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OBJECTIVE: The objective was to describe the successful thoracoscopic treatment of esophageal entrapment resulting from a vascular ring anomaly (VRA) comprising a persistent right aortic arch (PRAA) and left ligamentum arteriosum (LA) in a Babydoll sheep wether. STUDY DESIGN: Case report. ANIMAL: Eight month old Babydoll sheep wether, 13 kg. METHODS: The patient presented with a weight half that of its sibling, persistent regurgitation following eating, and delayed growth noted from the age of approximately 2 months, coinciding with the introduction of solid feed into the diet. Plain thoracic radiographs were within normal limits but computed tomography angiography (CTA) confirmed multiple congenital vascular anomalies. The primary finding was esophageal and tracheal entrapment by a PRAA and left LA. Thoracoscopic transection of the LA was performed with a bipolar vessel sealing device with the aid of transesophageal endoscopy. RESULTS: Immediate improvement in attitude and absence of regurgitation were observed. The patient was discharged and subsequently reintroduced to grazing and long-stem hay, which were previously not tolerated. By 6 months post discharge, the patient's weight was 36 kg, comparable to an age-matched sibling and considered appropriate for the stage of growth. CONCLUSION: Thoracoscopic transection of the LA in sheep is a feasible treatment for esophageal compression resulting from a VRA. Surgical intervention resolved the clinical signs and allowed normal digestive rumination, restoring bidirectional esophageal function in a ruminant.
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Toracoscopia , Animais , Toracoscopia/veterinária , Toracoscopia/métodos , Ovinos , Anel Vascular/veterinária , Anel Vascular/cirurgia , Doenças dos Ovinos/cirurgia , Masculino , Feminino , Aorta Torácica/cirurgia , Aorta Torácica/anormalidadesRESUMO
RATIONALE: αCGRP (α calcitonin gene-related peptide), one of the strongest vasodilators, is cardioprotective in hypertension by reducing the elevated blood pressure. OBJECTIVE: However, we hypothesize that endogenous, physical activity-induced αCGRP has blood pressure-independent cardioprotective effects in chronic hypertension. METHODS AND RESULTS: Chronically hypertensive (one-kidney-one-clip surgery) wild-type and αCGRP-/- sedentary or voluntary wheel running mice were treated with vehicle, αCGRP, or the αCGRP receptor antagonist CGRP8-37. Cardiac function and myocardial phenotype were evaluated echocardiographically and by molecular, cellular, and histological analysis, respectively. Blood pressure was similar among all hypertensive experimental groups. Endogenous αCGRP limited pathological remodeling and heart failure in sedentary, chronically hypertensive wild-type mice. In these mice, voluntary wheel running significantly improved myocardial phenotype and function, which was abolished by CGRP8-37 treatment. In αCGRP-/- mice, αCGRP treatment, in contrast to voluntary wheel running, improved myocardial phenotype and function. Specific inhibition of proliferation and myofibroblast differentiation of primary, murine cardiac fibroblasts by αCGRP suggests involvement of these cells in αCGRP-dependent blunting of pathological cardiac remodeling. CONCLUSIONS: Endogenous, physical activity-induced αCGRP has blood pressure-independent cardioprotective effects and is crucial for maintaining cardiac function in chronic hypertension. Consequently, inhibiting endogenous αCGRP signaling, as currently approved for migraine prophylaxis, could endanger patients with hypertension.
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Pressão Sanguínea/fisiologia , Peptídeo Relacionado com Gene de Calcitonina/sangue , Hipertensão/sangue , Hipertensão/terapia , Condicionamento Físico Animal/métodos , Condicionamento Físico Animal/fisiologia , Animais , Biomarcadores/sangue , Células Cultivadas , Doença Crônica , Hipertensão/prevenção & controle , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Resultado do TratamentoRESUMO
Analyzing electrocardiographic (ECG) recordings, making a diagnosis and assessment of any arrhythmias present, is an important part of the workup of many equine cases. Accurate analysis requires a good-quality recording, free of as many artifacts as possible, with clear P-QRS-T complex morphology. For sustained arrhythmias, short-term recordings are sufficient to make the appropriate diagnosis before instigating treatment. Longer-term recordings are essential for arrhythmias that are paroxysmal, intermittent, or occurring infrequently, while exercising ECGs are required for arrhythmias associated with physical activity. A stepwise, logical approach to ECG analysis will help the observer to recognize and correctly diagnose any arrhythmias present.
