RESUMO
INTRODUCTION: Neither the actual in vivo tissue temperatures reached with 90 W/4 s-very high-power short-duration (vHPSD) ablation for atrial fibrillation nor the safety and efficacy profile have been fully elucidated. METHODS: We conducted a porcine study (n = 15) in which, after right thoracotomy, we implanted 6-8 thermocouples epicardially in the superior vena cava, right pulmonary vein, and esophagus close to the inferior vena cava. We compared tissue temperatures close to a QDOT MICRO catheter, between during 90 W/4 s-vHPSD ablation during ablation index (AI: target 400)-guided 50 W-HPSD ablation, both targeting a contact force of 8-15 g. RESULTS: Maximum tissue temperature reached during 90 W/4 s-vHPSD ablation did not differ significantly from that during 50 W-HPSD ablation (49.2 ± 8.4°C vs. 50.0 ± 12.1°C; p = .69) and correlated inversely with distance between the catheter tip and the thermocouple, regardless of the power settings (r = -0.52 and r = -0.37). Lethal temperature (≥50°C) was best predicted at a catheter tip-to-thermocouple distance cut-point of 3.13 and 4.27 mm, respectively. All lesions produced by 90 W/4 s-vHPSD or 50 W-HPSD ablation were transmural. Although there was no difference in the esophageal injury rate (50% vs. 66%, p = .80), the thermal lesion was significantly shallower with 90 W/4 s-vHPSD ablation than with 50W-HPSD ablation (381.3 ± 127.3 vs. 820.0 ± 426.1 µm from the esophageal adventitia; p = .039). CONCLUSION: Actual tissue temperatures reached with 90 W/4 s-vHPSD ablation appear similar to those with AI-guided 50 W-HPSD ablation, with the distance between the catheter tip and target tissue being shorter for the former. Although both ablation settings may create transmural lesions in thin atrial tissues, any resulting esophageal thermal lesions appear shallower with 90 W/4 s-vHPSD ablation.
Assuntos
Fibrilação Atrial , Ablação por Cateter , Veias Pulmonares , Animais , Suínos , Temperatura , Ablação por Cateter/efeitos adversos , Ablação por Cateter/métodos , Veia Cava Superior , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/cirurgia , Esôfago/cirurgia , Esôfago/lesões , Veias Pulmonares/cirurgia , Resultado do TratamentoRESUMO
BACKGROUND: Neither the actual in vivo tissue temperatures reached with lesion size index (LSI)-guided high-power short-duration (HPSD) ablation for atrial fibrillation nor the safety profile has been elucidated. METHODS: We conducted a porcine study (n = 7) in which, after right thoracotomy, we implanted 6-8 thermocouples epicardially in the superior vena cava, right pulmonary vein, and esophagus close to the inferior vena cava. We compared tissue temperatures reached during 50 W-HPSD ablation with those reached during standard (30 W) ablation, both targeting an LSI of 5.0 (5-15 g contact force). RESULTS: Tmax (maximum tissue temperature when the thermocouple was located ≤5 mm from the catheter tip) reached during HPSD ablation was modestly higher than that reached during standard ablation (58.0 ± 10.1°C vs. 53.6 ± 9.2°C; p = .14) and peak tissue temperature correlated inversely with the distance between the catheter tip and the thermocouple, regardless of the power settings (HPSD: r = -0.63; standard: r = -0.66). Lethal temperature (≥50°C) reached 6.3 ± 1.8 s and 16.9 ± 16.1 s after the start of HPSD and standard ablation, respectively (p = .002), and it was best predicted at a catheter tip-to-thermocouple distance cut point of 2.8 and 5.3 mm, respectively. All lesions produced by HPSD ablation and by standard ablation were transmural. There was no difference between HPSD ablation and standard ablation in the esophageal injury rate (70% vs. 75%, p = .81), but the maximum distance from the esophageal adventitia to the injury site tended to be shorter (0.94 ± 0.29 mm vs. 1.40 ± 0.57 mm, respectively; p = .09). CONCLUSIONS: Actual tissue temperatures reached with LSI-guided HPSD ablation appear to be modestly higher, with a shorter distance between the catheter tip and thermocouple achieving lethal temperature, than those reached with standard ablation. HPSD ablation lasting <6 s may help minimize lethal thermal injury to the esophagus lying at a close distance.
