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Chinese Journal of Cardiology ; (12): 690-697, 2022.
Article in Chinese | WPRIM | ID: wpr-940908


Objective: To investigate the effect and mechanism of sacubitril/valsartan on left ventricular remodeling and cardiac function in rats with heart failure. Methods: A total of 46 SPF-grade male Wistar rats weighed 300-350 g were acclimatized to the laboratory for 7 days. Rats were then divided into 4 groups: the heart failure group (n=12, intraperitoneal injection of adriamycin hydrochloride 2.5 mg/kg once a week for 6 consecutive weeks, establishing a model of heart failure); heart failure+sacubitril/valsartan group (treatment group, n=12, intragastric administration with sacubitril/valsartan 1 week before the first injection of adriamycin, at a dose of 60 mg·kg-1·d-1 for 7 weeks); heart failure+sacubitril/valsartan+APJ antagonist F13A group (F13A group, n=12, adriamycin and sacubitril/valsartan, intraperitoneal injection of 100 μg·kg-1·d-1 APJ antagonist F13A for 7 weeks) and control group (n=10, intraperitoneal injection of equal volume of normal saline). One week after the last injection of adriamycin or saline, transthoracic echocardiography was performed to detect the cardiac structure and function, and then the rats were executed, blood and left ventricular specimens were obtained for further analysis. Hematoxylin-eosin staining and Masson trichrome staining were performed to analyze the left ventricular pathological change and myocardial fibrosis. TUNEL staining was performed to detect cardiomyocyte apoptosis. mRNA expression of left ventricular myocardial apelin and APJ was detected by RT-qRCR. ELISA was performed to detect plasma apelin-12 concentration. The protein expression of left ventricular myocardial apelin and APJ was detected by Western blot. Results: Seven rats survived in the heart failure group, 10 in the treatment group, and 8 in the F13A group. Echocardiography showed that the left ventricular end-diastolic diameter (LVEDD) and the left ventricular end-systolic diameter (LVESD) were higher (both P<0.05), while the left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) were lower in the heart failure group than in the control group (both P<0.05). Compared with the heart failure group, rats in the treatment group were featured with lower LVEDD and LVESD (both P<0.05), higher LVEF and LVFS (both P<0.05), these beneficial effects were reversed in rats assigned to F13A group (all P<0.05 vs. treatment group). The results of HE staining showed that the cardiomyocytes of rats in the control group were arranged neatly and densely structured, the cardiomyocytes in the heart failure group were arranged in disorder, distorted and the gap between cells was increased, the cardiomyocytes in the treatment group were slightly neat and dense, and cardiomyocytes in the F13A group were featured similarly as the heart failure group. Masson staining showed that there were small amount of collagen fibers in the left ventricular myocardial interstitium of the control group, while left ventricular myocardial fibrosis was significantly increased, and collagen volume fraction (CVF) was significantly higher in the heart failure group than that of the control group (P<0.05). Compared with the heart failure group, the left ventricular myocardial fibrosis and the CVF were reduced in the treatment group (both P<0.05), these effects were reversed in the F13A group (all P<0.05 vs. treatment group). TUNEL staining showed that the apoptosis index (AI) of cardiomyocytes in rats was higher in the heart failure group compared with the control group (P<0.05), which was reduced in the treatment group (P<0.05 vs. heart failure group), this effect again was reversed in the F13A group (P<0.05 vs. treatment group). The results of RT-qPCR and Western blot showed that the mRNA and protein levels of apelin and APJ in left ventricular myocardial tissue of rats were downregulated in heart failure group (all P<0.05) compared with the control group. Compared with the heart failure group, the mRNA and protein levels of apelin and APJ were upregulated in the treatment group (all P<0.05), these effects were reversed in the F13A group (all P<0.05 vs. treatment group). ELISA test showed that the plasma apelin concentration of rats was lower in the heart failure group compared with the control group (P<0.05); compared with the heart failure group, the plasma apelin concentration of rats was higher in the treatment group (P<0.05), this effect was reversed in the F13A group (P<0.05 vs. treatment group). Conclusion: Sacubitril/valsartan can partially reverse left ventricular remodeling and improve cardiac function in rats with heart failure through modulating Apelin/APJ pathways.

Animals , Male , Rats , Aminobutyrates/pharmacology , Apelin/metabolism , Biphenyl Compounds , Collagen/metabolism , Doxorubicin/pharmacology , Fibrosis , Heart Failure/pathology , Myocytes, Cardiac/pathology , RNA, Messenger/metabolism , Rats, Wistar , Valsartan/pharmacology , Ventricular Function, Left/drug effects , Ventricular Remodeling
Chinese Journal of Cardiology ; (12): 1207-1213, 2022.
Article in Chinese | WPRIM | ID: wpr-969728


Objective: To evaluate the impact of interventional therapy on top of drug therapy on cardiac function and structure in heart failure with reduced ejection fraction (HFrEF) patients complicating with middle aortic syndrome caused by Takayasu arteritis (TA-MAS). Methods: It was a retrospective longitudinal study. The data of patients with TA-MAS and HFrEF, who received interventional therapy on top of drug therapy in Fuwai Hospital from January 2010 to September 2020, were collected and analyzed. Baseline clinical data (including demographic data, basic treatment, etc.) were collected through the electronic medical record system. Changes of indexes such as New York Heart Association (NYHA) classification, N-terminal pro-brain natriuretic peptide (NT-proBNP), left ventricular end diastolic diameter (LVEDD), left ventricular ejection fraction (LVEF), left ventricular mass index (LVMI) before and after therapy were analyzed. Results: A total of 10 patients were collected. There were 8 females in this patient cohort, age was (18.4±5.0) years and onset age was (15.3±5.0) years. All 10 patients received standard heart failure medication therapy in addition to hormone and/or immunosuppressive anti-inflammatory therapy, but cardiac function was not improved, so aortic balloon dilatation and/or aortic stenting were performed in these patients. The median follow-up was 3.3(1.3, 5.6) years. On the third day after interventional therapy, the clinical symptoms of the 10 patients were significantly improved, NYHA classfication was restored from preoperative Ⅲ/Ⅳ to Ⅱ at 6 months post intervention(P<0.05). Compared with preoperation, NT-proBNP (P=0.028), LVEDD (P=0.011) and LVMI (P=0.019) were significantly decreased, LVEF was significantly increased (P<0.001) at 6 months after operation. Compared with preoperation, NT-proBNP (P=0.016), LVEDD (P=0.023) and LVMI (P=0.043) remained decreased, LVEF remained increased (P<0.001) at 1 year after operation. Conclusion: Results from short and medium term follow-up show that interventional therapy on top of heart failure drug therpay can effectively improve left cardiac function and attenuate cardiac remodeling in patients with TA-MAS comorbid with HFrEF.

