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1.
Acta Med Okayama ; 75(4): 517-521, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34511620

RESUMO

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetically mediated cardiomyopathy charac-terized by progressive myocardial loss of the right ventricle and its replacement by fibrofatty tissue, causing dyskinesia, aneurysm, and/or arrhythmia. The prevalence of ARVC is estimated to be 1 in 2,000-5,000, with the condition accounting for up to 20% of sudden cardiac deaths in individuals < 35 years old. This report describes the case of 61-year-old Japanese who was diagnosed with ARVC after cardiac arrest (CA) and successful resusci-tation. After the sudden CA, the restoration of spontaneous circulation was achieved with appropriate resusci-tation, followed by the introduction of target temperature management in the intensive care unit. He was diag-nosed with ARVC based on angiography and histology results. An ICD (implantable cardioverter-defibrillator) was implanted, and he was discharged without neurological sequelae 1 month post-CA. ARVC is an important cause of sudden CA, and successfully resuscitated patients with right ventricular dilation should undergo testing to rule out ARVC.

2.
J Cardiol ; 77(1): 72-78, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32826140

RESUMO

BACKGROUND: The impairment of short-term heart rate regulation in patients with heart failure with preserved ejection fraction (HFpEF) can cause acute hemodynamic collapse. Detrended fluctuation analysis (DFA) is a useful tool for the diagnosis of heart diseases and the prediction of mortality. In DFA, the short-term scaling exponent α is decreased in heart failure. However, its change in HFpEF patients remains unclear. METHODS: Twenty patients diagnosed with HFpEF [defined as brain natriuretic peptide (BNP) >100 pg/mL, ejection fraction (EF) ≥50%, and without significant valvular disease], 20 diagnosed with non-HFpEF (BNP > 100 pg/mL and EF < 50%), and 20 control subjects generally matched for age and gender were enrolled. Holter electrocardiography was performed, and heart rate variability was calculated. In the DFA, the scaling exponents in 1000 beats were calculated for each 15-min segment and the average of all segments was used. We compared both the short-term (<11 beats, α1) and long-term (≥11 beats, α2) scaling exponents among the three groups. RESULTS: In the HFpEF, non-HFpEF, and control groups, α1 was 0.73 ± 0.27, 0.66 ± 0.29, and 1.01 ± 0.20 (p < 0.01), and α2 was 0.95 ± 0.08, 0.88 ± 0.11, and 0.96 ± 0.07 (p < 0.01), respectively. The α1 exponent was significantly decreased in the HFpEF group (p < 0.01 vs. control) and the non-HFpEF group (p < 0.01 vs. control), while the α2 exponent was significantly decreased in the non-HFpEF group only (p < 0.05 vs. HFpEF and control). CONCLUSIONS: Short-term heart rate regulation is impaired in patients with HFpEF, while patients with non-HFpEF have both short-term and long-term impairment.


Assuntos
Arritmias Cardíacas/diagnóstico , Insuficiência Cardíaca/fisiopatologia , Frequência Cardíaca/fisiologia , Monitorização Hemodinâmica/métodos , Volume Sistólico/fisiologia , Idoso , Arritmias Cardíacas/etiologia , Feminino , Sistema de Condução Cardíaco , Insuficiência Cardíaca/complicações , Hemodinâmica , Humanos , Masculino , Pessoa de Meia-Idade
3.
J Am Heart Assoc ; 9(16): e015103, 2020 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-32805185

RESUMO

Background Effects of sodium-glucose cotransporter 2 inhibitors on reducing hospitalization for heart failure have been reported in randomized controlled trials, but their effects on patients with heart failure with preserved ejection fraction (HFpEF) are unknown. This study aimed to evaluate the drug efficacy of luseogliflozin, a sodium-glucose cotransporter 2 inhibitor, in patients with type 2 diabetes mellitus and HFpEF. Methods and Results We performed a multicenter, open-label, randomized, controlled trial for comparing luseogliflozin 2.5 mg once daily with voglibose 0.2 mg 3 times daily in patients with type 2 diabetes mellitus suffering from HFpEF (left ventricular ejection fraction >45% and BNP [B-type natriuretic peptide] concentrations ≥35 pg/mL) in a 1:1 randomization fashion. The primary outcome was the difference from baseline in BNP levels after 12 weeks of treatment between the 2 drugs. A total of 173 patients with diabetes mellitus and HFpEF were included. Of these, 83 patients were assigned to receive luseogliflozin and 82 to receive voglibose. There was no significant difference in the reduction in BNP concentrations after 12 weeks from baseline between the 2 groups. The ratio of the mean BNP value at week 12 to the baseline value was 0.79 in the luseogliflozin group and 0.87 in the voglibose group (percent change, -9.0% versus -1.9%; ratio of change with luseogliflozin versus voglibose, 0.93; 95% CI, 0.78-1.10; P=0.26). Conclusion In patients with type 2 diabetes mellitus and HFpEF, there is no significant difference in the degree of reduction in BNP concentrations after 12 weeks between luseogliflozin and voglibose. Registration URL: https://www.umin.ac.jp/ctr/index.htm; Unique identifier: UMIN000018395.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Insuficiência Cardíaca/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Inositol/análogos & derivados , Peptídeo Natriurético Encefálico/sangue , Sorbitol/análogos & derivados , Idoso , Biomarcadores/sangue , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Esquema de Medicação , Feminino , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/fisiopatologia , Humanos , Inositol/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Sorbitol/uso terapêutico , Volume Sistólico
4.
Heart Vessels ; 35(11): 1483-1493, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32444933