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Arritmias Cardíacas/veterinária , Eletrocardiografia/veterinária , Doenças dos Cavalos/diagnóstico , Animais , Arritmias Cardíacas/diagnóstico , Eletrocardiografia/métodos , CavalosRESUMO
BACKGROUND/AIMS: The PCK rat model of polycystic kidney disease is characterized by the progressive development of renal medullary cysts. Here, we evaluated the suitability of high resolution ultrasonography (HRU) to assess the kidney and cyst volume in PCK rats, testing three different ultrasound image analysis methods, and correlating them with kidneys weights and histological examinations. METHODS: After inducing anesthesia, PCK rats (n=18) were subjected to HRU to visualize the kidneys, to perform numeric and volumetric measurements of the kidney and any cysts observed, and to generate 3-dimensional images of the cysts within the kidney parenchyma. RESULTS: HRU provided superior information in comparison to microscopic analysis of stained kidney sections. HRU-based kidney volumes correlated strongly with kidney weights (R2=0.809; P<0.0001). CONCLUSION: HRU represents a useful diagnostic tool for kidney and cyst volume measurements in PCK rats. Sequential HRU examinations may be useful to study the effect of drugs on cyst growth without the need to euthanize experimental animals.
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Modelos Animais de Doenças , Rim/diagnóstico por imagem , Rim/patologia , Rim Policístico Autossômico Recessivo/diagnóstico por imagem , Rim Policístico Autossômico Recessivo/patologia , Animais , Cistos/diagnóstico por imagem , Cistos/patologia , Masculino , Ratos , Ratos Transgênicos , UltrassonografiaRESUMO
BACKGROUND AND AIM OF THE STUDY: Bioengineered living autologous valves with remodeling and growth capacity represent a promising concept for future cardiac and venous valve repair. A meticulous understanding of the mechanisms involved in recellularization and remodeling is essential for the safe and efficient clinical translation of this technology. In this context, the first investigations of bioengineered vascular grafts in immune-incompetent or transgenic rodents represented an important step. However, the in-vivo assessment of bioengineered synthetic scaffold-based (biodegradable) valve replacements in rodent models has not been achieved to date. METHODS: Miniaturized monocuspid PGA (polyglycolic acid)-P4HB (poly-4-hydroxybutyrate)-based valves were created, incorporated into metallic stents (length 2.0 mm, diameter 1.1 mm) and introduced into catheter-based implantation devices. Wistar outbred rats (n = 8) underwent a laparotomy, abdominal aorta arteriotomy and valve delivery into the abdominal aorta. Valve placement and function were evaluated following deployment using ultrasound (Doppler- and M-mode). Explanted tissues were analyzed both macroscopically and histopathologically. RESULTS: No significant physiological or hemodynamic changes were observed, including heart rate, pressure gradients, velocity values and cardiac output before and after valve implantation. The cross-sectional area at the level of the stented valve was reduced by 22%. Valvular leaflet oscillation was observed in two animals, and thrombus formation in the stent was observed in one animal. Histological evaluation revealed cellular infiltration within 3 h in vivo, and no signs of thrombus deposition on the valvular surface. CONCLUSIONS: This study demonstrated the technical feasibility of the transcatheter implantation of bioengineered stented miniaturized valves into the infrarenal rat aorta, without affecting the animal's physiological and hemodynamic variables and with valvular oscillation in part of the implants. These results could serve as a basis for the implementation of a chronic rat in-vivo model for mechanistic studies in bioengineered valvular tissues under systemic hemodynamic conditions. Video 1: 2D ultrasonographic projection revealing graft's leaflet oscillation.
