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Expert Opin Drug Metab Toxicol ; 16(1): 1-9, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31914334


Background: Warfarin acts in heart valve replacement patients to minimize thromboembolic complications. We investigated whether patients can be distinguished based on their genotypes to efficiently and safely administer warfarin therapy after heart valve replacements.Research design and methods: A retrospective analysis was conducted in patients with warfarin therapy who underwent elective heart valve replacements between January 2013 and September 2018. The patients were divided into normal, sensitive, and highly sensitive bins based on their CYP2C9 and VKORC1 genotypes. The primary endpoints were over-anticoagulation and overt bleeding.Results: 375 patients were enrolled, with 65 classified as normal, 281 as sensitive, and 29 as highly sensitive responders. Compared with normal responders, sensitive and highly sensitive responders spent more time on over-anticoagulation in the first 28 (P < 0.001) and 90 (P = 0.001) days; experienced more frequent bleeding events in the first 28 days (P = 0.029; OR, 2.18; 95% CI, 1.15-4.13); required lower warfarin doses to obtain stable INR (P < 0.001); had higher warfarin sensitivity indices (P < 0.001).Conclusion: Predicting evidence have been obtained with CYP2C9 and VKORC1 genotypes in identifying heart valve replacement patients with higher efficient sensitivity and with a higher risk of bleeding and over-anticoagulation.

Anticoagulantes/administração & dosagem , Citocromo P-450 CYP2C9/genética , Hemorragia/induzido quimicamente , Vitamina K Epóxido Redutases/genética , Varfarina/administração & dosagem , Adulto , Idoso , Anticoagulantes/efeitos adversos , Relação Dose-Resposta a Droga , Feminino , Genótipo , Implante de Prótese de Valva Cardíaca/métodos , Hemorragia/epidemiologia , Hemorragia/genética , Humanos , Coeficiente Internacional Normatizado , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tromboembolia/prevenção & controle , Varfarina/efeitos adversos
Int J Clin Exp Med ; 8(6): 9904-10, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26309674


BACKGROUND: Blood anticoagulation after heart valve replacement is a recognized difficulty all over the world. In this study, we identified the effect of amiodarone on the function of warfarin and confirmed the countermeasure by concluding the genotype distribution of vitamin K epoxide reductase complex 1 (VKORC1) and cytochrome P450 2C9 (CYP2C9) of the patient to predict the security dose of warfarin. METHODS: Studying on the VKORC1 (-1639G>A) and CYP2C9 genotype of 271 cases on heart valve replacement in the First Affiliated Hospital of Soochow University from Jan. 2012 to Jan. 2014. Warfarin's multivariable regression equation was taken to calculate their warfarin dosage. In the study, 80 of them were selected and divided into 4 groups according to their different warfarin dosage and their usage of amiodaron. The differences of INR values at the 5(th), 8(th), 11(th), 14(th) days of operation were analyzed. RESULTS: Among the 80 cases, VKORC1 (-1639G>A) AA types accounted for 90%, and AG types accounted for another 10%, while GG types were not found. In addition that, all of the patients (100%) had CYP2C9*1/*1 type, and CYP2C9*1/*3 had not appeared. There was significant difference in INR values between the groups who used amiodarone or not. The pharmacogenetic equation was accurate in the predicting of the warfarin dosage, so that satisfied anticoagulation efficacy had been achieved in 2 weeks after surgery. CONCLUSION: It is necessary for the patients to do the warfarin pharmacogenetic test to get the suitable dose before heart valve replacement. Amiodarone can enhance the anticoagulant efficacy of warfarin, so the dosages of warfarin should be reduced properly because of the medicine combination, and INR values must be monitored more frequently to make the anticoagulant process secure and efficient.

Differentiation ; 86(1-2): 57-64, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23974360


The objective of this study was to screen mouse bone marrow mesenchymal stromal cells (BMSCs) according to expression of cardiac stem cell (CSC) surface antigens and to assess the effects of resulting BMSC-like subsets on cardiac function after injection in a mouse myocardial infarct model. BMSCs were sorted by magnetic beads according to the expression of differentiation antigens on the surface of mouse CSCs, and four subsets were identified on the basis of CD45 and CD31 expression: stem cell antigen-1+ (Sca-1+)/CD45-/CD31-, Sca-1+/CD45-/CD31+, Sca-1+/CD45+/CD31-, and Sca-1+/CD45+/CD31+. When co-cultured with myocardial stem cells and 5-aza-2'-deoxycytidine for 14 days, each subset showed expression of cardiac markers α-actin, connexin 43, desmin, and cardiac troponin I; however, expression was greatest in Sca-1+/CD45+/CD31+ cells. To assess the ability of these cells to improve cardiac function, each subset was injected separately into mice with myocardial infarct induced by ligation of the left anterior descending coronary artery, and in vivo cardiac dual inversion recovery (DIR) imaging and Doppler echocardiography were performed 48 h, 96 h, and 7 days after injection. Results indicated that Sca-1+/CD45+/CD31+ cells were superior in improving cardiac function compared with the other subsets and with unsorted BMSCs. These results suggest that mouse BMSC cells are polyclonal and that the BMSC-like Sca-1+/CD45+/CD31+ subset was effective in directing cardiac differentiation and improving cardiac function in mice with myocardial infarcts.