RESUMO

The coronary artery calcium data and reporting system (CAC-DRS) is a novel reporting system based on CAC severity. Lung cancer patients have a high risk of cardiovascular disease (CVD), for which CAC severity may provide additional prognostic information. Using non-gated, non-contrast computed tomography (CT), we evaluated the CAC-DRS for predicting CVD and all-cause death in patients with potentially curable resected lung cancer. We retrospectively studied 309 consecutive patients without a history of CVD (mean age 67.4 ± 8.2 years, 61% male) who underwent curative surgery for non-small-cell lung cancer between May 2012 and March 2019 at the Japanese Red Cross Okayama Hospital. Time to incidence of major adverse cardiac events (MACEs) (non-fatal myocardial infarction, non-fatal stroke and cardiovascular death) and all-cause death was analyzed using Fine and Gray and Cox regression models. The CAC-DRS score was assessed using standard chest CT without electrocardiogram gating. During 52-months' median follow-up, 43 patients (13.4%) developed incident MACEs or died from any cause; the pathological cancer stages were Ia (n = 20), Ib (n = 8), IIa (n = 2), IIb (n = 2) and IIIa (n = 11). Patients had a graded increase in incidence of MACEs or all-cause death with increasing categories of CAC-DRS. The CAC-DRS score was significantly associated with incident MACEs or all-cause death after adjusting for confounding factors (hazard ratio 1.18; 95% confidence interval 1.10-1.25, p < 0.01). In conclusion, the CAC-DRS score on non-gated standard CT can predict incident MACEs and/or all-cause death in patients with potentially curable resected lung cancer. Lung cancer survivors with a greater CAC-DRS category may need more active management of cardiovascular risk factors.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Angiografia por Tomografia Computadorizada , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Neoplasias Pulmonares/diagnóstico por imagem , Tomografia Computadorizada Multidetectores , Calcificação Vascular/diagnóstico por imagem , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Doença da Artéria Coronariana/mortalidade , Feminino , Fatores de Risco de Doenças Cardíacas , Humanos , Incidência , Japão/epidemiologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Sistema de Registros , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença , Calcificação Vascular/mortalidade
5.
J Physiol Sci ; 68(2): 203, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29164388

RESUMO

The article Physiological insights of recent clinical diagnostic and therapeutic technologies for cardiovascular diseases, written by Kenji Shigemi, Soichiro Fuke, Dai Une, Keita Saku, Shuji Shimizu, Toru Kawada, Toshiaki Shishido, Kenji Sunagawa and Masaru Sugimachi, was originally published Online First without open access.

6.
Acta Med Okayama ; 71(6): 467-473, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29276219

RESUMO

Early mobilization is advocated to prevent intensive care unit-acquired physical weakness, but the patient's workload and its changes in response to body position changes have not been established. We used indirect calorimetry to determine the energy expenditure (EE) in response to body position changes, and we assessed EE's correlation with respiratory parameters in healthy volunteers: 8 males and 8 females, mean age 23.4±1.3 years. The subjects started in the resting supine position followed by a 30° head-up position, a 60° head-up position, an upright sitting position, a standing position, and the resting supine position. EE was determined in real time by indirect calorimetry monitoring the subject's respiratory rate, tidal volume (VT), and minute volume (MV). The highest values were observed immediately after the subjects transitioned from standing to supine, and this was significantly higher compared to the original supine position (1,450±285 vs. 2,004±519 kcal/day, p<0.01). Moderate correlations were observed between VT and EE (r=0.609, p<0.001) and between MV and EE (r=0.576, p<0.001). Increasing VT or MV indicates an increasing patient workload during mobilization. Monitoring these parameters may contribute to safe rehabilitation. Further studies should assess EE in critically ill patients.