Assuntos
Aorta Abdominal/cirurgia , Implante de Prótese de Valva Cardíaca/instrumentação , Próteses Valvulares Cardíacas , Ácido Poliglicólico/química , Polímeros/química , Stents , Engenharia Tecidual/métodos , Animais , Aorta Abdominal/diagnóstico por imagem , Aorta Abdominal/fisiopatologia , Estudos de Viabilidade , Hemodinâmica , Teste de Materiais , Metais/química , Modelos Animais , Desenho de Prótese , Ratos Wistar , Fatores de Tempo , Ultrassonografia Doppler em CoresRESUMO
BACKGROUND: Heterotopic heart transplantation (HHT) in rodent animal models represents an important technique enabling studies on organ transplantation immunology and pharmaceutical development. Recent investigations used nonworking HHT designs, with the left ventricle (LV) bypassed in the anastomosis system. In spite of their principal success, the lack of orthogonal ventricular filling leads to myocardial atrophy. However, when focusing on the cellular and molecular mechanisms involved in the in vivo remodeling of the myocardium or cell-based cardiovascular implants, a nonworking model is suboptimal as it lacks the native-analogous hemodynamic and metabolic situation. Here we present the hemodynamic and electrical assessment of a biventricularly loaded murine HHT method without the need for a combined heart-lung transplantation approach. METHODS: Heterotopic transplantations (n = 13) were performed on C57BL/6J-(H-2b) inbred mice (n = 13 donors, n = 13 recipients) by creating end-to-side anastomoses between the donors' cranial vena cava (CrVC) and the recipients' abdominal caudal vena cava (CVC), between the donors' ascending aorta and the recipients' abdominal aorta (aAo), and between the grafts' pulmonary trunk and the left atrium. After transplantation, a hemodynamic assessment using echocardiography (including 2D speckle tracking analysis) and electrocardiography was performed. RESULTS: The loaded HHT procedure in the mice was performed with an overall success rate of 61%. In 3 of the remaining 5 cases, only atrial function was restored. The median duration of the entire surgical procedure for the recipient animal was 190 (IQR 180-250) min. The mean heart rate in the loaded HHT group was 355 ± 6 bpm in comparison to the control group with an in situ heart rate of 418 ± 61 bpm. A native-like closing and opening pattern of the aortic and mitral valves (visible on both 2D and M-mode images) was observed, confirming a native-analogous loading of the LV. Pulsed-wave Doppler provided visualization of the flow across the region of anastomoses between the pulmonary trunk and the left atrium, reaching a mean maximum velocity of 382 ± 12 mm/s. Exemplary 2D speckle tracking analysis of the LV free wall and interventricular septum revealed some differences in vector directions in one animal when compared to the orthotopic native heart, indicating an asynchronous movement of the LV. CONCLUSIONS: These results demonstrate the technical (micro)surgical feasibility of a fully loaded HHT procedure in the murine model without using a combined heart-lung transplantation approach. The acute hemodynamic performance of the HHT grafts approximated the native orthotopic situation. This model may open up new options for the investigation of cellular and molecular questions in the murine cardiovascular in vivo system in the near future.
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Transplante de Coração/métodos , Hemodinâmica , Transplante Heterotópico/métodos , Anastomose Cirúrgica , Animais , Ecocardiografia , Feminino , Ventrículos do Coração , Camundongos , Camundongos Endogâmicos C57BL , Modelos AnimaisRESUMO
OBJECTIVE: To report a transnasal, endoscopically guided ventral surgical approach for accessing the cranial and caudal segments of the sphenopalatine sinus for mass removal in a horse. STUDY DESIGN: Case report. ANIMAL: Adult horse with acute onset blindness referable to a soft tissue mass within the sphenopalatine sinus. CLINICAL REPORT: A 7-year-old Warmblood gelding presented with a history of running into a fence and falling. No neurologic signs were identified at initial examination but acute blindness was noted 3 weeks later. On computed tomography (CT) the sphenopalatine sinus was filled with a large homogeneous mass with poor contrast enhancement that extended dorsally with thinning to the dorsal cortex of the sphenoid bone, just rostral to the entrance of the optic canals into the cranial cavity. Surgical access to the sphenopalatine sinus was achieved using a transnasal, endoscopically guided ventral pharyngotomy approach and the mass lesion was removed. A presumptive diagnosis of chondroma was made based on histopathology. The horse recovered well from surgery, and although it has not regained vision as of 6.5 years postoperatively, the disease has not progressed. CONCLUSION: Transnasal, endoscopically-guided ventral surgical access to the sphenopalatine sinus is possible in horses and may improve access in horses with disease extending caudally beyond the palatine portion of the sinus. Use of smaller diameter or specialized instruments, such as various endoscopic bone cutting instruments, and CT image guidance may improve sinus access by this route.
