Doppler Ultrasonographic Assessment of Abdominal Aortic Flow to Evaluate the Hemodynamic Relevance of Left-to-Right Shunting Patent Ductus Arteriosus in Dogs.

In this multicenter, prospective, observational study, abdominal aortic flow was examined with pulsed-wave Doppler ultrasound in dogs with a left-to-right shunting patent ductus arteriosus (PDA) and in apparently healthy dogs. Forty-eight dogs with a PDA and 35 controls were included. In the dogs with a PDA, 37/48 had hemodynamically significant PDAs (hsPDAs) while 11/48 had non-hsPDAs, based on the presence or absence of echocardiographic signs of left-sided volume overload, respectively. In 12 dogs (4/35 control dogs, 7/37 dogs with an hsPDA and 1/11 dogs with a non-hsPDA), the diastole was too short to visualize the end-diastolic flow. Antegrade end-diastolic flow was observed in 30/35 controls and 6/11 dogs with a non-hsPDA. Absent end-diastolic flow was observed in 1/35 control dogs and 3/11 dogs with a non-hsPDA. Retrograde end-diastolic flow was observed in 30/37 dogs with an hsPDA and 1/11 dogs with a non-hsPDA. Twenty-one dogs (15 with an hsPDA and 6 with a non-hsPDA) were reassessed after PDA closure, and, in 19/21, end-diastolic flow was visualized: 17/19 showed an antegrade flow, 1/19 an absent flow and 1/19 a retrograde flow. Sensitivity and specificity of retrograde end-diastolic flow for detection of hsPDAs were 100% and 90%, respectively. In conclusion, ultrasonographic assessment of abdominal aortic flow was feasible in dogs with PDA. However, end-diastolic flow was not always visualized. The presence of a retrograde end-diastolic flow was an accurate finding for discriminating hsPDAs and non-hsPDAs.

Genetic Variants at the Nebulette Locus Are Associated with Myxomatous Mitral Valve Disease Severity in Cavalier King Charles Spaniels.

The most common cardiovascular disease in domestic dogs is myxomatous mitral valve disease (MMVD), accounting for 75% of all cardiac disease. An increase in age is generally associated with increased incidence of the disease, but Cavalier King Charles Spaniels (CKCS) exhibit an unusually high prevalence of early-onset MMVD, and thus, potentially greater cardiac morbidity and mortality compared to other breeds. Previous research has suggested that selected candidate risk alleles for MMVD are fixed in CKCSs, including six locations within the Nebulette (NEBL) gene on CFA2. The current study analysed genotypes of 180 Australian CKCSs at the identified risk loci. Of these, 178 were phenotyped for severity of disease by echocardiographic measurements of left atrium to aortic root ratio (LA:Ao) and weight normalised left ventricular end diastolic diameter (LVIDdN). Genotyping array markers correctly predicted the genotype at the risk-variant loci in the CKCS population, and the NEBL1, NEBL2 and NEBL3 variants were observed to be in perfect linkage disequilibrium in this cohort. The CKCS cohort included 6/178 dogs being heterozygous for the protective/wild-type alleles at the NEBL locus. The mean LA:Ao and LVIDdN scores of these dogs heterozygous at NEBL1-3 variants were significantly smaller, and with significantly lower variance compared to age-matched CKCSs that were homozygous for risk alleles. The lower cardiac measurements in the heterozygous dogs indicate a significantly reduced risk of severe MMVD disease. Our analysis suggests that despite relative fixation of the NEBL risk alleles, healthy reference alleles at NEBL1-3 exist in low frequency in the CKCS breed and can be used to reduce MMVD severity and mortality.

Evaluation of pulsatile plasma concentrations of growth hormone in healthy dogs and dogs with dilated cardiomyopathy.

OBJECTIVE: To evaluate plasma concentrations of growth hormone (GH) and insulin-like growth factor I (IGF-I) in healthy dogs and large-breed dogs with dilated cardiomyopathy (DCM). ANIMALS: 8 dogs with DCM and 8 healthy control dogs of comparable age and body weight. PROCEDURES: Blood samples for determination of the pulsatile plasma GH profile were collected from all dogs at 10-minute intervals between 8:00 am and 8:00 pm. Plasma IGF-I concentration was determined in the blood sample collected at 8:00 am. RESULTS: No significant differences in plasma IGF-I concentrations, basal plasma GH concentration, GH pulse frequency, area under the curve above the zero line and above the baseline for GH, and GH pulse amplitude were found between dogs with DCM and control dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Results did not provide evidence for an association between DCM in dogs and a reduction in plasma concentrations of GH or IGF-I. Therefore, reported positive effects of GH administration are most likely attributable to local effects in the heart.

Bioprosthetic interstrut distance subtending the preserved anterior mitral leaflet mitigates left ventricular outflow tract obstruction.

