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1.
Fish Shellfish Immunol ; 94: 447-454, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31526847

RESUMO

Neutrophils are the first line defenders in the innate immune response, and rapidly migrate to an infected or injured area. Recently, bidirectional migration of neutrophils to the wound and the corresponding functions have become popular research pursuits. In zebrafish larvae, CXCR1/CXCL8 is the predominant chemoattractant pathway to recruit neutrophil to wound, while CXCR2/CXCL8 pathway mediate neutrophil dispersal in wound after injury. Here, we found that both CXCR1/CXCL8 and LTB4/BLT1 signals are activated in zebrafish heart after cryoinjury. And with a CXCR1/2 selective inhibitor (SB225002) treatment, the recruitment of neutrophils was not affected, but reverse migration of neutrophils was inhibited after cryoinjury of heart. We suggested that the neutrophil recruitment to cryoinjured area might be mediated by LTB4/BLT1 signals at the presence of SB225002. Therefore, SB225002 treatment resulted more accumulation and long retention of neutrophils in the injured heart. The long retention of neutrophils in the wound promoted revascularization in the injured heart; however, the AKT/mTOR pathway was inhibited and the regeneration was impaired. Our findings suggest that retention of neutrophils is a well-orchestrated process and might regulate regeneration by the AKT/mTOR pathway.


Assuntos
Congelamento/efeitos adversos , Coração/fisiologia , Regeneração , Transdução de Sinais/fisiologia , Peixe-Zebra/fisiologia , Animais , Criopreservação/veterinária , Traumatismos Cardíacos/etiologia , Traumatismos Cardíacos/fisiopatologia , Neutrófilos/imunologia
2.
Interv Cardiol Clin ; 8(4): 403-409, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31445724

RESUMO

Conduction disturbances following TAVR are a common occurrence given the proximity of the various conduction system tissues, including the AV node, His-bundle, and bundle branches to the left ventricular outflow tract and aortic root. Impairment of these conduction system abnormalities may necessitate permanent pacemaker implantation, which increases morbidity and mortality, as well as length of stay, for the patient. The incidence, mechanisms, and predictors of conduction abnormalities and treatment options are discussed in this up-to-date review of the topic.


Assuntos
Estenose da Valva Aórtica/cirurgia , Valva Aórtica/cirurgia , Eletrocardiografia , Sistema de Condução Cardíaco/lesões , Traumatismos Cardíacos/fisiopatologia , Complicações Intraoperatórias , Substituição da Valva Aórtica Transcateter/efeitos adversos , Sistema de Condução Cardíaco/fisiopatologia , Traumatismos Cardíacos/etiologia , Humanos
3.
Cell Physiol Biochem ; 53(1): 101-120, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31215778

RESUMO

In the recent decades, cardiovascular diseases emerged as the major leading cause of human mortality. However, current clinical approaches still do not encompass a thorough therapeutic solution for improving heart function of the patients who suffered an extensive myocardial injury. Based on this status quo, stem cells could become a novel option, as a natural source of the new myocardium lineage cells, being capable of paracrine factors secretion, protection or even regeneration of the damaged heart muscle. Efficient stem cell-based therapy of the heart should lead to repair or/and replacement of the degenerated tissue with functional myocardial and endothelial cells. Hereon, various types of pluripotent and multipotent stem cells have been already studied in the pre-clinical and clinical settings, demonstrating their cardiomyogenic and regenerative potential. In this context, as a type of male adult stem/ progenitors, spermatogonial stem cells feature a remarkable ability for a formation of cardiovascular lineages, based on our own observations. Presented data supports the presumption, that spermatogonial stem cells not only have a suitable capacity to generate functional heart cells but can also potentially improve the function of an injured myocardium. In this review article, we first describe the essential molecular and pathophysiological mechanisms involved in the heart tissue injury. Afterwards, based on our ongoing study, we review the impact of the stem cell technologies on the regeneration therapy in cardiovascular and myocardial diseases. Particular emphasis is being put on the usability of spermatogonial stem cells in cardiac therapy.


Assuntos
Células-Tronco Germinativas Adultas/citologia , Traumatismos Cardíacos/terapia , Coração/fisiologia , Regeneração , Transplante de Células-Tronco , Células-Tronco/citologia , Células-Tronco Germinativas Adultas/metabolismo , Células-Tronco Germinativas Adultas/transplante , Animais , Diferenciação Celular , Coração/fisiopatologia , Traumatismos Cardíacos/patologia , Traumatismos Cardíacos/fisiopatologia , Humanos , Miocárdio/citologia , Miocárdio/patologia , Miócitos Cardíacos/citologia , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Transplante de Células-Tronco/métodos , Células-Tronco/metabolismo
4.
J Cardiovasc Med (Hagerstown) ; 20(10): 709-717, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31246700

RESUMO

: Traumatic mitral valve regurgitation is a rare and often insidious condition. Clinical presentation is variable and influenced by the anatomic structures injured; when papillary muscles are damaged, the clinical presentation is often acute, whereas, in the case of involvement of other anatomic structures of the valvular apparatus (e.g. chordae tendinae), the onset of symptoms may be delayed (days, weeks, or months). Therefore, diagnosis may be belated because of the heterogeneous clinical presentation. Traumatic mitral valve injury should be excluded in patients admitted to the emergency services with blunt chest trauma, in particular when signs or symptoms of acute heart failure occur. Echocardiography, particularly with the transoesophageal approach, may play a pivotal role in this setting. Herein, we present a case of severe mitral regurgitation because of blunt chest trauma and a systematic review of the literature. We examined 192 described cases, classified according to epidemiology, aetiology, anatomic features, clinical presentation, diagnosis, surgical/clinical management and prognosis.


