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1.
Cardiovasc Pathol ; 46: 107196, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32006823

RESUMO

Myxomatous mitral valve degeneration (MMVD) is a leading cause of valve repair or replacement secondary to the production of mitral regurgitation, cardiac enlargement, systolic dysfunction, and heart failure. The pathophysiology of myxomatous mitral valve degeneration is complex and incompletely understood, but key features include activation and transformation of mitral valve (MV) valvular interstitial cells (VICs) into an active phenotype leading to remodeling of the extracellular matrix and compromise of the structural components of the mitral valve leaflets. Uncovering the mechanisms behind these events offers the potential for therapies to prevent, delay, or reverse myxomatous mitral valve degeneration. One such mechanism involves the neurotransmitter serotonin (5HT), which has been linked to development of valvulopathy in a variety of settings, including valvulopathy induced by serotonergic drugs, Serotonin-producing carcinoid tumors, and development of valvulopathy in laboratory animals exposed to high levels of serotonin. Similar to humans, the domestic dog also experiences naturally occurring myxomatous mitral valve degeneration, and in some breeds of dogs, the lifetime prevalence of myxomatous mitral valve degeneration reaches 100%. In dogs, myxomatous mitral valve degeneration has been associated with high serum serotonin, increased expression of serotonin-receptors, autocrine production of serotonin within the mitral valve leaflets, and downregulation of serotonin clearance mechanisms. One pathway closely associated with serotonin involves transforming growth factor beta (TGF-ß) and the two pathways share a common ability to activate mitral valve valvular interstitial cells in both humans and dogs. Understanding the role of serotonin and transforming growth factor beta in myxomatous mitral valve degeneration gives rise to potential therapies, such as 5HT receptor (5HT-R) antagonists. The main purposes of this review are to highlight the commonalities between myxomatous mitral valve degeneration in humans and dogs, with specific regards to serotonin and transforming growth factor beta, and to champion the dog as a relevant and particularly valuable model of human disease that can accelerate development of novel therapies.


Assuntos
Doenças do Cão/metabolismo , Insuficiência da Valva Mitral/veterinária , Prolapso da Valva Mitral/metabolismo , Valva Mitral/metabolismo , Serotonina/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Animais , Doenças do Cão/patologia , Cães , Humanos , Valva Mitral/patologia , Insuficiência da Valva Mitral/metabolismo , Insuficiência da Valva Mitral/patologia , Prolapso da Valva Mitral/patologia , Transdução de Sinais , Especificidade da Espécie
3.
PLoS One ; 15(1): e0227753, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31929595

RESUMO

BACKGROUND: Mitral annular calcification (MAC) is associated with risk of stroke. This study aimed to define the morphological and functional characteristics of MAC that are related to stroke. METHODS: A total of 460 subjects with MAC from transthoracic echocardiography in a single center from 2012 to 2016 was retrospectively reviewed. Subjects were classified into two groups according to history of stroke [Group 1 (n = 366): without stroke; Group 2 (n = 94): with stroke]. Morphological and functional features of MAC on echocardiogram were scored from 0 to 3 according to MAC mobility, presence of echodense mass with central echolucencies in the periannular region suggesting caseous necrosis, and functional stenosis. RESULTS: Significantly more patients in group 2 were men and had history of diabetes mellitus, dyslipidemia, atrial fibrillation, or infective endocarditis. Although MAC thickness and extent did not differ between the two groups, group 2 showed a considerably higher MAC score than group 1 (0.50 ± 0.77 vs. 0.23 ±0.52 p<0.001) as a result of the higher prevalence of each component in group 2 [mobility (22 vs. 11%, p = 0.003), echodense mass with central areas of echolucencies suggesting caseous necrosis (23 vs. 7%, p<0.001), and functional mitral stenosis (12 vs. 7%, p = 0.042)]. On logistic regression analysis, MAC score was independently associated with stroke and showed significant incremental value to demographic factors and comorbidities in association with stroke in a consecutive manner. CONCLUSIONS: In conclusion, morphological and functional characteristics of MAC had incremental value in association with stroke over traditional risk factors. MAC score consisting of MAC mobility, typical echodense mass with central echolucencies suggesting caseous necrosis, and functional mitral stenosis was independently associated with stroke. MAC with high-risk features may act as a source of stroke or more potent composite surrogate markers for stroke-related risk factors.


