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1.
J Cardiothorac Surg ; 19(1): 13, 2024 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-38245766

RESUMO

BACKGROUND: Left atrial myxoma is the most common benign tumor, with the growth rate remaining unknown because specific symptoms do not present until the tumor grows to a certain size. Early surgical management is performed in most cases once it is detected by physicians. Despite cardiac myxomas commonly being perceived as slow-growing tumors, rapid enlargement of myxomas has been reported. CASE PRESENTATION: A 64-year-old woman was referred to our hospital with a diagnosis of a left atrial tumor. The pointed tumor changed morphologically in a few hours, and her respiratory condition, which had been normal at admission, suddenly deteriorated. Emergent surgery was performed, and the diagnosis was myxoma with multiple intratumor massive hematomas. The patient recovered uneventfully and was discharged on postoperative day 12 without any complications. CONCLUSIONS: We report an extremely rare case of left atrial myxoma rapidly expanded due to acute multiple hemorrhages within itself. Massive internal hemorrhage alters the size, shape, and fragility of the tumor. We should recognize the potential risk of internal hemorrhage that may lead to acute deterioration of the so-called "slow-growing benign" tumors, such as myxomas.


Assuntos
Neoplasias Cardíacas , Mixoma , Humanos , Feminino , Pessoa de Meia-Idade , Neoplasias Cardíacas/diagnóstico , Neoplasias Cardíacas/diagnóstico por imagem , Hemorragia , Mixoma/complicações , Mixoma/diagnóstico , Mixoma/cirurgia , Átrios do Coração/cirurgia , Átrios do Coração/patologia , Hematoma/complicações
2.
Int J Surg Case Rep ; 115: 109260, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38219518

RESUMO

INTRODUCTION: Reconstructed gastric tube ulcers are common complications of esophagectomy. When the pericardium is penetrated, digestive juices can cause severe cardiac inflammation, leading to an extremely poor prognosis. We report the first case of pericardial penetration of a constructed stomach tube via the posterior mediastinal route and the first use of subxiphoid pericardial drainage and continuous irrigation lavage. PRESENTATION OF CASE: This case involved a 50-year-old woman who underwent an esophagectomy for esophageal cancer nine years prior with gastric tube reconstruction via the posterior mediastinal route. She developed pericardial penetration due to a gastric tube ulcer. Her respiratory and circulatory condition worsened, and pericardial drainage and a prophylactic tracheostomy were performed to prevent septic shock. A 5-cm longitudinal incision was made in the epigastric region, and a 4-cm T-shaped incision was made through the pericardium. Two double-lumen drainage tubes were placed in the anterior and posterior pericardium, and continuous irrigation was initiated via each tube. We successfully treated the patient without complications using subxiphoid pericardial drainage and continuous irrigation lavage, and she was discharged on postoperative day 23. DISCUSSION: We presented this case to discuss surgical techniques and optimal treatment strategies. CONCLUSION: Subxiphoid pericardial drainage and continuous irrigational lavage are effective for pericardial penetration of a constructed stomach tube via the posterior mediastinal route.

3.
Circ Rep ; 5(5): 198-209, 2023 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-37180477

RESUMO

Background: Data on the incidence of mid-term prognostic events in patients who developed acute coronary syndrome (ACS) in the late 2010s are scarce. Methods and Results: We retrospectively included and collected data for 889 patients with ACS (ST-elevation myocardial infarction [STEMI]/non-ST-elevation ACS [NSTE-ACS]) discharged alive from 2 tertiary hospitals in Izumo City, in rural Japan, between August 2009 and July 2018. Patients were divided into 3 time groups (T1: August 2009-July 2012; T2: August 2012-July 2015; T3: August 2015-July 2018). The cumulative incidence of major adverse cardiovascular events (MACE; comprising all-cause death, recurrent ACS, and stroke), major bleeding, and heart failure hospitalization within 2 years of discharge was compared among the 3 groups. The incidence of freedom from MACE was significantly higher in the T3 group than in the T1 and T2 groups (93 [95% confidence interval {CI} 90-96%] vs. 86% [95% CI 83-90] and 89% [95% CI 90-96], respectively; P=0.03). There was a tendency for a higher incidence of STEMI among patients in T3 (P=0.057). The incidence of NSTE-ACS was comparable among the 3 groups (P=0.31), as was the incidence of major bleeding and hospitalization for heart failure. Conclusions: The incidence of mid-term MACE in patients who developed ACS during the late 2010 s (2015-2018) was lower than that in prior periods (2009-2015).

