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1.
Artif Organs ; 47(3): 566-573, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36300650

RESUMO

BACKGROUND: Driveline infection (DLI) following left ventricular assist device (LVAD) implantation remains an unresolved problem. Negative pressure wound therapy (NPWT) promotes wound healing by applying negative pressure on the surface of the wound. Recently, the prophylactic application of NPWT to closed surgical incisions has decreased surgical site infections in various postsurgical settings. Therefore, we evaluated the efficacy and safety of prophylactic NPWT for preventing DLI in patients with LVAD implantation. METHODS: Prophylactic NPWT was provided to 50 patients who received continuous-flow LVADs as bridge-to-transplant therapy at our institution between May 2018 and October 2020 (NPWT group). The negative pressure dressing was applied immediately after surgery and retained on the driveline exit site for 7 days with a continuous application of -125 mm Hg negative pressure. The primary outcome was DLI within 1 year of LVAD implantation. We compared the rate of DLI incidence in the NPWT group with that in the historical control cohort (50 patients) treated with the standard dressing (SD) who received LVAD implantation between July 2015 and April 2018 (SD group). RESULTS: No severe complications were associated with the NPWT. During the follow-up period, DLI was diagnosed in 16 participants (32%) in the NPWT group and 21 participants (42%) in the SD group. The rates of DLI incidence and freedom from DLI did not differ between groups (p = 0.30 and p = 0.63). CONCLUSIONS: Prophylactic NPWT at the driveline exit site was safe following LVAD implantation. However, it did not significantly reduce the risk of DLI.


Assuntos
Coração Auxiliar , Tratamento de Ferimentos com Pressão Negativa , Infecções Relacionadas à Prótese , Procedimentos Cirúrgicos Torácicos , Humanos , Coração Auxiliar/efeitos adversos , Infecções Relacionadas à Prótese/prevenção & controle , Estudos Retrospectivos , Infecção da Ferida Cirúrgica
2.
Biol Pharm Bull ; 45(5): 625-634, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35491167

RESUMO

The mechanism of insulin-like growth factor type-I (IGF-I) secretion stimulated by S-allyl-L-cysteine (SAC) was investigated as part of a study of SAC-induced DNA synthesis and cell proliferation in primary cultures of adult rat hepatocytes. When 10-6 M SAC was added to the culture, the amount of IGF-I in the medium was significantly increased at 10 min. The peak IGF-I level (140 pg/mL) was observed 20 min after SAC stimulation. The SAC-induced IGF-I secretion was completely suppressed by a selective Janus kinase 2 (JAK2) inhibitor (TG101209), a selective phospholipase C (PLC) inhibitor (U-73122), an intracellular Ca2+ chelating agent (BAPTA-AM), and a granule secretion inhibitor (somatostatin). On the other hand, 10-6 M SAC-stimulated hepatocytes showed increased intracellular Ca2+ concentration in a time-dependent manner from 0 to 10 min. Phosphorylation of SAC-induced JAK2 and IGF-I receptor tyrosine kinase (RTK) was completely suppressed by TG101209. In addition, U-73122, BAPTA-AM, and somatostatin did not suppress SAC-induced JAK2 phosphorylation, but significantly suppressed SAC-induced IGF-I RTK phosphorylation. Furthermore, binding of the monoclonal antibody against growth hormone (GH) to GH receptor was dose-dependently suppressed by SAC on immunofluorescence. These results showed that SAC promotes cell proliferation by stimulating GH receptor/JAK2/phospholipase C pathways and promoting autocrine secretion of IGF-I in primary cultures of adult rat hepatocytes.


Assuntos
Fator de Crescimento Insulin-Like I , Receptores da Somatotropina , Animais , Proliferação de Células , Cisteína/metabolismo , Hepatócitos/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Fator de Crescimento Insulin-Like I/farmacologia , Janus Quinase 2/metabolismo , Ratos , Receptores da Somatotropina/metabolismo , Somatostatina/metabolismo , Fosfolipases Tipo C
3.
Heart Vessels ; 37(8): 1462-1469, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35124729