Assuntos
Calcinose/complicações , Estenose da Valva Mitral/complicações , Valva Mitral/fisiopatologia , Acidente Vascular Cerebral/etiologia , Idoso , Idoso de 80 Anos ou mais , Calcinose/patologia , Calcinose/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valva Mitral/patologia , Estenose da Valva Mitral/patologia , Estenose da Valva Mitral/fisiopatologia , Estudos Retrospectivos , Fatores de Risco , Acidente Vascular Cerebral/patologia , Acidente Vascular Cerebral/fisiopatologia
5.
Res Vet Sci ; 128: 99-106, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31765842

RESUMO

Myxomatous mitral valve disease (MMVD) is the single most important acquired cardiovascular disease of the dog. Much is known about the cellular changes and the contribution of activated myofibroblasts (valve interstitial cells (aVICs) to the valve extra-cellular matrix remodelling characteristic of the disease. However, little is known on how aVIC survival might contribute to disease pathogenesis. This study examined the temporal (disease severity-dependent) and spatial distribution of aVICs in MMVD valves, the expression of a range of apoptosis-related genes in cultured VICs from both normal (quiescent VIC (qVIC) and diseased (aVIC) valves, and the differential effects of doxorubicin treatment, as a trigger of apoptosis, on expression of the same genes. Activated myofibroblasts were identified in normal valves at the valve base only (the area closest to the annulus), and then became more numerous and apparent along the valve length as the disease progressed, with evidence of cell survival at the valve base. There were no significant differences in basal gene expression comparing qVICs and aVICs for CASP3, FAS, BID, BAX, BCL2, CASP8, DDIAS, XIAP and BIRC5. After doxorubicin treatment (2 mM) for 8 h there was significant difference (P < .05) in the expression of BID, BCL2, DDIAS, and CASP8, but when assessed for interactions using a mixed model ANOVA only CASP8 was significantly different because of treatment (P < .05). These data suggest aVIC survival in MMVD valves may be a consequence of heightened resistance of aVICs to apoptosis, but would require confirmation examining expression of the relevant proteins.


Assuntos
Apoptose/fisiologia , Doenças do Cão/patologia , Doenças das Valvas Cardíacas/veterinária , Valva Mitral/patologia , Miofibroblastos/fisiologia , Animais , Apoptose/genética , Doenças do Cão/metabolismo , Cães , Doxorrubicina/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Doenças das Valvas Cardíacas/metabolismo , Doenças das Valvas Cardíacas/patologia , Valva Mitral/citologia , Valva Mitral/metabolismo
7.
Acta Vet Hung ; 67(4): 517-528, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31842599

RESUMO

The goal of this study was to determine the distribution of left ventricular (LV) systolic and diastolic dysfunctions and their prognostic value in canine parvovirus-infected dogs suffering from severe sepsis and septic shock (SS/SS). Twenty dogs with SS/SS (experimental group) and 18 healthy dogs (control group) were used in the study. Systolic and diastolic dysfunction was present in three (15%) and 14 (70%) diseased dogs, respectively, with both types of dysfunction present in two (10%) of the patients. These dogs were split into two groups: survivors (Sv, n = 14) and non-survivors (non-Sv, n = 6). The pulsed wave tissue Doppler (PW-TDI) septal mitral annulus systolic velocity (LVS'), an index of systolic dysfunction, had a high sensitivity and specificity to differentiate Sv and non-Sv animals, with values of 83.3% (95% CI: 41.6-98.4) and 83.3% (95% CI: 59.8-94.8), respectively, at an optimum cut-off point of ≥ 9.90. The PW-TDI septal early mitral annulus early-diastolic peak velocity (E'), an index of diastolic dysfunction, had the best sensitivity and specificity to differentiate Sv and non-Sv dogs, with values of 100% (95% CI: 55.2-100) and 100% (95% CI: 78.9-100), respectively, at an optimum cut-off point of ≤ 6.50. Therefore, diastolic dysfunction determined by E' is a good independent outcome predictor.