Adolescent , Child , Female , Humans , Young Adult , Male , Heart Failure/surgery , Longitudinal Studies , Natriuretic Peptide, Brain , Peptide Fragments , Retrospective Studies , Stroke Volume , Takayasu Arteritis/surgery , Ventricular Function, Left/drug effects , Heart Ventricles/drug effects , Cardiovascular Agents/therapeutic use , Angioplasty, Balloon , Stents , Blood Vessel Prosthesis Implantation
Arq. bras. cardiol ; 111(5): 721-728, Nov. 2018. tab, graf
Article in English | LILACS | ID: biblio-973792


Abstract Background: Chemotherapy with doxorubicin and cyclophosphamide, although efficient for treating breast cancer, is associated with cardiovascular complications. Recent studies seek to identify methods that can early detect cardiological and vascular changes as a strategy to decrease the incidence of cardiovascular comorbidities. Objective: To evaluate the role of arterial stiffness measurement in the monitoring of doxorubicin and cyclophosphamide-induced cardiotoxicity in breast cancer patients. Methods: Prospective longitudinal study in 24 breast cancer patients undergoing treatment with doxorubicin and cyclophosphamide. Patients underwent an indirect evaluation of arterial stiffness through non-invasive measurement of hemodynamic parameters such as pulse wave velocity with the Mobil-O-Graph® 24H PWA device at three different times of the chemotherapy treatment (pre-chemotherapy, after the first and the fourth cycle). The left ventricular ejection fraction was also evaluated by Doppler echocardiography (pre-chemotherapy and after the fourth chemotherapy cycle). Data were considered significant when p ≤ 0.05. Results: Patients had a mean age of 52.33 ± 8.85 years and body mass index of 31 ± 5.87 kg/m2. There was no significant difference between the hemodynamic parameters evaluated by the oscillometric method or in the left ventricular ejection fraction in the different evaluated periods. Conclusion: Evaluations of arterial stiffness by oscillometry and measurement of left ventricular ejection fraction by Doppler echocardiography showed equivalence in the values found, suggesting that the evaluation method of arterial stiffness studied could be used as a marker for cardiovascular adverse events associated with doxorrubicin-based chemotherapy drugs.

Resumo Fundamento: O tratamento quimioterápico com doxorrubicina e ciclofosfamida, apesar de eficiente no combate ao câncer de mama, está associado a complicações cardiovasculares. Trabalhos recentes identificam métodos que possam detectar alterações cardiológicas e vasculares precocemente, visando a uma estratégia para diminuição na incidência de comorbidades cardiovasculares. Objetivo: Avaliar o papel da medida da rigidez arterial no acompanhamento da ocorrência de eventos adversos cardiovasculares induzidos por doxorrubicina e ciclofosfamida em pacientes com câncer de mama. Métodos: Estudo longitudinal prospectivo realizado com 24 pacientes com câncer de mama em tratamento com doxorrubicina e ciclofosfamida. As pacientes foram submetidas à avaliação indireta da rigidez arterial, por mensuração não invasiva de parâmetros hemodinâmicos, como a velocidade de onda de pulso, pelo equipamento Mobil-O-Graph® 24H PWA em três diferentes momentos do tratamento quimioterápico (pré-quimioterapia, após o primeiro e após o quarto ciclos). Foi avaliada também a fração de ejeção do ventrículo esquerdo pelo ecoDopplercardiograma (pré-quimioterapia e após o quarto ciclo quimioterápico). Os valores de p ≤ 0,05 foram considerados significativos. Resultados: As pacientes apresentaram média de idade de 52,33 ± 8,85 anos e índice de massa corporal de 31 ± 5,87 kg/m2. Não houve diferença significativa entre os parâmetros hemodinâmicos avaliados pelo método oscilométrico ou na fração de ejeção do ventrículo esquerdo, nos diferentes períodos avaliados. Conclusão: As avaliações de rigidez arterial por oscilometria e medida da fração de ejeção do ventrículo esquerdo por ecoDopplercardiograma mostraram equivalência nos valores encontrados, sugerindo que o método de avaliação da rigidez arterial estudado possa ser utilizado como mais um marcador para eventos adversos cardiovasculares associados aos medicamentos quimioterápicos baseados em doxorrubicina.

Humans , Female , Adult , Middle Aged , Cardiovascular Diseases/chemically induced , Doxorubicin/adverse effects , Anthracyclines/adverse effects , Cyclophosphamide/adverse effects , Vascular Stiffness , Antineoplastic Agents/adverse effects , Breast Neoplasms/drug therapy , Cardiovascular Diseases/prevention & control , Echocardiography, Doppler , Doxorubicin/therapeutic use , Doxorubicin/pharmacology , Pilot Projects , Longitudinal Studies , Ventricular Function, Left/drug effects , Anthracyclines/therapeutic use , Anthracyclines/pharmacology , Cyclophosphamide/therapeutic use , Cyclophosphamide/pharmacology , Cardiotoxicity/physiopathology , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/pharmacology
Arch. endocrinol. metab. (Online) ; 62(4): 392-398, July-Aug. 2018. tab
Article in English | LILACS | ID: biblio-950084