Assuntos
Calorimetria Indireta/métodos , Metabolismo Energético , Postura , Adulto , Feminino , Humanos , Masculino , Respiração
7.
J Physiol Sci ; 67(6): 655-672, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28681363

RESUMO

Diagnostic and therapeutic methods for cardiovascular diseases continue to be developed in the 21st century. Clinicians should consider the physiological characteristics of the cardiovascular system to ensure successful diagnosis and treatment. In this review, we focus on the roles of cardiovascular physiology in recent diagnostic and therapeutic technologies for cardiovascular diseases. In the first section, we discuss how to evaluate and utilize left ventricular arterial coupling in the clinical settings. In the second section, we review unique characteristics of pulmonary circulation in the diagnosis and treatment of pulmonary hypertension. In the third section, we discuss physiological and anatomical factors associated with graft patency after coronary artery bypass grafting. In the last section, we discuss the usefulness of mechanical ventricular unloading after acute myocardial infarction. Clinical development of diagnostic methods and therapies for cardiovascular diseases should be based on physiological insights of the cardiovascular system.


Assuntos
Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/terapia , Fenômenos Fisiológicos Cardiovasculares , Ponte de Artéria Coronária , Humanos
8.
J Cardiol ; 70(1): 35-40, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-27836373

RESUMO

BACKGROUND: Although some studies have examined platelet reactivity (PR) during prasugrel treatment, little is known about PR during the early treatment period and its clinical significance in Japan. METHODS: We investigated the early and medium-term efficacy and safety of prasugrel in patients with acute myocardial infarction (AMI) undergoing primary percutaneous coronary intervention (PCI). Seventy-eight patients were enrolled and PR was measured (in P2Y12 reaction units; PRU) by the VerifyNow P2Y12 assay (Accumetrics, San Diego, CA, USA). RESULTS: In 44 patients, serial measurement revealed that PR was significantly higher at 2h after administration of the 20-mg loading dose of prasugrel than on the morning of the second day at 17.6±6.6h after administration (191.6±75.5 vs. 138.5±68.9PRU). During the 8-month follow-up period, bleeding events occurred in 18 patients (23.1%) (GUSTO minor: 15 patients). Multivariate regression analysis identified oral anticoagulant use as a significant predictor of bleeding events during admission [odds ratio (OR): 4.214, 95% confidence interval (CI): 1.005-17.669, p=0.049]. Administration of prasugrel via a nasogastric tube was a significant predictor of high on-treatment platelet reactivity (HTPR) (PRU≥230) (OR: 43.100, 95% CI: 4.517-411.251, p=0.001). In addition, HTPR was a significant predictor of major adverse cardiac events (cardiovascular death, non-fatal myocardial infarction, stent thrombosis, stroke, and sustained ventricular tachycardia) during the 8-month follow-up period (OR: 4.911, 95% CI: 1.164-20.722, p=0.030). CONCLUSIONS: It is feasible to treat AMI patients with prasugrel. HTPR is a significant independent risk factor for adverse events in AMI patients receiving prasugrel after primary PCI.


Assuntos
Plaquetas/efeitos dos fármacos , Infarto do Miocárdio/tratamento farmacológico , Inibidores da Agregação Plaquetária/uso terapêutico , Cloridrato de Prasugrel/uso terapêutico , Doença Aguda , Idoso , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/terapia , Razão de Chances , Intervenção Coronária Percutânea , Inibidores da Agregação Plaquetária/administração & dosagem , Inibidores da Agregação Plaquetária/efeitos adversos , Testes de Função Plaquetária , Cloridrato de Prasugrel/efeitos adversos , Estudos Prospectivos , Fatores de Risco , Resultado do Tratamento
9.
Int Heart J ; 57(5): 535-40, 2016 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-27581670

RESUMO

The usefulness of coronary magnetic resonance angiography (cMRA) has been reported, although the difference in the diagnostic accuracy of different protocols has not been established.We compared conventional coronary angiography (CAG) and cMRA, conducted within 6 months in 24 consecutive patients between September 2012 and July 2014. Three cMRA protocols were examined, cMRA1, free-breathing wholeheart coronary angiography (WHCA) without contrast; cMRA2, free-breathing WHCA with contrast; and cMRA3, breath-hold steady-state free precession with contrast using a 3.0 T scanner. Image quality was graded on a 4-point scale: 1) nonassessable; 2) assessable, fair vessel contrast; 3) assessable, good vessel contrast; and 4) assessable, excellent vessel contrast. Significant narrowing of the coronary arteries was visually assessed.Stenosis was observed in 34 segments, with a prevalence of 10.3%. For cMRA1, cMRA2, and cMRA3, the numbers of assessable segments were 245 (74.2%), 287 (87.0%), and 164 (49.7%), respectively (P < 0.001 by the McNemar test). For assessable segments, the sensitivity, specificity, positive predictive value, and negative predictive value were 89.3%, 99.1%, 92.6%, and 98.6% for cMRA1, 90.0%, 98.1%, 84.4%, and 98.8% for cMRA2, and 76.5%, 93.9%, 59.1%, and 97.1% for cMRA3, respectively. For the assessable segments, the image quality score was better with cMRA2 than with the other two protocols.cMRA is a useful modality to rule out coronary artery disease, especially the cMRA2 protocol, which performed better than the other two protocols.