Assuntos
Valva Mitral/diagnóstico por imagem , Sepse/diagnóstico por imagem , Choque Séptico/diagnóstico por imagem , Animais , Doenças do Cão , Cães , Feminino , Masculino , Valva Mitral/patologia , Contração Miocárdica , Sepse/patologia , Choque Séptico/patologia
8.
Medicine (Baltimore) ; 98(44): e17548, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31689756

RESUMO

BACKGROUND: The incidence of atrial fibrillation (AF) varies from 5.4% to 47.1% in patients with mitral annulus calcification (MAC). We conducted a systematic review and meta-analysis on the association between MAC and AF, as well as the relation between MAC and major cardiac adverse events (MACEs) in AF patients. METHODS: We conducted comprehensive search for literature on associations between MAC and AF using the following databases: MEDLINE, PubMed, Embase, and the Web of Science. The pooled odds ratio (OR) or relative risk and the corresponding 95% confidence intervals (CIs) were calculated to assess the relationship between MAC and AF, as well as the rates of MACEs in AF patients with or without MAC. RESULTS: Thirteen studies met our eligibility criteria on associations between MAC and AF, including 6232 patients with MAC and 15,199 patients without MAC. Moreover, 5 studies met our eligibility criteria on the rates of MACEs in AF patients with or without MAC. The pooled analysis demonstrated a statistically significant increased risk of development of incident AF in patients with MAC than those without MAC (random effects OR: 2.34; 95% CI: 1.91, 2.85; P = .000). And the pooled analysis demonstrated a statistically significant increased risk of development of MACEs in AF patients with MAC (random effects OR: 2.34; 95% CI: 1.24, 4.41; P = .009). CONCLUSION: MAC was independently associated with AF and AF patients with MAC were at greater risk for cardiovascular and cerebrovascular events.


Assuntos
Fibrilação Atrial/epidemiologia , Calcinose/epidemiologia , Cardiomiopatias/epidemiologia , Valva Mitral/patologia , Fatores Etários , Doenças Cardiovasculares/epidemiologia , Humanos , Razão de Chances , Fatores de Risco , Fatores Sexuais
9.
BMC Vet Res ; 15(1): 425, 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31775756

RESUMO

BACKGROUND: Myxomatous mitral valve disease (MMVD), the most common naturally-occurring heart disease in dogs, is associated with alterations in energy metabolism, oxidative stress and inflammation. Energy deprivation plays a causal role in the development of heart failure. This study was designed to determine if a cardiac protection blend (CPB) of nutrients containing medium-chain triglycerides as an alternative energy source, fish oil to reduce inflammation, antioxidants, and other key nutrients important to cardiac health and function could slow or prevent MMVD progression. Nineteen dogs with early stage MMVD and 17 breed-, age-, and sex-matched healthy dogs were enrolled for a 6-month blinded, placebo-controlled study. Dogs in each cardiac health group were randomly assigned to either control diet (CON) or CPB-supplemented diet. Echocardiography was performed at baseline, 3 months and 6 months. RESULTS: No changes were found in healthy dogs. While MMVD-CON dogs had an average 10% increase over baseline in left atrial diameter (LAD) and left atrial to aortic root ratio (LA/Ao) at 6 months, MMVD-CPB dogs showed 3% decreases, resulting significant diet by time interactions (P = 0.037, P = 0.005, respectively). More MMVD-CON dogs progressed from stage B1 to B2 during the study. A positive correlation was found between 6-month changes in LAD and blood pressures in MMVD-CPB dogs (systolic: P = 0.050, diastolic: P = 0.035) but not MMVD-CON dogs. CONCLUSIONS: Our results demonstrated efficacy of CPB-based dietary intervention in reducing LA size and mitral regurgitation, and in slowing or preventing the progression of early MMVD in dogs.


Assuntos
Dietoterapia/veterinária , Doenças do Cão/dietoterapia , Doenças das Valvas Cardíacas/veterinária , Ração Animal/análise , Animais , Antioxidantes , Doenças do Cão/diagnóstico por imagem , Cães , Ecocardiografia/veterinária , Feminino , Óleos de Peixe , Átrios do Coração/diagnóstico por imagem , Átrios do Coração/patologia , Doenças das Valvas Cardíacas/diagnóstico por imagem , Doenças das Valvas Cardíacas/dietoterapia , Masculino , Valva Mitral/patologia , Triglicerídeos
10.
J Cardiothorac Surg ; 14(1): 205, 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31775821