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Condroma/veterinária , Doenças dos Cavalos/cirurgia , Faringectomia/veterinária , Crânio/cirurgia , Animais , Condroma/diagnóstico , Condroma/cirurgia , Endoscopia/veterinária , Doenças dos Cavalos/diagnóstico , Cavalos , Masculino , Faringectomia/métodosRESUMO
Primary hyperthyroidism is a rarely diagnosed endocrinopathy in equids and there have been no previous reports of structural and functional cardiac changes associated with hyperthyroidism in these species. This case report investigates a 20-year-old mule gelding that presented for a three-month history of thin body condition despite polyphagia, with a heart murmur and elevated free and total thyroid hormone concentrations. On presentation, physical exam revealed a body condition score of two out of nine, persistent tachycardia, pansystolic heart murmur and firm bilateral ventral proximal cervical masses. Bloodwork confirmed markedly elevated free T4, total T4 and T3 concentrations. Echocardiogram demonstrated left ventricular concentric hypertrophy with increased ventricular and atrial systolic function. Bilateral thyroidectomy was performed under standing sedation without complications. Histopathology demonstrated adenocarcinoma of the left thyroid gland and multiple adenomas with osseous metaplasia within the right thyroid. The mule was supplemented with levothyroxine sodium two weeks post-op after a thyroid panel demonstrated undetectable concentrations. Polyphagia resolved following surgery and the mule began gaining weight. Echocardiographic changes improved but did not resolve at two years post-operative. Continued bi-annual follow up and monitoring of thyroid levels was recommended. This case represents the first documentation of hemodynamically relevant cardiac remodeling in an equid associated with primary hyperthyroidism.
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BACKGROUND: The recurrence rate of atrial fibrillation (AF) in horses after cardioversion to sinus rhythm (SR) is relatively high. Atrial fibrillatory rate (AFR) derived from surface ECG is considered a biomarker for electrical remodelling and could potentially be used for the prediction of successful AF cardioversion and AF recurrence. OBJECTIVES: Evaluate if AFR was associated with successful treatment and could predict AF recurrence in horses. STUDY DESIGN: Retrospective multicentre study. METHODS: Electrocardiograms (ECG) from horses with persistent AF admitted for cardioversion with either medical treatment (quinidine) or transvenous electrical cardioversion (TVEC) were included. Bipolar surface ECG recordings were analysed by spatiotemporal cancellation of QRST complexes and calculation of AFR from the remaining atrial signal. Kaplan-Meier survival curve and Cox regression analyses were performed to assess the relationship between AFR and the risk of AF recurrence. RESULTS: Of the 195 horses included, 74 received quinidine treatment and 121 were treated with TVEC. Ten horses did not cardiovert to SR after quinidine treatment and AFR was higher in these, compared with the horses that successfully cardioverted to SR (median [interquartile range]), (383 [367-422] vs 351 [332-389] fibrillations per minute (fpm), P < .01). Within the first 180 days following AF cardioversion, 12% of the quinidine and 34% of TVEC horses had AF recurrence. For the horses successfully cardioverted with TVEC, AFR above 380 fpm was significantly associated with AF recurrence (hazard ratio = 2.4, 95% confidence interval 1.2-4.8, P = .01). MAIN LIMITATIONS: The treatment groups were different and not randomly allocated, therefore the two treatments cannot be compared. Medical records and the follow-up strategy varied between the centres. CONCLUSIONS: High AFR is associated with failure of quinidine cardioversion and AF recurrence after successful TVEC. As a noninvasive marker that can be retrieved from surface ECG, AFR can be clinically useful in predicting the probability of responding to quinidine treatment as well as maintaining SR after electrical cardioversion.