Assuntos
Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Angiografia por Ressonância Magnética , Idoso , Meios de Contraste , Feminino , Humanos , Aumento da Imagem , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos
10.
J Pharmacol Sci ; 120(3): 206-12, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23117888

RESUMO

Acute vasoreactivity testing for patients with pulmonary arterial hypertension (PAH) has been reported to be useful to identify patients with sustained beneficial response to oral calcium-channel blockers (CCBs), but there is a risk of exacerbation during the testing with oral CCBs. Therefore, we developed a testing method utilizing intravenous nicardipine, a short-acting CCB, and examined the safety and usefulness of acute vasoreactivity testing with nicardipine in PAH patients. Acute vasoreactivity testing with nicardipine was performed in 65 PAH patients. Nicardipine was administered by short-time continuous infusion (1 µg·kg⁻¹·min⁻¹ for 5 min and 2 µg·kg⁻¹·min⁻¹ for 5 min) followed by bolus injection (5 µg/kg). Hemodynamic responses were continuously measured using a right heart catheter. Acute responders were defined as patients who showed a decrease in mean pulmonary artery pressure of at least 10 mmHg to an absolute level below 40 mmHg with preserved or increased cardiac output. Two acute responders and sixty-three non-acute responders were identified. There was no hemodynamic instability requiring additional inotropic agents or death during the testing. Acute responders had good responses to long-term oral CCBs. The acute vasoreactivity testing with nicardipine might be safe and useful for identifying CCB responders in PAH patients.


Assuntos
Anti-Hipertensivos/efeitos adversos , Bloqueadores dos Canais de Cálcio/efeitos adversos , Monitoramento de Medicamentos/métodos , Hipertensão Pulmonar/tratamento farmacológico , Nicardipino/efeitos adversos , Vasodilatação/efeitos dos fármacos , Vasodilatadores/efeitos adversos , Adulto , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/uso terapêutico , Bloqueadores dos Canais de Cálcio/administração & dosagem , Bloqueadores dos Canais de Cálcio/uso terapêutico , Débito Cardíaco/efeitos dos fármacos , Relação Dose-Resposta a Droga , Resistência a Medicamentos , Hipertensão Pulmonar Primária Familiar , Feminino , Hemodinâmica/efeitos dos fármacos , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Nicardipino/administração & dosagem , Nicardipino/uso terapêutico , Guias de Prática Clínica como Assunto , Pressão Propulsora Pulmonar/efeitos dos fármacos , Vasodilatadores/administração & dosagem , Vasodilatadores/uso terapêutico , Adulto Jovem
11.
J Cardiol ; 60(5): 361-6, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22890073

RESUMO

BACKGROUND: Although percutaneous coronary intervention (PCI) in patients with diabetes mellitus (DM) is associated with worse clinical outcomes, the efficacy of drug-eluting stents (DES) in Japanese patients and differences in effectiveness between different DES types remain unknown. METHODS AND SUBJECTS: Five-hundred and sixty-two consecutive patients (183 with DM, 379 without DM) with 676 lesions were treated with sirolimus-eluting stents (SES, n=531; 160 DM group, 371 non-DM group) or paclitaxel-eluting stents (PES, n=145; 64 and 81, respectively). We assessed the initial and 8-month follow-up clinical and angiographic outcomes. RESULTS: There were no significant differences in clinical and lesion characteristics, although the pre-minimum luminal diameter was smaller in the DM group (p=0.016). The risk of major adverse cardiac events (MACE), defined as cardiac death, non-fatal myocardial infarction, congestive heart failure, or recurrent angina pectoris, was higher in the DM group compared with the non-DM group (17.4% vs 9.5%, p=0.007). Among diabetic patients, although SES reduced late loss by 0.45 mm (p<0.001) and the binary restenosis rate by 66.4% (7.4% vs 22.0%, p<0.001) compared with PES at 8 months, it did not reduce target lesion revascularization or MACE, as in the non-DM group. CONCLUSIONS: Diabetic patients have worse mid-term prognosis than non-diabetic patients undergoing PCI with DES. Although the superiority of SES in terms of late loss or restenosis may not play a clinically meaningful role in the treatment of diabetic patients, this phenomenon was independent of the presence of diabetes.


Assuntos
Angiografia Coronária , Doença das Coronárias/diagnóstico por imagem , Doença das Coronárias/terapia , Complicações do Diabetes , Stents Farmacológicos/efeitos adversos , Paclitaxel , Intervenção Coronária Percutânea/efeitos adversos , Sirolimo , Idoso , Idoso de 80 Anos ou mais , Doença das Coronárias/complicações , Reestenose Coronária/etiologia , Reestenose Coronária/prevenção & controle , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento
12.
Cardiovasc Interv Ther ; 27(3): 189-95, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22798196