RESUMO

BACKGROUND: Good mid-term durability of mitral valve repair of bileaflet lesions has been reported; however, patients may develop failure during follow-up. This study assessed late outcomes and mechanisms of failure associated with mitral valve repair of bileaflet lesions. METHODS: Fifty-six patients (mean age 67 ± 12 years) underwent mitral valve repair of bileaflet lesions due to degenerative disease in 2011-2018. Mitral annuloplasty was added to all procedures except for 1 patient with annular calcification. Mitral valve lesions were identified by surgical inspection. Mean clinical and echocardiography follow-up occurred at 2.7 ± 2.1 and 2.5 ± 1.9 years, respectively. RESULTS: Additional mitral valve repair techniques involved triangular resection (n = 15 patients), quadrangular resection with sliding plasty (n = 12), neochordoplasty (n = 52), and commissural plication (n = 26). Prolapse of ≥2 anterior and posterior leaflet scallops occurred in 22 (39%) and 30 (54%) patients, respectively. During follow-up, 10 (17.8%) patients developed moderate or severe mitral regurgitation. Whereas prolapse or tethering was observed early after neochordoplasty or quadrangular resection, recurrent regurgitation occurred late after commissural repair. Five-year freedom from recurrent moderate or severe mitral regurgitation rates was 71.1 ± 11.0%. CONCLUSIONS: Seventeen percent of patients developed recurrent mitral regurgitation during follow-up. Repair failure in the early phase occurred owing to aggressive resection of the posterior mitral leaflet or maladjustment of the artificial neochordae. Recurrent mitral regurgitation might occur in the late phase even after acceptable commissural repair. A sequential approach may be useful to improve the quality of mitral valve repair in bileaflet lesions.


Assuntos
Anuloplastia da Valva Mitral , Insuficiência da Valva Mitral/cirurgia , Prolapso da Valva Mitral/cirurgia , Valva Mitral/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Ecocardiografia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Valva Mitral/patologia , Insuficiência da Valva Mitral/diagnóstico , Insuficiência da Valva Mitral/patologia , Prolapso da Valva Mitral/diagnóstico , Prolapso da Valva Mitral/patologia , Recidiva , Resultado do Tratamento
11.
PLoS One ; 14(10): e0223164, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31581204

RESUMO

Pimobendan has gained enormous importance in the treatment of mitral valve disease in dogs. The current consensus statement of the American College of Veterinary Internal Medicine (ACVIM) recommends a treatment for dogs with symptomatic disease and dogs with asymptomatic disease with radiographic and echocardiographic signs of cardiomegaly. To investigate whether these dogs also benefit from a therapy with pimobendan, 21 dogs with mitral valve disease ACVIM B1 underwent a standardized submaximal exercise test on a treadmill. In this double-blinded and randomized study, the animals were divided into two groups, one receiving pimobendan and the other a placebo. At the first visit and at every follow-up appointment (at days 90 and 180), heart rate during the complete exercise test and lactate before and after running were measured. In addition to this, a questionnaire was completed by the dogs' owners and all dogs were given an echocardiographic examination to detect any changes and to observe if the disease had progressed. Due to the diagnosis of leishmaniosis, one dog in the pimobendan group was retrospectively removed from the study so that 20 dogs were included for statistical analysis. No differences were observed at any time between the pimobendan-group and the placebo-group regarding heart rate. At day 180, the increase in lactate after exercise was significantly lower than in the placebo-group. The increase in the pimobendan-group at day 180 was lower than at day 90. Most of the dog owners from the pimobendan-group declared that their dogs were more active at day 90 (6/10) and at day 180 (8/10), while most dog owners from the placebo-group observed no changes regarding activity at day 90 (8/10) and day 180 (6/10). It can be concluded that the results of this study indicate that some dogs with mitral valve disease ACVIM B1 might benefit from a therapy with pimobendan.


Assuntos
Cardiomegalia/complicações , Ecocardiografia , Doenças das Valvas Cardíacas/tratamento farmacológico , Doenças das Valvas Cardíacas/veterinária , Ácido Láctico/sangue , Valva Mitral/patologia , Aptidão Física/fisiologia , Piridazinas/farmacologia , Animais , Cardiomegalia/fisiopatologia , Doenças do Cão/tratamento farmacológico , Cães , Teste de Esforço , Feminino , Sopros Cardíacos/complicações , Sopros Cardíacos/fisiopatologia , Frequência Cardíaca/efeitos dos fármacos , Doenças das Valvas Cardíacas/diagnóstico por imagem , Doenças das Valvas Cardíacas/fisiopatologia , Masculino , Valva Mitral/diagnóstico por imagem , Valva Mitral/fisiopatologia , Corrida
12.
Arkh Patol ; 81(5): 70-73, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31626207

RESUMO

Lambl's excrescences are a rare disease that is characterized by a lesion of the heart valves as filamentous growths on their surface mainly along the coaptation lines and that is mostly asymptomatic. Due to traumatic injuries during heart contractions, fibrin masses can be deposited on the surface of the growths, contributing to thromboembolic events or infection. The paper provides the data available in the literature and demonstrates a postmortem observation of Lambl's excrescences on the ventricular surface of the mitral valve concurrent with myocardial infarction.


