testis and clamping of both spermatic cords. Group S reached its highest f_R significantly earlier. Group L (eight dogs) required additional propofol 33 ± 18 minutes after the start of surgery and Group S (seven dogs) at 19 ± 17 minutes; this difference was not statistically significant. Seven dogs in Group L and 12 dogs in Group S required rescue analgesia with morphine (GCMPS-SF score ≥6); this difference was not statistically significant. No adverse effects were reported postoperatively.Conclusions and clinical relevanceBased on this study, the authors recommend the use of intratesticular lidocaine for surgical castration in dogs.     

Treatment of canine generalized demodicosis associated with hyperadrenocorticism with spot-on moxidectin and imidacloprid

Background

Canine generalized demodicosis associated with hyperadrenocorticism is often problematic and might be intractable. The aim of this study was to report the efficacy of a weekly application of spot-on moxidectin/imidacloprid in dogs with hyperadrenocorticism and secondary generalized demodicosis.

Methods

Dogs with hyperadrenocorticism and secondary generalized demodicosis were included. The condition of hyperadrenocorticism was treated and stabilized with trilostane before and throughout the study period in all dogs.

Results

Average total live adult mite counts before treatment and after four, eight and 12 weeks of spot-on moxidectin/imidacloprid (2.5/10 mg/kg) applications were 20.1 ± 6.3 (range, 13–33), 0.5 ± 0.7 (range, 0–2; 6/11 were negative), 0.2 ± 0.4 (range, 0–1; 9/11 were negative), 0.2 ± 0.4 (range, 0–1; 9/11 were negative) and 0.1 ± 0.3 (range, 0–1; 10/11 were negative) respectively; this difference was significant (P < 0.001). Ten of 11 dogs (90.1%) achieved clinical remission, as demonstrated by the absence of demodectic mites at any life stage at monthly scrapings for eight consecutive weeks, and maintained remission throughout the 12-month follow-up period.

Conclusion

The weekly application of spot-on moxidectin/imidacloprid appeared to be effective and safe against generalized adult onset canine demodicosis associated with hyperadrenocorticism.     

Short‐ and Long‐Term Cure Rates of Short‐Duration Trimethoprim‐Sulfamethoxazole Treatment in Female Dogs with Uncomplicated Bacterial Cystitis

Background

Long‐duration beta‐lactam antibiotics are used for empirical treatment in female dogs with uncomplicated bacterial cystitis. However, women with bacterial cystitis are treated with short‐duration potentiated sulfonamides because longer courses of beta‐lactams result in lower cure and higher recurrence rates.

Hypothesis/Objectives

Short‐duration potentiated sulfonamide treatment is more efficacious than long‐duration beta‐lactam treatment in achieving clinical and microbiological cures in female dogs with uncomplicated bacterial cystitis.

Animals

Thirty‐eight client‐owned female dogs.

Methods

Randomized, double‐blinded, placebo‐controlled clinical trial. Dogs were treated with TMP‐SMX (15 mg/kg PO q12h for 3 days followed by a placebo capsule PO q12h for 7 days; Group SDS; n = 20) or cephalexin (20 mg/kg PO q12h for 10 days; Group LDBL; n = 18). Dogs were monitored for clinical and microbiological cure during treatment and at short‐ and long‐term follow‐up.

Results

No statistically significant differences were found between treatment groups in clinical cure rates after 3 days of treatment (89% SDS, 94% LDBL; P = 1.00) and 4 days (85% SDS, 72% LDBL; P = .44) or >30 days (50% SDS, 65% LDBL; P = .50) after conclusion of treatment or in microbiological cure rates 4 days (59% SDS, 36% LDBL; P = .44) or >30 days (44% SDS, 20% LDBL; P = .40) after conclusion of treatment.

Conclusions and Clinical Importance

We did not identify a difference in cure rates between short‐duration sulfonamide and long‐duration beta‐lactam treatments in female dogs with uncomplicated cystitis. Long‐term cure rates in both treatment groups were low. In some female dogs, “uncomplicated” bacterial cystitis may be more complicated than previously recognized.     

Influence of Beta Blockers on Survival in Dogs with Severe Subaortic Stenosis

Background

Subaortic stenosis (SAS) is one of the most common congenital cardiac defects in dogs. Severe SAS frequently is treated with a beta adrenergic receptor blocker (beta blocker), but this approach largely is empirical.