RESUMO

Root infection or dissection involving coronary artery frequently necessitates an emergent Bentall procedure, with low left ventricular ejection fraction (LVEF). In contrast, concerning an elective Bentall for aneurysm, surgeons should balance the risk and benefit of surgery, especially in low LVEF cases. We investigated the association between preoperative LVEF and outcomes after Bentall. We analyzed 98 patients undergoing Bentall between April 2000 and March 2020. The patients were stratified into three groups: (a) 65 with LVEF ≥ 60%, (b) 21 with LVEF 45 to < 60%, and (c) 12 with LVEF < 45%. Baseline characteristics, survivals, and major adverse cardiovascular events (MACE) were compared. To assess potential non-linear relationship between LVEF and mortality, cubic spline analysis was conducted. Median age was similar (a vs b vs c, 52 vs 50 vs 44). In all groups, elective root aneurysm was 50-60%, indicating the rest were complicated and sick. Operative mortality was the highest in group c (4.6% vs 9.5% vs 16.7%, p = 0.294). Survival and MACE-free rate were the worst in group c, though their 10-year survival was 40%. LVEF was an independent risk for mortality, and cubic spline analysis showed potential non-linear association between LVEF and mortality. Although LVEF is an independent predictor of mortality after Bentall, long-term survival was occasionally achieved in low LVEF cases. While surgeons should carefully balance the risk of low LVEF and the benefit of surgery in elective cases, we should perform a non-elective procedure as needed, even if LVEF is low.


Assuntos
Procedimentos Cirúrgicos Eletivos , Função Ventricular Esquerda , Humanos , Estudos Retrospectivos , Volume Sistólico , Resultado do Tratamento
4.
J Pharm Pharm Sci ; 24: 1-15, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33434118

RESUMO

BACKGROUND: We investigated the signal transduction pathway associated with growth hormone (GH)-stimulated DNA synthesis and proliferation in primary cultured hepatocytes. METHODS: Adult rat hepatocytes were isolated from normal livers by two-step in situ collagenase perfusion to facilitate disaggregation of the adult rat liver. Then hepatocytes were cultured in serum-free Williams' medium E supplemented with GH (1-100 ng/ml) in the presence or absence of test reagents. GH-induced hepatocyte DNA synthesis and proliferation were determined, and the phosphorylation activities of Janus kinase (JAK) 2 (JAK2) (p125 kDa), p95-kDa RTK, and ERK1/2 were measured by western blotting. RESULTS: Hepatocytes grown in serum-free defined medium proliferated within 5 h of culture in the presence of GH (100 ng/ml) in a concentration- and time-dependent manner (EC50 75 ng/ml). These proliferative effects of GH were almost completely blocked by an anti-GH receptor monoclonal antibody (85 ng/ml) and an anti-insulin-like growth factor (IGF)-I receptor monoclonal antibody. In addition, the proliferative effects of GH were significantly blocked by a JAK2 inhibitor (TG101209, 10-6 M), as well as specific signal-transducing inhibitors of phospholipase C (PLC; U-73122, 10-6 M), RTK (AG538, 10-6 M), phosphoinositide 3-kinase (PI3K; LY294002, 10-6 M), mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (MEK/ERK; PD98059, 10-6 M), and mammalian target of rapamycin (mTOR; rapamycin, 10 ng/ml). GH significantly induced the phosphorylations of JAK2 (p125 kDa), p95-kDa IGF-I receptor tyrosine kinase (RTK), and ERK2 in this order according to western blotting analysis. CONCLUSIONS: The proliferative action of GH is mediated by two main signaling pathways. One includes activation of the GH receptor/JAK2/PLC/Ca2+ pathway, and the other involves activation of the p95-kDa IGF-I RTK/PI3K/ERK2/mTOR pathway in primary cultures of adult rat hepatocytes.


Assuntos
DNA/biossíntese , Hormônio do Crescimento/metabolismo , Hepatócitos/metabolismo , Animais , Proliferação de Células , Células Cultivadas , Hepatócitos/citologia , Humanos , Masculino , Ratos , Ratos Wistar , Transdução de Sinais
5.
Biol Pharm Bull ; 43(11): 1776-1784, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33132323

RESUMO

Two-thirds partial hepatectomy (PHx) was performed in rats, and the differences in effects between S-allylcysteine (SAC) and other sulfur-containing compounds on regeneration of the remaining liver and restoration of the injury were examined. Three days after two-thirds PHx, rats treated with 300 mg/kg/d, per os (p.o.) SAC showed a 1.2-fold increase in liver weight per 100 g body weight compared with saline-treated controls. In contrast, S-methylcysteine (SMC) (300 mg/kg/d, p.o.) or cysteine (Cys) (300 mg/kg/d, p.o.) did not have a regeneration-promoting effect. In the comparison with control rats, the regenerating liver of SAC-treated rats showed a significantly higher 5-bromo-2'-deoxyuridine labeling index on day 1. In contrast, serum alanine aminotransferase activity, which increases following PHx, was significantly inhibited by SAC and SMC (but not Cys) on day 1 after two-thirds PHx. In addition, SAC induced increases in insulin-like growth factor (IGF)-1 and its receptor mRNA expressions at 1 h after two-thirds PHx, and it increased phosphorylation of extracellular signal-regulated kinase (ERK)2 and Akt at 3 h after two-thirds PHx without affecting serum growth hormone levels. These results demonstrate that SAC is a mitogenic effector of normal remnant liver and promotes recuperation of liver function after two-thirds PHx. Moreover, SAC-induced proliferative effects are mediated via increased mRNA expressions of IGF-1 and its receptor and subsequent phosphorylation of ERK2 and Akt.


