RESUMEN
Little is known about how plasma and whole blood taurine and plasma carnitine correlate to concentrations in skeletal and cardiac muscle and the effects of diet in dogs. The purpose of this study was to evaluate the correlation among plasma, skeletal and cardiac muscle carnitine and taurine and whole blood taurine and determine the effect of diet. The study protocol was approved by the Pet Food Solutions Institutional Animal Care and Use Committee. Thirty-three mixed-breed hounds and 32 beagles were evaluated at Day 0 then removed from their baseline diet and randomized to a test diet: high animal protein, grain-inclusive (HA-GI), low animal protein, grain-free (LA-GF), low animal protein, grain-inclusive (LA-GI), or high animal protein, grain-free (HA-GF). Blood was drawn every 30 days and endomyocardial (mixed breeds only) and skeletal muscle biopsies were collected at Days 0 and 180. The correlations between plasma and whole blood taurine, or plasma carnitine and skeletal and cardiac muscle concentrations were weak (p < 0.01-0.05). Mixed-breed hounds had increased (p = 0.029) whole blood taurine compared to beagles. Plasma taurine was lower with diet HA-GF, (p = 0.009) however, all diets had increased taurine from Day 0 and were, on average within the laboratory reference range. Dogs fed the HA-GI diet had increased cardiac muscle carnitine esters (p = 0.014). Increased carnitine esters were also appreciated in cardiac muscle in all diets from Day 0 to 180 (p = 0.0001). On Day 180 mixed-breed hounds had increased skeletal total carnitine (p < 0.001) compared to all time points and breeds. This study observed no correlation between plasma, whole blood, skeletal and cardiac muscle taurine concentrations but noted some effects between time, breed and diet.
Asunto(s)
Alimentación Animal , Carnitina , Dieta , Músculo Esquelético , Miocardio , Taurina , Animales , Perros/sangre , Femenino , Masculino , Alimentación Animal/análisis , Fenómenos Fisiológicos Nutricionales de los Animales , Carnitina/sangre , Dieta/veterinaria , Músculo Esquelético/metabolismo , Músculo Esquelético/química , Miocardio/metabolismo , Taurina/sangreRESUMEN
BACKGROUND: The melanocortin 4 antagonist TCMCB07 is safe and effective in reversing cachexia caused by sepsis or cancer in rodents. The safety and pharmacokinetics of TCMCB07 are demonstrated in healthy beagle dogs. HYPOTHESIS/OBJECTIVES: The objectives of this study were to investigate the safety, peak plasma concentrations, and potential for efficacy of TCMCB07 in pet dogs with naturally occurring cachexia over a 4-week time period. ANIMALS: Fourteen dogs with cachexia of any underlying cause, except cancer of the oral cavity or gastrointestinal tract, were eligible for enrollment with informed client consent. METHODS: This study was a prospective, 1-armed open-label trial. Physical examination, complete blood count, chemistry panel, and owner-assessed quality of life surveys were checked at weeks 1, 2, and 4. Due to potential for bradycardia and hypotension, Holter monitoring and blood pressure evaluations were scheduled at pre-enrollment and week 4. RESULTS: Fourteen dogs completed the trial. Significant changes detected included increased mean body weight (18.6-19.5 kg, P < .02), increased body condition score (median Tufts 5-point thin dog scale score P < .004 and WSAVA muscle condition score P < .02) and increased mean blood urea nitrogen (21.79-30.43 mg dL-1 , P < .004). On quality of life surveys, pet owners perceived their dog appeared to be panting less (P < .002) and that the general health improved (P < .03). Four dogs had a change in coat pigmentation. The peak plasma concentration of TCMCB07 in cachectic dogs was similar to that in healthy beagle dogs. CONCLUSIONS AND CLINICAL IMPORTANCE: TCMCB07 was safe and has potential efficacy in pet dogs with cachexia.