Assuntos
Doenças das Valvas Cardíacas/complicações , Valva Mitral/patologia , Infarto do Miocárdio/complicações , Autopsia , Doenças das Valvas Cardíacas/patologia , Humanos , Infarto do Miocárdio/patologia
13.
Morphologie ; 103(343): 139-147, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31570309

RESUMO

OBJECTIVE OF THE STUDY: Transcatheter mitral valve interventions are emerging as a viable alternative for patients at high risk. Two key aspects are crucial during the preoperative planning: left ventricular outflow tract assessment and anatomical analysis. Given that the manual anatomical analysis is time-consuming, an automated approach may introduce efficiency during preoperative planning. In this study, we present an automatic method to detect the mitral valve annulus and discuss possible implementation of this method in clinical practice. PATIENTS: This retrospective study used the data of 71 patients collected from multiple centra. The mean age of this cohort was 74.2±13.1 years, and 56.1% of the patients were female and 43.9% male. MATERIALS AND METHODS: We trained three deep learning models to segment the area around the mitral valve annulus. In a post-processing step, we extracted the mitral valve annulus from this segmentation. As a final step, clinically relevant measurements such as 2D perimeter, trigone-to-trigone (TT) distance, septal-to-lateral (SL) distance and commissure-to-commissure (IC) distance were derived from the predicted mitral valve annulus. The method was cross-validated with k-folding. RESULTS: The predicted measurements showed excellent correlation with the manually obtained clinical measurements: 2D perimeter: R2=0.93, TT-distance: R2=0.86, SL-distance: R2=0.86 and IC-distance: R2=0.90. The total analysis time per patient of the automatic method was less than 1 second, which is an enormous speed-up as compared to the manual process (25minutes). CONCLUSION: The efficiency and accuracy of the proposed method give the confidence to move towards implementation of this technology in clinical practice. We propose a possible implementation of this method in clinical practice, which, in our opinion, will facilitate safe and efficient preoperative planning of transcatheter mitral valve interventions.


Assuntos
Implante de Prótese de Valva Cardíaca/métodos , Insuficiência da Valva Mitral/cirurgia , Valva Mitral/diagnóstico por imagem , Planejamento de Assistência ao Paciente , Complicações Pós-Operatórias/prevenção & controle , Idoso , Idoso de 80 Anos ou mais , Aprendizado Profundo , Feminino , Próteses Valvulares Cardíacas/efeitos adversos , Implante de Prótese de Valva Cardíaca/efeitos adversos , Implante de Prótese de Valva Cardíaca/instrumentação , Humanos , Masculino , Pessoa de Meia-Idade , Valva Mitral/patologia , Valva Mitral/cirurgia , Insuficiência da Valva Mitral/diagnóstico por imagem , Tomografia Computadorizada Multidetectores , Complicações Pós-Operatórias/etiologia , Desenho de Prótese , Estudos Retrospectivos
14.
Am J Case Rep ; 20: 1422-1426, 2019 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-31558692

RESUMO

BACKGROUND Immediate evaluation, diagnosis, and treatment of a patient with infective endocarditis, an infection of the endocardium and/or integral structures found within the heart, is essential to patient survival. CASE REPORT We present the case of a 41-year-old man who was brought to the Emergency Department for altered mental status and fever. He was found to have methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia complicated with severe respiratory failure and metabolic encephalopathy, necessitating intubation and mechanical ventilation. As part of the workup for persistent Staphylococcal bacteremia, 2 transthoracic echocardiograms (TTE) failed to reveal any valvular abnormalities. However, a transesophageal echocardiogram (TEE) detected a 30×30 mm large vegetation on the anterior mitral valve leaflet. Due to the overall size and risk of systemic embolization, and the fact that the patient developed new-onset heart failure, the mitral valve was replaced using an open approach. The patient tolerated the procedure well and was discharged after an extended period of hospitalization. CONCLUSIONS Although the literature emphasizes that the sensitivity of TTE significantly increases when the vegetation size is above 1 cm, it is of utmost importance for clinicians to keep in mind that this is not always true, and clinicians should consider performing a TEE to rule out infective endocarditis whenever a TTE is unable to detect any vegetation in a patient with persistent Staphylococcal bacteremia. This is clearly demonstrated by the present case, in which two TTEs failed to detect a 30×30 mm vegetation.