Assuntos
Fibrilação Atrial , Ablação por Cateter , Veias Pulmonares , Suínos , Animais , Temperatura , Veia Cava Superior , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/cirurgia , Esôfago/cirurgia , Esôfago/lesões , Catéteres , Ablação por Cateter/efeitos adversos , Veias Pulmonares/cirurgia , Resultado do TratamentoRESUMO
Whether a nodular calcification (NC), which is the precursor to intracoronary thrombosis, is focally or diffusely distributed in the coronary tree has major implications for ongoing efforts to identify. This study aimed to investigate the frequency and spatial distribution patterns of sheet calcification (SC) and NC in a 3-vessel examination of autopsied human hearts.A total of 323 coronary artery specimens from 110 cadavers were obtained from autopsy cases. After fixation and decalcification, the coronary artery trees were cut every 5 mm into 4-µm transverse cross-sections for histological assessment. An SC was defined as a plate-like calcification of > 1 quadrant of the vessel or > 3 mm in diameter, and NC as nodular calcium deposits separated by fibrin, and a deposit size > 1 mm in diameter.Of the 6,306 histological cross-sections, SCs and NCs were identified in 1,627 (26%) and 233 (4%) cross-sections, respectively. SCs and NCs had a similar distribution pattern in all 3 coronary arteries. In the left anterior descending artery (LAD), NCs were predominantly located in the proximal segment: the first 45 mm from the LAD ostium (72%) and the first 60 mm from the LAD ostium (84%), respectively. However, NCs were evenly distributed throughout the length of the coronary artery in the right coronary artery (RCA) and left circumflex artery (LCX).NCs coexisted with SCs, and tended to cluster in predictable parts within the proximal segments of the LAD, but were evenly distributed throughout the RCA and LCX in coronary arteries from cadavers.
Assuntos
Calcinose , Vasos Coronários , Humanos , Vasos Coronários/patologia , População do Leste Asiático , Calcinose/patologia , Coração , Angiografia CoronáriaRESUMO
The effects of recombinant semaphorin 3A (Sema3A) on myocardial contractility and electrical remodeling in mice with isoproterenol (ISP) -induced heart failure were investigated.C57BL/6J mice intraperitoneally received ISP (480 mg/kg/day, ISP group; n = 24) or saline (control group; n = 31) for 14 days. Twenty-one ISP-treated mice received 0.5 mg/kg Sema3A intravenously on days 7 and 11 (ISP+Sema3A group). The sympathetic nervous system was activated upon ISP treatment, but was reduced upon Sema3A administration. Greater myocardial tissue fibrosis was observed in the ISP group than in the control group. However, fibrosis was not significantly different between the ISP+Sema3A and control groups. Fractional shortening of the left ventricle was lower in the ISP group than in the control group and was restored in the ISP+Sema3A group (control, 53 ± 8%; ISP, 37 ± 7%; ISP+Sema3A, 48 ± 3%; P < 0.05). Monophasic action potential duration at 20% repolarization (MAPD20) was prolonged in the ISP group (compared to control group), but this was reversed upon Sema3A administration (control, 29 ± 3 ms; ISP, 35 ± 6 ms; ISP+Sema3A, 29 ± 3 ms; P < 0.05). qPCR revealed Kv4.3, KChIP2, and SERCA2 downregulation in the ISP group and upregulation in the ISP+Sema3A group; however, Western blotting revealed similar changes only for Kv4.3 (P < 0.05).Intravenous Sema3A may maintain myocardial contractility by suppressing the sympathetic innervation of the myocardium and reducing myocardial tissue damage, in addition to restoring MAPD via Kv4.3 upregulation.