Assuntos
Cisteína/análogos & derivados , Fator de Crescimento Insulin-Like I/genética , Regeneração Hepática/efeitos dos fármacos , Fígado/efeitos dos fármacos , Receptor IGF Tipo 1/genética , Animais , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Cisteína/administração & dosagem , Hepatectomia , Fígado/cirurgia , Regeneração Hepática/genética , Masculino , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Modelos Animais , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar
6.
Heart Vessels ; 35(2): 207-213, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31327031

RESUMO

The precise physiological changes associated with the use of left ventricular assist device (LVAD) are not well characterized. We examined the impact of changes in hemodynamic state using LVAD on endothelial function. We measured flow-mediated vasodilation (FMD) to evaluate endothelial vasodilator function of the brachial artery in 53 patients (dilated cardiomyopathy: 39, ischemic cardiomyopathy: 4, and others: 10) with an implanted LVAD (DuraHeart, EVAHEART, or HeartMate II). We found that FMD value in the HeartMateII LVAD group (9.3% ± 2.9%) was significantly higher than those in the other two groups (EVAHEART: 6.7% ± 2.8% and DuraHeart: 6.2% ± 4.0%). Other factors that affected the FMD value were age (r = - 0.31, p = 0.026), Brinkman index (r = - 0.30, p = 0.029); however, aortic opening, aortic regurgitation, and other hemodynamic parameters such as cardiac index or pulmonary capillary wedge pressure did not correlate with FMD. Multivariate analyses revealed that the difference among the LVAD models most significantly affected the FMD values after adjusting for age and smoking status (t = 2.6, p = 0.014). Event free survival rate of death and cerebral infarction was not significantly different according to the value of FMD. The difference among the LVAD groups most significantly affected the state of endothelial function and it had more impact than other clinical factors.


Assuntos
Artéria Braquial/fisiopatologia , Endotélio Vascular/fisiopatologia , Insuficiência Cardíaca/terapia , Coração Auxiliar , Implantação de Prótese/instrumentação , Vasodilatação , Disfunção Ventricular Esquerda/terapia , Função Ventricular Esquerda , Adulto , Feminino , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Desenho de Prótese , Implantação de Prótese/efeitos adversos , Implantação de Prótese/mortalidade , Recuperação de Função Fisiológica , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Disfunção Ventricular Esquerda/diagnóstico , Disfunção Ventricular Esquerda/mortalidade , Disfunção Ventricular Esquerda/fisiopatologia
7.
BMC Cardiovasc Disord ; 19(1): 151, 2019 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-31226943

RESUMO

BACKGROUND: Continuous-flow left ventricular assist devices (LVADs) improve survival and morbidity in patients with stage D heart failure. Management of LVADs for longer durations is necessary in some clinical settings, and a better understanding of the hemodynamics of patients using LVADs is warranted. Arrhythmia, including atrial (AA) and ventricular (VAs) arrhythmias, is a modifying factor of hemodynamics that is highly prevalent among patients with LVADs. However, the clinical impact of arrhythmias in various clinical settings in patients with LVAD, in which the hemodynamic load is likely to present as worsening of right heart failure, remains to be completely elucidated. CASE PRESENTATION: We describe the case of a patient under sustained ventricular fibrillation for extraordinarily long duration who was stabilized using LVAD support and in whom newly developed atrial fibrillation led to a significant worsening of right heart failure while using an LVAD. CONCLUSION: This case demonstrates the substantial clinical impact of AAs in the management of right heart failure using an LVAD.