4.
ESC Heart Fail ; 9(5): 3505-3518, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35894764

RESUMO

AIMS: Data regarding prognostic events following catheter ablation (CA) for atrial fibrillation (AF) in patients with heart failure with preserved ejection fraction (HFpEF) are scarce. We conducted this study to compare the incidence of major adverse clinical events (MACE) following CA for AF between patients with HFpEF and those with systolic heart failure (HF). METHODS AND RESULTS: This single-centre observational study included 142 patients with HF who underwent CA for AF (median follow-up: 4.0 [2.6, 6.3] years). The patients were grouped based on the presence of HFpEF (n = 84) and systolic HF (left ventricular ejection fraction <50%, n = 58). We compared the cumulative incidence and incidence rate of MACE, comprising all-cause death, unplanned cardiovascular hospitalization (CVH), and HF hospitalization (HFH) between both groups and the number of HFH before and after CA in each group. Multivariate analysis was performed to identify the predictors of MACE in patients with HFpEF. The incidence of MACE was comparable between the groups (following the first procedure: HFpEF: 23%, 4.7/100 person-years, vs. systolic HF: 28%, 6.6/100 person-years, P = 0.18; last procedure: 20%, 4.8/100 person-years, vs. 24%, 6.9/100 person-years, P = 0.21). Although the incidence of HFH was lower in patients with HFpEF than in those with systolic HF (first procedure: 14%, 2.9/100 person-years, vs. 24%, 5.7/100 person-years, P = 0.07; last procedure: 11%, 2.5/100 person-years, vs. 24%, 6.9/100 person-years, P = 0.01), the incidence of CVH was higher (first procedure: 8%, 1.7/100 person-years, vs. 5%, 1.2/100 person-years, P = 0.74; last procedure: 6%, 1.4/100 person-years, vs. 2%, 0.5/100 person-years, P = 0.4). The number of HFH significantly decreased in both groups after CA (HFpEF: 1 hospitalization [the first and third quartiles: 0, 1] in pre-CA, vs. 0 hospitalizations [0, 0] in post-CA, P < 0.0001; systolic HF: 1 hospitalization [0, 1], vs. 0 hospitalizations [0, 0], P < 0.005). The proportion of HFH among total clinical events was significantly smaller in patients with HFpEF than in those with systolic HF (following the first procedure: 56% vs. 88%, P < 0.005; last procedure: 52% vs. 92%, P < 0.005). CONCLUSIONS: CA for AF could be beneficial for patients with HFpEF, similar to those with systolic HF. However, clinical events other than HFH should be considered cautiously in such patients.


Assuntos
Fibrilação Atrial , Ablação por Cateter , Insuficiência Cardíaca , Humanos , Volume Sistólico , Fibrilação Atrial/complicações , Fibrilação Atrial/cirurgia , Fibrilação Atrial/epidemiologia , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/cirurgia , Função Ventricular Esquerda , Ablação por Cateter/efeitos adversos , Catéteres
5.
J Clin Med ; 11(6)2022 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-35330056

RESUMO

Long-duration atrial high-rate episodes (AHREs) monitored using cardiac implantable electronic devices (CIEDs) can predict long-term major adverse cardiovascular events (MACEs). This study aimed to compare the impact of long-duration AHRE on MACE development between patients with and without a history of atrial fibrillation (AF). This single-center observational study included 132 CIED-implanted patients with AHREs detected via remote monitoring. The population was dichotomized into groups: with (n = 69) and without (n = 63) AF. In each group, cumulative incidences of MACEs comprising all-cause deaths, heart failure hospitalizations, strokes, and acute coronary syndromes were compared between patients with AHRE durations of ≥24 h and <24 h. Multivariate analysis was performed to identify predictors of MACEs among patients without AF. MACE incidence was significantly higher in patients with AHRE ≥24 h than in those with <24 h in the group without AF (92% vs. 30%, p = 0.005). MACE incidence did not significantly differ between AHRE ≥24 h and <24 h in the group with AF (54% vs. 26%, p = 0.44). After a multivariate adjustment, AHRE duration of ≥24 h emerged as the only independent predictor of MACEs among patients without AF (p = 0.03). In conclusion, a long-duration AHRE was prognostic in patients without a history of AF but not in patients with a history of AHREs.