Background: The anterior mitral leaflet (AML) contributes to left ventricular (LV) function but is normally excised at the time of a bioprosthetic valve insertion. This study aimed to investigate methods of safely retaining the AML at the time of mitral valve replacement. Methods: Five adult sheep (57 ± 3.8 kg) each underwent 3 insertions of a bioprosthetic mitral valve (asymmetric interstrut sectors) alternating the wide and narrow interstrut distance under the AML. Each insertion was performed on normothermic beating-heart cardiopulmonary bypass, with full retention of the native valve. After each valve insertion, continuous measurements of LV and aortic pressures were recorded with echocardiographic assessment of mitral valve function. If LV outflow tract obstruction (LVOTO) was not seen on the resumption of normal cardiac output, a bolus of adrenaline was given to precipitate it. Results: Thirteen of 15 valve insertions resulted in LVOTO caused by systolic anterior motion (SAM), independent of valve orientation. The wide interstrut distance subtending the AML was associated with a greater requirement for inotropic stress to precipitate an obstruction and was associated with late systolic rather than holosystolic obstruction. Conclusions: The predisposition to and nature of LVOTO due to SAM were associated with the bioprosthetic valve interstrut distance subtending the fully retained AML and may explain the survival differences in such patients. This model represents an effective method for research into prevention of LVOTO following mitral valve replacement with preservation of the native valve.

A large deletion on CFA28 omitting ACSL5 gene is associated with intestinal lipid malabsorption in the Australian Kelpie dog breed.

Inborn errors of metabolism are genetic conditions that can disrupt intermediary metabolic pathways and cause defective absorption and metabolism of dietary nutrients. In an Australian Kelpie breeding population, 17 puppies presented with intestinal lipid malabsorption. Juvenile dogs exhibited stunted postnatal growth, steatorrhea, abdominal distension and a wiry coat. Using genome-wide association analysis, an associated locus on CFA28 (Praw = 2.87E-06) was discovered and validated in a closely related population (Praw = 1.75E-45). A 103.3 kb deletion NC_006610.3CFA28:g.23380074_23483377del, containing genes Acyl-CoA Synthetase Long Chain Family Member 5 (ACSL5) and Zinc Finger DHHC-Type Containing 6 (ZDHHC6), was characterised using whole transcriptomic data. Whole transcriptomic sequencing revealed no expression of ACSL5 and disrupted splicing of ZDHHC6 in jejunal tissue of affected Kelpies. The ACSL5 gene plays a key role in long chain fatty acid absorption, a phenotype similar to that of our affected Kelpies has been observed in a knockout mouse model. A PCR-based diagnostic test was developed and confirmed fully penetrant autosomal recessive mode of inheritance. We conclude the structural variant causing a deletion of the ACSL5 gene is the most likely cause for intestinal lipid malabsorption in the Australian Kelpie.

Cardiorenal and endocrine effects of synthetic canine BNP1-32 in dogs with compensated congestive heart failure caused by myxomatous mitral valve disease.

BACKGROUND: The effects of synthetic brain natriuretic peptide (BNP1-32) on cardiorenal and renin angiotensin aldosterone system in dogs with naturally occurring congestive heart failure (CHF) are unknown. OBJECTIVES: To evaluate the cardiorenal and endocrine effects of SC administered synthetic canine BNP1-32, with or without furosemide, in dogs with CHF caused by myxomatous mitral valve disease (MMVD). ANIMALS: Seven client-owned male dogs with compensated American College of Veterinary Internal Medicine stage C CHF caused by MMVD on chronic treatment with furosemide, benazepril, and pimobendan. METHODS: A single-dose, crossover, pilot study. Each dog received a dose of BNP1-32 (5 µg/kg), furosemide (2 mg/kg), and both BNP1-32/furosemide (5 µg/kg and 2 mg/kg, respectively) SC with a 2-week washout period among each treatment. Between- and within-treatment effects were evaluated using linear mixed modeling with restricted maximum likelihood estimation and evaluation of least square differences. RESULTS: Rapid absorption of BNP1-32 and a corresponding rise in urinary cyclic guanosine monophosphate excretion was observed at 1-2 hours after any treatment containing BNP1-32 (P < .05). However, BNP1-32 did not influence measured cardiorenal variables. Plasma aldosterone concentrations were below quantifiable levels in majority of the samples. CONCLUSIONS AND CLINICAL IMPORTANCE: No beneficial cardiorenal effects were detected. It is possible that dogs with chronic CHF have a reduction in natriuretic peptide responsiveness.

Use of sildenafil citrate in a cat with Eisenmenger's syndrome and an atrial septal defect.

A 2-year-old male neutered Siamese cat presenting with weakness and dyspnoea was diagnosed with an atrial septal defect and pulmonary hypertension, which resulted in right-to-left shunting (Eisenmenger's syndrome). The cat was treated with sildenafil (0.25-0.6 mg/kg) for 10 months. There were no apparent treatment-related adverse effects. Improvement in clinical signs was noted, although increasing doses of sildenafil were required. After 10 months the cat significantly deteriorated and was euthanased.