ABSTRACT Objective: Treatment of subclinical hypothyroidism (ScH), especially the mild form of ScH, is controversial because thyroid hormones influence cardiac function. We investigate left ventricular systolic and diastolic function in ScH and evaluate the effect of 5-month levothyroxine treatment. Subjects and methods: Fifty-four patients with newly diagnosed mild ScH (4.2 <TSH < 10.0 mU/L) and 30 euthyroid subjects matched by age were analysed. Laboratory analyses and an echocardiography study were done at the first visit and after 5 months in euthyroid stage in patients with ScH. Results: Compared to healthy controls, patients with ScH had a lower E/A ratio (1.03 ± 0.29 vs. 1.26 ± 0.36, p < 0.01), higher E/e' sep. ratio (762 ± 2.29 vs. 6.04 ± 1.64, p < 0.01), higher myocardial performance index (MPI) (0.47 ± 0.08 vs. 0.43 ± 0.07, p < 0.05), lower global longitudinal strain (GLS) (-19.5 ± 2.3 vs. −20.9 ± 1.7%, p < 0.05), and lower S wave derived by tissue Doppler imaging (0.077 ± 0.013 vs. 0.092 ± 0.011 m/s, p < 0.01). Levothyroxine treatment in patients with ScH contributed to higher EF (62.9 ± 3.9 vs. 61.6 ± 4.4%, p < 0.05), lower E/e' sep. ratio (6.60 ± 2.06 vs. 762 ± 2.29, p < 0.01), lower MPI (0.43 ± 0.07 vs. 0.47 ± 0.08%, p < 0.01), and improved GLS (-20.07 ± 2.7 vs. −19.55 ± 2.3%, p < 0.05) compared to values in ScH patients at baseline. Furthermore, in all study populations (ScH patients before and after levothyroxine therapy and controls), TSH levels significantly negatively correlated with EF (r = −0.15, p < 0.05), E/A (r = −0.14, p < 0.05), GLS (r = −0.26, p < 0.001), and S/TDI (r = −0.22, p < 0.01) and positively correlated with E/e' sep. (r = 0.14, p < 0.05). Conclusion: Patients with subclinical hypothyroidism versus healthy individuals had subtle changes in certain parameters that indicate involvement of systolic and diastolic function of the left ventricle. Although the values of the parameters were in normal range, they were significantly different compared to ScH and the control group at baseline, as well as to the ScH groups before and after treatment.The results of our study suggest that patients with ScH must be followed up during treatment to assess improvement of the disease. Some of the echocardiography obtained parameters were reversible after levothyroxine therapy.

Humans , Male , Female , Adult , Middle Aged , Systole/drug effects , Thyroxine/pharmacology , Ventricular Function, Left/drug effects , Diastole/drug effects , Hypothyroidism/drug therapy , Systole/physiology , Thyroxine/administration & dosage , Thyroxine/blood , Thyroxine/therapeutic use , Triiodothyronine/blood , Thyrotropin/blood , Case-Control Studies , Prospective Studies , Echocardiography, Doppler, Pulsed , Diastole/physiology , Heart Ventricles/physiopathology , Heart Ventricles/diagnostic imaging
Arq. bras. cardiol ; 110(2): 140-150, Feb. 2018. tab, graf
Article in English | LILACS | ID: biblio-888016


Abstract Background: The high cardiotoxicity morbidity and mortality rates associated with the antineoplastic therapy for breast cancer could be reduced with the early use of cardioprotective drugs. However, the low sensitivity of left ventricular ejection fraction limits its use in that preventive strategy. New parameters, such as global longitudinal strain, are being used in the early detection of contractile function changes. Objectives: To assess the incidence of cardiotoxicity in patients treated for breast cancer, the independent factors associated with that event, and the ability of strain to identify it early. Methods: Prospective observational study of consecutive outpatients diagnosed with breast cancer, with no previous antineoplastic treatment and no ventricular dysfunction, who underwent anthracycline and/or trastuzumab therapy. The patients were quarterly evaluated on a 6- to 12-month follow-up by an observer blind to therapy. Cox regression was used to evaluate the association of cardiotoxicity with clinical, therapeutic and echocardiographic variables. A ROC curve was built to identify the strain cutoff point on the third month that could predict the ejection fraction reduction on the sixth month. For all tests, the statistical significance level adopted was p ≤ 0.05. Results: Of 49 women (mean age, 49.7 ± 12.2 years), cardiotoxicity was identified in 5 (10%) on the third (n = 2) and sixth (n = 3) months of follow-up. Strain was independently associated with the event (p = 0.004; HR = 2.77; 95%CI: 1.39-5.54), with a cutoff point for absolute value of -16.6 (AUC = 0.95; 95%CI: 0.87-1.0) or a cutoff point for percentage reduction of 14% (AUC = 0.97; 95%CI: 0.9-1.0). Conclusion: The 14% reduction in strain (absolute value of -16.6) allowed the early identification of patients who could develop anthracycline and/or trastuzumab-induced cardiotoxicity.

Resumo Fundamentos: A elevada morbimortalidade da cardiotoxicidade associada à terapia antineoplásica para o câncer de mama poderia ser reduzida com uso precoce de drogas cardioprotetoras. No entanto, a baixa sensibilidade da fração de ejeção limita sua utilização nessa estratégia preventiva. Novos parâmetros, como o strain longitudinal global, estão sendo utilizados na detecção precoce das alterações da função contrátil. Objetivos: Avaliar a incidência de cardiotoxicidade entre pacientes tratados para câncer de mama, os fatores independentes associados a esse evento e a capacidade do strain em identificá-la precocemente. Métodos: Estudo prospectivo observacional de pacientes ambulatoriais consecutivos com diagnóstico de câncer de mama, sem tratamento antineoplásico prévio, sem disfunção ventricular, submetidos ao uso de antracíclicos e/ou trastuzumab, avaliados trimestralmente de forma cega em relação à terapia, seguidos por 6 a 12 meses. Regressão de Cox foi utilizada para avaliar a associação de variáveis clínicas, terapêuticas e ecocardiográficas com cardiotoxicidade. Curva ROC foi construída para identificar o ponto de corte do strain capaz de prever redução da fração de ejeção. Para todos os testes, o nível de significância estatística foi definido com p ≤ 0,05. Resultados: Dentre 49 mulheres com idade média de 49,7 ± 12,2 anos, identificamos 5 casos de cardiotoxicidade (10%), aos 3 (n = 2) e 6 (n = 3) meses de seguimento. Strain foi associado de forma independente ao evento (p = 0,004; HR = 2,77; IC95%: 1,39-5,54), tendo como ponto de corte o valor absoluto de -16,6 (ASC = 0,95; IC95%: 0,87-1,0) ou redução de 14% (ASC = 0,97; IC95%: 0,9-1,0). Conclusão: A redução de 14% do strain (ou valor absoluto de -16,6) foi capaz de identificar precocemente pacientes que podem evoluir com cardiotoxicidade associada ao antracíclico e/ou trastuzumab.