Assuntos
Fibrilação Atrial/etiologia , Insuficiência Cardíaca/terapia , Frequência Cardíaca , Coração Auxiliar , Implantação de Prótese/instrumentação , Fibrilação Ventricular/complicações , Função Ventricular Esquerda , Função Ventricular Direita , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/fisiopatologia , Progressão da Doença , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Implantação de Prótese/efeitos adversos , Fibrilação Ventricular/diagnóstico , Fibrilação Ventricular/fisiopatologia
8.
Biol Pharm Bull ; 42(4): 631-637, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30713268

RESUMO

Serotonin (5-hydroxytryptamine; 5-HT) can induce hepatocyte DNA synthesis and proliferation by autocrine secretion of transforming growth factor (TGF)-α through 5-HT2B receptor/phospholipase C (PLC)/Ca2+ and a signaling pathway involving epidermal growth factor (EGF)/TGF-α receptor tyrosine kinase (RTK)/extracellular signal-regulated kinase 2 (ERK2)/mammalian target of rapamycin (mTOR). In the present study, we investigated whether 5-HT or a selective 5-HT2B receptor agonist BW723C86, would stimulate phosphorylation of TGF-α RTK and ribosomal p70 S6 kinase (p70S6K) in primary cultures of adult rat hepatocytes. Western blotting analysis was used to detect 5-HT- or BW723C86 (10-6 M)-induced phosphorylation of EGF/TGF-α RTK and p70S6K. Our results showed that 5-HT- or BW723C86 (10-6 M)-induced phosphorylation of EGF/TGF-α RTK peaked at between 5 and 10 min. On the other hand, 5-HT- or BW723C86 (10-6 M)-induced phosphorylation of p70S6K peaked at about 30 min. Furthermore, a selective 5-HT2B receptor antagonist LY272015, a specific PLC inhibitor U-73122, a membrane-permeable Ca2+ chelator BAPTA/AM, an L-type Ca2+ channel blocker verapamil, somatostatin, and a specific p70S6K inhibitor LY2584702 completely abolished the phosphorylation of p70S6K induced by both 5-HT and BW723C86. These results indicate that phosphorylation of p70S6K is dependent on the 5-HT2B-receptor-mediated autocrine secretion of TGF-α. In addition, these results demonstrate that the hepatocyte proliferating action of 5-HT and BW723C86 are mediated by phosphorylation of p70S6K, a downstream element of the EGF/TGF-α RTK signaling pathway.


Assuntos
Receptores ErbB/metabolismo , Hepatócitos/efeitos dos fármacos , Indóis/farmacologia , Receptor 5-HT2B de Serotonina/metabolismo , Proteínas Quinases S6 Ribossômicas 70-kDa/metabolismo , Agonistas do Receptor 5-HT2 de Serotonina/farmacologia , Tiofenos/farmacologia , Animais , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Hepatócitos/metabolismo , Masculino , Fosforilação , Cultura Primária de Células , Ratos Wistar
9.
Biol Pharm Bull ; 42(1): 144-148, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30606986

RESUMO

The transnasal route for the delivery of water-soluble macromolecules, such as bioactive peptides and proteins, has attracted interest, although the use of permeation enhancers is required due to the poor permeabilities of these macromolecules across the nasal mucosa. With polycationic compounds, such as poly-L-arginine and chitosan, the nasal absorption of hydrophilic macromolecules is molecular weight- and concentration-dependently enhanced without causing cytotoxicity. In the present study, we evaluated the effect of various molecular weights and concentrations of poly-L-ornithine (PLO), a polycationic compound, on the nasal absorption and the damage to the nasal mucosa in vivo. PLO enhanced the nasal absorption of fluorescein isothiocyanate-dextran (FD-4), used as a model drug, and the bioavailability of FD-4 increased with the concentration of PLO. The enhancement effect was also dependent on the molecular weight. The administration of PLO at a concentration that sufficed for enhancing the nasal absorption had no effect on the activity of lactic dehydrogenase and the protein leakage in the nasal fluid, as indices of nasal mucosa damage. These findings suggest that a transnasal delivery system using PLO is a useful strategy for improving the nasal absorption of water-soluble macromolecules without toxicity to the nasal mucosa.