Asunto(s)
Enfermedades de los Perros , Neoplasias , Humanos , Animales , Perros , Caquexia/tratamiento farmacológico , Caquexia/veterinaria , Estudios Prospectivos , Calidad de Vida , Melanocortinas , Péptidos , Neoplasias/veterinaria , Enfermedades de los Perros/tratamiento farmacológicoRESUMEN
BACKGROUND: Nonhemorrhagic ascites (NHA) can be caused by cardiac diseases (cNHA) and noncardiac diseases (ncNHA). N-terminal brain natriuretic peptide (NT-proBNP), cardiac troponin-I (cTnI), and point-of-care ultrasound (POCUS) may differentiate between cNHA and ncNHA. HYPOTHESIS/OBJECTIVES: We compared NT-proBNP and cTnI concentrations as well as POCUS findings in dogs presented with cNHA and ncNHA. ANIMALS: Dogs (n = 60) were enrolled based on identification of NHA with an effusion packed cell volume < 10%. METHODS: Blood samples were collected and POCUS was performed on all dogs. Dogs were diagnosed with cNHA (n = 28) or ncNHA (n = 32) based on echocardiography. The cNHA group was subdivided into cardiac non-pericardial disease (n = 17) and pericardial disease (n = 11). RESULTS: The NT-proBNP concentration (median; range pmol/L) was significantly higher in the cNHA group (4510; 250-10 000) compared to the ncNHA group (739.5; 250-10 000; P = .01), with a sensitivity of 53.8% and specificity of 85.7% using a cut-off of 4092 pmol/L. The NT-proBNP concentrations were significantly higher in the cardiac non-pericardial disease group (8339; 282-10 000) compared with the pericardial disease group (692.5; 250-4928; P = .002). A significant difference in cTnI concentration (median; range ng/L) between the cNHA group (300; 23-112 612) and ncNHA group (181; 17-37 549) was not detected (P = .41). A significantly higher number of dogs had hepatic venous and caudal vena cava distension in the cNHA group compared to the ncNHA group, respectively (18/28 vs 3/29, P < .0001 and 13/27 vs 2/29, P < .001). Gall bladder wall edema was not significantly different between groups (4/28 vs 3/29, P = .74). CONCLUSIONS AND CLINICAL IMPORTANCE: NT-proBNP concentration and POCUS help distinguish between cNHA and ncNHA.
Asunto(s)
Enfermedades de los Perros , Cardiopatías , Perros , Animales , Troponina I , Sistemas de Atención de Punto , Péptido Natriurético Encefálico , Ascitis/diagnóstico por imagen , Ascitis/veterinaria , Cardiopatías/diagnóstico por imagen , Cardiopatías/veterinaria , Fragmentos de Péptidos , Biomarcadores , Enfermedades de los Perros/diagnóstico por imagenRESUMEN
In collaboration with the American College of Veterinary Pathologists.
Asunto(s)
Patología Veterinaria , Veterinarios , Animales , Humanos , Estados UnidosRESUMEN
Two juvenile alpacas, 1 male and 1 female, were presented for evaluation of grade V/VI bilateral basilar systolic heart murmurs. Both animals were ultimately diagnosed with severe valvular pulmonic stenosis and a small ventricular septal defect. Transvenous balloon valvuloplasty was performed in each animal using methods described in the dog. A double balloon technique was employed in the first case, with a balloon-annulus ratio of ~1.55. For the second case, a high-pressure dilatation balloon catheter with a balloon-annulus ratio of ~1.33 was selected. Experience with both procedures indicates that balloon pulmonary valvuloplasty is technically feasible in alpacas using techniques extrapolated from those used in dogs. Furthermore, accepted criteria for procedural success were fulfilled for both alpacas, with more than a 50% reduction in the echocardiographically derived transpulmonic pressure gradient after intervention.