RESUMO

Percutaneous coronary intervention in patients with diabetes mellitus (DM) is associated with worse clinical outcomes; however, the long-term efficacy of sirolimus-eluting stents (SES) in diabetic patients remains uncertain. We evaluated 5-year clinical outcomes after SES implantation in 197 consecutive patients (85 in the DM group and 112 in the non-DM group), and 246 lesions (106 and 140, respectively). The primary end point was major adverse cardiac events (MACE) defined as cardiac death, nonfatal myocardial infarction, target lesion revascularization (TLR), stent thrombosis or admission for congestive heart failure. Diabetic patient characteristics included 32 % who used insulin. The risk of congestive heart failure was significantly higher [20.0 vs. 5.4 %, odds ratio (OR) 4.417, 95 % confidence interval (CI) 1.659 to 11.759, p = 0.003] in the DM group compared with the non-DM group; however, MACE did not occur significantly more often (27.1 vs. 16.1 %, p = 0.060). Multivariate logistic regression analysis showed that diabetes was associated with congestive heart failure (OR 4.715, 95 % CI 1.743 to 12.759, p = 0.002) and multivessel disease was associated with major adverse cardiac events (OR 2.709, 95 % CI 1.053 to 6.965, p = 0.039). The cumulative rates (%) of TLR were as follows: after 1 year; 5.9 versus 5.4, 2 years; 7.1 versus 5.4, 3 years; 9.4 versus 7.1, 4 years; 9.4 versus 8.9, 5 years; 9.4 versus 8.9 (p = 0.652) in the DM group and the non-DM group, respectively. Diabetic patients had worse long-term prognosis in terms of congestive heart failure than non-diabetic patients undergoing PCI, even with SES. TLR was performed steadily for up to 5 years of follow-up following the late catch-up phenomenon both in diabetic and non-diabetic patients.


Assuntos
Diabetes Mellitus/cirurgia , Stents Farmacológicos/efeitos adversos , Intervenção Coronária Percutânea/efeitos adversos , Sirolimo/efeitos adversos , Idoso , Angiografia Coronária , Morte , Diabetes Mellitus/diagnóstico por imagem , Diabetes Mellitus/tratamento farmacológico , Feminino , Seguimentos , Insuficiência Cardíaca/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Intervenção Coronária Percutânea/métodos , Prognóstico , Fatores de Risco , Sirolimo/uso terapêutico , Trombose/epidemiologia , Resultado do Tratamento
13.
Int J Cardiol ; 159(2): 100-6, 2012 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-21376411

RESUMO

BACKGROUND: Remodeling of the pulmonary artery by an inappropriate increase of pulmonary artery smooth muscle cells (PASMCs) is problematic in the treatment of idiopathic pulmonary arterial hypertension (IPAH). Effective treatment that achieves reverse remodeling is required. The aim of this study was to assess the pro-apoptotic effects of imatinib, a platelet-derived growth factor (PDGF)-receptor tyrosine kinase inhibitor, on PASMCs obtained from patients with IPAH. METHODS: PASMCs were obtained from 8 patients with IPAH undergoing lung transplantation. Cellular proliferation was assessed by (3)H-thymidine incorporation. Pro-apoptotic effects of imatinib were examined using TUNEL and caspase-3,7 assays and using transmission electron microscopy. RESULTS: Treatment with imatinib (0.1 to 10 µg/mL) significantly inhibited PDGF-BB (10 ng/mL)-induced proliferation of PASMCs from IPAH patients. Imatinib (1 µg/mL) did not induce apoptosis in quiescent IPAH-PASMCs, but it had a pro-apoptotic effect on IPAH-PASMCs stimulated with PDGF-BB. Imatinib did not induce apoptosis in normal control PASMCs with or without PDGF-BB stimulation. PDGF-BB induced phosphorylation of Akt at 15 min, and Akt phosphorylation was inhibited by imatinib in IPAH-PASMCs. Akt-I-1/2 (1 µmol/L), an Akt inhibitor, in the presence of PDGF-BB significantly increased apoptotic cells compared with the control condition. Thus, Akt-I-1/2 could mimic the effects of imatinib on PASMCs. CONCLUSION: Imatinib has anti-proliferative and pro-apoptotic effects on IPAH-PASMCs stimulated with PDGF. The inhibitory effect of imatinib on Akt phosphorylation induced by PDGF plays an important role in the pro-apoptotic effect.