Assuntos
Acidentes de Trabalho , Traumatismos Cardíacos/etiologia , Insuficiência da Valva Mitral/etiologia , Valva Mitral/lesões , Ferimentos não Penetrantes/etiologia , Traumatismos Cardíacos/diagnóstico por imagem , Traumatismos Cardíacos/fisiopatologia , Traumatismos Cardíacos/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Valva Mitral/diagnóstico por imagem , Valva Mitral/fisiopatologia , Valva Mitral/cirurgia , Anuloplastia da Valva Mitral , Insuficiência da Valva Mitral/diagnóstico por imagem , Insuficiência da Valva Mitral/fisiopatologia , Insuficiência da Valva Mitral/cirurgia , Recuperação de Função Fisiológica , Índice de Gravidade de Doença , Resultado do Tratamento , Ferimentos não Penetrantes/diagnóstico por imagem , Ferimentos não Penetrantes/fisiopatologia , Ferimentos não Penetrantes/cirurgia
5.
Fish Shellfish Immunol ; 89: 117-126, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30928664

RESUMO

Inflammation plays a crucial role in cardiac regeneration. Numerous advantages, including a robust regenerative ability, make the zebrafish a popular model to study cardiovascular diseases. The zebrafish breakdance (bre) mutant shares several key features with human long QT syndrome that predisposes to ventricular arrhythmias and sudden death. However, how inflammatory response and tissue regeneration following cardiac damage occur in bre mutant is unknown. Here, we have found that inflammatory response related genes were markedly expressed in the injured heart and excessive leukocyte accumulation occurred in the injured area of the bre mutant zebrafish. Furthermore, bre mutant zebrafish exhibited aberrant apoptosis and impaired heart regenerative ability after ventricular cryoinjury. Mild dosages of anti-inflammatory or prokinetic drugs protected regenerative cells from undergoing aberrant apoptosis and promoted heart regeneration in bre mutant zebrafish. We propose that immune or prokinetic therapy could be a potential therapeutic regimen for patients with genetic long QT syndrome who suffers from myocardial infarction.


Assuntos
Regulação para Baixo , Traumatismos Cardíacos/fisiopatologia , Inflamação/fisiopatologia , Regeneração , Peixe-Zebra/fisiologia , Animais , Temperatura Baixa/efeitos adversos , Modelos Animais de Doenças , Coração , Traumatismos Cardíacos/etiologia , Inflamação/etiologia
6.
J Cardiothorac Surg ; 14(1): 28, 2019 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-30717747

RESUMO

BACKGROUND: Isolated right atrial rupture (IRAR) from blunt chest trauma is rare. There are no physical exam findings and non-invasive testing specific to the condition, which result in diagnostic delays and poor outcomes. We present a case of IRAR along with a systematic review of similar cases in the literature. CASE REPORT: A 23-year-old male presented following a motor vehicle accident (MVA). He was bradycardic and hypotensive during transportation; and required intubation. There were contusions along the right chest wall with clear breath sounds, and no jugular venous distension, muffled heart sounds. Hemodynamic status progressively worsened, ultimately leading to his death. However, no external sources of bleeding or evidence of cardiac tamponade was found. METHODS: A search of PubMed, Ovid, and the Cochrane Library using: (Blunt OR Blunt trauma) AND (Laceration OR Rupture OR Tear) AND (Right Atrium OR Right Atrial). Articles were included if they were original articles describing cases of IRAR. RESULTS: Forty-five reports comprising seventy-five (n = 75) cases of IRAR. CONCLUSION: IRAR most commonly occurs following MVAs as the result of blunt chest trauma. Rupture occurs at four distinct sites and is most commonly at the right atrial appendage. IRAR is a diagnostic challenge and requires a high index of suspicion, as patients' hemodynamics can rapidly deteriorate. The presentations vary depending on multiple factors including rupture size, pericardial integrity, and concomitant injuries. Cardiac tamponade may have a protective effect by prompting the search for a bleeding source. A pericardial window can be diagnostic and therapeutic in IRAR. Outcomes are favourable with timely recognition and prompt surgical intervention.