6.
J Am Heart Assoc ; 11(4): e023640, 2022 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-35112883

RESUMO

Background Catheter ablation can improve long-term prognosis of patients with atrial fibrillation with systolic impairment. However, atrial tachyarrhythmia (ATA) recurrence increases during long-term follow-up. We aimed to investigate the impact of ATA recurrence on the development of long-term adverse clinical events following catheter ablation for atrial fibrillation and to identify predictors for the development of adverse clinical events. Methods and Results This single-center observational study included 75 patients with systolic impairment (left ventricular ejection fraction <50%) who underwent the first catheter ablation procedure for atrial fibrillation at our institution (median follow-up period: 3.5 [range: 2.4-4.7] years). We compared the cumulative incidence of adverse clinical events (all-cause death, heart failure hospitalization, stroke, or acute myocardial infarction) between the groups with and without ATA recurrence following the first and last procedures. Multivariable analyses were performed to identify predictors for developing adverse clinical events. Twenty-one patients (28%) developed adverse clinical events at a median of 2.2 (range: 0.64-2.8) years following the first procedure. The proportion of freedom from adverse clinical events following the first procedure was significantly lower in the ATA recurrence group than in the nonrecurrence group (41% [n=40] versus 95% [n=35], P<0.0005); the proportion following the last procedure also showed a similar tendency (35% [n=26] versus 57% [n=49], P<0.0001). ATA recurrence emerged as an independent predictor for adverse clinical events following both procedures after multivariable adjustment. Conclusions ATA recurrence following catheter ablation procedure could predict adverse clinical events in patients with atrial fibrillation with systolic impairment.


Assuntos
Fibrilação Atrial , Ablação por Cateter , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/cirurgia , Ablação por Cateter/efeitos adversos , Ablação por Cateter/métodos , Humanos , Recidiva , Volume Sistólico , Taquicardia , Resultado do Tratamento , Função Ventricular Esquerda
7.
Heart Rhythm ; 19(6): 986-997, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35134547

RESUMO

BACKGROUND: Right ventricular (RV) dysfunction and its associated arrhythmias are recognized as important determinants of the prognosis of pulmonary arterial hypertension (PAH). OBJECTIVE: Here, we aimed to investigate whether direct pharmacological intervention in the RV muscle with dantrolene (DAN), a stabilizer of the cardiac ryanodine receptor (RyR2), has a protective effect against RV dysfunction and arrhythmia in a monocrotaline (MCT)-induced PAH rat model. METHODS: Male 8-week-old Sprague-Dawley rats were injected with MCT for the induction of PAH. Induction of ventricular tachycardia (VT) by catecholamines was also evaluated in association with RyR2-mediated Ca2+ release properties in isolated cardiomyocytes. A pulmonary artery-banding model has also been established to assess the independent effects of chronic pressure overload on RV morphology and function. RESULTS: In the MCT-induced PAH rat model, RV hypertrophy, dilation, and functional decline were observed, with a survival rate of 0% 2 months after MCT induction. In contrast, chronic DAN treatment improved all these RV parameters and increased survival by 80%. Chronic DAN treatment also prevented the dissociation of calmodulin from RyR2, thereby inhibiting Ca2+ sparks and spontaneous Ca2+ transients in MCT-induced hypertrophied RV cardiomyocytes. Epinephrine induced VT in more than 50% of rats with MCT-induced PAH, but complete suppression of VT was achieved by chronic DAN treatment. CONCLUSION: Stabilization of RyR2 by DAN has potential as a new therapeutic agent against the development of RV dysfunction and fatal arrhythmia associated with PAH.


Assuntos
Hipertensão Pulmonar , Disfunção Ventricular Direita , Animais , Arritmias Cardíacas/etiologia , Arritmias Cardíacas/prevenção & controle , Dantroleno/farmacologia , Modelos Animais de Doenças , Hipertensão Pulmonar/tratamento farmacológico , Masculino , Monocrotalina , Prognóstico , Ratos , Ratos Sprague-Dawley , Canal de Liberação de Cálcio do Receptor de Rianodina , Função Ventricular Direita
9.
J Arrhythm ; 37(4): 965-974, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34386123