Objective

To determine the influence of beta blocker treatment on survival time in dogs with severe SAS.

Methods

Retrospective review of medical records of dogs diagnosed with severe, uncomplicated SAS (pressure gradient [PG] ≥80 mmHg) between 1999 and 2011.

Results

Fifty dogs met the inclusion criteria. Twenty‐seven dogs were treated with a beta blocker and 23 received no treatment. Median age at diagnosis was significantly greater in the untreated group (1.2 versus 0.6 years, respectively; P = .03). Median PG at diagnosis did not differ between the treated and untreated groups (127 versus 121 mmHg, respectively; P = .2). Cox proportional hazards regression was used to identify the influence of PG at diagnosis, age at diagnosis, and beta blocker treatment on survival. In the all‐cause multivariate mortality analysis, only age at diagnosis (P = .02) and PG at diagnosis (P = .03) affected survival time. In the cardiac mortality analysis, only PG influenced survival time (P = .03). Treatment with a beta blocker did not influence survival time in either the all‐cause (P = .93) or cardiac‐cause (P = .97) mortality analyses.

Conclusions

Beta blocker treatment did not influence survival in dogs with severe SAS in our study, and a higher PG at diagnosis was associated with increased risk of death.     

Serum Adipokine Concentrations in Dogs with Naturally Occurring Pituitary‐Dependent Hyperadrenocorticism

Background

An excess of intra‐abdominal fat is observed frequently in dogs with hyperadrenocorticism (HAC). Adipokine dysregulation is a possible cause of complications related to visceral obesity, but little information is available on adipokine in dogs with naturally occurring HAC.

Objectives

To examine the differences in the circulating adipokines concentrations in overweight dogs with and without pituitary‐dependent HAC (PDH).

Animals

Thirty healthy dogs and 15 client‐owned dogs with PDH.

Methods

Case–controlled observational study, which enrolled 15 overweight dogs diagnosed with PDH and 30 otherwise healthy dogs of similar body condition score. Nine of 15 dogs with PDH were treated with low‐dose trilostane twice daily and reassessed after treatment.

Results

The serum leptin (P < .0001) and insulin (P < .0001) concentrations were significantly higher in the PDH group (leptin, 22.8 ± 8.8 [mean ± SD]; insulin, 9.1 ± 6.1) than the healthy group (leptin, 4.9 ± 3.7; insulin, 1.9 ± 0.9). However, there were no significant differences in the adiponectin, resistin, tumor necrosis factor (TNF)‐α, interleukin (IL)‐1β, IL‐6, IL‐10, and IL‐18 levels between the 2 groups. In the PDH group, the serum cortisol concentrations had a linear association with the leptin concentrations, and there were significant decreases in the leptin (P = .0039) and insulin (P = .0039) levels after trilostane treatment. However, the leptin and insulin levels remained higher after trilostane treatment than in healthy control dogs with similar body condition score.

Conclusions and Clinical Importance

Hypercortisolemia in dogs with PDH might upregulate the circulating leptin levels. However, a large population‐based study will be necessary to determine whether the upregulation of leptin is involved directly with the complications caused by HAC.     

Discrepancies in Identification of Left Atrial Enlargement Using Left Atrial Volume versus Left Atrial‐to‐Aortic Root Ratio in Dogs

Background

Left atrial size is prognostically important in dogs with myxomatous mitral valve disease (MMVD).

Hypothesis/Objectives

To compare the level of agreement in identification of left atrial enlargement (LAE) between the left atrial‐to‐aortic root ratio (LA : Ao) and left atrial volume using the biplane area‐length method indexed to body weight (LA Vol/BW).

Animals

Sixty dogs with MMVD and 22 normal dogs were prospectively studied with 2‐dimensional echocardiography.

Methods

The upper limit of normal for LA Vol/BW was defined as 1.1 mL/kg. LA : Ao was deemed normal if ≤1.5. To define overall disease severity, each dog was assigned a mitral regurgitation severity score (MRSS) based on echocardiographic parameters that did not include left atrial size. ACVIM staging also was utilized.