Assuntos
Imidazóis/metabolismo , Absorção Nasal/efeitos dos fármacos , Peptídeos/metabolismo , Éteres Fenílicos/metabolismo , Tensoativos/metabolismo , Água , Animais , Sinergismo Farmacológico , Imidazóis/administração & dosagem , Masculino , Absorção Nasal/fisiologia , Peptídeos/administração & dosagem , Éteres Fenílicos/administração & dosagem , Ratos , Ratos Wistar , Solubilidade/efeitos dos fármacos , Tensoativos/administração & dosagem , Água/metabolismo
10.
Artif Organs ; 43(9): 909-912, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31066907

RESUMO

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a heart muscle disorder characterized by right ventricular enlargement, right heart failure (HF), and ventricular arrhythmias which lead to sudden death especially in young adults. Current recommendations for management of patients with ARVC are antiarrhythmic medications, catheter ablation, and implantable cardioverter defibrillator therapy to prevent sudden cardiac death. However, despite these treatments, few patients suffer from recurrent ventricular arrhythmias or HF unresponsive to conventional management. Heart transplantation (HTx) is a preferred treatment for these cases, but because of a persistent donor heart shortage in Japan, ventricular assist device (VAD) support has become an important option for a management of the end-stage ARVC. Previous articles reported 4 cases of a successful management by left ventricular assist device (LVAD), but the longest interval of LVAD support was only 333 days. We present 3 cases of ARVC patients who were successfully managed by LVAD implantation for more than a year. These 3 cases are unconventional examples of ARVC patients, considering the nature of the disease. The novelty of these cases should be taken in the context of the extremely long waiting period for HTx in Japan.


Assuntos
Displasia Arritmogênica Ventricular Direita/cirurgia , Ventrículos do Coração/cirurgia , Coração Auxiliar , Adulto , Displasia Arritmogênica Ventricular Direita/fisiopatologia , Gerenciamento Clínico , Ventrículos do Coração/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Implantação de Prótese
11.
J Artif Organs ; 21(4): 405-411, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29943370

RESUMO

Currently, we use the Nipro paracorporeal VAD (p-VAD) for initial short-term ventricular support, as a bridge to decision (BTD) or a bridge to candidacy (BTC) treatment, in Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) levels 1 and 2 patients. However, it is possible that compared to patients with primary implantable-VADs (P-iVAD), the bridge-to-bridge (BTB) patients are more likely to develop complications. This retrospective study used data from 24 consecutive BTB patients who were initially implanted with Nipro p-VAD as BTD or BTC treatments between April 2011 and March 2016, and subsequently underwent conversion to an i-VAD. The data from 72 patients who underwent a primary i-VAD (P-iVAD) procedure were used for comparison. Between the two groups, there was no significant difference in the incidence of infectious events (p = 0.72) or stroke (p = 0.44). Orthotropic heart transplantation was performed in 6 of the 24 patients in the BTB group and in 21 of the 72 patients in the P-iVAD group. The 1- and 2-year survival rates were 95.8% and 95.8% in the BTB group and 91% and 85.8% in the P-iVAD group; these values were not significantly different between groups (p = 0.91). Based on these results we conclude that BTB using Nipro p-VAD is a reasonable strategy for treating patients with severe decompensated end-stage heart failure.


Assuntos
Insuficiência Cardíaca/cirurgia , Transplante de Coração , Coração Auxiliar , Adulto , Desenho de Equipamento , Feminino , Seguimentos , Humanos , Masculino , Estudos Retrospectivos , Resultado do Tratamento
12.
Biol Pharm Bull ; 40(2): 205-211, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28154261

RESUMO

Polycationic compounds, such as poly-L-arginine and poly-L-ornithine (PLO), enhance the nasal absorption of hydrophilic macromolecular drugs. However, the bio availability corresponding to the dose of these enhancers has not been obtained in an open system study, where an administered solution is transferred to the pharynx because they do not exhibit mucoadhesion/retention in the nasal cavity. In this study, we prepared PEGylated-poly-L-ornithine (PEG-PLO) and investigated the effects of PEGylation on in vitro adhesion/retention properties, permeation enhancement efficiency, and cytotoxicity. PEG-PLO bearing 3-4 polyethylene glycol (PEG) chains per PLO molecule was more retentive than unmodified PLO on an inclined plate. The permeability of a model drug, FD-4, across Caco-2 cell sheets was enhanced by PEG-PLO as well as by PLO. PLO showed cytotoxicity at high concentrations, whereas PEG-PLO did not decrease cell viability, even above the concentration giving a sufficient enhancement effect. These findings suggest that PEGylation of polycationic absorption enhancers improves their adhesion/retention and decreases their cytotoxicity, which may lead to enhancers with greater utility.