Assuntos
Remodelamento Atrial , Insuficiência Cardíaca , Camundongos , Animais , Isoproterenol , Semaforina-3A , Camundongos Endogâmicos C57BL , Insuficiência Cardíaca/induzido quimicamente , Insuficiência Cardíaca/tratamento farmacológicoRESUMO
BACKGROUND: Actual in vivo tissue temperatures and the safety profile during high-power short-duration (HPSD) ablation of atrial fibrillation have not been clarified. METHODS: We conducted an animal study in which, after a right thoracotomy, we implanted 6-8 thermocouples epicardially in the superior vena cava, right pulmonary vein, and esophagus close to the inferior vena cava. We recorded tissue temperatures during a 50 W-HPSD ablation and 30 W-standard ablation targeting an ablation index (AI) of 400 (5-15 g contact force). RESULTS: Maximum tissue temperatures reached with HSPD ablation were significantly higher than that reached with standard ablation (62.7 ± 12.5 vs. 52.7 ± 11.4°C, p = 0.033) and correlated inversely with the distance between the catheter tip and thermocouple, regardless of the power settings (HPSD: r = -0.71; standard: r = -0.64). Achievement of lethal temperatures (≥50°C) was within 7.6 ± 3.6 and 12.1 ± 4.1 s after HPSD and standard ablation, respectively (p = 0.003), and was best predicted at cutoff points of 5.2 and 4.4 mm, respectively. All HPSD ablation lesions were transmural, but 19.2% of the standard ablation lesions were not (p = 0.011). There was no difference between HPSD and standard ablation regarding the esophageal injury rate (30% vs. 33.3%, p > 0.99), with the injury appearing to be related to the short distance from the catheter tip. CONCLUSIONS: Actual tissue temperatures reached with AI-guided HPSD ablation appeared to be higher with a greater distance between the catheter tip and target tissue than those with standard ablation. HPSD ablation for <7 s may help prevent collateral tissue injury when ablating within a close distance.
Assuntos
Fibrilação Atrial , Ablação por Cateter , Veias Pulmonares , Animais , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/cirurgia , Ablação por Cateter/efeitos adversos , Veias Pulmonares/cirurgia , Temperatura , Resultado do Tratamento , Veia Cava Superior/cirurgiaRESUMO
A 74-year-old woman was taken to our hospital with a chief complaint of chest and back pain. She was diagnosed with Stanford type A acute aortic dissection and underwent ascending aortic replacement. Fifteen months after surgery, a giant anastomotic aneurysm was found at the proximal and distal anastomoses on chest computed tomography (CT), and reoperation was indicated. Following sternal re-entry, anastomotic dehiscence was found where BioGlue, albumin/glutaraldehyde sealant, had been applied during the previous surgery, and caused aneurysm. Severe postoperative adhesion precluded extensive surgery, and redo replacement of the ascending aorta was carried out. Histopathological examination revealed extensive necrosis of smooth muscle cells in the aortic wall at the anastomotic site and a marked inflammatory cell infiltration around the aortic wall and the artificial graft, and association of BioGlue use was suggested. The use of appropriate tissue adhesives to reinforce the dissected aortic wall is important, as well as careful long-term follow-up.
Assuntos
Aneurisma da Aorta Torácica , Aneurisma Aórtico , Dissecção Aórtica , Implante de Prótese Vascular , Adesivos Teciduais , Feminino , Humanos , Idoso , Aneurisma Aórtico/diagnóstico por imagem , Aneurisma Aórtico/cirurgia , Glutaral , Adesivos Teciduais/uso terapêutico , Dissecção Aórtica/diagnóstico por imagem , Dissecção Aórtica/cirurgia , Reoperação , Albuminas , Aneurisma da Aorta Torácica/diagnóstico por imagem , Aneurisma da Aorta Torácica/cirurgiaRESUMO
BACKGROUND: How obesity and epicardial fat influence atrial fibrillation (AF) is unknown. METHODS: To investigate the effect of obesity/epicardial fat on the AF substrate, we divided 20 beagle dogs of normal weight into four groups (n = 5 each): one of the four groups (Obese-rapid atrial pacing [RAP] group) served as a novel canine model of obesity and AF. The other three groups comprised dogs fed a standard diet without RAP (Control group), dogs fed a high-fat diet without RAP (Obese group), or dogs fed a standard diet with RAP (RAP group). All underwent electrophysiology study, and hearts were excised for histopathologic and fibrosis-related gene expression analyses. RESULTS: Left atrial (LA) pressure was significantly higher in the Obese group than in the Control, RAP, and Obese-RAP groups (23.4 ± 6.9 vs. 11.4 ± 2.1, 11.9 ± 6.4, and 13.5 ± 2.9 mmHg; p = .005). The effective refractory period of the inferior PV was significantly shorter in the RAP and Obese-RAP groups than in the Control group (p = .043). Short-duration AF was induced at greatest frequency in the Obese-RAP and Obese groups (p < .05). Epicardial fat/Fatty infiltration was greatest in the Obese-RAP group, and greater in the Obese and RAP groups than in the Control group. %interstitial fibrosis/fibrosis-related gene expression was significantly greater in the Obese-RAP and RAP groups (p < .05). CONCLUSIONS: Vulnerability to AF was associated with increased LA pressure and increased epicardial fat/fatty infiltration in our Obese group, and with increased epicardial fat/fibrofatty infiltration in the RAP and Obese-RAP groups. These may explain the role of obesity/epicardial fat in the pathogenesis of AF.