Assuntos
Ecocardiografia Transesofagiana , Endocardite Bacteriana/diagnóstico por imagem , Valva Mitral/diagnóstico por imagem , Valva Mitral/microbiologia , Adulto , Bacteriemia/diagnóstico , Bacteriemia/microbiologia , Ecocardiografia , Endocardite Bacteriana/patologia , Endocardite Bacteriana/cirurgia , Implante de Prótese de Valva Cardíaca , Humanos , Masculino , Valva Mitral/patologia , Valva Mitral/cirurgia , Infecções Estafilocócicas/diagnóstico
15.
Innovations (Phila) ; 14(6): 558-563, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31476935

RESUMO

Minimally invasive mitral valve surgery has become routine in many institutions. Disadvantages of this approach include prolonged aortic cross-clamp and cardiopulmonary bypass times. Mitral valve replacement with a continuous suture technique may reduce operative times. We present a case of a 51-year-old man suffering from severe rheumatic mitral disease to highlight our continuous suture technique for minimally invasive mitral valve replacement. We also report preliminary results from our series of 15 patients suffering various rheumatic mitral pathology treated with this technique.


Assuntos
Procedimentos Cirúrgicos Minimamente Invasivos/efeitos adversos , Estenose da Valva Mitral/cirurgia , Valva Mitral/cirurgia , Cardiopatia Reumática/cirurgia , Adulto , Aorta/cirurgia , Procedimentos Cirúrgicos Cardíacos/métodos , Ecocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Valva Mitral/diagnóstico por imagem , Valva Mitral/patologia , Estenose da Valva Mitral/patologia , Duração da Cirurgia , Cardiopatia Reumática/complicações , Índice de Gravidade de Doença , Instrumentos Cirúrgicos/estatística & dados numéricos , Técnicas de Sutura/tendências , Resultado do Tratamento
16.
PLoS One ; 14(8): e0221126, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31415646

RESUMO

The utility of cells cultured from the mitral valve as models of myxomatous diseases needs to be properly validated. In this study valve interstitial cells (VICs) and valve endothelial cells (VECs) were cultured from normal and diseased canine mitral valves in 2% (v/v) or 10% FBS media, in the presence of TGFß1, 2 and 3, the TGFß RI kinase inhibitor SB431542 and TGFß neutralising antibodies, 5HT and the 5HT2RB antagonist LY272015. Cultures were examined by morphology, transcriptomic profiling, protein expression of the cell specific markers αSMA and SM22α (VICs), and CD31 (VECs), deposition of proteoglycans (PG), the PG versican, and the TGFßs themselves. VECs derived from normal valves were CD31+/αSMA-, but those from diseased valves were αSMA+, indicating endothelial-to-mesenchymal (EndoMT) transition had occurred. The TGFßs induced EndoMT in normal VECs, and this was abolished by SB431542, with significant changes in αSMA, CD31 and HAS2 expression (P<0.05). Normal VICs cultured in 10% FBS media were αSMA+ (activated myofibroblast (disease) phenotype), but were αSMA- when grown in 2% FBS. VICs from diseased dogs were αSMA+ in 2% FBS (retention of the activated myofibroblast disease phenotype), with significantly increased TGFß1 expression (P<0.05) compared to normal cells. Treatment of normal and diseased VICs with the TGFßs significantly increased expression of αSMA, SM22α, versican, the TGFßs themselves, and deposition of PGs (P<0.05), with TGFß1 being the most potent activator. These effects were either abolished or markedly reduced by SB431542 and a pan-TGFß neutralizing antibody (P<0.05). SB431542 also markedly reduced αSMA expression in VICs from diseased valves, but 5HT and LY272015 had no effect on VIC phenotype. Transcriptomic profiling identified clear differences in gene expression for the different conditions and treatments that partially matched that seen in native diseased valve tissue, including changes in expression of ACTA2 (αSMA), 5HTR2B, TAGLN (SM22α) and MYH10 (SMemb), gene ontology terms and canonical signalling pathways. Normal and diseased VICs and normal VECs from canine mitral valves can be successfully grown in culture with retention of phenotype, which can be manipulated using TGFß1 and the TGFß RI kinase inhibitor SB431542. This optimized cell system can now be used to model MMVD to elucidate disease mechanisms and identify key regulators of disease progression.