Assuntos
Apêndice Atrial/lesões , Traumatismos Cardíacos/diagnóstico , Ferimentos não Penetrantes/complicações , Acidentes de Trânsito , Evolução Fatal , Traumatismos Cardíacos/etiologia , Traumatismos Cardíacos/fisiopatologia , Hemodinâmica , Humanos , Masculino , Adulto Jovem
7.
Molecules ; 24(2)2019 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-30634603

RESUMO

Guinep is traditionally used in the management of cardiovascular ailments. This study aims to evaluate its medicinal constituents and effects in the management of myocardial injury in an experimental isoproterenol (ISO) rat model. Sprague-Dawley rats were randomly assigned to four groups: Group 1 was the control group; Group 2 received M. bijugatus extract (100 mg/Kg; MB) for six weeks; Group 3 was given ISO (85 mg/Kg) i.p. twice during a 24-hour period; and Group 4 was given ISO (85 mg/Kg) i.p. and MB extract (100 mg/Kg) for six weeks. The MB was administered orally by gavage, daily. The blood pressure of conscious animals was measured, while ECG was performed under anesthesia. Blood and serum were collected for biochemical and hematological analysis. The ISO group treated with MB showed a significant decrease (p < 0.001) in (SBP), diastolic (DBP), mean arterial (MAP) and heart rate (HR) compared to the ISO only group. Conversely, MB treated rats that were not induced with ISO displayed a significant decreases (p < 0.001) in SBP, DBP, MAP, and HR. ISO significantly elevated the ST segment (p < 0.001) and shortened the QTc interval (p < 0.05), which were recovered after treatment with 100 mg/Kg of MB. In addition, the results showed a significant decrease (p < 0.001) in the heart to body weight ratio of the ISO group treated with MB compared to the ISO only group. Furthermore, the extract normalized the hematological values depressed by the ISO while significantly elevating the platelet count. UHPLC high-resolution orbitrap mass spectrometry analysis results revealed the presence of several antioxidants like vitamin C and related compounds, phenolic acids, flavonoid, fatty acids (oxylipins), and terpene derivatives. The results of this study indicated that Melicoccus bijugatus did display some cardio-protective effects in relation to myocardial injury.


Assuntos
Traumatismos Cardíacos/prevenção & controle , Isoproterenol/efeitos adversos , Magnoliopsida/química , Metabolômica/métodos , Extratos Vegetais/administração & dosagem , Administração Oral , Animais , Determinação da Pressão Arterial , Cromatografia Líquida de Alta Pressão , Eletrocardiografia , Frutas , Sucos de Frutas e Vegetais/análise , Traumatismos Cardíacos/induzido quimicamente , Traumatismos Cardíacos/fisiopatologia , Frequência Cardíaca/efeitos dos fármacos , Masculino , Espectrometria de Massas , Camundongos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Ratos , Ratos Sprague-Dawley , Ratos Wistar
8.
Br J Anaesth ; 122(2): 188-197, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30686304

RESUMO

BACKGROUND: The aetiology of perioperative myocardial injury is poorly understood and not clearly linked to pre-existing cardiovascular disease. We hypothesised that loss of cardioprotective vagal tone [defined by impaired heart rate recovery ≤12 beats min-1 (HRR ≤12) 1 min after cessation of preoperative cardiopulmonary exercise testing] was associated with perioperative myocardial injury. METHODS: We conducted a pre-defined, secondary analysis of a multi-centre prospective cohort study of preoperative cardiopulmonary exercise testing. Participants were aged ≥40 yr undergoing non-cardiac surgery. The exposure was impaired HRR (HRR≤12). The primary outcome was postoperative myocardial injury, defined by serum troponin concentration within 72 h after surgery. The analysis accounted for established markers of cardiac risk [Revised Cardiac Risk Index (RCRI), N-terminal pro-brain natriuretic peptide (NT pro-BNP)]. RESULTS: A total of 1326 participants were included [mean age (standard deviation), 64 (10) yr], of whom 816 (61.5%) were male. HRR≤12 occurred in 548 patients (41.3%). Myocardial injury was more frequent amongst patients with HRR≤12 [85/548 (15.5%) vs HRR>12: 83/778 (10.7%); odds ratio (OR), 1.50 (1.08-2.08); P=0.016, adjusted for RCRI). HRR declined progressively in patients with increasing numbers of RCRI factors. Patients with ≥3 RCRI factors were more likely to have HRR≤12 [26/36 (72.2%) vs 0 factors: 167/419 (39.9%); OR, 3.92 (1.84-8.34); P<0.001]. NT pro-BNP greater than a standard prognostic threshold (>300 pg ml-1) was more frequent in patients with HRR≤12 [96/529 (18.1%) vs HRR>12 59/745 (7.9%); OR, 2.58 (1.82-3.64); P<0.001]. CONCLUSIONS: Impaired HRR is associated with an increased risk of perioperative cardiac injury. These data suggest a mechanistic role for cardiac vagal dysfunction in promoting perioperative myocardial injury.