RESUMO

BACKGROUND: This study aimed to investigate the correlation between left atrial low-voltage areas (LVAs) and an arrhythmogenic superior vena cava (SVC) and the impact on the efficacy of an empiric SVC isolation (SVCI) along with a pulmonary vein isolation (PVI) of non-paroxysmal atrial fibrillation (non-PAF) with or without LVAs. METHODS: We retrospectively enrolled 153 consecutive patients with non-PAF who underwent a PVI alone (n = 51) or empiric PVI plus an SVCI (n = 102). Left atrial voltage maps were constructed during sinus rhythm to identify the LVAs (<0.5 mV). An arrhythmogenic SVC was defined as firing from the SVC and an SVC associated with the maintenance of AF-like rapid SVC activity. RESULTS: An arrhythmogenic SVC and LVAs were identified in 28% and 65% of patients with a PVI alone and 36% and 73% of patients with a PVI plus SVCI, respectively (P = .275 and P = .353). In the multivariate analysis a female gender, higher pulmonary artery systolic pressure (PAPs), and arrhythmogenic SVC were associated with the presence of LVAs. In the PVI plus SVCI strategy, there was no significant difference in the atrial tachyarrhythmia/AF-free survival between the patients with and without LVAs after initial and multiple sessions (50% vs. 61%; P = .386, 73% vs. 79%; P = .530), however, differences were observed in the PVI alone group (27% vs. 61%; P = .018, 49% vs. 78%; P = .046). CONCLUSIONS: The presence of LVAs was associated with an arrhythmogenic SVC. An SVCI may have the potential to compensate for an impaired outcome after a PVI in non-PAF patients with LVAs.

10.
Commun Biol ; 3(1): 714, 2020 11 26.
Artigo em Inglês | MEDLINE | ID: mdl-33244105

RESUMO

Cardiac hypertrophy is a well-known major risk factor for poor prognosis in patients with cardiovascular diseases. Dysregulation of intracellular Ca2+ is involved in the pathogenesis of cardiac hypertrophy. However, the precise mechanism underlying cardiac hypertrophy remains elusive. Here, we investigate whether pressure-overload induced hypertrophy can be induced by destabilization of cardiac ryanodine receptor (RyR2) through calmodulin (CaM) dissociation and subsequent Ca2+ leakage, and whether it can be genetically rescued by enhancing the binding affinity of CaM to RyR2. In the very initial phase of pressure-overload induced cardiac hypertrophy, when cardiac contractile function is preserved, reactive oxygen species (ROS)-mediated RyR2 destabilization already occurs in association with relaxation dysfunction. Further, stabilizing RyR2 by enhancing the binding affinity of CaM to RyR2 completely inhibits hypertrophic signaling and improves survival. Our study uncovers a critical missing link between RyR2 destabilization and cardiac hypertrophy.


Assuntos
Sinalização do Cálcio , Calmodulina/metabolismo , Cardiomegalia , Canal de Liberação de Cálcio do Receptor de Rianodina , Animais , Cálcio/metabolismo , Sinalização do Cálcio/genética , Sinalização do Cálcio/fisiologia , Cardiomegalia/metabolismo , Cardiomegalia/fisiopatologia , Feminino , Coração/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Miocárdio/citologia , Miocárdio/metabolismo , Miocárdio/patologia , Pressão , Ligação Proteica , Canal de Liberação de Cálcio do Receptor de Rianodina/genética , Canal de Liberação de Cálcio do Receptor de Rianodina/metabolismo
11.
Gen Thorac Cardiovasc Surg ; 68(11): 1234-1239, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32253633

RESUMO

OBJECTIVES: Uncomplicated type B acute aortic dissection (UTBAAD) has traditionally been treated medically. Although patients are treated based on the rehabilitation program established by the Japanese Circulation Society, we sometimes encounter patients with complications related to the long duration of bed rest. We performed novel fast-track rehabilitation for UTBAAD, which consisted of short-duration bed rest and the early initiation of walking under secure blood pressure control. METHODS AND RESULTS: From April 2009 to February 2017, there were 73 consecutive cases of UTBAAD. Conventional medical treatment was administered to 39 patients (group G) during the early period. From August 2013, 34 patients (group F) received our 'fast-track' rehabilitation program, which consisted of the following: oral intake and assuming a sitting position from day 1 after the onset, standing by the bed from day 2, walking in their room from day 4, and discharge from day 16 if all goes smoothly. Group F had a significantly earlier initiation of standing and walking, first defecation, and weaning from oxygen and intravenous antihypertensive agents than group G. The pneumonia complication rate was significantly lower in group F than in group G. The hospitalization duration was markedly shorter and the in-hospital expense lower in group F than in group G. There were no significant differences in the rate of late adverse aortic events within 12 months after onset. CONCLUSIONS: Our fast-track rehabilitation program for patients with UTBAAD resulted in a better in-hospital clinical course and lower expense than conventional medical treatment without any adverse aortic events.