Humans , Female , Adult , Middle Aged , Breast Neoplasms/drug therapy , Anthracyclines/adverse effects , Cardiotoxicity/diagnosis , Trastuzumab/adverse effects , Heart Ventricles/diagnostic imaging , Antineoplastic Agents/adverse effects , Brazil/epidemiology , Echocardiography, Doppler , Incidence , Prospective Studies , Regression Analysis , Follow-Up Studies , Ventricular Function, Left/drug effects , Early Diagnosis , Cardiotoxicity/etiology , Cardiotoxicity/epidemiology , Heart Diseases/chemically induced , Heart Diseases/diagnostic imaging
Rev. chil. cardiol ; 36(3): 209-220, dic. 2017. tab, graf
Article in Spanish | LILACS | ID: biblio-899588


Resumen: Objetivo: Determinar algunos mecanismos moleculares por los cuales la activación de ROCK cardíaca post infarto del miocardio (IAM) participa en el remodelado y en deterioro de la función sistólica. Métodos: Determinación simultánea de niveles de proteínas blanco de ROCK cardíaca, de función sistólica in vivo del ventrículo izquierdo (VI) y de fibrosis e hipertrofia cardíaca en ratas con IAM en condiciones de inhibición de ROCK con fasudil. Resultados : Siete días post IAM la masa ventricular relativa aumentó significativamente en un 30% en el grupo MI y se redujo con fasudil. La disfunción sistólica VI mejoró significativamente con fasudil mientras que la activación de ROCK cardíaca se redujo a niveles del grupo control. El inhibidor de ROCK también redujo significativamente los niveles cardíacos elevados de las isoformas ROCK1 y ROCK2, de MHC-β y del colágeno miocárdico. En el grupo con IAM aumentaron significativamente los niveles de fosforilación de ERK 42 y ERK 44 (en 2 veces y en 63%, respectivamente), mientras que en el grupo IAM tratado con fasudil estos niveles fueron similares a los del grupo control. El IAM aumentó significativamente los niveles fosforilados del factor de transcripción GATA-4, que se normalizaron con el inhibidor de ROCK. Conclusiones: La disfunción sistólica post IAM se asoció fuertemente con la activación del ROCK cardíaca y con la fosforilación de proteínas río abajo de ROCK que promueven remodelado cardíaco como β-MHC y la vía ERK / GATA-4.

Abstracts: Objective: to determine some molecular mechanisms by which cardiac ROCK activation after myocardial infarction (MI) intervene in cardiac systolic function decline and remodeling. Methods: simultaneous measurement of different cardiac ROCK target proteins levels, in vivo left ventricular (LV) systolic function, myocardial fibrosis, and hypertrophy in rats with MI under ROCK inhibition with fasudil were performed. Results: seven days after MI the relative ventricular mass increased significantly by 30% in the MI groupand was reduced with fasudil. LV systolic dysfunction improved significantly with fasudil whereas at the same time cardiac ROCK activation was reduced to sham levels. The ROCK inhibitor also reduced increased cardiac levels of both ROCK1 and ROCK2 isoforms, β-MHC levels and myocardial collagen volume fraction decline. MI significantly increased phosphorylation levels of ERK 42 and ERK 44 by 2-fold and 63% respectively whereas in the fasudil-treated MI group these levels were similar to those in the sham group. MI significantly increased phosphorylated levels of the transcription factor GATA-4 which were normalyzed by the ROCK inhibitor. Conclusion: LV systolic dysfunction after MI was strongly associated to cardiac ROCK activation and subsequent phosphorylation of ROCK target proteins that promote ventricular remodeling, such as β-MHC and the ERK/GATA-4 pathway. ROCK inhibition with fasudil significantly improved systolic function, diminished myocardial fibrosis, and normalized β-MHC and ERK/GATA-4 phosphorylation levels.

Animals , Rats , 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine/analogs & derivatives , Protein Kinase Inhibitors/pharmacology , rho-Associated Kinases/antagonists & inhibitors , Myocardial Infarction/drug therapy , Organ Size/drug effects , Phosphorylation , Blotting, Western , Ventricular Function, Left/drug effects , Rats, Sprague-Dawley , Cardiomegaly/drug therapy , 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine/pharmacology , Ventricular Remodeling/drug effects , Disease Models, Animal , Myocardial Infarction/enzymology
Arq. bras. cardiol ; 108(1): 12-20, Jan. 2017. tab, graf
Article in English | LILACS | ID: biblio-838670


Abstract Background: Radionuclide ventriculography (RV) is a validated method to evaluate the left ventricular systolic function (LVSF) in small rodents. However, no prior study has compared the results of RV with those obtained by other imaging methods in this context. Objectives: To compare the results of LVSF obtained by RV and echocardiography (ECHO) in an experimental model of cardiotoxicity due to doxorubicin (DXR) in rats. Methods: Adult male Wistar rats serving as controls (n = 7) or receiving DXR (n = 22) in accumulated doses of 8, 12, and 16 mg/kg were evaluated with ECHO performed with a Sonos 5500 Philips equipment (12-MHz transducer) and RV obtained with an Orbiter-Siemens gamma camera using a pinhole collimator with a 4-mm aperture. Histopathological quantification of myocardial fibrosis was performed after euthanasia. Results: The control animals showed comparable results in the LVSF analysis obtained with ECHO and RV (83.5 ± 5% and 82.8 ± 2.8%, respectively, p > 0.05). The animals that received DXR presented lower LVSF values when compared with controls (p < 0.05); however, the LVSF values obtained by RV (60.6 ± 12.5%) were lower than those obtained by ECHO (71.8 ± 10.1%, p = 0.0004) in this group. An analysis of the correlation between the LVSF and myocardial fibrosis showed a moderate correlation when the LVSF was assessed by ECHO (r = -0.69, p = 0.0002) and a stronger correlation when it was assessed by RV (r = -0.79, p < 0.0001). On multiple regression analysis, only RV correlated independently with myocardial fibrosis. Conclusion: RV is an alternative method to assess the left ventricular function in small rodents in vivo. When compared with ECHO, RV showed a better correlation with the degree of myocardial injury in a model of DXR-induced cardiotoxicity.