Assuntos
Tolerância ao Exercício , Traumatismos Cardíacos/fisiopatologia , Coração/inervação , Complicações Pós-Operatórias/fisiopatologia , Procedimentos Cirúrgicos Operatórios , Nervo Vago/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Teste de Esforço , Feminino , Frequência Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Valor Preditivo dos Testes , Cuidados Pré-Operatórios , Estudos Prospectivos , Resultado do Tratamento
9.
Circulation ; 138(4): 412-423, 2018 07 24.
Artigo em Inglês | MEDLINE | ID: mdl-30571359

RESUMO

BACKGROUND: The adult mammalian heart is incapable of meaningful functional recovery after injury, and thus promoting heart regeneration is 1 of the most important therapeutic targets in cardiovascular medicine. In contrast to the adult mammalian heart, the neonatal mammalian heart is capable of regeneration after various types of injury. Since the first report in 2011, a number of groups have reported their findings on neonatal heart regeneration. The current review provides a comprehensive analysis of heart regeneration studies in neonatal mammals conducted to date, outlines lessons learned, and poses unanswered questions. METHODS: We performed a PubMed search using the keywords "neonatal" and "heart" and "regeneration." In addition, we assessed all publications that cited the first neonatal heart regeneration reports: Porrello et al, Science, Feb 2011 for apical resection injury; Porrello et al, PNAS, Dec 2012 for coronary ligation injury; and Mahmoud et al, Nature Methods, Jan 2014 for surgical methodology. Publications were examined for surgical models used, timing of surgery, and postinjury assessment including anatomic, histological, and functional assessment, as well as conclusions drawn. RESULTS: We found 30 publications that performed neonatal apical resection, 19 publications that performed neonatal myocardial infarction by coronary artery ligation, and 6 publications that performed cryoinjury using liquid nitrogen-cooled metal probes. Both apical resection and ischemic infarction injury in neonatal mice result in a robust regenerative response, mediated by cardiomyocyte proliferation. On the other hand, several reports have demonstrated that cryoinjury is associated with incomplete heart regeneration in neonatal mice. Not surprisingly, several studies suggest that injury size, as well as surgical and histological techniques, can strongly influence the observed regenerative response and final conclusions. Studies have utilized these neonatal cardiac injury models to identify factors that either inhibit or stimulate heart regeneration. CONCLUSIONS: Overall, there is consensus that both apical resection and coronary ligation injuries during the first 2 days of life result in heart regeneration in neonatal mammals, whereas cryoinjury was not associated with a similar regenerative response. This regenerative response is mediated by proliferation of preexisting cardiomyocytes, and is modifiable by injury size and surgical technique, as well as metabolic, immunologic, genetic, and environmental factors.


Assuntos
Proliferação de Células , Traumatismos Cardíacos/patologia , Traumatismos Cardíacos/fisiopatologia , Coração/fisiopatologia , Infarto do Miocárdio/patologia , Infarto do Miocárdio/fisiopatologia , Miócitos Cardíacos/patologia , Regeneração , Animais , Animais Recém-Nascidos , Modelos Animais de Doenças , Traumatismos Cardíacos/metabolismo , Humanos , Recém-Nascido , Camundongos , Infarto do Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo , Recuperação de Função Fisiológica , Transdução de Sinais
10.
Proc Natl Acad Sci U S A ; 115(52): E12245-E12254, 2018 12 26.
Artigo em Inglês | MEDLINE | ID: mdl-30530645

RESUMO

The significance of cardiac stem cell (CSC) populations for cardiac regeneration remains disputed. Here, we apply the most direct definition of stem cell function (the ability to replace lost tissue through cell division) to interrogate the existence of CSCs. By single-cell mRNA sequencing and genetic lineage tracing using two Ki67 knockin mouse models, we map all proliferating cells and their progeny in homoeostatic and regenerating murine hearts. Cycling cardiomyocytes were only robustly observed in the early postnatal growth phase, while cycling cells in homoeostatic and damaged adult myocardium represented various noncardiomyocyte cell types. Proliferative postdamage fibroblasts expressing follistatin-like protein 1 (FSTL1) closely resemble neonatal cardiac fibroblasts and form the fibrotic scar. Genetic deletion of Fstl1 in cardiac fibroblasts results in postdamage cardiac rupture. We find no evidence for the existence of a quiescent CSC population, for transdifferentiation of other cell types toward cardiomyocytes, or for proliferation of significant numbers of cardiomyocytes in response to cardiac injury.


Assuntos
Proliferação de Células , Traumatismos Cardíacos/fisiopatologia , Animais , Células Cultivadas , Modelos Animais de Doenças , Feminino , Fibroblastos/citologia , Fibroblastos/metabolismo , Proteínas Relacionadas à Folistatina/genética , Proteínas Relacionadas à Folistatina/metabolismo , Traumatismos Cardíacos/genética , Traumatismos Cardíacos/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Miocárdio/metabolismo , Miócitos Cardíacos/citologia , Miócitos Cardíacos/metabolismo , Gravidez , Células-Tronco/citologia , Células-Tronco/metabolismo
12.
Biomed Res Int ; 2018: 8503109, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30515415