Assuntos
Técnicas de Cultura de Células , Doenças do Cão/metabolismo , Células Endoteliais/metabolismo , Prolapso da Valva Mitral/metabolismo , Valva Mitral/metabolismo , Modelos Cardiovasculares , Miofibroblastos/metabolismo , Animais , Antígenos de Diferenciação/metabolismo , Doenças do Cão/patologia , Cães , Células Endoteliais/patologia , Valva Mitral/patologia , Prolapso da Valva Mitral/patologia , Miofibroblastos/patologia
17.
Vet J ; 250: 36-43, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31383418

RESUMO

Higher concentrations of circulating serotonin have been reported in Cavalier King Charles spaniels (CKCS) compared to other dog breeds. The CKCS is also a breed highly predisposed to myxomatous mitral valve disease (MMVD). The aim of this study was to determine urine concentrations of 5-hydroxyindoleacetic acid (5-HIAA), the major metabolite and excretion product of serotonin, in a population of CKCS with preclinical MMVD, and to evaluate whether urine 5-HIAA concentrations were associated with MMVD severity, dog characteristics, setting for urine sampling, platelet count, and serotonin concentration in serum and platelet-poor plasma (PPP). The study population consisted of 40 privately-owned CKCS (23 females; 17 males) with and without preclinical MMVD as follows: American College of Veterinary Internal Medicine (ACVIM) group A (n = 11), ACVIM group B1 (n = 21) and ACVIM group B2 (n = 8). Urine 5-HIAA concentrations were not significantly associated with preclinical MMVD disease, platelet count or circulating concentrations of serotonin (in serum and PPP; P > 0.05). Females had higher 5-HIAA concentrations than males in morning urine collected at home (females, 3.1 [2.9-3.7] µmol/mmol creatinine [median and quartiles]; males, 1.7 [1.2-2.2] µmol/mmol creatinine; P = 0.0002) and urine collected at the clinic (females, 3.5 [3.1-3.9] µmol/mmol creatinine; males, 1.6 [1.3-2.1] µmol/mmol creatinine; P < 0.0001). Five-HIAA concentrations in urine collected at home and at the clinic were significantly associated (P = 0.0004; r = 0.73), and higher concentrations were found in urine collected at the clinic (P = 0.013). Urine 5-HIAA concentration was influenced by sex and setting of urine sampling. Urine 5-HIAA concentration was not associated with MMVD severity or circulating concentrations of serotonin in CKCS with preclinical disease.


Assuntos
Doenças do Cão/metabolismo , Doenças das Valvas Cardíacas/veterinária , Ácido Hidroxi-Indolacético/urina , Serotonina/sangue , Animais , Cães , Feminino , Doenças das Valvas Cardíacas/urina , Masculino , Valva Mitral/patologia , Contagem de Plaquetas/veterinária , Especificidade da Espécie
18.
Pan Afr Med J ; 32: 157, 2019.
Artigo em Francês | MEDLINE | ID: mdl-31303927

RESUMO

Infectious endocarditis is regarded as a potentially serious pathology despite the advances in diagnostic and treatment options. Valves on the left side of the heart are most affected and embolic events, mycotic aneurysms, abscesses as well as valve perforations are life-threatening consequences of this disease. We here report a case of endocarditis with aortic and mitral valve involvement complicated by splenic and renal infarction, cerebral mycotic aneurysm and mitral valve perforation. The interest in the subject of this case study is the positive medico-surgical treatment outcome obtained despite a multitude of complications.


Assuntos
Valva Aórtica/microbiologia , Endocardite Bacteriana/diagnóstico , Aneurisma Cardíaco/diagnóstico , Valva Mitral/microbiologia , Idoso , Aneurisma Infectado/diagnóstico , Aneurisma Infectado/microbiologia , Valva Aórtica/patologia , Endocardite Bacteriana/microbiologia , Aneurisma Cardíaco/microbiologia , Humanos , Masculino , Valva Mitral/patologia , Infarto do Baço/diagnóstico
19.
Mol Biol Rep ; 46(5): 5225-5236, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31359379