Assuntos
Fibrilação Atrial , Remodelamento Atrial , Tecido Adiposo , Animais , Fibrilação Atrial/etiologia , Modelos Animais de Doenças , Cães , Átrios do Coração , Obesidade/complicações , PericárdioRESUMO
Cardiac hemangioma is relatively rare, accounting for approximately 1-3% of all primary heart tumors. This benign tumor may be an incidental lesion, but can also cause arrhythmias, pericardial effusion, congestive heart failure or outflow obstruction. We report a rare case with exophytic cardiac hemangioma arising from the right ventricle. Echocardiography showed an approximately 40 mm round protruding mass on the anterior wall of the right ventricle. Cardiovascular magnetic resonance demonstrated isointense and hyperintense signals on T1- and T2-weighted images, respectively. These imaging studies suggested a pericardial cyst. Perioperative findings indicated a globular, exophytic mass, vascular in nature, arising from the right ventricle. The lesion was resected directly, and the space left by defect in the right ventricular wall was covered with a bovine pericardial patch. Cardiac hemangiomas are generally endoluminal tumors, but we must keep in mind that the differential diagnoses include various pericardial lesions by medical images.
Assuntos
Ventrículos do Coração/patologia , Hemangioma Cavernoso , Idoso , Diagnóstico Diferencial , Células Endoteliais/patologia , Neoplasias Cardíacas/diagnóstico , Neoplasias Cardíacas/diagnóstico por imagem , Neoplasias Cardíacas/patologia , Hemangioma Cavernoso/diagnóstico , Hemangioma Cavernoso/diagnóstico por imagem , Hemangioma Cavernoso/patologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Cisto Mediastínico/patologia , Pericárdio/patologiaRESUMO
Dipeptidyl peptidase-4 (DPP-4) inhibitors have potential as a treatment for atherosclerosis. However, it is unclear whether DPP-4 inhibitors stabilize atherosclerotic plaque or alter the composition of complex plaque. Sixteen Watanabe heritable hyperlipidemic rabbits aged 10-12 weeks with atherosclerotic plaque in the brachiocephalic artery detected by iMap™ intravascular ultrasound (IVUS) were divided into a DPP-4 inhibitor group and a control group. Linagliptin was administered to the DPP-4 inhibitor group via nasogastric tube at a dose of 10 mg/kg/day for 16 weeks, and control rabbits received the same volume of 0.5% hydroxyethylcellulose. After evaluation by IVUS at 16 weeks, the brachiocephalic arteries were harvested for pathological examination. IVUS revealed that linagliptin significantly reduced the plaque volume and vessel volume (control group vs. DPP-4 inhibitor group: ∆plaque volume, 1.02 ± 0.96 mm3 vs. - 3.59 ± 0.92 mm3, P = 0.004; ∆vessel volume, - 1.22 ± 2.36 mm3 vs. - 8.66 ± 2.33 mm3, P = 0.04; %change in plaque volume, 6.90 ± 5.62% vs. - 15.06 ± 3.29%, P = 0.005). With regard to plaque composition, linagliptin significantly reduced the volume of fibrotic, lipidic, and necrotic plaque (control group vs. DPP-4 inhibitor group: ∆fibrotic volume, 0.56 ± 1.27 mm3 vs. - 5.57 ± 1.46 mm3, P = 0.04; ∆lipidic volume, 0.24 ± 0.24 mm3 vs. - 0.42 ± 0.16 mm3 P = 0.04; ∆necrotic volume, 0.76 ± 0.54 mm3 vs. - 0.84 ± 0.25 mm3, P = 0.02). Pathological examination did not show any significant differences in the %smooth muscle cell area or %fibrotic area, but infiltration of macrophages into plaque was reduced by linagliptin treatment (%macrophage area: 12.03% ± 1.51% vs. 7.21 ± 1.65%, P < 0.05). These findings indicate that linagliptin inhibited plaque growth and stabilized plaque in Watanabe heritable hyperlipidemic rabbits.