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Fibrilação Atrial , Doenças dos Cavalos , Animais , Fibrilação Atrial/terapia , Fibrilação Atrial/veterinária , Cardioversão Elétrica/veterinária , Eletrocardiografia/veterinária , Átrios do Coração , Doenças dos Cavalos/terapia , Cavalos , QuinidinaRESUMO
Heart rate variability (HRV) analysis has been performed on ECG-derived data sets for more than 170 years but is currently undergoing a rapid evolution, thanks to the expansion of the human and veterinary medical technology sector. Traditional HRV analysis was initially performed to identify changes in vago-sympathetic balance, while the most recent focus has expanded to include the use of complex computer algorithms, neural networks and machine learning technology to identify cardiac arrhythmias, particularly atrial fibrillation (AF). Some of these techniques have recently been translated for use in the field of equine cardiology, with particular focus on improving the diagnosis of arrhythmias both at rest and during exercise. This review focuses on understanding the basic HRV variables and important factors to consider when collecting data for use in HRV analysis. In addition, the use of HRV analysis for the diagnosis of arrhythmias is discussed from human, small animal and equine perspectives. Finally, the future of HRV analysis is briefly introduced, including an overview of future developments in this rapidly expanding and exciting field.
Assuntos
Fibrilação Atrial/veterinária , Determinação da Frequência Cardíaca/veterinária , Frequência Cardíaca/fisiologia , Doenças dos Cavalos/diagnóstico , Animais , Fibrilação Atrial/diagnóstico , Determinação da Frequência Cardíaca/métodos , CavalosRESUMO
BACKGROUND: Little is known about normal heart rate variability (HRV) in horses during exercise. It can be difficult to separate premature beats from normal beat-to-beat variation at higher heart rates. OBJECTIVES: The aim was to quantify HRV in healthy horses during a high-speed treadmill-standardized exercise test (HSET) and to compare with the HRV in horses observed to have arrhythmias during exercise. ANIMALS: Thirteen healthy horses (Group H), 30 horses with arrhythmias (Group A), and 11 horses with poor performance but no observed arrhythmias (Group O). METHODS: Prospective, observational study. All horses performed a HSET with simultaneous electrocardiograph (ECG) recorded. The ECGs were corrected for artifacts, and arrhythmias noted. Percent instantaneous beat-to-beat cycle length variation (% R-R variation) was calculated, and HRV analyses were performed on trot, canter, and recovery segments. RESULTS: Group H showed between -4.4 and +3.8% R-R variation during trot and between -6.1 and +5.4% R-R variation during the canter phase of the HSET. Group A had significantly larger maximum and 1st percentile R-R shortening and lengthening compared with Group H and Group O during the recovery phase where most arrhythmias were observed. During recovery, a cutoff of 6% maximum % R-R shortening predicted the presence of arrhythmia with 88% sensitivity and 97% specificity and likelihood ratio of 26. CONCLUSIONS AND CLINICAL IMPORTANCE: Healthy horses have little instantaneous R-R variation during exercise. If a cardiac cycle shortens more than 6% from the previous cycle during the recovery phase, this R-R interval is likely to represent an arrhythmic event.