Assuntos
Aneurisma da Aorta Torácica/reabilitação , Dissecção Aórtica/reabilitação , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Prontuários Médicos , Pessoa de Meia-Idade , Alta do Paciente , Estudos Retrospectivos , Resultado do Tratamento
12.
Biochem Biophys Res Commun ; 524(2): 431-438, 2020 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-32007269

RESUMO

AIMS: Ca2+/calmodulin-dependent protein kinase II (CaMKII) has been shown to induce aberrant Ca2+ release from the cardiac ryanodine receptor (RyR2) in various diseased hearts. However, the precise pathogenic mechanism remains to be elucidated. Here, we investigated the effect of dantrolene (DAN): a RyR2 stabilizer on local Ca2+ release, cardiac function, and lethal arrhythmia in CaMKIIδc transgenic (TG) mice. METHODS AND RESULTS: The TG mice showed an increase in left ventricular end-diastolic diameter (LVEDD) and left ventricular end-systolic diameter (LVESD) with a reduction in LV fractional shortening (LVFS). The phosphorylation levels of Ser2814 in RyR2 and Thr287 in CaMKII increased in TG mice. In TG cardiomyocytes, peak cell shortening (CS) decreased, and the frequency of spontaneous Ca2+ transients (sCaTs) increased. Endogenous RyR2-associated calmodulin (CaM) markedly decreased in TG cardiomyocytes. After chronic DAN treatment for 1 month, LVESD (but not LVEDD) decreased with an increase in LVFS. In the chronic DAN-treated cardiomyocytes, CS increased, sCaTs decreased, and the endogenous CaM binding to RyR2 normally restored. The phosphorylation levels of Ser2814 in RyR2 and Thr287 in CaMKII remained elevated even after DAN treatment. Moreover, in TG mice, chronic DAN treatment prevented sustained ventricular tachycardia induced by epinephrine. CONCLUSIONS: Defective association of CaM with RyR2 is most likely to be involved in the pathogenesis of CaMKII-mediated cardiac dysfunction and lethal arrhythmia.


Assuntos
Arritmias Cardíacas/prevenção & controle , Arritmias Cardíacas/fisiopatologia , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Coração/fisiopatologia , Canal de Liberação de Cálcio do Receptor de Rianodina/metabolismo , Animais , Arritmias Cardíacas/genética , Arritmias Cardíacas/metabolismo , Cálcio/metabolismo , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/genética , Células Cultivadas , Dantroleno/uso terapêutico , Técnicas de Introdução de Genes , Coração/efeitos dos fármacos , Camundongos , Camundongos Transgênicos , Relaxantes Musculares Centrais/uso terapêutico , Fosforilação/efeitos dos fármacos , Canal de Liberação de Cálcio do Receptor de Rianodina/genética , Regulação para Cima/efeitos dos fármacos
13.
Ann Vasc Dis ; 13(3): 308-311, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-33384735

RESUMO

We report a case of stent graft occlusion, severe lower extremity ischemia, and ruptured abdominal aortic aneurysm due to type B acute aortic dissection 3 years after endovascular aneurysm repair. He admitted our hospital because of abrupt back pain and dysesthesia of bilateral lower limb. Contrast-enhanced computed tomography (CT) scan showed type B acute aortic dissection and occlusion of the stent graft due to dynamic compression by the false lumen. Emergent right axillo-bifemoral bypass operation was done for his critical limb ischemia. Immediately after the successful operation, he fell into shock vital and dissecting abdominal aortic aneurysm rupture was revealed by CT scan. We performed the stump occlusion of the infrarenal abdominal aorta and the bilateral common iliac arteries by abdominal midline incision. Postoperative myonephropathicmetabolic syndrome due to the left ischemia resulted in amputation of his left lower leg for lifesaving. While EVAR cases are increasing, various its complications come to be reported. We consider that this case report might be cautious about the indication of EVAR for the younger generation. (This is a translation of Jpn J Vasc Surg 2019; 28: 367-371.).