Assuntos
Apoptose/efeitos dos fármacos , Benzamidas/farmacologia , Hipertensão Pulmonar/tratamento farmacológico , Miócitos de Músculo Liso/efeitos dos fármacos , Piperazinas/farmacologia , Proteínas Proto-Oncogênicas c-sis/farmacologia , Artéria Pulmonar/efeitos dos fármacos , Pirimidinas/farmacologia , Adolescente , Adulto , Apoptose/fisiologia , Becaplermina , Proliferação de Células/efeitos dos fármacos , Criança , Hipertensão Pulmonar Primária Familiar , Feminino , Humanos , Hipertensão Pulmonar/patologia , Mesilato de Imatinib , Masculino , Miócitos de Músculo Liso/fisiologia , Proteínas Proto-Oncogênicas c-sis/antagonistas & inibidores , Artéria Pulmonar/citologia , Artéria Pulmonar/fisiologia , Resultado do Tratamento , Adulto Jovem
14.
J Cardiol Cases ; 4(1): e31-e33, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30546711

RESUMO

A 50-year-old man diagnosed with liver cirrhosis type C was referred to our hospital because of right heart failure with pulmonary hypertension. Echocardiography revealed enlargement of the right atrium and ventricle with severe tricuspid regurgitation. The peak flow velocity of tricuspid regurgitation by continuous wave Doppler echocardiography was 452 cm/s. Right heart catheterization demonstrated severe pulmonary hypertension [pulmonary arterial pressure (PAP) systolic/diastolic/mean = 73/20/41 mmHg and pulmonary vascular resistance (PVR) = 509 dyn s cm-5] with portal hypertension. We diagnosed the patient as having portopulmonary hypertension (PoPH). Although we treated the patient with a prostacyclin analog, tricuspid regurgitation velocity was increased to 480 cm/s four years after the start of the therapy. To select drugs for the treatment of PoPH, we performed an acute vasoreactivity test of sildenafil during right heart catheterization. Since single administration of sildenafil (20 mg) decreased PAP (93/30/55-77/27/44 mmHg) and PVR (908-833 dyn s cm-5), we added sildenafil (20 mg, t.i.d.) to the prostacyclin analog. Tricuspid regurgitation velocity decreased to 403 cm/s one year after the addition of sildenafil. An acute vasoreactivity test of sildenafil during right heart catheterization was useful for the decision of the drug to be used in the treatment of PoPH.

15.
Int J Cardiol ; 140(3): 328-35, 2010 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-19106010

RESUMO

BACKGROUND: Amiodarone (AMD) is a strong antiarrhythmic drug but has severe side effects such as pulmonary toxicity. There are no indicators or drugs that can prevent the development of amiodarone-induced pulmonary toxicity (AIPT). METHODS: We collected data for 96 consecutive patients treated with AMD and analyzed clinical factors related to AIPT. In addition, we examined the effect of AMD and angiotensin II (Ang II) on human lung alveolar epithelial cells (AEC) and verified the protective efficacy of an Ang II type 1 receptor blocker (ARB) in vitro. RESULTS: During a follow-up period of 33.8+/-34.6 months, AIPT developed in 11 patients (11.5%). There were no differences in the dose of AMD, left ventricular ejection fraction, serum KL-6 and %DLCO level before starting AMD between patients with and those without AIPT. However, repeated episodes of congestive heart failure (CHF) were observed more frequently in patients with AIPT than in patients without AIPT (81.8% vs. 41.2%, P<0.011). In vitro examination, AMD progressively increased apoptosis of AEC and Ang II enhanced this effect of AMD (P<0.001). However, ARB inhibited the enhancement by Ang II of the AMD-induced apoptosis effect (P<0.001). Furthermore, patients with AIPT were administrated a lower dose of angiotensin system antagonists than were those without AIPT (P<0.05). CONCLUSIONS: The results indicate that Ang II induced by CHF increases the risk of AMD-induced pulmonary toxicity. An angiotensin-converting enzyme inhibitor or ARB should be given at a sufficient dose during AMD treatment.


Assuntos
Amiodarona/efeitos adversos , Angiotensina II/efeitos dos fármacos , Antiarrítmicos/efeitos adversos , Pneumopatias/induzido quimicamente , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Células Epiteliais Alveolares/efeitos dos fármacos , Angiotensina II/sangue , Angiotensina II/farmacologia , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Apoptose/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Feminino , Insuficiência Cardíaca/sangue , Humanos , Modelos Logísticos , Pneumopatias/prevenção & controle , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Alvéolos Pulmonares/efeitos dos fármacos , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida
16.
J Card Fail ; 15(8): 709-16, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19786260

RESUMO

BACKGROUND: It has been reported that that the amount of 4-hydroxy-2-nonenal (HNE), which is a major lipid peroxidation product and a cytotoxic aldehyde, is increased in the human failing myocardium. This study was designed to determine whether HNE has a pro-oxidant effect in cardiac myocytes and whether HNE causes Ca(2+) overload. METHODS AND RESULTS: Exposure to HNE for 10 minutes in the presence of ferric nitrilotriacetate induced the production of hydroxyl radical (.OH) in the rat myocardium as assessed by electron spin resonance spectroscopy, and HNE induced the generation of reactive oxygen species (ROS) in a dose-dependent manner as assessed by 2', 7'-dichlorofluorescein diacetate fluorescence. HNE increased intracellular Ca(2+) concentration ([Ca(2+)](i)) as assessed by fura-2 ratio in a dose- and time-dependent manner. After 20 minutes of HNE (400 micromol/L) exposure, hypercontracture was induced in 67% of the cells. Catalase, an antioxidative enzyme that can decompose hydrogen peroxide (H(2)O(2)), significantly attenuated the increase in [Ca(2+)](i) and completely inhibited hypercontracture. Carvedilol, a beta-blocker with potent antioxidant activity, also significantly attenuated the increase in [Ca(2+)](i) and completely inhibited hypercontracture, but propranolol had no effect on either [Ca(2+)](i) increase or hypercontracture. CONCLUSIONS: HNE induces the formation of ROS, especially H(2)O(2) and .OH, in cardiomyocytes and subsequently ROS cause intracellular Ca(2+) overload. HNE formation may play an important role as a mediator of oxidative stress in heart failure.