Resumo Fundamento: A ventriculografia radioisotópica (VRI) é um método validado para avaliação da função sistólica do ventrículo esquerdo (FSVE) em pequenos roedores. Contudo, nenhum estudo prévio comparou os resultados obtidos com VRI com os obtidos por outros métodos de imagem neste contexto. Objetivos: Comparar os resultados de FSVE obtidos por VRI e por ecocardiografia (ECO) em modelo experimental de cardiotoxicidade por doxorrubicina (DXR) em ratos. Métodos: Ratos Wistar machos adultos controles (n = 7) e tratados com DXR (n = 22) em doses acumuladas de 8, 12 e 16 mg/kg, foram avaliados com ECO com equipamento Sonos 5500 Philips (transdutor de 12 MHz) e VRI adquirida em gama-câmara Orbiter-Siemens com colimador pinhole de 4 mm de abertura. Após eutanásia, foi realizada a quantificação histopatológica da fibrose miocárdica. Resultados: Os animais controles apresentaram valores comparáveis na análise da FSVE à ECO e à VRI (83,5 ± 5% e 82,8 ± 2,8%, respectivamente, p > 0,05). Os animais que receberam DXR apresentaram valores menores de FSVE quando comparados aos dos controles (p < 0,05); entretanto, observou-se neste grupo menores valores de FSVE obtidos por VRI (60,6 ± 12,5%) quando comparados aos obtidos pela ECO (71,8 ± 10,1%, p = 0,0004). A análise da correlação entre a FSVE e a fibrose miocárdica mostrou uma correlação moderada quando a FSVE foi estimada com a ECO (r = -0,69, p = 0,0002) e mais forte quando a FSVE foi obtida por VRI (r = -0,79, p < 0,0001). Apenas a VRI apresentou correlação de forma independente com a fibrose miocárdica à análise de regressão múltipla. Conclusão: A VRI é um método alternativo para avaliação da função ventricular esquerda in vivo em pequenos roedores, exibindo comparativamente à ECO melhor correlação com o grau de lesão miocárdica no modelo de cardiotoxicidade por DXR.

Animals , Male , Echocardiography , Radionuclide Ventriculography , Ventricular Function, Left/drug effects , Ventricular Dysfunction, Left/diagnostic imaging , Reference Values , Fibrosis , Doxorubicin , Reproducibility of Results , Rats, Wistar , Ventricular Dysfunction, Left/chemically induced , Ventricular Dysfunction, Left/pathology , Statistics, Nonparametric , Disease Models, Animal , Cardiotoxicity/diagnostic imaging , Antibiotics, Antineoplastic
Yonsei Medical Journal ; : 105-113, 2017.
Article in English | WPRIM | ID: wpr-65056


PURPOSE: Urapidil is putatively effective for patients with hypertension and acute heart failure, although randomized controlled trials thereon are lacking. We investigated the efficacy and safety of intravenous urapidil relative to that of nitroglycerin in older patients with hypertension and heart failure in a randomized controlled trial. MATERIALS AND METHODS: Patients (>60 y) with hypertension and heart failure were randomly assigned to receive intravenous urapidil (n=89) or nitroglycerin (n=91) for 7 days. Hemodynamic parameters, cardiac function, and safety outcomes were compared. RESULTS: Patients in the urapidil group had significantly lower mean systolic blood pressure (110.1±6.5 mm Hg) than those given nitroglycerin (126.4±8.1 mm Hg, p=0.022), without changes in heart rate. Urapidil was associated with improved cardiac function as reflected by lower N terminal-pro B type natriuretic peptide after 7 days (3311.4±546.1 ng/mL vs. 4879.1±325.7 ng/mL, p=0.027) and improved left ventricular ejection fraction (62.2±3.4% vs. 51.0±2.4%, p=0.032). Patients given urapidil had fewer associated adverse events, specifically headache (p=0.025) and tachycardia (p=0.004). The one-month rehospitalization and all-cause mortality rates were similar. CONCLUSION: Intravenous administration of urapidil, compared with nitroglycerin, was associated with better control of blood pressure and preserved cardiac function, as well as fewer adverse events, for elderly patients with hypertension and acute heart failure.

Aged , Female , Humans , Male , Middle Aged , Acute Disease , Antihypertensive Agents/administration & dosage , Blood Pressure/drug effects , Cause of Death , Heart Failure/drug therapy , Heart Rate/drug effects , Hemodynamics , Hypertension/drug therapy , Injections, Intravenous , Natriuretic Peptide, Brain/blood , Nitroglycerin/administration & dosage , Peptide Fragments/blood , Piperazines/administration & dosage , Ventricular Function, Left/drug effects
Braz. j. med. biol. res ; 49(10): e5294, 2016. tab, graf
Article in English | LILACS | ID: lil-792520


Determination of left ventricular ejection fraction (LVEF) using in vivo imaging is the cardiac functional parameter most frequently employed in preclinical research. However, there is considerable conflict regarding the effects of anesthetic agents on LVEF. This study aimed at assessing the effects of various anesthetic agents on LVEF in hamsters using transthoracic echocardiography. Twelve female hamsters were submitted to echocardiography imaging separated by 1-week intervals under the following conditions: 1) conscious animals, 2) animals anesthetized with isoflurane (inhaled ISO, 3 L/min), 3) animals anesthetized with thiopental (TP, 50 mg/kg, intraperitoneal), and 4) animals anesthetized with 100 mg/kg ketamine plus 10 mg/kg xylazine injected intramuscularly (K/X). LVEF obtained under the effect of anesthetics (ISO=62.2±3.1%, TP=66.2±2.7% and K/X=75.8±1.6%) was significantly lower than that obtained in conscious animals (87.5±1.7%, P<0.0001). The K/X combination elicited significantly higher LVEF values compared to ISO (P<0.001) and TP (P<0.05). K/X was associated with a lower dispersion of individual LVEF values compared to the other anesthetics. Under K/X, the left ventricular end diastolic diameter (LVdD) was increased (0.60±0.01 cm) compared to conscious animals (0.41±0.02 cm), ISO (0.51±0.02 cm), and TP (0.55±0.01 cm), P<0.0001. The heart rate observed with K/X was significantly lower than in the remaining conditions. These results indicate that the K/X combination may be the best anesthetic option for the in vivo assessment of cardiac systolic function in hamsters, being associated with a lower LVEF reduction compared to the other agents and showing values closer to those of conscious animals with a lower dispersion of results.