Assuntos
Aterosclerose/tratamento farmacológico , Artéria Femoral/diagnóstico por imagem , Hiperlipidemias/tratamento farmacológico , Linagliptina/uso terapêutico , Lipídeos/sangue , Ultrassonografia de Intervenção/métodos , Animais , Aterosclerose/diagnóstico , Aterosclerose/etiologia , Biomarcadores/sangue , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Modelos Animais de Doenças , Hiperlipidemias/sangue , Hiperlipidemias/complicações , Coelhos , Resultado do TratamentoRESUMO
Embolic myocardial infarction (MI) caused by infective endocarditis (IE) is rare, but it is increasingly recognized as an important complication. This complication typically occurs in patients with aortic valve endocarditis during the acute phase of the infection. It is also known to have a high mortality rate; however, the best practice for its management is unclear owing to scarce available data. In addition, most cases of embolic acute MI (AMI) caused by IE are indirectly diagnosed with a combination of angiographic examination such as coronary angiography or cardiac computed tomography. Herein, we report a case of fatal embolic ST-elevation MI (STEMI) caused by mitral valve IE during the healed phase, which was clearly proven by the pathology findings.
Assuntos
Embolia/complicações , Endocardite Bacteriana/complicações , Valva Mitral/diagnóstico por imagem , Infarto do Miocárdio com Supradesnível do Segmento ST/etiologia , Idoso , Angiografia Coronária , Ecocardiografia , Embolia/diagnóstico , Endocardite Bacteriana/diagnóstico , Evolução Fatal , Feminino , Humanos , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnósticoRESUMO
BACKGROUND: Myenteric ganglionitis is a disorder that causes intestinal motor dysfunction. It may be caused due to neoplastic, central nervous system, or systemic infectious disorders. However, some cases are considered to be idiopathic in origin. CASE PRESENTATION: A 33-year-old man was admitted to the hospital with sudden severe abdominal pain accompanied by watery diarrhea. Computed tomography imaging revealed edema of the entire small intestinal wall without ischemic changes. Detailed examination could not be performed for identifying the cause of abdominal pain because of the patient's worsened general condition, and he died 7 days after onset. The autopsy results confirmed the cause of the patient's severe abdominal pain as an idiopathic myenteric ganglionitis. CONCLUSION: Some patients with idiopathic myenteric ganglionitis might die without a definitive diagnosis during their lifetime because of the rarity of this disease. When encountering severe intestinal motility abnormalities of unknown cause, physicians should consider idiopathic myenteric ganglionitis when choosing therapy.
Assuntos
Motilidade Gastrointestinal , Plexo Mientérico , Dor Abdominal/etiologia , Adulto , Autopsia , Causas de Morte , Humanos , MasculinoRESUMO
BACKGROUND: Embolism during percutaneous coronary intervention (PCI) causes microcirculation impairment. The aim of this study was to clarify the relationship between the pathological characteristics of tissue captured by distal protection device (DPD) and amount of tissue accumulated in DPD. MethodsâandâResults: A total of 671 consecutive lesions in PCI using DPD were examined. The amount of necrotic debris, fibrous tissue, calcified particle, platelet thrombus and organized thrombus in the DPD baskets was histologically evaluated. The DPD tissue amount was assessed semi-quantitatively, and the relationship between the captured DPD tissue characteristics and tissue amount was investigated. On pathology, 40.7% of the lesions had necrotic debris, 41.4% had fibrous tissue, and 18.0% had calcified particle. The prevalence of lesions in patients with acute coronary syndrome (ACS) was 62.1%. Tissue amount score distribution was as follows: score 1 (tissue invisible), 3.9%; score 2 (tissue clinging to the basket), 52.0%; score 3 (tissue accumulated at the bottom of the basket), 38.5%; and score 4 (tissue accumulated in more than half of the basket), 5.7%. On multivariate analysis, necrotic debris and fibrous tissue were associated with greater tissue amount as well as clinical presentation of ACS. CONCLUSIONS: The presence of atherosclerotic plaque component, such as necrotic debris and fibrous tissue, might be a risk for distal embolism during PCI.