RESUMO

Dangguibuxue decoction (DBD), a kind of Chinese herbal medicine, has been widely used to treat blood deficiency disease in China. In this experiment, we studied the effects of the Dangguibuxue decoction (DBD) on the myocardial injury induced by cyclophosphamide in mice. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatine kinase (CK), and lactic dehydrogenase (LDH) in serum were detected by commercial kits. Total white blood cell (WBCs), platelets, and cytokines pathological changes of heart tissue were also examined. In addition, the protein levels of the NF-кB pathway were detected to reveal its mechanism. The results showed that DBD significantly decreased the levels of ALT, AST, CK, and LDH and increased WBCs in CTX-induced mice. In addition, DBD significantly alleviated pathological changes of heart tissue. DBD significantly reduced the protein expressions of NF-кB signaling pathway. In summary, DBD can be considered an effective drug to alleviate CTX-induced heart damage in mice.


Assuntos
Medicamentos de Ervas Chinesas/administração & dosagem , Traumatismos Cardíacos/tratamento farmacológico , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Plaquetas/metabolismo , Creatina Quinase/sangue , Ciclofosfamida/toxicidade , Coração/efeitos dos fármacos , Coração/fisiopatologia , Traumatismos Cardíacos/sangue , Traumatismos Cardíacos/induzido quimicamente , Traumatismos Cardíacos/fisiopatologia , Humanos , L-Lactato Desidrogenase/sangue , Leucócitos/metabolismo , Camundongos , NF-kappa B/genética , Transdução de Sinais/efeitos dos fármacos
13.
Lipids Health Dis ; 17(1): 279, 2018 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-30526612

RESUMO

BACKGROUND: Hyperlipidemia is a well-established risk factor for cardiac damage, which can lead to cardiovascular diseases. Many studies have shown that Coenzyme Q10(CoQ10) protects against cardiac damage in vivo. The aim of this study was to investigate the possible protective effects of CoQ10 against cardiac damage in apolipoprotein E-deficient (ApoE-/-) mice. METHODS: Eight-week-old male C57BL/6 and ApoE-/- mice were randomly divided into four groups: C57BL/6 mice fed a normal diet (C57BL/6 group); C57BL/6 mice fed a normal diet + CoQ10 (C57BL/6 + CoQ10 group); ApoE-/- mice fed a high-fat diet (ApoE-/- HD group), and ApoE-/- mice fed a high-fat diet + CoQ10 (ApoE-/- HD + CoQ10 group). All groups were fed the different diets for 16 weeks. Blood samples were obtained from the inferior vena cava and collected in serum tubes. The samples were then stored at - 80 °C until used. Coronal sections of heart tissues were fixed in 10% formalin and then embedded in paraffin for histological evaluation. The remainder of the heart tissues was snap-frozen in liquid nitrogen for mRNA or immunohistochemical analysis. RESULTS: The metabolic parameters such as total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-c), and triglycerides (TG) levels were lower in ApoE-/-HD + CoQ10 mice than in ApoE-/- HD mice. There were significant pathophysiological changes (H&E, PAS, Masson and CD68 staining) in ApoE-/- mice in the HD group compared with those in the HD + CoQ10 group. CoQ10 reduced HD-induced cardiac tissue damage via autophagy (p62 and LC3), as evidenced by immunoblotting, immunohistochemistry, and RT-qPCR. CoQ10 also inhibited inflammation (IL-6 and TNF-α) gene expression in ApoE-/- mice. CONCLUSIONS: These results indicate that CoQ10 is a potential therapeutic target for cardiac damage caused by hyperlipidemia.


Assuntos
Apolipoproteínas E/genética , Aterosclerose/tratamento farmacológico , Doenças Cardiovasculares/tratamento farmacológico , Hiperlipidemias/tratamento farmacológico , Ubiquinona/análogos & derivados , Animais , Aorta/efeitos dos fármacos , Aorta/lesões , Aorta/fisiopatologia , Aterosclerose/sangue , Aterosclerose/complicações , Aterosclerose/prevenção & controle , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/fisiopatologia , Dieta Hiperlipídica , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Traumatismos Cardíacos/sangue , Traumatismos Cardíacos/tratamento farmacológico , Traumatismos Cardíacos/fisiopatologia , Hiperlipidemias/sangue , Hiperlipidemias/complicações , Hiperlipidemias/fisiopatologia , Interleucina-6/genética , Camundongos , Substâncias Protetoras/administração & dosagem , Fatores de Risco , Triglicerídeos/sangue , Fator de Necrose Tumoral alfa/genética , Ubiquinona/administração & dosagem
14.
PLoS One ; 13(11): e0206744, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30408050