Animals , Female , Anesthetics/pharmacology , Stroke Volume/drug effects , Ventricular Function, Left/drug effects , Drug Combinations , Echocardiography/methods , Heart Rate/drug effects , Heart Ventricles/diagnostic imaging , Heart Ventricles/drug effects , Isoflurane/pharmacology , Ketamine/pharmacology , Mesocricetus , Reference Values , Systole/drug effects , Thiopental/pharmacology , Time Factors , Xylazine/pharmacology
Article in English | WPRIM | ID: wpr-36003


BACKGROUND/AIMS: We evaluated the association between coding region variants of adrenergic receptor genes and therapeutic effect in patients with congestive heart failure (CHF). METHODS: One hundred patients with stable CHF (left ventricular ejection fraction [LVEF] < 45%) were enrolled. Enrolled patients started 1.25 mg bisoprolol treatment once daily, then up-titrated to the maximally tolerable dose, at which they were treated for 1 year. RESULTS: Genotypic analysis was carried out, but the results were blinded to the investigators throughout the study period. At position 389 of the beta-1 adrenergic receptor gene (ADRB1), the observed minor Gly allele frequency (Gly389Arg + Gly389Gly) was 0.21, and no deviation from Hardy-Weinberg equilibrium was observed in the genotypic distribution of Arg389Gly (p = 0.75). Heart rate was reduced from 80.8 +/- 14.3 to 70.0 +/- 15.0 beats per minute (p < 0.0001). There was no significant difference in final heart rate across genotypes. However, the Arg389Arg genotype group required significantly more bisoprolol compared to the Gly389X (Gly389Arg + Gly389Gly) group (5.26 +/- 2.62 mg vs. 3.96 +/- 2.05 mg, p = 0.022). There were no significant differences in LVEF changes or remodeling between two groups. Also, changes in exercise capacity and brain natriuretic peptide level were not significant. However, interestingly, there was a two-fold higher rate of readmission (21.2% vs. 10.0%, p = 0.162) and one CHF-related death in the Arg389Arg group. CONCLUSIONS: The ADRB1 Gly389X genotype showed greater response to bisoprolol than the Arg389Arg genotype, suggesting the potential of individually tailoring beta-blocker therapy according to genotype.

Adult , Aged , Female , Humans , Male , Middle Aged , Adrenergic beta-1 Receptor Antagonists/adverse effects , Bisoprolol/adverse effects , Gene Frequency , Genotype , Heart Failure/diagnosis , Heart Rate/drug effects , Maximum Tolerated Dose , Pharmacogenomic Testing , Phenotype , Polymorphism, Genetic , Precision Medicine , Receptors, Adrenergic, beta-1/drug effects , Republic of Korea , Stroke Volume/drug effects , Time Factors , Treatment Outcome , Ventricular Function, Left/drug effects , Ventricular Remodeling/drug effects
Cad. saúde pública ; 31(3): 586-596, 03/2015. tab
Article in Portuguese | LILACS | ID: lil-744827


O objetivo deste estudo foi identificar fatores associados à utilização dos serviços odontológicos, públicos (básicos e especializados) e privados. Foi realizado inquérito populacional de base domiciliar em dois municípios da Bahia, Brasil. Informantes-chave forneceram dados socioeconômicos e de utilização dos serviços odontológicos (desfecho). A organização do serviço público odontológico local foi classificada em pior/melhor. Realizou-se regressão logística politômica uni e múltipla. Do total de 1.290 indivíduos, 38,76% usaram o serviço privado, 33,80% atenção básica e 17,29% atenção básica e o Centro de Especialidades Odontológicas (CEO). Um perfil de vulnerabilidade social foi associado ao uso do serviço público, quando comparado ao privado. Menor escolaridade (OR = 1,47; IC95%: 1,03-2,10) e pior organização do serviço (OR = 1,74; IC95%: 1,22-2,48) foram associados ao menor uso da rede de serviços atenção básica e CEO em comparação ao uso exclusivo da atenção básica. A desigualdade na utilização dos serviços odontológicos foi observada mesmo quando comparados grupos mais homogêneos, como os usuários dos serviços públicos.

The aim of this study was to identify factors associated with the use of primary and specialized public dental health services and private services. A population-based household survey was conducted in two cities of Bahia State, Brazil. Key informants provided data on socioeconomic variables and use of dental health services. Organization of the local public dental health service was ranked as worse versus better. Univariate and multivariate polytomous logistic regression was performed. Of the total of 1,290 individuals, 38.76% used private services, 33.80% used public primary care, and 17.29% used both primary care and the Center for Dental Specialties. Less use of both primary care and specialized public services was associated with lower education (OR = 1.47; 95%CI: 1.03-2.10) and worse organization of services (OR = 1.74; 95%CI: 1.22-2.48), when compared to the exclusive use of primary care. The study showed inequality in the use of dental services, even when comparing more homogeneous groups, namely users of public services.

El objetivo de este estudio fue identificar los factores asociados al uso de los servicios odontológicos (primarios y especializados) públicos y privados. Se realizó una encuesta poblacional en dos ciudades de Bahía, Brasil. Los informantes clave contestaron cuestiones socioeconómicas y de utilización de los servicios odontológicos (resultado). La organización de los servicios odontológicos públicos locales fue clasificada en peor/mejor. Se realizó regresión simple y múltiple con variable politómica. Del total de 1.290 personas, un 38,76% utilizaron el servicio privado, un 33,80% la atención primaria y un 17,29% atención primaria y el Centro de Especialidades Dentales (CED). Una menor escolaridad (OR = 1,47; IC95%: 1.03-2.10) y una peor organización de servicio (OR = 1,74; IC95%: 1,22-2,48) se asociaron con un menor uso de la red de servicios de atención primaria y CED, en comparación con el uso exclusivo de la atención primaria. La desigualdad en el uso de los servicios dentales se observó incluso cuando se comparan grupos más homogéneos, como usuarios de servicios públicos.

Animals , Rabbits , Action Potentials/physiology , Membrane Potentials/physiology , Myocytes, Cardiac/physiology , Potassium/metabolism , Tacrolimus Binding Proteins/metabolism , Ventricular Function, Left/drug effects , Action Potentials/drug effects , Cells, Cultured , Membrane Potentials/drug effects , Myocytes, Cardiac/drug effects , Up-Regulation/physiology
Article in English | WPRIM | ID: wpr-126100


BACKGROUND/AIMS: This study was designed to evaluate the dose-effect relationship of statins in patients with ischemic congestive heart failure (CHF), since the role of statins in CHF remains unclear. METHODS: The South koreAn Pitavastatin Heart FaIluRE (SAPHIRE) study was designed to randomize patients with ischemic CHF into daily treatments of 10 mg pravastatin or 4 mg pitavastatin. RESULTS: The low density lipoprotein cholesterol level decreased by 30% in the pitavastatin group compared with 12% in the pravastatin (p < 0.05) group. Left ventricular systolic dimensions decreased significantly by 9% in the pitavastatin group and by 5% in the pravastatin group. Left ventricular ejection fraction (EF) improved significantly from 37% to 42% in the pitavastatin group and from 35% to 39% in the pravastatin group. Although the extent of the EF change was greater in the pitavastatin group (16% vs. 11%) than that in the pravastatin group, no significant difference was observed between the groups (p = 0.386). Exercise capacity, evaluated by the 6-min walking test, improved significantly in the pravastatin group (p < 0.001), but no change was observed in the pitavastatin group (p = 0.371). CONCLUSIONS: Very low dose/low potency pravastatin and high dose/high potency pitavastatin had a beneficial effect on cardiac reverse remodeling and improved systolic function in patients with ischemic CHF. However, only pravastatin significantly improved exercise capacity. These findings suggest that lowering cholesterol too much may not be beneficial for patients with CHF.