14.
Eur J Cardiothorac Surg ; 57(4): 701-708, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-31638700

RESUMO

OBJECTIVES: To compare different configurations of the bilateral internal thoracic arteries for the left coronary system and examine early and late outcomes, including mid-term graft patency. METHODS: We reviewed 877 patients who underwent primary isolated coronary artery bypass grafting using in situ bilateral internal thoracic arteries [in situ right internal thoracic artery (RITA)-to-left anterior descending artery (LAD) grafting, n = 683; in situ left internal thoracic artery (LITA)-to-LAD grafting, n = 194]. We compared mid-term patency between the grafts. Propensity score matching was performed to investigate early and long-term outcomes. RESULTS: The 2-year patency rate for RITA-to-LAD and LITA-to-LAD grafts were similar. Multivariate analysis revealed that RITA-to-non-LAD anastomosis (P = 0.029), postoperative length of stay (P = 0.003) and chronic obstructive pulmonary disease (P = 0.005) were associated with graft failure. After statistical adjustment, 176 propensity-matched pairs were available for comparison. RITA-to-LAD grafting enabled a more distal anastomosis. Kaplan-Meier analysis revealed that the incidences of death, repeat revascularization and myocardial infarction were significantly higher in the LITA-to-LAD group among both the unmatched and matched samples (P = 0.045 and 0.029, respectively). CONCLUSIONS: The mid-term patency and outcomes of RITA-to-LAD grafting are good and reduces future cardiac event, in contrast to LITA-to-LAD grafting.


Assuntos
Artéria Torácica Interna , Angiografia Coronária , Vasos Coronários , Humanos , Anastomose de Artéria Torácica Interna-Coronária , Artéria Torácica Interna/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Grau de Desobstrução Vascular
15.
Biochem Biophys Res Commun ; 521(1): 57-63, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31635807

RESUMO

Aberrant Ca2+ release from cardiac ryanodine receptors (RyR2) has been shown to be one of the most important causes of lethal arrhythmia in various types of failing hearts. We previously showed that dantrolene, a specific agent for the treatment of malignant hyperthermia, inhibits Ca2+ leakage from the RyR2 by correcting the defective inter-domain interaction between the N-terminal (1-619 amino acids) and central (2000-2500 amino acids) domains of the RyR2 and allosterically enhancing the binding affinity of calmodulin to the RyR2 in diseased hearts. In this study, we examined whether dantrolene inhibits this Ca2+ leakage, thereby preventing the pharmacologically inducible ventricular tachycardia in ventricular pressure-overloaded failing hearts. Ventricular tachycardia (VT) was easily induced after an injection of epinephrine in mice after 8 weeks of transverse aortic constriction-induced pressure-overload. Pretreatment with dantrolene almost completely inhibited the pharmacologically inducible VT. In the presence of dantrolene, the occurrence of both Ca2+ sparks and spontaneous Ca2+ transients was inhibited, which was associated with enhanced calmodulin binding affinity to the RyR2. These results suggest that dantrolene could be a new potent agent in the treatment of lethal arrhythmia in cases of acquired heart failure.


Assuntos
Dantroleno/farmacologia , Insuficiência Cardíaca/tratamento farmacológico , Relaxantes Musculares Centrais/farmacologia , Substâncias Protetoras/farmacologia , Canal de Liberação de Cálcio do Receptor de Rianodina/metabolismo , Taquicardia Ventricular/tratamento farmacológico , Animais , Insuficiência Cardíaca/patologia , Camundongos , Pressão , Taquicardia Ventricular/metabolismo , Taquicardia Ventricular/patologia
16.
Kyobu Geka ; 72(8): 630-633, 2019 Aug.
Artigo em Japonês | MEDLINE | ID: mdl-31353358

RESUMO

An 80-year-old woman was incidentally found to have a cardiac tumor on the aortic valve by echocardiography. Papillary fibroelastoma(PFE) was strongly suspected, and urgent operation was performed to prevent embolism. Two tumors were identified arising from the left and right cusps with wide stalks, and aortic valve replacement was performed. By pathological examination, the tumors were diagnosed as PFEs. A small tumor was also found on the non-coronary cusp, which was considered as possible PFE or Lambl's excrescence. In the case of multiple PFEs on one valve, valve replacement, instead of simple excision of tumors, should be considered.