Assuntos
Dispositivos de Proteção Embólica , Embolia/etiologia , Intervenção Coronária Percutânea/efeitos adversos , Placa Aterosclerótica/patologia , Síndrome Coronariana Aguda/complicações , Idoso , Angiografia Coronária , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Ativação Plaquetária , Estudos Retrospectivos , Fatores de Risco , Trombose/fisiopatologiaRESUMO
BACKGROUND: Coronary angioscopy (CAS) is used to comprehensively evaluate vascular responses after drug-eluting stent (DES) implantation. This study sought to evaluate the capability of CAS for evaluating DES strut coverage grade and color grade of the intima compared with histological images in coronary autopsy specimens. MethodsâandâResults: A total of 23 DES extracted from 11 autopsy hearts were imaged by CAS. All stent segments were graded as white or yellow according to the luminal surface color, and thrombus was evaluated according to a previous report. Neointimal coverage over the DES was graded as 0 (stent struts fully visible) to grade 3 (stent struts fully embedded and invisible). Of 76 segments, neointimal coverage was graded as 0 in 35 (46%), 1 in 22 (29%), 2 in 8 (11%), and 3 in 11 (14%). The neointimal thickness increased significantly with increasing neointimal coverage grade on angioscopy. Neointimal color was graded as white in 40 (53%) and yellow in 36 segments (47%). Histological analysis revealed that yellow neointima contained fibroatheroma, foam cells accumulation or superficial calcium deposition. A thrombus was identified in 13 segments. Thrombi adherent around the stent strut were partly intimal erythrocyte accumulation around the strut. CONCLUSIONS: In-stent yellow segment had atherosclerotic components. CAS could evaluate vascular status comprehensively after DES implantation.
Assuntos
Doença da Artéria Coronariana , Stents Farmacológicos , Neointima , Placa Aterosclerótica , Sirolimo/administração & dosagem , Idoso , Doença da Artéria Coronariana/metabolismo , Doença da Artéria Coronariana/patologia , Doença da Artéria Coronariana/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neointima/metabolismo , Neointima/patologia , Placa Aterosclerótica/metabolismo , Placa Aterosclerótica/patologiaRESUMO
We report the case of a 53-year-old male with a history of acute myelogenous leukemia, who suffered the rupturing of a right-sided pulmonary artery pseudoaneurysm combined with pneumonia. He underwent a right-sided lower lobectomy. The resected lung tissue demonstrated a mycotic pseudoaneurysm of a pulmonary artery branch together with a filamentous fungal infection. Pseudoaneurysms are caused by the breaching of all layers of a blood vessel wall. The extravasated blood is trapped by the surrounding extravascular tissue or clots. Cladosporium was detected during a polymerase chain reaction-based analysis followed by DNA sequencing of formalin-fixed paraffin-embedded lung tissue samples. Although previous cases of pulmonary artery pseudoaneurysms caused by fungal infections, e.g., Candida or Aspergillus sp., have been reported, to the best of our knowledge this is the first case to involve cladosporiosis.
Assuntos
Falso Aneurisma/microbiologia , Micoses/complicações , Artéria Pulmonar/patologia , Antineoplásicos/uso terapêutico , Cladosporium , Humanos , Hospedeiro Imunocomprometido , Leucemia Mieloide Aguda/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Micoses/imunologiaRESUMO
We report the case of a 38-year-old woman who was admitted for acute cerebral infarction linked to a cardiac calcified amorphous tumor (CAT) and related mitral annular calcification (MAC). The cardiac mass was removed, and mitral valve replacement surgery was performed. Pathological examination revealed an amorphous accumulation of degenerating material within both lesions, indicating that build-up of calcium along the mitral annulus and subsequent rupture of the fibrotic tissue may be involved in the initiation and progression of CAT.