Aged , Female , Humans , Male , Middle Aged , Biomarkers/blood , Cholesterol, LDL/blood , Down-Regulation , Dyslipidemias/blood , Exercise Tolerance/drug effects , Heart Failure/diagnosis , Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage , Myocardial Ischemia/diagnosis , Pravastatin/administration & dosage , Prospective Studies , Quinolines/administration & dosage , Recovery of Function , Republic of Korea , Stroke Volume/drug effects , Time Factors , Treatment Outcome , Ventricular Function, Left/drug effects , Ventricular Remodeling/drug effects
Arq. bras. cardiol ; 100(4): 328-332, abr. 2013. ilus, tab
Article in Portuguese | LILACS | ID: lil-674197


FUNDAMENTO: O trastuzumabe (TZB) é um anticorpo monoclonal humanizado recombinante usado no tratamento do câncer de mama HER2-positivo, com reconhecida cardiotoxicidade associada. Os métodos para sua detecção subclínica precoce não estão bem estabelecidos. OBJETIVO: Avaliar a cardiotoxicidade induzida por TZB em pacientes (pts) portadoras de câncer de mama acompanhadas por um período de 3 meses de tratamento. MÉTODOS: Estudo prospectivo de pts consecutivas em tratamento com TZB para câncer de mama HER2-positivo avançado, admitidas entre maio e setembro de 2010. Foram comparados dados clínicos, laboratoriais e ecocardiográficos antes da introdução de TZB e 3 meses após o início do tratamento com a droga. Foram estudadas a deterioração da função sistólica do ventrículo esquerdo (segundo critérios do Comitê de Avaliação e Revisão Cardíaca) e a função diastólica (classificação da Sociedade Americana de Ecocardiografia). RESULTADOS: Estavam disponíveis dados de 51 pacientes, cuja idade média era de 55,4±14,0 anos. Nenhuma paciente apresentou insuficiência cardíaca sintomática no terceiro mês. Não houve diferenças na fração de ejeção do ventrículo esquerdo (FEVE) aos 3 meses (69,3 ± 7,4 contra 67,1 ± 6,5%, p > 0,05), tendo sido observada redução em 57,9% pts (em apenas uma a FEVE foi < 55%). Houve aumento significativo da relação E/e' (3,9 ± 0,8 contra 8,0 ± 1,9, p < 0,001) devido a uma redução da velocidade e' (0,19 ± 0,02 contra 0,10 ± 0,03, p < 0,001). Os demais parâmetros diastólicos permaneceram inalterados. Tanto o volume atrial esquerdo quanto o ventricular esquerdo permaneceram inalterados. Não houve aumento dos níveis de peptídeo natriurético tipo pró-B N-terminal. Durante o período de seguimento, duas pacientes morreram e duas foram internadas, todas por causas não cardiovasculares. CONCLUSÃO: Durante os três primeiros meses de tratamento com TZB, nenhuma das pacientes apresentou insuficiência cardíaca franca ou deterioração significativa da FEVE. Detectou-se redução significativa da relação e/e', porém sem alterações importantes dos parâmetros de carga e da FEVE.

BACKGROUND: Trastuzumab (TZB) is a recombinant humanized monoclonal antibody, used for the treatment of HER2-positive breast cancer, with recognized associated-cardiotoxicity. The methods for its early sub-clinical detection are not well defined. OBJECTIVE: To evaluate TZB-induced cardiotoxicity in patients (pts) with breast cancer followed for a 3-month period of treatment. METHODS: Prospective study of consecutive pts treated with TZB for advanced HER2-positive breast cancer enrolled between May-September/2010. A comparison of clinical, laboratory and echocardiographic data, prior to and at the 3rd month after starting TZB was performed. Left ventricular systolic function deterioration (Cardiac Review and Evaluation Committee criteria) and diastolic function (American Society of Echocardiography classification) were studied. RESULTS: Data were available for 51 women, mean age = 55.4 ± 14.0y. At the 3rd month, no patient had symptomatic heart failure. Left ventricular ejection fraction (LVEF) did not differ at 3 months (69.3 ± 7.4 vs. 67.1 ± 6.5%, p > 0.05), decreasing in 57.9% pts (only one to LVEF < 55%). There was a significant increase in the E/e' ratio (3.9 ± 0.8 vs. 8.0 ± 1.9, p < 0,001) due to an e' velocity reduction (0.19 ± 0.02 vs. 0.10 ± 0.03, p < 0.001). Other diastolic parameters remained unchanged. Both the left atrial and the left ventricular volumes remained unchanged. N-terminal pro-B type natriuretic peptide levels did not increase. During the follow up period two pts died and two were admitted to the hospital, all for non-cardiovascular causes. CONCLUSIONS: During the first 3 months of TZB treatment none of the pts presented overt heart failure or significant LVEF deterioration. A significant reduction in the E/e' ratio was detected, but neither the loading parameters nor LVEF changed significantly .