Diferenciação Celular , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/metabolismo , Infarto do Miocárdio/cirurgia , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Animais , Antígenos Ly/genética , Antígenos Ly/metabolismo , Antígenos Comuns de Leucócito/genética , Antígenos Comuns de Leucócito/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Células-Tronco Mesenquimais/citologia , Camundongos , Mioblastos Cardíacos/citologia , Mioblastos Cardíacos/metabolismo , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/fisiopatologia , Miócitos Cardíacos/citologia , Miócitos Cardíacos/metabolismo , Molécula-1 de Adesão Celular Endotelial a Plaquetas/genética
Zhonghua Xin Xue Guan Bing Za Zhi ; 41(3): 210-4, 2013 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-23879945


OBJECTIVE: To search for the bone mesenchymal stem cell (MSC) subgroup which might be more effective on repairing myocardial damage. METHODS: In this experiment, four MSC subgroups were defined based on the surface differentiation antigen detection of mouse bone mesenchymal stem cells (mBMSCs): SCA-1(+)/CD45(+)/CD31(+), SCA-1(+)/CD45(+)/CD31(-), SCA-1(+)/CD45(-)/CD31(-) and SCA-1(+)/CD45(-)/CD31(+). These subgroup cells and unselected mBMSCs were injected into infarcted mouse via tail vein. Echocardiographic heart function measurement and in vivo DiR-labeled stem cells imaging were performed at 48 h after injection. In situ C-kit (a flag antigen of cardiac stem cells) and cardiac-specific differentiation antigen immunohistochemistry detection was made in the infarcted myocardium. RESULTS: The capacity of the SCA-1(+)/CD45(+)/CD31(+) cells on improving heart function was significantly higher than other cell groups (all P < 0.05). In vivo imaging showed that the mean fluorescence intensity of the SCA-1(+)/CD45(+)/CD31(+) cells was also higher than other cell groups (all P < 0.05). Number of cardiac stem cells in the infracted myocardium was significantly increased after the injection of all subgroup cells and unsorted mBMSCs cells for 48 h compared untreated infracted myocardium. The capacity of mobilizing cardiac stem cells is as follows: SCA-1(+)/CD45(+)/CD31(+) >SCA-1(+)/CD45(-)/CD31(+) >SCA-1(+)/CD45(-)/CD31(-) >SCA-1(+)/CD45(+)/CD31(-). CONCLUSION: The SCA-1(+)/CD45(+)/CD31(+) subgroups of mBMSCs exhibites the highest capacity to improve cardiac function after myocardial infarction and to mobilize autologous cardiac stem cells compared with other mBMSCs subgroups and unsorted mBMSCs cells.

Transplante de Células-Tronco Mesenquimais , Infarto do Miocárdio/cirurgia , Animais , Células Cultivadas , Modelos Animais de Doenças , Camundongos , Camundongos Endogâmicos C57BL
J Cardiothorac Surg ; 7: 27, 2012 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-22443513


BACKGROUND: Tricuspid regurgitation (TR) is common in patients with mitral valve disease; however, there are no straightforward, rapidly determinably criteria available for deciding whether TR repair should be performed during mitral valve replacement. The aim of our retrospective study was to identify a simple and fast criterion for determining whether TR repair should be performed in patients undergoing mitral valve replacement. METHODS: We reviewed the records of patients who underwent mitral valve replacement with or without (control) TR repair (DeVega or Kay procedure) from January 2005 to December 2008. Preoperative and 2-year postoperative echocardiographic measurements included right ventricular and atrial diameter, interventricular septum size, TR severity, ejection fraction, and pulmonary artery pressure. RESULTS: A total of 89 patients were included (control, n = 50; DeVega, n = 27; Kay, n = 12). Demographic and clinical characteristics were similar between groups. Cardiac variables were similar between the DeVega and Kay groups. Right atrium and ventricular diameter and ejection fraction were significantly decreased postoperatively both in the control and operation (DeVega + Kay) group (P < 0.05). Pulmonary artery pressure was significantly decreased postoperatively in-operation groups (P < 0.05). Our findings indicate that surgical intervention for TR should be considered during mitral valve replacement if any of the following preoperative criteria are met: right atrial transverse diameter > 57 mm; right ventricular end-diastolic diameter > 55 mm; pulmonary artery pressure > 58 mmHg. CONCLUSIONS: Our findings suggest echocardiography may be used as a rapid and simple means of determining which patients require TR repair during mitral valve replacement.

Anuloplastia da Valva Cardíaca , Técnicas de Apoio para a Decisão , Implante de Prótese de Valva Cardíaca , Insuficiência da Valva Mitral/cirurgia , Índice de Gravidade de Doença , Insuficiência da Valva Tricúspide/cirurgia , Adulto , Idoso , Pressão Sanguínea , Feminino , Seguimentos , Átrios do Coração/diagnóstico por imagem , Ventrículos do Coração/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência da Valva Mitral/complicações , Insuficiência da Valva Mitral/diagnóstico por imagem , Artéria Pulmonar/diagnóstico por imagem , Artéria Pulmonar/fisiologia , Estudos Retrospectivos , Cardiopatia Reumática/complicações , Cardiopatia Reumática/diagnóstico por imagem , Cardiopatia Reumática/cirurgia , Resultado do Tratamento , Insuficiência da Valva Tricúspide/complicações , Insuficiência da Valva Tricúspide/diagnóstico por imagem , Ultrassonografia