Assuntos
Absorção Gastrointestinal/fisiologia , Peptídeos/metabolismo , Polietilenoglicóis/metabolismo , Tensoativos/metabolismo , Células CACO-2 , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Avaliação Pré-Clínica de Medicamentos/métodos , Absorção Gastrointestinal/efeitos dos fármacos , Humanos , Peptídeos/síntese química , Peptídeos/farmacologia , Polietilenoglicóis/síntese química , Polietilenoglicóis/farmacologia , Tensoativos/síntese química , Tensoativos/farmacologia
13.
J Artif Organs ; 20(1): 99-101, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27744498

RESUMO

Aortic insufficiency (AI) is a significant complication of long-term support of continuous flow left ventricular assist device (CF-LVAD) for patients with end-stage heart failure. A 26-year-old female with osteogenesis imperfecta (OI) was diagnosed with dilated phase hypertrophic cardiomyopathy (d-HCM)) and was implanted with Jarvik 2000, for bridge to transplantation. AI gradually developed and surgical intervention was indicated. We performed central aortic valve closure (CAVC) instead of valve replacement 20 months after CF-LVAD implantation. Patient's symptoms dramatically improved postoperatively. This is the first report of CAVC for a patient supported with Jarvik 2000.


Assuntos
Insuficiência da Valva Aórtica/etiologia , Insuficiência da Valva Aórtica/cirurgia , Valva Aórtica/cirurgia , Insuficiência Cardíaca/terapia , Coração Auxiliar/efeitos adversos , Adulto , Feminino , Humanos , Resultado do Tratamento
14.
J Artif Organs ; 20(4): 311-317, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28752193

RESUMO

Continuous flow left ventricular assist device (CF-LVAD) therapy has improved the survival of patients with advanced heart failure. However, the readmission rate of CF-LVAD patients is still relatively high. A total of 90 patients who received CF-LVADs between April 2011 and March 2016 at our institute and were discharged home were analyzed retrospectively. They were followed up through March 2017. Clinical data, including frequency, length and etiology of readmission, were obtained from medical records. The mean observation period after initial discharge was 713 ± 322 days. In total, 73 patients (81%) had 236 readmissions, 214 unplanned and 22 planned. The overall and unplanned readmission rates were 1.34 and 1.22 per patient-year, respectively. The rate of freedom from unplanned first readmission at 1 year after initial discharge was 39%. The median interval between the previous hospital discharge and first and second readmissions was 311 and 213 days, respectively (log-rank test, p = 0.117). The rate of readmission after more than three readmissions was significantly higher than that of first or second readmission (log-rank test, p < 0.001). The most common etiology of readmission was driveline infection (DLI) (36%), followed by stroke (9%). The median length of hospital stay due to DLI was 23 days. The patients with repeated unplanned readmissions had significantly lower EuroQol 5 dimensions questionnaire utility score than those with no or just one readmission. Readmission was common in CF-LVAD patients, and the most common etiology of readmissions was DLI. The interval to the next readmission seemed shorter for patients with repeated readmissions.


Assuntos
Insuficiência Cardíaca/terapia , Coração Auxiliar/estatística & dados numéricos , Readmissão do Paciente/estatística & dados numéricos , Adulto , Feminino , Coração Auxiliar/efeitos adversos , Humanos , Infecções/etiologia , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Estudos Retrospectivos , Acidente Vascular Cerebral/etiologia
15.
Biol Pharm Bull ; 39(4): 570-7, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26804134

RESUMO

The mechanism of serotonin 5-HT2 receptor subtype-stimulated DNA synthesis and proliferation was investigated in primary cultures of adult rat hepatocytes to elucidate the intracellular signal transduction pathways. DNA synthesis and proliferation were detected in hepatocyte parenchymal cells grown in serum-free, defined medium containing 5-HT (10(-6) M) or the selective 5-HT2B receptor agonist BW723C86 (10(-6) M). In addition, exogenous transforming growth factor (TGF)-α (1.0 ng/mL) significantly increased hepatocyte DNA synthesis and proliferation, which reached plateau after 4 h of culture. Use of blocking monoclonal antibodies demonstrated that TGF-α, but not insulin-like growth factor-I, was involved in hepatocyte proliferation mediated by 5-HT or BW723C86. TGF-α levels in the culture medium increased significantly versus baseline within 5 min in response to 5-HT (10(-6) M) or BW723C86 (10(-6) M), and the maximum TGF-α level (30 pg/mL) was reached 10 min after 5-HT or BW723C86 stimulation. Secretion of TGF-α into the culture medium was inhibited by addition of the selective phospholipase C (PLC) inhibitor, U-73122 (10(-6) M), or somatostatin (10(-7) M). These results indicate that the proliferative mechanism of action of 5-HT is mediated mainly through a 5-HT2B receptor/Gq/PLC-stimulated increase in autocrine secretion of TGF-α from primary cultured hepatocytes.