Results

Of 60 affected dogs, 20 were ACVIM Stage B1, 25 were Stage B2, and 15 were Stage C. LA Vol/BW identified LAE in 12 cases in which LA : Ao was normal; 7 of these were Stage B1 and 5 were Stage B2. This diagnostic disagreement was significant (P = .00012). Of the 12 cases in which diagnostic discrepancies were identified, 5/5 of the B2 dogs and 3/7 B1 dogs had a moderate MRSS, whereas 4/7 B1 dogs had a mild MRSS. No diagnostic discrepancies between LA : Ao and LA Vol/BW were apparent in dogs with a severe MRSS.

Conclusions and Clinical Importance

This study shows evidence of diagnostic disagreement between LA : Ao and LA Vol/BW for assessment of LAE. LA Vol/BW may be superior to LA : Ao for identification of mild LAE.     

The relative plasma availabilities of ivermectin in reindeer (Rangifer tarandus tarandus) following subcutaneous and two different oral formulation applications

Background

Overwintering (breeding) reindeer (Rangifer tarandus tarandus) are commonly treated with ivermectin against parasitic infestations once yearly in autumn-winter roundups. The only preparations registered to reindeer are those for subcutaneous injection. However, also oral extra-label ivermectin administration is used. Twenty-six, 8-month-old reindeer calves were randomly allocated into three groups. Group 1 (n = 9) received oral ivermectin mixture (Ivomec® vet mixt. 0.8 mg/ml, oral ovine liquid drench formulation), Group 2 (n = 9) oral ivermectin paste (Ivomec® vet 18.7 mg/g equine paste), and Group 3 (n = 8) subcutaneous injection of ivermectin (Ivomec® 10 mg/ml vet inj.), each group at a dose of 200 μg/kg body weight. Blood samples were collected at treatment and at days 1, 2, 3, 6, 9 and 16 post treatment. Plasma concentrations of ivermectin were determined by high-pressure liquid chromatography (HPLC) with fluorescence detection.

Results

The peak plasma concentration (C_max) was reached by 2 days after each treatment. The C_max and Area Under Curve (AUC) differed significantly between the groups: C_max was 30.2 ± 3.9, 14.9 ± 5.7 and 63.1 ± 13.1 ng/ml, and AUC_∞ was 2881 ± 462, 1299 ± 342 and 6718 ± 1620 ng*h/ml for groups 1, 2 and 3, respectively (mean ± standard deviation).

Conclusions

The differences in plasma concentrations of ivermectin are concomitant with earlier observed differences in antiparasitic efficacy, which discounts the use of the equine paste in reindeer in favour of the oral ovine liquid drench formulation, or preferably, the reindeer-registered subcutaneous injection formulation.     

Effect of Trilostane on Hormone and Serum Electrolyte Concentrations in Dogs with Pituitary‐Dependent Hyperadrenocorticism

Background

The effects of trilostane on key hormones and electrolytes over 24 hours in dogs with pituitary‐dependent hyperadrenocorticism (PDH) are unknown.

Objectives

To determine the plasma concentration of cortisol, endogenous adrenocorticotropic hormone (ACTH), aldosterone, sodium, potassium, and ionized calcium concentrations, and plasma renin activity over a 24‐hour period after administration of trilostane to dogs with well‐controlled PDH.

Animals

Nine dogs (mean age 9.3 ± 0.67 years, mean weight 31.9 ± 6.4 kg) with confirmed PDH.

Methods

Prospective study. Thirty days after the first administration of trilostane, blood samples were taken at −30, 0 (baseline), 15, 30, 60, and 90 minutes, and 2, 3, 4, 6, 8, 12, 16, 20, and 24 hours after administration of trilostane and plasma concentration of cortisol, endogenous ACTH, aldosterone, sodium, potassium, ionized calcium, and renin activity were determined.

Results

Cortisol concentrations decreased significantly (P < .001) 2–4 hours after trilostane administration. From baseline, there was a significant (P < .001) increase in endogenous ACTH concentrations between hours 3–12, a significant increase (P < .001) in aldosterone concentration between hours 16–20, and a significant (P < .001) increase in renin activity between hours 6–20. Potassium concentration decreased significantly (P < .05) between hours 0.5–2.

Conclusion and Clinical Importance

Treatment with trilostane did not cause clinically relevant alterations in plasma aldosterone and potassium concentration. Results suggest that in dogs with PDH, the optimal time point for an ACTH‐stimulation test to be performed is 2–4 hours after trilostane dosing. Future studies are necessary to establish interpretation criteria for a 2‐ to 4‐hour postpill ACTH‐stimulation test.