Assuntos
Fibroma , Neoplasias Cardíacas , Doenças das Valvas Cardíacas/etiologia , Próteses Valvulares Cardíacas , Idoso de 80 Anos ou mais , Valva Aórtica , Ecocardiografia , Feminino , Fibroma/complicações , Neoplasias Cardíacas/complicações , Humanos
17.
JCI Insight ; 4(11)2019 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-31167968

RESUMO

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is caused by a single point mutation in the cardiac type 2 ryanodine receptor (RyR2). Using a knockin (KI) mouse model (R2474S/+), we previously reported that a single point mutation within the RyR2 sensitizes the channel to agonists, primarily mediated by defective interdomain interaction within the RyR2 and subsequent dissociation of calmodulin (CaM) from the RyR2. Here, we examined whether CPVT can be genetically rescued by enhancing the binding affinity of CaM to the RyR2. We first determined whether there is a possible amino acid substitution within the CaM-binding domain in the RyR2 (3584-3603 residues) that can enhance its binding affinity to CaM and found that V3599K substitution showed the highest binding affinity of CaM to the CaM-binding domain. Hence, we generated a heterozygous KI mouse model (V3599K/+) with a single amino acid substitution in the CaM-binding domain of the RyR2 and crossbred it with the heterozygous CPVT-associated R2474S/+-KI mouse to obtain a double-heterozygous R2474S/V3599K-KI mouse model. The CPVT phenotypes - bidirectional or polymorphic ventricular tachycardia, spontaneous Ca2+ transients, and Ca2+ sparks - were all inhibited in the R2474S/V3599K mice. Thus, enhancement of the CaM-binding affinity of the RyR2 is essential to prevent CPVT-associated arrhythmogenesis.


Assuntos
Calmodulina , Canal de Liberação de Cálcio do Receptor de Rianodina , Taquicardia Ventricular , Substituição de Aminoácidos/genética , Animais , Sítios de Ligação/genética , Cálcio/metabolismo , Calmodulina/química , Calmodulina/metabolismo , Células Cultivadas , Modelos Animais de Doenças , Técnicas de Introdução de Genes , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Miócitos Cardíacos , Ligação Proteica/genética , Canal de Liberação de Cálcio do Receptor de Rianodina/química , Canal de Liberação de Cálcio do Receptor de Rianodina/genética , Canal de Liberação de Cálcio do Receptor de Rianodina/metabolismo , Taquicardia Ventricular/metabolismo , Taquicardia Ventricular/fisiopatologia
18.
J Mol Cell Cardiol ; 125: 87-97, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30359562

RESUMO

In cardiac myocytes Calmodulin (CaM) bound to the ryanodine receptor (RyR2) constitutes a large pool of total myocyte CaM, but the CaM-RyR2 affinity is reduced in pathological conditions. Knock-in mice expressing RyR2 unable to bind CaM also developed hypertrophy and early death. However, it is unknown whether CaM released from this RyR2-bound pool participates in pathological cardiac hypertrophy. We found that angiotensin II (AngII) or phenylephrine (PE) both cause CaM to dissociate from the RyR2 and translocate to the nucleus. To test whether this nuclear CaM accumulation depends on CaM released from RyR2, we enhanced CaM-RyR2 binding affinity (with dantrolene), or caused CaM dissociation from RyR2 (using suramin). Dantrolene dramatically reduced AngII- and PE-induced nuclear CaM accumulation. Conversely, suramin enhanced nuclear CaM accumulation. This is consistent with nuclear CaM accumulation coming largely from the CaM-RyR2 pool. CaM lacks a nuclear localization signal (NLS), but G-protein coupled receptor kinase 5 (GRK5) binds CaM, has a NLS and translocates like CaM in response to AngII or PE. Suramin also promoted GRK5 nuclear import, and caused nuclear export of histone deacetylase 5 (HDAC5). Dantrolene prevented these effects. After 2-8 weeks of pressure overload (TAC) CaM binding to RyR2 was reduced, nuclear CaM and GRK5 were both elevated and there was enhanced nuclear export of HDAC5. Stress (acute AngII or TAC) causes CaM dissociation from RyR2 and translocation to the nucleus with GRK5 with parallel HDAC5 nuclear export. Thus CaM dissociation from RyR2 may be an important step in driving pathological hypertrophic gene transcription.