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Arritmias Cardíacas/veterinária , Teste de Esforço/veterinária , Frequência Cardíaca/fisiologia , Doenças dos Cavalos/diagnóstico , Animais , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/fisiopatologia , Estudos de Casos e Controles , Feminino , Doenças dos Cavalos/fisiopatologia , Cavalos/fisiologia , MasculinoRESUMO
BACKGROUND: Noninvasive blood pressures (NIBP) and pulse pressures (PP) have not been published in horses with aortic and mitral regurgitation (AR or MR). OBJECTIVES: To investigate NIBP and PP in healthy Warmblood horses and horses with AR and MR and propose PP cutoffs to identify and stage AR severity. ANIMALS: Seventy-three Warmblood horses (healthy, 10; AR, 31; MR, 32). METHODS: Retrospective study. All horses had NIBP and an echocardiogram recorded. Cases were categorized based on severity of regurgitation. Pulse pressures were compared among healthy, MR, and AR groups and among AR severity groups. Cutoffs were determined by receiver operating characteristic curve analyses. RESULTS: Horses with AR had higher PP than horses with MR (mean difference [95% confidence interval (CI)], +17 [9-26] mm Hg, P < .001) and controls (+17 [5-30] mm Hg; P =.004). Horses with severe AR had higher PP compared those with mild (+38 [20-54] mm Hg; P < 0.001) and moderate AR (+33 [18-47] mm Hg; P < .001). The PP cutoffs to distinguish AR from MR and controls were 38 mm Hg (sensitivity [Sn], 100%; specificity [Sp], 19%) for maximal Sn and 61 mm Hg (Sn, 43%; Sp, 100%) for maximal Sp. The PP cutoffs to distinguish severe AR from mild and moderate AR were 57 mm Hg (Sn, 100%; Sp, 70%) for maximal Sn and 77 mm Hg (Sn, 75%; Sp, 100%) for maximal Sp. CONCLUSIONS AND CLINICAL IMPORTANCE: Horses with AR have increased PP. Noninvasive PP measurements interpreted with provided cutoffs may aid clinicians in diagnosing and staging severity of AR in horses.
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Insuficiência da Valva Aórtica/veterinária , Pressão Sanguínea/fisiologia , Doenças dos Cavalos/diagnóstico , Insuficiência da Valva Mitral/veterinária , Animais , Insuficiência da Valva Aórtica/diagnóstico , Insuficiência da Valva Aórtica/diagnóstico por imagem , Ecocardiografia/veterinária , Feminino , Doenças dos Cavalos/diagnóstico por imagem , Cavalos , Masculino , Insuficiência da Valva Mitral/diagnóstico , Insuficiência da Valva Mitral/diagnóstico por imagem , Estudos RetrospectivosRESUMO
AIMS: Hyperglycaemia-induced reactive oxygen species (ROS) are key mediators of cardiac dysfunction. Intensive glycaemic control (IGC) has failed to reduce risk of heart failure in patients with diabetes but the underlying mechanisms remain to be elucidated. The present study investigates whether epigenetic regulation of the pro-oxidant adaptor p66Shc contributes to persistent myocardial dysfunction despite IGC. METHODS AND RESULTS: p66Shc expression was increased in the heart of diabetic mice, and 3-week IGC by slow-release insulin implants did not revert this phenomenon. Sustained p66Shc upregulation was associated with oxidative stress, myocardial inflammation and left ventricular dysfunction, as assessed by conventional and 2D speckle-tracking echocardiography. In vivo gene silencing of p66Shc, performed during IGC, inhibited ROS production and restored cardiac function. Furthermore, we show that dysregulation of methyltransferase DNMT3b and deacetylase SIRT1 causes CpG demethylation and histone 3 acetylation on p66Shc promoter, leading to persistent transcription of the adaptor. Altered DNMT3b/SIRT1 axis in the diabetic heart was explained by upregulation of miR-218 and miR-34a. Indeed, in human cardiomyocytes exposed to high glucose, inhibition of these miRNAs restored the expression of DNMT3b and SIRT1 and erased the adverse epigenetic signatures on p66Shc promoter. Consistently, reprogramming miR-218 and miR-34a attenuated persistent p66Shc expression and ROS generation. CONCLUSIONS: In diabetic left ventricular dysfunction, a complex epigenetic mechanism linking miRNAs and chromatin modifying enzymes drives persistent p66Shc transcription and ROS generation. Our results set the stage for pharmacological targeting of epigenetic networks to alleviate the clinical burden of diabetic cardiomyopathy.