Assuntos
Aldeídos/toxicidade , Cálcio/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Animais , Morte Celular/efeitos dos fármacos , Morte Celular/fisiologia , Células Cultivadas , Relação Dose-Resposta a Droga , Masculino , Miócitos Cardíacos/patologia , Ratos , Ratos Wistar
17.
J Thorac Cardiovasc Surg ; 138(1): 222-6, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19577083

RESUMO

OBJECTIVE: The aim of this study was to evaluate right and left ventricular functions in patients with pulmonary arterial hypertension after living-donor lobar lung transplantation compared with those without hypertension. METHODS: Thirty-three recipients of living-donor lobar lung transplantation were divided into two groups: those with pulmonary arterial hypertension (PAH group; n = 12) and those without (non-PAH group; n = 21). Their systolic pulmonary artery pressure was 93.1 +/- 6.7 mm Hg versus 31.4 +/- 2.9 mm Hg, respectively. Right and left ventricular ejection fractions, systolic pulmonary artery pressure, and cardiac index were serially measured by radionuclide ventriculography and right heart catheterization, respectively. RESULTS: Pretransplant right and left ventricular ejection fractions were lower in the PAH group (29.8% +/- 7.0%, 49.9% +/- 6.6%) than in the non-PAH group (49.7% +/- 3.3%, 65.2% +/- 1.9%) (P = .010, .068). Two months after living-donor lobar lung transplantation, right ventricular ejection fraction and systolic pulmonary artery pressure in the PAH group (57.3% +/- 5.1%, 25.7 +/- 1.8 mm Hg) improved dramatically, equal to those in the non-PAH group. In contrast, left ventricular ejection fraction and cardiac index in the PAH group (50.9% +/- 3.7%, 2.66 +/- 0.12 L x min(-1) x m(-2)) were still significantly lower than in the non-PAH group (65.4% +/- 2.8%, 3.13 +/- 0.15 L x min(-1) x m(-2)) (P = .0038, .037). At 6 to 12 months, the PAH group demonstrated a significant rise in left ventricular ejection fraction and cardiac index that reached similar values in the non-PAH group measured at 2 months. These values were stable for up to 3 years. CONCLUSIONS: Right ventricular function recovered early after living-donor lobar lung transplantation in the PAH group. In contrast, recovery of left ventricular function required 6 to 12 months. Improved cardiac function was sustained for up to 3 years, suggesting long-term durability of cardiac function recovery after living-donor lobar lung transplantation.


Assuntos
Hipertensão Pulmonar/cirurgia , Doadores Vivos , Transplante de Pulmão , Função Ventricular Esquerda , Função Ventricular Direita , Adulto , Pressão Sanguínea , Débito Cardíaco , Feminino , Humanos , Hipertensão Pulmonar/fisiopatologia , Pneumopatias/fisiopatologia , Pneumopatias/cirurgia , Masculino , Artéria Pulmonar/fisiopatologia , Volume Sistólico
18.
J Am Coll Cardiol ; 51(12): 1169-75, 2008 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-18355654

RESUMO

OBJECTIVES: The goal of our work was to examine the relationships of atrial fibrillation (AF) with genetic, clinical, and electrophysiological backgrounds in Brugada syndrome (BrS). BACKGROUND: Atrial fibrillation is often observed in patients with BrS and indicates that electrical abnormality might exist in the atrium as well as in the ventricle. SCN5A, a gene encoding the cardiac sodium channel, has been reported to be causally related to BrS. However, little is known about the relationships of atrial arrhythmias with genetic, clinical, and electrophysiological backgrounds of BrS. METHODS: Seventy-three BrS patients (49 +/- 12 years of age, men/women = 72/1) were studied. The existence of SCN5A mutation and clinical variables (syncopal episode, documented ventricular fibrillation [VF], and family history of sudden death) were compared with spontaneous AF episodes. Genetic and clinical variables were also compared with electrophysiologic (EP) parameters: atrial refractory period, interatrial conduction time (CT), repetitive atrial firing, and AF induction by atrial extra-stimulus testing. RESULTS: Spontaneous AF occurred in 10 (13.7%) of the BrS patients and SCN5A mutation was detected in 15 patients. Spontaneous AF was associated with higher incidence of syncopal episodes (60.0% vs. 22.2%, p < 0.03) and documented VF (40.0% vs. 14.3%, p < 0.05). SCN5A mutation was associated with prolonged CT (p < 0.03) and AF induction (p < 0.05) in EP study, but not related to the spontaneous AF episode and other clinical variables. In patients with documented VF, higher incidence of spontaneous AF (30.8% vs. 10.0%, p < 0.05), AF induction (53.8% vs. 20.0%, p < 0.03), and prolonged CT was observed. CONCLUSIONS: Spontaneous AF and VF are closely linked clinically and electrophysiologically in BrS patients. Patients with spontaneous AF have more severe clinical backgrounds in BrS. SCN5A mutation is associated with electrical abnormality but not disease severity.