Assuntos
DNA/metabolismo , Hepatócitos/metabolismo , Receptor 5-HT2B de Serotonina/metabolismo , Fator de Crescimento Transformador alfa/metabolismo , Animais , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Estrenos/farmacologia , Hepatócitos/efeitos dos fármacos , Indóis/farmacologia , Masculino , Compostos Orgânicos/farmacologia , Pirrolidinonas/farmacologia , Ratos Wistar , Serotonina/farmacologia , Agonistas do Receptor 5-HT2 de Serotonina/farmacologia , Antagonistas do Receptor 5-HT2 de Serotonina/farmacologia , Tiofenos/farmacologia , Fosfolipases Tipo C/antagonistas & inibidores
16.
Biol Pharm Bull ; 39(1): 121-9, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26567725

RESUMO

The involvement of serotonin (5-hydroxytryptamine; 5-HT) and the 5-HT2 receptor subtypes in the induction of DNA synthesis and proliferation was investigated in primary cultures of adult rat hepatocytes to elucidate the intracellular signal transduction mechanisms. Hepatocyte parenchymal cells maintained in a serum-free, defined medium, synthesized DNA and proliferated in the presence of 5-HT or a selective 5-HT2B receptor agonist, BW723C86, but not in the presence of 5-HT2A, or 5-HT2C receptor agonists (TCB-2 and CP809101, respectively), in a time- and dose-dependent manner. A selective 5-HT2B receptor antagonist, LY272015 (10(-7) M), and a specific phospholipase C (PLC) inhibitor, U-73122 (10(-6) M), as well as specific inhibitors of growth-related signal transducers-including AG1478, LY294002, PD98059, and rapamycin-completely inhibited 5-HT (10(-6) M)- or BW723C86 (10(-6) M)-induced hepatocyte DNA synthesis and proliferation. Both 5-HT and BW723C86 were shown to significantly stimulate the phosphorylation of epidermal growth factor (EGF)/transforming growth factor (TGF)-α receptor tyrosine kinase (p175 kDa) and extracellular signal-regulated kinase (ERK) 2 on Western blot analysis. These results suggest that the proliferative mechanism of activating 5-HT is mediated mainly through 5-HT2B receptor-stimulated Gq/PLC and EGF/TGF-α-receptor/phosphatidylinositol 3-kinase (PI3K)/ERK2/mammalian target of rapamycin (mTOR) signaling pathways in primary cultured hepatocytes.


Assuntos
Proliferação de Células/fisiologia , DNA/biossíntese , Hepatócitos/efeitos dos fármacos , Receptores 5-HT2 de Serotonina/metabolismo , Serotonina/farmacologia , Transdução de Sinais/fisiologia , Animais , Relação Dose-Resposta a Droga , MAP Quinases Reguladas por Sinal Extracelular/genética , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/fisiologia , Hepatócitos/metabolismo , Indóis/farmacologia , Fosforilação , Ratos , Receptores 5-HT2 de Serotonina/classificação , Receptores 5-HT2 de Serotonina/genética , Serotonina/metabolismo , Antagonistas do Receptor 5-HT2 de Serotonina/farmacologia , Transdução de Sinais/efeitos dos fármacos , Tiofenos/farmacologia
17.
J Artif Organs ; 19(4): 392-395, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27430944

RESUMO

We successfully managed a splenic injury and delayed splenic rupture in a patient with an implantable left ventricular assist device (iLVAD). A 42-year-old man with an iLVAD for idiopathic dilated cardiomyopathy was admitted to our department complaining of dizziness. Laboratory data showed severe anemia, and computed tomography demonstrated a traumatic splenic injury. Following conservative treatment, partial splenic embolization was performed. Fifteen days after the intervention, the patient went into hemorrhagic shock due to delayed splenic rupture. Emergency total splenic embolization was performed, and total splenectomy was conducted later to prevent re-bleeding or abscess formation. His postoperative course was uneventful, and he was discharged on postoperative day 22. Finally, he underwent orthotropic heart transplantation without post-splenectomy sepsis or thrombotic complications 472 days after splenectomy. Splenic injury should be considered as a possible complication of iLVAD. In addition, careful follow-up after transcatheter arterial embolization for splenic injury is essential for managing delayed splenic rupture.