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Diabetes Mellitus Experimental/metabolismo , Epigênese Genética/fisiologia , Hiperglicemia/metabolismo , Proteína 1 de Transformação que Contém Domínio 2 de Homologia de Src/biossíntese , Disfunção Ventricular Esquerda/metabolismo , Animais , Diabetes Mellitus Experimental/genética , Hiperglicemia/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Espécies Reativas de Oxigênio/metabolismo , Proteína 1 de Transformação que Contém Domínio 2 de Homologia de Src/deficiência , Disfunção Ventricular Esquerda/genéticaRESUMO
Congenital heart disease should be considered when evaluating calves with chronic respiratory signs, failure to thrive, poor growth, or if a murmur is heard on physical examination. Echocardiography is currently the gold standard for diagnosing congenital heart defects. A wide variety of defects, either alone or in combination with a ventricular septal defect, are possible. A standardized approach using sequential segmental analysis is required to fully appreciate the nature and severity of more complex malformations. The prognosis for survival varies from guarded to poor and depends on the hemodynamic relevance of the defects and the degree of cardiac compensation.
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Doenças dos Bovinos/diagnóstico por imagem , Cardiopatias Congênitas/veterinária , Comunicação Interventricular/veterinária , Animais , Animais Recém-Nascidos , Bovinos , Ecocardiografia/veterinária , Cardiopatias Congênitas/diagnóstico por imagem , Comunicação Interventricular/diagnóstico por imagemRESUMO
The sodium-glucose-cotransporter-2 (SGLT2) inhibitor dapagliflozin (DAPA) induces glucosuria and osmotic diuresis via inhibition of renal glucose reabsorption. Since increased diuresis retards the progression of polycystic kidney disease (PKD), we investigated the effect of DAPA in the PCK rat model of PKD. DAPA (10 mg/kg/d) or vehicle was administered by gavage to 6 week old male PCK rats (n=9 per group). Renal function, albuminuria, kidney weight and cyst volume were assessed after 6 weeks of treatment. Treatment with DAPA markedly increased glucose excretion (23.6 ± 4.3 vs 0.3 ± 0.1 mmol/d) and urine output (57.3 ± 6.8 vs 19.3 ± 0.8 ml/d). DAPA-treated PCK rats had higher clearances for creatinine (3.1 ± 0.1 vs 2.6 ± 0.2 ml/min) and BUN (1.7 ± 0.1 vs 1.2 ± 0.1 ml/min) after 3 weeks, and developed a 4-fold increase in albuminuria. Ultrasound imaging and histological analysis revealed a higher cyst volume and a 23% higher total kidney weight after 6 weeks of DAPA treatment. At week 6 the renal cAMP content was similar between DAPA and vehicle, and staining for Ki67 did not reveal an increase in cell proliferation. In conclusion, the inhibition of glucose reabsorption with the SGLT2-specific inhibitor DAPA caused osmotic diuresis, hyperfiltration, albuminuria and an increase in cyst volume in PCK rats. The mechanisms which link glucosuria to hyperfiltration, albuminuria and enhanced cyst volume in PCK rats remain to be elucidated.