RESUMO

PURPOSE: Chordae rupture is one of the main lesions observed in traumatic heart events that might lead to severe tricuspid valve (TV) regurgitation. TV regurgitation following chordae rupture is often well tolerated with few or no symptoms for most patients. However, early repair of the TV is of great importance, as it might prevent further exacerbation of the regurgitation due to remodeling responses. To understand how TV regurgitation develops following this acute event, we investigated the changes on TV geometry, mechanics, and function of ex-vivo porcine hearts following chordae rupture. METHODS: Sonomicrometry techniques were employed in an ex-vivo heart apparatus to identify how the annulus geometry alters throughout the cardiac cycle after chordae rupture, leading to the development of TV regurgitation. RESULTS: We observed that the TV annulus significantly dilated (~9% in area) immediately after chordae rupture. The annulus area and circumference ranged from 11.4 ± 2.8 to 13.3 ± 2.9 cm2 and from 12.5 ± 1.5 to 13.5 ± 1.3 cm, respectively, during the cardiac cycle for the intact heart. After chordae rupture, the annulus area and circumference were larger and ranged from 12.3 ± 3.0 to 14.4 ± 2.9 cm2 and from 13.0 ± 1.5 to 14.0 ± 1.2 cm, respectively. CONCLUSIONS: In our ex-vivo study, we showed for the first time that the TV annulus dilates immediately after chordae rupture. Consequently, secondary TV regurgitation may be developed because of such changes in the annulus geometry. In addition, the TV leaflet and the right ventricle myocardium are subjected to a different mechanical environment, potentially causing further negative remodeling responses and exacerbating the detrimental outcomes of chordae rupture.


Assuntos
Cordas Tendinosas/lesões , Traumatismos Cardíacos/patologia , Insuficiência da Valva Tricúspide/etiologia , Insuficiência da Valva Tricúspide/cirurgia , Valva Tricúspide/lesões , Animais , Fenômenos Biomecânicos , Cordas Tendinosas/fisiopatologia , Cordas Tendinosas/cirurgia , Dilatação , Modelos Animais de Doenças , Traumatismos Cardíacos/fisiopatologia , Traumatismos Cardíacos/cirurgia , Hemodinâmica , Técnicas In Vitro , Modelos Cardiovasculares , Sus scrofa , Valva Tricúspide/fisiopatologia , Valva Tricúspide/cirurgia , Insuficiência da Valva Tricúspide/fisiopatologia
15.
Circ Cardiovasc Interv ; 11(10): e006598, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30354627

RESUMO

BACKGROUND: High-pressure balloon and stent angioplasty are frequently necessary to prepare the dysfunctional right ventricular outflow tract conduit before transcatheter pulmonary valve replacement (TPVR). Conduit injury can result, which may be catastrophic to the patient or prevent successful TPVR. METHODS AND RESULTS: The PARCS trial (Pulmonary Artery Repair With Covered Stent) was a pivotal, prospective multicenter trial to evaluate the safety and efficacy of the NuMED Covered CP Stent (CCPS) for treatment of conduit injury occurring during TPVR. The study also evaluated immediate and short-term TPVR function in patients receiving covered stents. A total of 616 patients were consented; 120 (19.5%) had a wall injury identified and were treated with CCPS. Severe conduit injuries were uncommon (5%), but predictors for severe injury were not identified. Stenotic homografts had the highest incidence of injury (29%), compared with other conduit substrates. Among patients receiving CCPS implant, 96% required no further therapy for conduit injury, and 94% underwent TPVR at that procedure. Only 2 patients (1.6%) required urgent surgery for conduit injury, despite CCPS implant. There were few CCPS-related complications. TPVR function was similar between CCPS and non-CCPS groups at follow-up. CONCLUSIONS: Conduit injury during TPVR is common, although severe injury is rare. The CCPS was a safe and effective treatment for right ventricular outflow tract conduit injury during preparation for TPVR, allowing nearly all patients to complete the procedure without identifiable impact on valve performance. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01824160.


Assuntos
Angioplastia Coronária com Balão/instrumentação , Cateterismo Cardíaco/instrumentação , Cardiopatias Congênitas/cirurgia , Traumatismos Cardíacos/terapia , Implante de Prótese de Valva Cardíaca/instrumentação , Próteses Valvulares Cardíacas , Valva Pulmonar/cirurgia , Stents , Adolescente , Adulto , Angioplastia Coronária com Balão/efeitos adversos , Cateterismo Cardíaco/efeitos adversos , Cateterismo Cardíaco/métodos , Criança , Feminino , Cardiopatias Congênitas/diagnóstico por imagem , Cardiopatias Congênitas/fisiopatologia , Traumatismos Cardíacos/diagnóstico por imagem , Traumatismos Cardíacos/etiologia , Traumatismos Cardíacos/fisiopatologia , Implante de Prótese de Valva Cardíaca/efeitos adversos , Implante de Prótese de Valva Cardíaca/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Desenho de Prótese , Valva Pulmonar/diagnóstico por imagem , Valva Pulmonar/fisiopatologia , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Estados Unidos , Adulto Jovem
16.
Biochem Biophys Res Commun ; 503(4): 3174-3179, 2018 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-30170731