Assuntos
Calmodulina/metabolismo , Cardiomegalia/metabolismo , Núcleo Celular/metabolismo , Canal de Liberação de Cálcio do Receptor de Rianodina/metabolismo , Angiotensina II/farmacologia , Animais , Transporte Biológico/efeitos dos fármacos , Células Cultivadas , Dantroleno/farmacologia , Histona Desacetilases/metabolismo , Camundongos , Sinais de Localização Nuclear/metabolismo , Fenilefrina/farmacologia , Receptores Acoplados a Proteínas G/metabolismo , Suramina/farmacologia
19.
J Cardiol ; 72(6): 501-505, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30219614

RESUMO

BACKGROUND: Transradial intervention (TRI) may cause damage to the radial artery (RA). We have demonstrated intima-media thickening and luminal narrowing of the distal RA after TRI using intravascular ultrasound (IVUS). This study aimed to determine the predictors of intima-media thickening of RA after TRI in the same patients using serial IVUS. METHODS AND RESULTS: We enrolled 110 consecutive patients who underwent TRI. IVUS of RA was immediately performed after TRI and repeated 6 months later. Volumetric analyses were performed for the distal RA. The intima-media volume (IMV) increased from 53.56±10.85mm3 to 58.70±13.04mm3 (p=0.0022), whereas the lumen volume (LV) decreased from 146.87±40.53mm3 to 129.64±45.78mm3 (p=0.0018) and vessel volume (VV) decreased from 201.23±44.55mm3 to 188.34±52.25mm3 (p=0.0306). Multiple regression analysis revealed diabetes as the most powerful independent predictor of the percentage change in IMV of the distal RA after TRI. The percentage change in IMV significantly increased in the DM group compared with non-DM group (p<0.001). The percentage change in IMV was significantly positively correlated with HbA1c. CONCLUSIONS: Serial IVUS of the distal RA revealed a significant increase in IMV and decreases in LV and VV. Diabetes was the most powerful independent predictor of the percentage change in IMV of the distal RA after TRI. The percentage change in IMV was significantly positively correlated with HbA1c.


Assuntos
Intervenção Coronária Percutânea/efeitos adversos , Complicações Pós-Operatórias/diagnóstico por imagem , Artéria Radial/diagnóstico por imagem , Túnica Íntima/diagnóstico por imagem , Ultrassonografia de Intervenção/estatística & dados numéricos , Idoso , Feminino , Humanos , Hipertrofia , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/métodos , Complicações Pós-Operatórias/patologia , Artéria Radial/patologia , Fatores de Tempo , Túnica Íntima/patologia , Ultrassonografia de Intervenção/métodos
20.
Circ J ; 82(11): 2837-2844, 2018 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-30175800

RESUMO

BACKGROUND: This study compared the diagnostic value of myocardial perfusion imaging (MPI) between the rest-stress 99 mTc-tetrofosmin protocol (Tc/Tc protocol) and simultaneous acquisition rest 99 mTc-tetrofosmin/stress 201Tl dual-isotope protocol (SDI protocol) with a semiconductor camera.Methods and Results: We retrospectively studied 147 patients who underwent stress MPI using a cadmium-zinc-telluride camera and invasive coronary angiography within a 3-month interval. The Tc/Tc and SDI protocols were used in 59 and 88 patients, respectively. The sensitivity, specificity, and accuracy of the summed difference score in per-patient analysis were 56%, 85%, and 69%, respectively, for the Tc/Tc protocol and 89%, 82%, and 85%, respectively, for the SDI protocol. The area under the receiver operating characteristic curve was significantly better for the SDI than Tc/Tc protocol for the left anterior descending artery (0.836 vs. 0.674; P=0.0380), the left circumflex artery (0.754 vs. 0.599; P=0.0441), and in per-patient analysis (0.875 vs. 0.707; P=0.0135). There was no significant difference in the diagnostic accuracy of the summed stress score for any vessel or in per-patient analysis between the 2 protocols. CONCLUSIONS: The SDI protocol had a higher diagnostic accuracy for the detection of coronary ischemia than the Tc/Tc protocol.


Assuntos
Angiografia Coronária , Isquemia Miocárdica/diagnóstico , Isquemia Miocárdica/fisiopatologia , Imagem de Perfusão do Miocárdio , Compostos Organofosforados/administração & dosagem , Compostos de Organotecnécio/administração & dosagem , Radioisótopos de Tálio/administração & dosagem , Tomografia Computadorizada de Emissão de Fóton Único , Idoso , Idoso de 80 Anos ou mais , Teste de Esforço , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
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