Asunto(s)
Valvuloplastia con Balón , Camélidos del Nuevo Mundo , Enfermedades de los Perros , Estenosis de la Válvula Pulmonar , Animales , Valvuloplastia con Balón/veterinaria , Enfermedades de los Perros/diagnóstico por imagen , Enfermedades de los Perros/terapia , Perros , Femenino , Masculino , Estenosis de la Válvula Pulmonar/diagnóstico por imagen , Estenosis de la Válvula Pulmonar/terapia , Estenosis de la Válvula Pulmonar/veterinariaRESUMEN
The melanocortin-4 receptor (MC4R) antagonistic peptide TCMCB07 was developed for the treatment of cachexia. The objectives of this study were to examine pharmacokinetics and safety of TCMCB07 administered subcutaneously to healthy dogs. Dogs were treated with high- (2.25 mg kg-1 ) (n = 5) and low-dose TCMCB07 (0.75 mg kg-1 ) (n = 5) once daily for 28 days with a 14-day washout period between groups. Histamine levels, complete blood count, chemistry panel, blood pressure, 24-hour Holter recording, and pharmacokinetic parameters were monitored in the high-dose group. Physical examination changes were limited to weight gain and darkening of the coat color. There was no elevation of plasma histamine within 24 hours of injection but there was a significant elevation of plasma histamine across time. An approximately doubled eosinophil count and an approximately 25% increase, and then 25% decrease back to pre-treatment plasma phosphorous were also found, although both remained within the reference interval. Serial blood pressure and 24-hour Holter monitors revealed no clinically relevant changes. A difference was found in the AUC between dosing groups and a significant effect of dose, time, and interaction was noted for Vd . Low-dose TCMCB07 had a Cmax of 2.1 ug ml-1 at day 28, compared to high-dose TCMCB07 which had a Cmax 3.6 ug ml-1 at day 28. Once-daily subcutaneous administration of TCMCB07 was well-tolerated for up to 28 days in dogs when administered at doses one and three times (0.75 mg kg-1 and 2.25 mg kg-1 ) the predicted therapeutic dose and pharmacokinetic parameters are described. SIGNIFICANCE STATEMENT: Melanocortin-4 receptor (MC4R) antagonistic peptide TCMCB07 is safe at both low and high doses in dogs. Therapy was tolerated well as determined by physical examination, clinical pathology, and cardiovascular parameters; darkening of the coat was noted with treatment and resolved with discontinuation. Pharmacokinetics are described and further study in the naturally occurring canine model is warranted.
Asunto(s)
Péptidos Cíclicos/farmacocinética , Receptor de Melanocortina Tipo 4/antagonistas & inhibidores , Animales , Arritmias Cardíacas/inducido químicamente , Presión Arterial/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Perros , Femenino , Histamina/sangre , Inyecciones Subcutáneas , Masculino , Péptidos Cíclicos/efectos adversos , Fósforo/sangreRESUMEN
Background: Veterinary management of mitral valve regurgitation due to mxyomatous valve disease in dogs is limited to medical treatments, which only postpones the onset of congestive heart failure or alleviates clinical symptoms. Most surgical procedures to manage this condition in humans require cardiopulmonary bypass and have a high risk of complications. Animals: Eight dogs with naturally occurring mitral valve regurgitation. Methods: Prospective observational study. All dogs were treated with a novel edge-to-edge transcatheter device named ValveClamp. The total surgical procedural time and total catheterization time were recorded. Echocardiographic variables measured pre- and post-procedure were compared using Wilcoxin-signed rank test with a P < 0.05 considered significant. Data were expressed as median and interquartile range and absolute numbers and percentages. Results: The procedural success rate was 100% and all the dogs survived without complications. The median (interquartile range) total surgical procedural time was 86.5 (76-96.2) minutes and catheterization time was 23.5 (22-33.8) minutes. Echocardiography revealed a significant reduction in mitral regurgitation severity in all dogs following the procedure based on both a reduced mitral regurgitant maximum jet area (P = 0.012) and a reduced mitral regurgitant maximum jet area to left atrial area (P = 0.018). Conclusion: The ValveClamp device is effective at reducing the severity of mitral regurgitation in dogs with naturally occurring myxomatous valve disease.
RESUMEN
The objectives of this study were to determine a breed-specific vertebral heart scale (VHS) range for the dachshund and compare results to the established reference range of 9.7 ± 0.5, calculate inter-observer variability, and correlate VHS with echocardiography. Fifty-one normal dachshunds had radiographs and an echocardiogram performed. Five observers measured VHS to the nearest 0.25 vertebra. The data was analyzed using one-way analysis of variance, Wilcoxon Rank Sum test, Mann-Whitney rank sum test, calculation of reference and confidence intervals, Spearman rank-order correlations, and generation of intra-class correlations and confidence intervals. P < .05 was considered significant. The median for right lateral VHS was significantly larger than left (10.3 [range 9.25-11.55] versus 10.1 [range, 8.7-11.31], p < .0001). VHS for females was significantly larger than for males (left: 10.56 [9.2-11.31] versus 9.74 [8.7-10.88] and right: 10.8 [9.5-11.55] versus 9.99 [9.25-10.8], p = .0002). Observer consistency was high with an intra-class correlation coefficient of 0.95. No significant correlation was found between left atrial echocardiographic parameters and VHS. Results indicate normal dachshunds have a median VHS above the published generic canine reference range, and VHS can be reliably performed by observers with varying degrees of clinical experience.