RESUMO

Obesity is associated with increased cardiovascular morbidity and mortality, but the effects of circulating factors on cardiac function is not fully elucidated. Present study aims to explore the pathophysiological role of microRNA (miR)-194, one of hepatic enriched miRs, in the process of obesity-related cardiomyopathy in human subjects and mice. The expression level of circulating exosomal miR-194 was measured in 39 lean and 35 obese human subjects, and correlated with cardiac parameters. The effects of miR-194 on mitochondrial activity and cardiac function were investigated by administration of miR-194 sponge in mouse cardiomyocytes and obesity-related cardiomyopathy. The upregulation of circulating miR-194 level was closely correlated with impaired human cardiac function, including ejection fraction (r = -0.5002, p < 0.01) and NT-proBNP levels (r = 0.3670, p < 0.01). Exosomes from obese mice impaired myocyte mitochondrial activity, but blocking with miR-194 sponge attenuated the exosomal miR-194-induced reduction of ATP production (p < 0.05), basal oxygen consumption (p < 0.01) and mitochondrial complex I activity (p < 0.001). In vivo mouse study, high fat diet damaged cardiac function, normal structure and mitochondrial activity, whereas miR-194 sponge improved the cardiac status. Present study uncovered the correlation between circulating miR-194 and cardiac parameters in human subjects, and provided solid evidence of the therapeutic application of miR-194 sponge in combating obesity-mediated cardiac dysfunction.


Assuntos
Exossomos/genética , Traumatismos Cardíacos/etiologia , MicroRNAs/genética , Mitocôndrias/patologia , Obesidade/complicações , Obesidade/genética , Adulto , Animais , Exossomos/patologia , Coração/fisiopatologia , Traumatismos Cardíacos/sangue , Traumatismos Cardíacos/genética , Traumatismos Cardíacos/fisiopatologia , Frequência Cardíaca , Humanos , Masculino , Camundongos Endogâmicos C57BL , Camundongos Obesos , MicroRNAs/sangue , Pessoa de Meia-Idade , Mitocôndrias/genética , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Obesidade/sangue , Obesidade/fisiopatologia
17.
Mol Med Rep ; 18(5): 4468-4476, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30221717

RESUMO

Aconitum plants, which have analgesic, diuretic and anti­inflammatory effects, have been widely used to treat various types of disease. However, the apparent toxicity of Aconitum­derived agents, particularly in the cardiovascular system, has largely limited their clinical use. Thus, the present study investigated whether berberine (Ber), an isoquinoline alkaloid, may reduce myocardial injury induced by aconitine (AC) in rats and the underlying mechanisms. Rats (n=40) were randomly divided into four groups: Control, Chuan­wu and Chuan­wu + Ber (8 and 16 mg/kg doses). Electrocardiograms (ECG) of the rats were recorded and serum biomarkers of cardiac function [lactate dehydrogenase (LDH), creatine kinase (CK) and CK­MB] were assayed. Histopathological changes were assessed using myocardial tissue sectioning and hematoxylin and eosin staining. Additionally, the effects of Ber on AC­induced arrhythmias in rats were observed. The changes in ECG following AC perfusion were observed, and the types and onset time of arrhythmias were analyzed. Furthermore, the effects of Ber and AC on papillary muscle action potentials were observed. The results suggested that Ber ameliorated myocardial injury induced by Chuan­wu, which was indicated by reduced arrhythmias and decreased LDH, CK and CK­MB levels in serum. Furthermore, histological damage, including dilation of small veins and congestion, was also markedly attenuated by Ber. In addition, the occurrence of arrhythmias was significantly delayed, and the dosage of AC required to induce arrhythmias was also increased by Ber pretreatment. Additionally, AC­induced changes in action potential amplitude, duration of 30% repolarization and duration of 90% repolarization in the papillary muscle were attenuated by Ber. All of these results indicate that Ber had a preventive effect on acute myocardial injury induced by Chuan­wu and arrhythmias caused by AC, which may be associated with the inhibition of delayed depolarization and triggered activity caused by AC. Thus, combination treatment of Ber with Aconitum plants may be a novel strategy to prevent AC­induced myocardial injury in clinical practice.


Assuntos
Aconitum/toxicidade , Berberina/administração & dosagem , Traumatismos Cardíacos/tratamento farmacológico , Miocárdio/patologia , Aconitum/química , Animais , Creatina Quinase Forma MB/sangue , Eletrocardiografia , Traumatismos Cardíacos/sangue , Traumatismos Cardíacos/induzido quimicamente , Traumatismos Cardíacos/fisiopatologia , Humanos , L-Lactato Desidrogenase/sangue , Extratos Vegetais/efeitos adversos , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico , Ratos
19.
Intensive Care Med ; 44(6): 857-867, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29872882