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Compostos Benzidrílicos/farmacologia , Glucosídeos/farmacologia , Doenças Renais Policísticas/metabolismo , Proteínas de Transporte de Sódio-Glucose/antagonistas & inibidores , Albuminúria/tratamento farmacológico , Animais , Compostos Benzidrílicos/administração & dosagem , Biópsia , Peso Corporal/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , AMP Cíclico/metabolismo , Modelos Animais de Doenças , Progressão da Doença , Diurese/efeitos dos fármacos , Eletrólitos/sangue , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Glucosídeos/administração & dosagem , Rim/diagnóstico por imagem , Rim/metabolismo , Rim/patologia , Testes de Função Renal , Masculino , Doenças Renais Policísticas/diagnóstico , Doenças Renais Policísticas/tratamento farmacológico , Ratos , UltrassonografiaRESUMO
Nosocomial salmonellosis continues to pose an important threat to veterinary medical teaching hospitals. The objectives of this study were to describe an outbreak of salmonellosis caused by Salmonella enterica serovar Oranienburg within our hospital and to highlight its unique features, which can be used to help mitigate or prevent nosocomial outbreaks in the future. We retrospectively analyzed data from patients that were fecal culture-positive for Salmonella Oranienburg between January 1, 2006, and June 1, 2011, including historical, clinical, and pulsed-field gel electrophoresis (PFGE) data. Salmonella Oranienburg was identified in 20 horses, five alpacas, and three cows during this time frame, with dates of admission spanning the period from August, 2006, through January, 2008. We consider most of these patients to have become infected through either nosocomial or on-farm transmission, as evidenced by molecular subtyping results and supportive epidemiologic data. Interpretation of PFGE results in this outbreak was challenging because of the identification of several closely related Salmonella Oranienburg subtypes. Furthermore, a high percentage of cases were fecal culture-positive for Salmonella Oranienburg within 24 h of admission. These patients initially appeared to represent new introductions of Salmonella into the hospital, but closer inspection of their medical records revealed epidemiologic links to the hospital following the index case. Cessation of this outbreak was observed following efforts to further heighten biosecurity efforts, with no known cases or positive environmental samples after January, 2008. This study demonstrates that a Salmonella-positive culture result within 24 h of admission does not exclude the hospital as the source of infection, and it underscores the important role played by veterinary medical teaching hospitals as nodes of Salmonella infection that can promote transmission outside of the hospital setting.
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Camelídeos Americanos/microbiologia , Doenças dos Bovinos/epidemiologia , Surtos de Doenças/veterinária , Doenças dos Cavalos/epidemiologia , Salmonelose Animal/epidemiologia , Salmonella enterica/isolamento & purificação , Animais , Antibacterianos/farmacologia , Bovinos , Doenças dos Bovinos/microbiologia , Doenças dos Bovinos/transmissão , Infecção Hospitalar/veterinária , Farmacorresistência Bacteriana Múltipla , Eletroforese em Gel de Campo Pulsado/veterinária , Fezes/microbiologia , Feminino , Doenças dos Cavalos/microbiologia , Doenças dos Cavalos/transmissão , Cavalos , Hospitais Veterinários , New York/epidemiologia , Estudos Retrospectivos , Salmonelose Animal/microbiologia , Salmonelose Animal/transmissão , Salmonella enterica/efeitos dos fármacos , Salmonella enterica/genética , SorogrupoRESUMO
OBJECTIVE: To determine the apparent prevalence of shedding of Cryptosporidium spp in healthy alpaca crias and their dams on 14 farms in New York and 1 farm in Pennsylvania. DESIGN: Cross-sectional study. ANIMALS: 110 alpaca crias and their 110 dams. PROCEDURES: Fecal samples were obtained from 220 alpacas at 14 alpaca farms in New York and 1 farm in Pennsylvania. For each animal, age, sex, and health condition were recorded. A fecal score (1 = normally formed; 2 = soft or loose; 3 = diarrhetic) was recorded for each cria. Cryptosporidium oocysts were identified in fecal samples by a direct immunofluorescence assay. RESULTS: Apparent prevalence of fecal shedding of Cryptosporidium oocysts was 8% (95% confidence interval, 4% to 15%) in dams and was 7% (95% confidence interval, 3% to 13%) in crias. There was no significant difference in age between dams with positive fecal test results for Cryptosporidium oocysts (median age, 4 years; range, 3 to 8 years) and dams with negative results (median age, 4 years; range, 2.5 to 19 years). No significant difference was found in age between crias with positive fecal test results (median age, 20 days; range, 7 to 53 days) and those with negative results (median, 36 days; range, 2 to 111 days). No significant difference in fecal scores was found between crias with positive versus negative fecal test results. CONCLUSIONS AND CLINICAL RELEVANCE: A higher than previously reported apparent prevalence of fecal shedding of Cryptosporidium oocysts in healthy alpacas was found. A zoonotic risk should be considered, especially for Cryptosporidium parvum.