Assuntos
Embolização Terapêutica , Coração Auxiliar , Esplenectomia , Ruptura Esplênica/cirurgia , Adulto , Transplante de Coração , Humanos , Masculino , Choque Hemorrágico/etiologia , Ruptura Esplênica/complicações , Ruptura Esplênica/diagnóstico por imagem , Tomografia Computadorizada por Raios X
18.
J Artif Organs ; 19(4): 387-391, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27401710

RESUMO

We successfully controlled infection of a left ventricular assist device by performing pump exchange. A 53-year-old man was implanted with DuraHeart for ischemic cardiomyopathy as a bridge to transplantation. Two years later, he was hospitalized with the diagnosis of driveline infection. The blood cultures detected Pseudomonas aeruginosa. During the admission, he developed brain hemorrhage perhaps due to septic emboli. The chest computed tomography scan revealed a small defect inside the outflow graft of the DuraHeart, which was highly suspected of vegetation. He underwent pump exchange, from DuraHeart to Jarvik 2000 with concomitant omentopexy. His postoperative course was uneventful, and he was discharged with no sequela of the brain hemorrhage. Four months after the pump exchange, he successfully underwent heart transplantation. No infectious tissue was observed in the pericardial space at the time of heart transplantation. Pump exchange is an effective way to manage refractory left ventricular assist device infection, and the timing of surgical intervention is of great importance.


Assuntos
Insuficiência Cardíaca/cirurgia , Coração Auxiliar/efeitos adversos , Infecções por Pseudomonas/etiologia , Transplante de Coração , Humanos , Masculino , Pessoa de Meia-Idade , Infecções por Pseudomonas/terapia , Pseudomonas aeruginosa/isolamento & purificação
19.
J Artif Organs ; 19(4): 396-398, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27507585

RESUMO

Nipro-Toyobo-paracorporeal pulsatile flow VAD (Nipro VAD; Nipro, Osaka, Japan) has been used most commonly as a paracorporeal VAD (p-VAD) in Japan. There are few reports describing clinical course of post LVAD explantation and its complication. We herein present two cases of apical abscess after the explantation of the device. SSI is a main risk factor of formation of the apical abscess at the time of LVAD explantation. It is mandatory to perform sufficient debridement and closure of the layers including abdominal muscle and anterior abdominal fascia at exit sites in the explantation surgery. Omentopexy is also helpful for prevention from infection. Routine removal of apical cuff and outflow graft could be considered as one of the options when LVAD is explanted as bridge to recovery.


Assuntos
Abscesso/etiologia , Remoção de Dispositivo , Coração Auxiliar/efeitos adversos , Infecção da Ferida Cirúrgica/etiologia , Abscesso/cirurgia , Adulto , Insuficiência Cardíaca/cirurgia , Humanos , Masculino , Omento/cirurgia , Fatores de Risco , Infecção da Ferida Cirúrgica/cirurgia
20.
Int Heart J ; 56(5): 574-7, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26370363

RESUMO

The use of implantable continuous-flow left ventricular assist devices (LVADs) as a bridge to transplant is effective for patients with congestive heart failure (HF). However, some patients develop congestive symptoms due to right-sided HF even with LVAD support. Tolvaptan, a vasopressin type 2 receptor antagonist, corrects both congestion and hyponatremia in patients with advanced HF. We report herein a case involving a patient who underwent LVAD implantation and developed hyponatremia and congestive symptoms after negative-pressure wound therapy and omental transposition for postoperative mediastinitis. Hemodynamic evaluation performed after negative-pressure wound therapy revealed elevation of both right arterial pressure and pulmonary capillary wedge pressure, and suggested biventricular dysfunction despite LVAD support. Symptoms improved after starting administration of tolvaptan. Tolvaptan may be useful for correcting hyponatremia and volume overload in patients under LVAD support.


Assuntos
Benzazepinas/administração & dosagem , Insuficiência Cardíaca , Mediastinite , Omento/transplante , Complicações Pós-Operatórias , Implantação de Prótese , Adulto , Antagonistas dos Receptores de Hormônios Antidiuréticos/administração & dosagem , Feminino , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/terapia , Coração Auxiliar , Hemodinâmica , Humanos , Hiponatremia/diagnóstico , Hiponatremia/etiologia , Hiponatremia/fisiopatologia , Hiponatremia/terapia , Mediastinite/diagnóstico , Mediastinite/etiologia , Mediastinite/fisiopatologia , Mediastinite/cirurgia , Tratamento de Ferimentos com Pressão Negativa/métodos , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/fisiopatologia , Complicações Pós-Operatórias/terapia , Implantação de Prótese/efeitos adversos , Implantação de Prótese/instrumentação , Implantação de Prótese/métodos , Transplante de Tecidos/métodos , Tolvaptan , Resultado do Tratamento
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