Assuntos
Fibrilação Atrial/genética , Fibrilação Atrial/fisiopatologia , Síndrome de Brugada/genética , Síndrome de Brugada/fisiopatologia , Taquicardia Ventricular/genética , Adulto , Fibrilação Atrial/diagnóstico , Síndrome de Brugada/diagnóstico , Eletrocardiografia , Eletrofisiologia , Feminino , Sistema de Condução Cardíaco , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Musculares , Mutação , Canal de Sódio Disparado por Voltagem NAV1.5 , Índice de Gravidade de Doença , Canais de Sódio
19.
Int Heart J ; 48(2): 269-76, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17409592

RESUMO

We report a rescued 37-year-old woman in her 30(th) week of gestation with massive pulmonary thromboembolism who was admitted to our cardiac care unit with progressive dyspnea and 2 episodes of syncope. Helical chest CT showed massive pulmonary thromboembolism of both pulmonary arteries. Although 26,000 U/day of heparin was administered following insertion of a temporary filter, hemodynamic evaluation documented no improvement. Since pulmonary artery (PA) pressure increased from 62/22 mmHg to 80/24 mmHg just after an emergency cesarean section on day 2, an emergency transcatheter thrombectomy was performed and it showed decreased PA pressure following extensive thrombus aspiration. Mother and baby were discharged with no complications.


Assuntos
Embolectomia/métodos , Complicações Cardiovasculares na Gravidez/cirurgia , Embolia Pulmonar/cirurgia , Adulto , Cateterismo , Cesárea , Feminino , Humanos , Gravidez , Complicações Cardiovasculares na Gravidez/diagnóstico , Embolia Pulmonar/diagnóstico
20.
Circ J ; 71(2): 220-5, 2007 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17251671

RESUMO

BACKGROUND: Sirolimus inhibits endothelial cell proliferation in vitro, but although the sirolimus-eluting stent (SES) is widely used because of the very low rates of in-stent restenosis, the influence of SES on coronary endothelial vasomotor function in humans is not well known. METHODS AND RESULTS: The present study included 21 patients treated with SES, and 12 patients treated with conventional bare metal stent (BMS). Endothelium-dependent vasomotor function was evaluated 6 months after stent implantation, using intracoronary acetylcholine infusion. Changes in diameter at the 5-mm proximal and distal edges of the stent, and at the control segment were assessed by quantitative coronary angiography. To evaluate native endothelial function, an intracoronary acetylcholine test was performed before stenting. In the 21 SES patients acetylcholine infusion at 10(-8) mol/L and 10(-7) mol/L produced significant vasoconstriction in the proximal stent segment (-11.3+/-10.3%, and -14.1+/-11.3%, respectively) and the distal stent segment (-13.7+/-9.3%, and -17.5+/-12.5%, respectively). In contrast, in the 12 BMS patients, acetylcholine infusion at the same concentrations did not produce a vasoconstrictive response in the proximal stent segment (5.0+/-8.2% and 4.9+/-9.1%, respectively) or the distal stent segment (4.2+/-7.6% and 5.1+/-7.7%, respectively). Intracoronary nitroglycerin induced a similar grade of vasodilation in the peri-stent area in both groups. Local endothelial function before SES implantation showed no vasoconstrictive response. CONCLUSIONS: In contrast to vasodilation in BMS patients, SES implantation in the peri-stent area resulted in a vasoconstrictive response to acetylcholine. SES implantation may impair endothelial function in humans.


Assuntos
Implante de Prótese Vascular/efeitos adversos , Endotélio Vascular/efeitos dos fármacos , Imunossupressores/administração & dosagem , Sirolimo/administração & dosagem , Stents/efeitos adversos , Sistema Vasomotor/fisiopatologia , Acetilcolina/farmacologia , Idoso , Idoso de 80 Anos ou mais , Endotélio Vascular/inervação , Feminino , Humanos , Imunossupressores/efeitos adversos , Masculino , Pessoa de Meia-Idade , Nitroglicerina/farmacologia , Sirolimo/efeitos adversos , Vasoconstrição/efeitos dos fármacos , Vasodilatação/efeitos dos fármacos , Vasodilatadores/farmacologia
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