Asunto(s)
Perros/anatomía & histología , Corazón/anatomía & histología , Radiografía Torácica/veterinaria , Vértebras Torácicas/anatomía & histología , Animales , Femenino , Corazón/diagnóstico por imagen , Masculino , Valores de Referencia , Vértebras Torácicas/diagnóstico por imagenRESUMEN
Dilated cardiomyopathy (DCM) is the most common myocardial disorder of dogs, typically affecting large and giant breeds. The purpose of this study was to describe the clinical features of DCM in standard schnauzers. Medical records for 15 standard schnauzers diagnosed with DCM were reviewed. The median age at diagnosis of DCM was 1.6 yr, with all dogs developing left-sided congestive heart failure (CHF). The median age of onset of CHF was 1.6 yr, and was significantly shorter in males (1.5 yr) than for females (2.35 yr). The median survival time after diagnosis of CHF was 22 days, and was shorter in males (13 days) than females (62 days). The occurrence of early onset DCM in multiple closely related standard schnauzers suggests a familial predisposition in this breed. Pedigree analysis confirmed common ancestry for all DCM affected dogs with a most likely autosomal recessive mode of inheritance.
Asunto(s)
Cardiomiopatía Dilatada/veterinaria , Enfermedades de los Perros/diagnóstico , Animales , Cruzamiento , Cardiomiopatía Dilatada/diagnóstico , Cardiomiopatía Dilatada/epidemiología , Enfermedades de los Perros/epidemiología , Perros , Femenino , Masculino , Estudios RetrospectivosRESUMEN
INTRODUCTION: Cardiac involvement is a common feature in muscular dystrophies. It presents as heart failure and/or arrhythmia. Traditionally, dystrophic cardiomyopathy is treated with symptom-relieving medications. Identification of disease-causing genes and investigation on pathogenic mechanisms have opened new opportunities to treat dystrophic cardiomyopathy with gene therapy. Replacing/repairing the mutated gene and/or targeting the pathogenic process/mechanisms using alternative genes may attenuate heart disease in muscular dystrophies. AREAS COVERED: Duchenne muscular dystrophy is the most common muscular dystrophy. Duchenne cardiomyopathy has been the primary focus of ongoing dystrophic cardiomyopathy gene therapy studies. Here, we use Duchenne cardiomyopathy gene therapy to showcase recent developments and to outline the path forward. We also discuss gene therapy status for cardiomyopathy associated with limb-girdle and congenital muscular dystrophies, and myotonic dystrophy. EXPERT OPINION: Gene therapy for dystrophic cardiomyopathy has taken a slow but steady path forward. Preclinical studies over the last decades have addressed many fundamental questions. Adeno-associated virus-mediated gene therapy has significantly improved the outcomes in rodent models of Duchenne and limb girdle muscular dystrophies. Validation of these encouraging results in large animal models will pave the way to future human trials.
RESUMEN
Arrhythmogenic right ventricular cardiomyopathy (ARVC) was diagnosed postmortem in a weimaraner dog. Syncope, ventricular arrhythmias, and sudden death in this patient combined with the histopathological fatty tissue infiltration affecting the right ventricular myocardium are consistent with previous reports of ARVC in non-boxer dogs. Arrhythmogenic right ventricular cardiomyopathy has not been previously reported in weimaraners.
Cardiomyopathie ventriculaire droite arythmogène chez un Weimaraner. Une cardiomyopathie ventriculaire droite arythmogène (CVDA) a été diagnostiquée post-mortem chez un chien Weimaraner. Une syncope, des arythmies ventriculaires et une mort soudaine chez ce patient, combinées à une infiltration histopathologique par du tissu adipeux affectant le myocarde droit, correspondent à des rapports antérieurs de CVDA chez des chiens autres que des Boxers. La cardiomyopathie ventriculaire droite arythmogène n'a pas été signalée antérieurement chez des Weimaraners.(Traduit par Isabelle Vallières).