Assuntos
Calcinose/complicações , Procedimentos Cirúrgicos Cardíacos/métodos , Infarto Cerebral/etiologia , Neoplasias Cardíacas/complicações , Doença Aguda , Adulto , Calcinose/diagnóstico , Calcinose/cirurgia , Infarto Cerebral/diagnóstico , Diagnóstico Diferencial , Ecocardiografia Transesofagiana , Feminino , Neoplasias Cardíacas/diagnóstico , Neoplasias Cardíacas/cirurgia , Humanos , Valva Mitral/patologia , Valva Mitral/cirurgiaRESUMO
For atherosclerotic cardiovascular diseases (ACD), gene therapy may be a potential therapeutic strategy; however, lack of effective and safe methods for gene delivery to atherosclerotic plaques have limited its potential therapeutic applications. To overcome this limitation, we developed a novel antibody-based gene delivery system (anti-HB-EGF/NA vector) by chemically crosslinking antibodies against human heparin-binding epidermal growth factor-like growth factor (HB-EGF). It has been shown to be excessively expressed in human atherosclerotic plaques and NeutrAvidin (NA) for conjugating biotinylated siRNA. Immunofluorescence staining and quantitative flow cytometry analysis using human HB-EGF-expressing cells showed both antibody-mediated selective cellular targeting and efficient intracellular delivery of conjugated biotin-fluorescence. Moreover, we demonstrated antibody-mediated significant and selective gene knockdown via conjugation with anti-HB-EGF/NA vector and biotinylated siRNA (anti-HB-EGF/NA/b-siRNA) in vitro. Furthermore, using high fat-fed human HB-EGF knock-in and apolipoprotein E-knockout (Hbegf hz/hz; Apoe-/-) mice, we demonstrated that the anti-HB-EGF/NA vector, conjugating biotin-fluorescence, increasingly accumulated within the atherosclerotic plaques of the ascending aorta in which human HB-EGF expression levels were highly elevated. Moreover, in response to a single intravenous injection of anti-HB-EGF/NA/b-siRNA in a dose-dependent manner, qPCR analysis of laser-dissected atherosclerotic plaques of the ascending aorta showed significant knockdown of the reporter gene expression. These results suggest that the anti-HB-EGF antibody-mediated siRNA delivery could be a promising delivery system for gene therapy of ACD.
Assuntos
Anticorpos/uso terapêutico , Aterosclerose/terapia , Avidina/imunologia , Terapia Genética/métodos , Fator de Crescimento Semelhante a EGF de Ligação à Heparina/imunologia , RNA Interferente Pequeno/uso terapêutico , Animais , Aterosclerose/metabolismo , Humanos , Camundongos , Camundongos Knockout , Resultado do TratamentoAssuntos
Transplante de Células-Tronco Hematopoéticas , Linfoma de Zona Marginal Tipo Células B , Linfoma Difuso de Grandes Células B , Adolescente , Classe I de Fosfatidilinositol 3-Quinases/genética , Mutação em Linhagem Germinativa , Humanos , Japão , Linfoma de Zona Marginal Tipo Células B/patologia , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/terapia , Condicionamento Pré-TransplanteRESUMO
Pineal anlage tumor (PAT) is a rare subtype of pineoblastoma (PB), which shows a poor prognosis. We report a case of a 5-year-old boy with PB with a rhabdomyoblastic component. He presented at a local clinic with vomiting and was transferred to our hospital following discovery of a pineal mass. An endoscopic biopsy was performed and was diagnosed as a PB with a rhabdomyoblastic component. Histopathology of PAT is characterized by both neuroectodermal and ectomesenchymal differentiation, and only a few confirmed cases have been reported. Although the histopathological features of the reported case resembled that of PAT, the ectomesenchymal component in the presented case was only a rhabdomyoblastic one. Therefore, we have diagnosed this case as PB with a rhabdomyoblastic component. As PAT is a rare pineal tumor, clinical, histopathological and genetic evaluation of additional cases is needed to define the characteristics of PAT as one of the pineal gland tumors.