RESUMO

PURPOSE: Current guidelines recommend maintaining a mean arterial pressure (MAP) ≥ 65 mmHg in septic patients. However, the relationship between hypotension and major complications in septic patients remains unclear. We, therefore, evaluated associations of MAPs below various thresholds and in-hospital mortality, acute kidney injury (AKI), and myocardial injury. METHODS: We conducted a retrospective analysis using electronic health records from 110 US hospitals. We evaluated septic adults with intensive care unit (ICU) stays ≥ 24 h from 2010 to 2016. Patients were excluded with inadequate blood pressure recordings, poorly documented potential confounding factors, or renal or myocardial histories documented within 6 months of ICU admission. Hypotension exposure was defined by time-weighted average mean arterial pressure (TWA-MAP) and cumulative time below 55, 65, 75, and 85 mmHg thresholds. Multivariable logistic regressions determined the associations between hypotension exposure and in-hospital mortality, AKI, and myocardial injury. RESULTS: In total, 8,782 patients met study criteria. For every one unit increase in TWA-MAP < 65 mmHg, the odds of in-hospital mortality increased 11.4% (95% CI 7.8%, 15.1%, p < 0.001); the odds of AKI increased 7.0% (4.7, 9.5%, p < 0.001); and the odds of myocardial injury increased 4.5% (0.4, 8.7%, p = 0.03). For mortality and AKI, odds progressively increased as thresholds decreased from 85 to 55 mmHg. CONCLUSIONS: Risks for mortality, AKI, and myocardial injury were apparent at 85 mmHg, and for mortality and AKI risk progressively worsened at lower thresholds. Maintaining MAP well above 65 mmHg may be prudent in septic ICU patients.


Assuntos
Lesão Renal Aguda/terapia , Traumatismos Cardíacos/terapia , Mortalidade Hospitalar , Hipotensão/terapia , Unidades de Terapia Intensiva/estatística & dados numéricos , Sepse/complicações , Sepse/mortalidade , Lesão Renal Aguda/etiologia , Lesão Renal Aguda/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Traumatismos Cardíacos/etiologia , Traumatismos Cardíacos/fisiopatologia , Humanos , Hipotensão/etiologia , Hipotensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Morbidade , Razão de Chances , Estudos Retrospectivos , Fatores de Risco , Estados Unidos
20.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 34(1): 8-13, 2018 Jan 08.
Artigo em Chinês | MEDLINE | ID: mdl-29926651

RESUMO

OBJECTIVE: To investigate the effects of excessive endoplasmic reticulum stress on lung ischemia/reperfusion (I/R) induced myocardial injury in mice. METHODS: Forty healthy SPF male C57BL/6J mice were divided into 4 groups randomly (n=10):sham operation group (Sham group), lung I/R group (I/R group), endoplasmic reticulum stress (ERS) pathway agonist Tunicamycin group (TM) and ERS inhibitor 4-phenyl butyric acid group (4-PBA). The model of lung I/R injury was established by clamping the left hilum of lung for 30 min followed by 180 min of reperfusion. In sham group, only sternotomy was performed, the hilum of lung was not clamped, and the mice were mechanically ventilated for 210 min. In TM and 4-PBA groups, TM 1mg/kg and 4-PBA 400 mg/kg were injected intraperitoneally, respectively, at 30 min before establishment of the model. At 180 min of reperfusion, blood samples were collected from the orbit for determination of myocardial enzyme. The animals were then sacrificed, and hearts were removed for determination of light microscope, TUNEL, Caspase 3 enzymatic activity, real-time polymerase chain reaction and Western blot. RESULTS: Compared with sham group, the cardiomyocytes had obvious damage under light microscope, and the serum creatine kinase-MB (CK-MB) and lactic dehydrogenase (LDH) activities, apoptosis index and Caspase 3 enzymatic activity were increased significantly, the expressions of p-Jun N-terminalkinase(p-JNK), Caspase 12, CCAAT/enhancer-binding protein homologous protein (CHOP) and glucose regulated protein 78(GRP78) protein and mRNA were up-regulated in I/R, TM and 4-PBA groups (P<0.01). Compared with I/R group, the cardiomyocytes damage was obvious under light microscope, and the serum CK-MB and LDH activities, apoptosis index and Caspase 3 enzymatic activity were increased significantly, the expressions of p-JNK, Caspase 12, CHOP and GRP78 protein and mRNA were up-regulated in group TM; while all above changes were relieved in group 4-PBA (P<0.01). Compared with TM group, the cardiomyocytes damage was relieved under light microscope, and the serum CK-MB and LDH activities, apoptosis index and Caspase 3 enzymatic activity were decreased significantly, the expressions of p-JNK, Caspase 12,CHOP and GRP78 protein and mRNA were down-regulated in group 4-PBA. CONCLUSIONS: The excessive endoplasmic reticulum stress participates in myocardial injury induced by lung ischemia/reperfusion (I/R) and inhibit excessive endoplasmic reticulum stress response can relieved myocardial injury.


Assuntos
Estresse do Retículo Endoplasmático , Traumatismos Cardíacos/fisiopatologia , Pulmão/patologia , Traumatismo por Reperfusão , Animais , Apoptose , Caspase 12 , Caspase 3/metabolismo , Creatina Quinase Forma MB/sangue , Proteínas de Choque Térmico/metabolismo , L-Lactato Desidrogenase/sangue , MAP Quinase Quinase 4/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Miocárdio/patologia , Distribuição Aleatória , Fator de Transcrição CHOP/metabolismo
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