Asunto(s)
Displasia Ventricular Derecha Arritmogénica/veterinaria , Enfermedades de los Perros/diagnóstico , Animales , Displasia Ventricular Derecha Arritmogénica/diagnóstico , Displasia Ventricular Derecha Arritmogénica/patología , Enfermedades de los Perros/patología , Perros , MasculinoRESUMEN
A 5-year-old domestic shorthair cat that had been previously diagnosed with diabetes mellitus was presented for episodes of coughing and respiratory distress. Diagnostic testing revealed congestive heart failure secondary to hypertrophic cardiomyopathy and concurrent asthma. All clinical signs and eosinophilic airway inflammation resolved with oral ciclosporin while the cat was concurrently receiving medications for treatment of heart failure (furosemide and enalapril). Ciclosporin should be considered for treatment of feline asthma in patients with concurrent diseases (eg, diabetes mellitus, severe heart disease) that may contraindicate use of oral glucocorticoid therapy.
Asunto(s)
Asma/veterinaria , Enfermedades de los Gatos/tratamiento farmacológico , Ciclosporina/uso terapéutico , Inmunosupresores/uso terapéutico , Animales , Asma/tratamiento farmacológico , Cardiomiopatía Hipertrófica/veterinaria , Enfermedades de los Gatos/diagnóstico , Gatos , Diabetes Mellitus/veterinaria , Relación Dosis-Respuesta a Droga , Insuficiencia Cardíaca/veterinaria , Resultado del TratamientoRESUMEN
STUDY DESIGN: Prospective porcine animal model. OBJECTIVE: Determine if injecting FloSeal into pedicles for hemostasis causes emboli. SUMMARY OF BACKGROUND DATA: Bleeding from spinal deformity cases can be substantial, especially when surgical procedures involve bilateral fixation at multiple segments. It is not unusual to observe hemorrhage from vascular pedicles during each step of pedicle screw tract preparation. When multiple fixation points are required, blood loss can be excessive. To minimize estimated blood loss and associated morbidity, surgeons have injected liquefied gelatin into pedicles after drilling, palpating, and/or tapping. FloSeal is one of the most popular commercially available injectable agents and we sought to investigate the potential for embolization when used as an intrapedicular hemostatic agent. METHODS: Two adult minipigs were anesthetized and underwent sequential bilateral pedicle cannulation from T-spine to sacrum. At every level, tracts were cannulated, palpated, and tapped. In every tract, FloSeal was injected into each pedicle until back pressure was detected on the syringe or to a maximum volume of 2 mL, then pedicle screws were inserted. The right ventricular outflow tract was visualized real time using transesophageal echocardiography. Postmortem evaluation of heart and lungs was performed. RESULTS: FloSeal injected into pedicles caused a consistent large showering of the right ventricular outflow tract in both pigs as visualized on intraoperative transesophageal echocardiography. A second large showering occurred during screw insertion after FloSeal was injected. Microscopic examination of lungs clearly identified amphophilic amorphous material in many small vessels consistent with FloSeal. CONCLUSION: This study suggests caution when injecting gelatin hemostatic agents into pedicles to stop bleeding during spinal surgery as we saw clear evidence of fat and gelatin emboli when used in this animal model. Further investigation into how to minimize this embolic showering may help the cardiopulmonary at risk patient who requires spinal surgery, especially when multiple points of pedicle screw fixation are used. LEVEL OF EVIDENCE: N/A.
Asunto(s)
Pérdida de Sangre Quirúrgica/prevención & control , Extravasación de Materiales Terapéuticos y Diagnósticos/etiología , Gelatina/efectos adversos , Hemostáticos/efectos adversos , Procedimientos Ortopédicos/métodos , Fusión Vertebral/métodos , Animales , Gelatina/uso terapéutico , Hemostáticos/uso terapéutico , Estudios Prospectivos , PorcinosRESUMEN
Myotonia congenita (MC) is a skeletal muscle channelopathy characterized by inability of the muscle to relax following voluntary contraction. Worldwide population prevalence in humans is 1:100,000. Studies in mice, dogs, humans and goats confirmed myotonia associated with functional defects in chloride channels and mutations in a skeletal muscle chloride channel (CLCN1). CLCN1 encodes for the most abundant chloride channel in the skeletal muscle cell membrane. Five random bred cats from Winnipeg, Canada with MC were examined. All cats had a protruding tongue, limited range of jaw motion and drooling with prominent neck and proximal limb musculature. All cats had blepharospasm upon palpebral reflex testing and a short-strided gait. Electromyograms demonstrated myotonic discharges at a mean frequency of 300 Hz resembling the sound of a 'swarm of bees'. Muscle histopathology showed hypertrophy of all fiber types. Direct sequencing of CLCN1 revealed a mutation disrupting a donor splice site downstream of exon 16 in only the affected cats. In vitro translation of the mutated protein predicted a premature truncation and partial lack of the highly conserved CBS1 (cystathionine ß-synthase) domain critical for ion transport activity and one dimerization domain pivotal in channel formation. Genetic screening of the Winnipeg random bred population of the cats' origin identified carriers of the mutation. A genetic test for population screening is now available and carrier cats from the feral population can be identified.