Assuntos
Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/patologia , Glândula Pineal/patologia , Pinealoma/complicações , Pinealoma/patologia , Rabdomiólise/complicações , Rabdomiólise/patologia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Neoplasias Encefálicas/diagnóstico por imagem , Pré-Escolar , Humanos , Imageamento por Ressonância Magnética , Masculino , Glândula Pineal/diagnóstico por imagem , Pinealoma/diagnóstico por imagem , Rabdomiólise/diagnóstico por imagemRESUMO
OBJECTIVE: Although iron is an essential element for maintaining physiological function, excess iron leads to tissue damage caused by oxidative stress and inflammation. Oxidative stress and inflammation play critical roles for the development of abdominal aortic aneurysm (AAA). However, it has not been investigated whether iron plays a role in AAA formation through oxidative stress and inflammation. We, therefore, examined whether iron is involved in the pathophysiology of AAA formation using human AAA walls and murine AAA models. APPROACH AND RESULTS: Human aortic walls were collected from 53 patients who underwent cardiovascular surgery (non-AAA=34; AAA=19). Murine AAA was induced by infusion of angiotensin II to apolipoprotein E knockout mice. Iron was accumulated in human and murine AAA walls compared with non-AAA walls. Immunohistochemistry showed that both 8-hydroxy-2'-deoxyguanosine and CD68-positive areas were increased in AAA walls compared with non-AAA walls. The extent of iron accumulated area positively correlated with that of 8-hydroxy-2'-deoxyguanosine expression area and macrophage infiltration area in human and murine AAA walls. We next investigated the effects of dietary iron restriction on AAA formation in mice. Iron restriction reduced the incidence of AAA formation with attenuation of oxidative stress and inflammation. Aortic expression of transferrin receptor 1, intracellular iron transport protein, was increased in human and murine AAA walls, and transferrin receptor 1-positive area was similar to areas where iron accumulated and F4/80 were positive. CONCLUSIONS: Iron is involved in the pathophysiology of AAA formation with oxidative stress and inflammation. Dietary iron restriction could be a new therapeutic strategy for AAA progression.
Assuntos
Aorta/metabolismo , Aneurisma da Aorta Abdominal/fisiopatologia , Inflamação/metabolismo , Sobrecarga de Ferro/fisiopatologia , Estresse Oxidativo , 8-Hidroxi-2'-Desoxiguanosina , Idoso , Idoso de 80 Anos ou mais , Animais , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Aneurisma da Aorta Abdominal/dietoterapia , Aneurisma da Aorta Abdominal/metabolismo , Desoxiguanosina/análogos & derivados , Desoxiguanosina/metabolismo , Feminino , Fibrose , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Macrófagos/metabolismo , Masculino , Metaloproteinases da Matriz/metabolismo , Camundongos Knockout , Fosforilação , Receptores da Transferrina/metabolismoRESUMO
OBJECTIVE: Cardiovascular disease (CVD), the most common morbidity resulting from atherosclerosis, remains a frequent cause of death. Efforts to develop effective therapeutic strategies have focused on vascular inflammation as a critical pathology driving atherosclerosis progression. Nonetheless, molecular mechanisms underlying this activity remain unclear. Here, we ask whether angiopoietin-like protein 2 (Angptl2), a proinflammatory protein, contributes to vascular inflammation that promotes atherosclerosis progression. APPROACH AND RESULTS: Histological analysis revealed abundant Angptl2 expression in endothelial cells and macrophages infiltrating atheromatous plaques in patients with cardiovascular disease. Angptl2 knockout in apolipoprotein E-deficient mice (ApoE(-/-)/Angptl2(-/-)) attenuated atherosclerosis progression by decreasing the number of macrophages infiltrating atheromatous plaques, reducing vascular inflammation. Bone marrow transplantation experiments showed that Angptl2 deficiency in endothelial cells attenuated atherosclerosis development. Conversely, ApoE(-/-) mice crossed with transgenic mice expressing Angptl2 driven by the Tie2 promoter (ApoE(-/-)/Tie2-Angptl2 Tg), which drives Angptl2 expression in endothelial cells but not monocytes/macrophages, showed accelerated plaque formation and vascular inflammation because of increased numbers of infiltrated macrophages in atheromatous plaques. Tie2-Angptl2 Tg mice alone did not develop plaques but exhibited endothelium-dependent vasodilatory dysfunction, likely because of decreased production of endothelial cell-derived nitric oxide. Conversely, Angptl2(-/-) mice exhibited less severe endothelial dysfunction than did wild-type mice when fed a high-fat diet. In vitro, Angptl2 activated proinflammatory nuclear factor-κB signaling in endothelial cells and increased monocyte/macrophage chemotaxis. CONCLUSIONS: Endothelial cell-derived Angptl2 accelerates vascular inflammation by activating proinflammatory signaling in endothelial cells and increasing macrophage infiltration, leading to endothelial dysfunction and atherosclerosis progression.