RESUMO

To assess the association between vitamin D-Binding Protein (VDBP rs7041T>G) and vitamin D receptor (VDR rs1544410G>A) gene polymorphisms with susceptibility to cardiovascular diseases in population from west of Iran. Two hundred forty-nine individuals with cardiovascular disease (92 with aortic and Mitral Valves Calcification (AMVC) and 157 with Coronary Artery Diseases (CAD) that their diseases were confirmed by echocardiography and angiography and unrelated 182 healthy controls (gender and age-matched) were selected for this case-control study. The VDR 1544410G>A, and VDBP 7041T>G genotyping were detected by PCR-RFLP, serum vitamin D and lipid concentrations were measured by ELISA and enzyme assay, respectively. The VDR rs1544410G>A gene is a strong risk factor for CAD (OR = 1.28, p = 0.002) and the dominant genotype (T/G+G/G) of VDBP 7041 T>G SNP plays a protective role (OR = 0.67, p = 0.003) in AMVC development in studied population. In addition, lower level of vitamin D strongly increased the risk of CAD (15 ± 11.02 vs. 21.3 ± 18 µg/L, p = 0.043) and AMVC (12.1 ± 13.1 vs.21.3 ± 18 µg/L, p = 0.014) development in individuals carrying T/T genotype of VDBP 7041 T>G gene polymorphism. There was a strong interaction between A allele VDR rs1544410 and G allele of VDBP rs7041 genes in a protective role (OR = 0.74, p = 0.044) in AMVC patients). CAD and AMVC patients were deficient in vitamin D, i.e. their level of vitamin D was strongly lower than that in the control group. Our findings for the first time indicated that there is a strong association between vitamin D deficiency, lipid profile and the VDR rs1544410G>A and rs7T41>G VDBP genes polymorphisms. These interactions may be one of the important factors for CAD and AMVC incidence.


Assuntos
Calcinose/genética , Doença da Artéria Coronariana/genética , Polimorfismo de Nucleotídeo Único , Receptores de Calcitriol/genética , Proteína de Ligação a Vitamina D/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/patologia , Calcinose/sangue , Calcinose/diagnóstico por imagem , Estudos de Casos e Controles , Angiografia Coronária , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/diagnóstico por imagem , Ecocardiografia , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Valva Mitral/diagnóstico por imagem , Valva Mitral/patologia , Vitamina D/análogos & derivados , Vitamina D/sangue
20.
J Cardiovasc Surg (Torino) ; 60(5): 617-623, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31274274

RESUMO

BACKGROUND: Mitral valve (MV) repair has been recommended for MV diseases. Good repair requires a full understanding of the three-dimensional (3D) structure of the MV, however, currently little is known about the 3D structure of the rheumatic MV. METHODS: A total of 82 cases underwent 3DTEE. Of these, 41 patients with rheumatic valvular disease (RVD) were studied intraoperatively (17 had severe mitral stenosis, 8 had severe mitral regurgitation, 16 had severe mitral stenosis coupled with regurgitation). There were 19 patients with degenerative MV disease (mitral valve prolapse [MVP] with severe regurgitation) and 22 cases with normal MV served as control subjects (CS). RESULTS: Compared with CS, the anteroposterior diameter, anterolateral posteromedial, annulus circumference, and annulus area of both pathological groups, i.e., the RVD and MVP groups, were understandably greater. Though the sphericity index was greater in the RVD group vis-à-vis CS, the MVP group had nearly the same sphericity index as CS. The mitral annulus of patients with RVD tended to be round. Annular unsaddling, defined as annular height to commissural width ratio (an indicator of saddle degree) less than 15%, was significantly more prevalent in the group with degenerative MV disease. Automatic dynamic analysis revealed that the parameters of annular maximum displacement and annulus area fraction (two-dimensional) were considerably decreased in the RVD group. CONCLUSIONS: Annular unsaddling was significantly more prevalent in the degenerative MV disease group. The mitral annulus of patients with RVD tended to be round and stiff.


Assuntos
Ecocardiografia Tridimensional , Ecocardiografia Transesofagiana , Implante de Prótese de Valva Cardíaca , Anuloplastia da Valva Mitral , Insuficiência da Valva Mitral/diagnóstico por imagem , Estenose da Valva Mitral/diagnóstico por imagem , Valva Mitral/patologia , Cardiopatia Reumática/diagnóstico por imagem , Adulto , Idoso , Tomada de Decisão Clínica , Feminino , Próteses Valvulares Cardíacas , Implante de Prótese de Valva Cardíaca/instrumentação , Hemodinâmica , Humanos , Masculino , Pessoa de Meia-Idade , Valva Mitral/fisiopatologia , Valva Mitral/cirurgia , Anuloplastia da Valva Mitral/instrumentação , Insuficiência da Valva Mitral/fisiopatologia , Insuficiência da Valva Mitral/cirurgia , Estenose da Valva Mitral/fisiopatologia , Estenose da Valva Mitral/cirurgia , Seleção de Pacientes , Valor Preditivo dos Testes , Estudos Prospectivos , Desenho de Prótese , Recuperação de Função Fisiológica , Cardiopatia Reumática/fisiopatologia , Cardiopatia Reumática/cirurgia , Índice de Gravidade de Doença , Resultado do Tratamento
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