Asunto(s)
Enfermedades de los Gatos , Membrana Celular , Canales de Cloruro , Músculo Esquelético , Mutación , Miotonía Congénita , Animales , Enfermedades de los Gatos/genética , Enfermedades de los Gatos/metabolismo , Enfermedades de los Gatos/patología , Enfermedades de los Gatos/fisiopatología , Gatos , Membrana Celular/genética , Membrana Celular/metabolismo , Canales de Cloruro/genética , Canales de Cloruro/metabolismo , Perros , Electromiografía , Exones , Cabras , Humanos , Ratones , Músculo Esquelético/metabolismo , Músculo Esquelético/patología , Músculo Esquelético/fisiopatología , Miotonía Congénita/genética , Miotonía Congénita/metabolismo , Miotonía Congénita/mortalidad , Miotonía Congénita/fisiopatología , Miotonía Congénita/veterinaria , Sitios de Empalme de ARNAsunto(s)
Arritmias Cardíacas/veterinaria , Electrocardiografía/veterinaria , Enfermedades de los Caballos/diagnóstico , Animales , Antibacterianos/uso terapéutico , Arritmias Cardíacas/etiología , Líquido Ascítico/microbiología , Endotoxemia/complicaciones , Endotoxemia/patología , Endotoxemia/veterinaria , Infecciones por Escherichia coli/tratamiento farmacológico , Infecciones por Escherichia coli/microbiología , Infecciones por Escherichia coli/veterinaria , Femenino , Enfermedades de los Caballos/patología , CaballosRESUMEN
The absence of dystrophin in the heart leads to Duchenne cardiomyopathy. Dystrophin-deficient dogs represent a critical model to translate novel therapies developed in mice to humans. Unfortunately, little is known about cardiophysiology changes in these dogs. We performed prospective electrocardiographic and echocardiographic examinations at 3, 6 and 12 months of age in four normal and three affected dogs obtained from the same litter. Affected dogs showed growth retardation and serum creatine kinase elevation. Necropsy confirmed cardiac dystrophin deficiency and histopathology. Q/R ratio elevation and diastolic left ventricular (LV) internal diameter reduction were the most consistent findings in affected dogs at all ages. At 6 and 12 months, dystrophic dogs also showed significant reduction of PR intervals, LV end diastolic/systolic volumes and systolic LV internal diameters. Epicardial and endocardial slope times were significantly reduced in affected dogs at 12 months. These results establish the baseline for evaluating experimental therapies in the future.
Asunto(s)
Cardiomiopatías/diagnóstico , Distrofina/deficiencia , Animales , Cardiomiopatías/diagnóstico por imagen , Cardiomiopatías/patología , Creatina Quinasa/sangre , Modelos Animales de Enfermedad , Perros , Electrocardiografía , Corazón/fisiopatología , Distrofia Muscular de Duchenne/patología , Distrofia Muscular de Duchenne/fisiopatología , Miocardio/patología , UltrasonografíaRESUMEN
An 8-year-old, castrated male Basset Hound was evaluated for congestive heart failure and atrial fibrillation. Echocardiography and angiography demonstrated a left-to-right shunting aorticopulmonary fistula. Coil embolization of the fistula was initially successful in reducing the volume of blood flow through the vascular network. The dog was medically managed for congestive heart failure until it was euthanized 6 months after initial presentation. The physiology and treatment of centrally located arteriovenous fistulae are discussed.