Female , Humans , Middle Aged , Antibodies, Monoclonal, Humanized/adverse effects , Antineoplastic Agents/adverse effects , Breast Neoplasms/drug therapy , Heart Failure/chemically induced , Echocardiography, Doppler/methods , Heart Failure , Prospective Studies , /metabolism , Stroke Volume/drug effects , Treatment Outcome , Ventricular Function, Left/drug effects
Braz. j. med. biol. res ; 45(12): 1248-1254, Dec. 2012. ilus, tab
Article in English | LILACS | ID: lil-659638


Little is known about age-related differences in short-term effects of estradiol on ischemia-reperfusion (I/R) insults. The present study was designed to evaluate the effects of short-term treatment with estradiol on reperfusion arrhythmias in isolated hearts of 6-7-week-old and 12-14-month-old female rats. Wistar rats were sham-operated, ovariectomized and treated with vehicle or ovariectomized and treated with 17β-estradiol (E2; 5 µg·100 g-1·day-1) for 4 days. Hearts were perfused by the Langendorff technique. Reperfusion arrhythmias, i.e., ventricular tachycardia and/or ventricular fibrillation, were induced by 15 min of left coronary artery ligation and 30 min of reperfusion. The duration and incidence of I/R arrhythmias were significantly higher in young rats compared to middle-aged rats (arrhythmia severity index: 9.4 ± 1.0 vs 3.0 ± 0.3 arbitrary units, respectively, P < 0.05). In addition, middle-aged rats showed lower heart rate, systolic tension and coronary flow. Four-day E2 treatment caused an increase in uterine weight. Although E2 administration had no significant effect on the duration of I/R arrhythmias in middle-aged rats, it induced a marked reduction in the rhythm disturbances of young rats accompanied by a decrease in heart rate of isolated hearts. Also, this reduction was associated with an increase in QT interval. No significant changes were observed in the QT interval of middle-aged E2-treated rats. These data demonstrate that short-term estradiol treatment protects against I/R arrhythmias in hearts of young female rats. The anti-arrhythmogenic effect of estradiol might be related to a lengthening of the QT interval.

Animals , Female , Arrhythmias, Cardiac/prevention & control , Estradiol/pharmacology , Myocardial Reperfusion Injury/physiopathology , Age Factors , Arrhythmias, Cardiac/physiopathology , Coronary Circulation/drug effects , Coronary Circulation/physiology , Electrocardiography , Estradiol/administration & dosage , Ovariectomy , Rats, Wistar , Ventricular Function, Left/drug effects
Ann Card Anaesth ; 2012 Apr; 15(2): 128-133
Article in English | IMSEAR | ID: sea-139654


We aimed to investigate whether low-dose vasopressin administered to patients undergoing coronary artery bypass grafting (CABG) surgery with preexisting mild to moderate systolic dysfunction can produce sustained improvement in cardiac function. This double-blind randomized study was conducted in a hospital where a single anesthetic and surgical team performed elective CABG. Twenty patients aged 32-61 years who underwent elective CABG between January 2007 and December 2007 were enrolled in this study. The patients randomly received either vasopressin 0.03 IU/min (Group A) or normal saline (Group B) in equal volume for 60 min after cardiopulmonary bypass (CPB). The cardiac output, cardiac index, stroke volume index, fractional area of contraction and systemic vascular resistance index were significantly higher in Group A than in Group B. Adrenaline (mean dose: 0.06 μg/kg•min-1) was required in seven patients from Group B but in none of the Group A patients on initial separation from CPB (P< 0.05). Of the 10 patients in Group B, five required phenylepherine to maintain the mean arterial pressure (MAP) >65 mmHg, whereas none of the Group A patients required phenylephrine for MAP regulation (P< 0.05). We conclude that Infusion of low-dose vasopressin for patients with mild to moderate left ventricular systolic dysfunction during separation from CPB is beneficial for the postoperative hemodynamic profile, reduces the catecholamine doses required and improves left ventricular systolic function.

Adult , Anesthesia , Blood Pressure/drug effects , Cardiac Catheterization , Cardiac Output/drug effects , Cardiopulmonary Bypass/methods , Double-Blind Method , Echocardiography, Transesophageal , Female , Hemostatics/administration & dosage , Hemostatics/therapeutic use , Humans , Male , Middle Aged , Myocardial Contraction/drug effects , Phenylephrine/therapeutic use , Stroke Volume/drug effects , Vascular Resistance/drug effects , Vasoconstrictor Agents/therapeutic use , Vasopressins/administration & dosage , Vasopressins/therapeutic use , Ventricular Function, Left/drug effects
Rev. bras. cir. cardiovasc ; 27(1): 110-116, jan.-mar. 2012. ilus, tab
Article in English | LILACS | ID: lil-638658


BACKGROUND: There is a growing need to improve myocardial protection, which will lead to better performance of cardiac operations and reduce morbidity and mortality. Therefore, the objective of this study was to compare the efficacy of myocardial protection solution using both intracellular and extracellular crystalloid type regarding the performance of the electrical conduction system, left ventricular contractility and edema, after being subjected to ischemic arrest and reperfusion. METHODS: Hearts isolated from male Wistar (n=32) rats were prepared using Langendorff method and randomly divided equally into four groups according the cardioprotective solutions used Krebs-Henseleit-Buffer (KHB), Bretschneider-HTK (HTK), St. Thomas-1 (STH-1) and Celsior (CEL). After stabilization with KHB at 37ºC, baseline values (control) were collected for heart rate (HR), left ventricle systolic pressure (LVSP), maximum first derivate of rise left ventricular pressure (+dP/dt), maximum first derivate of fall left ventricular pressure (-dP/dt) and coronary flow (CF). The hearts were then perfused at 10ºC for 5 min and kept for 2 h in static ischemia at 20ºC in each cardioprotective solution. Data evaluation was done using analysis of variance in completely randomized One-Way ANOVA and Tukey's test for multiple comparisons. The level of statistical significance chosen was P<0.05. RESULTS: HR was restored with all the solutions used. The evaluation of left ventricular contractility (LVSP, +dP/ dt and -dP/dt) showed that treatment with CEL solution was better compared to other solutions. When analyzing the CF, the HTK solution showed better protection against edema. CONCLUSION: Despite the cardioprotective crystalloid solutions studied are not fully able to suppress the deleterious effects of ischemia and reperfusion in the rat heart, the CEL solution had significantly higher results followed by HTK>KHB>STH-1.

INTRODUÇÃO: Existe crescente necessidade de aprimorar a proteção miocárdica, para melhor desempenho das operações cardíacas e diminuição da morbimortalidade. Portanto, o objetivo deste estudo foi comparar a eficácia da proteção miocárdica usando tanto solução cristaloide tipo intracelular como extracelular quanto ao desempenho do sistema de condução elétrica, contratilidade do ventrículo esquerdo e edema, após parada isquêmica e posterior reperfusão. MÉTODOS: Corações isolados de ratos Wistar foram montados em Langendorff e aleatoriamente divididos em quatro grupos. de acordo com as soluções cardioprotetoras utilizadas Krebs-Henseleit-Buffer (KHB), Bretschneider-HTK (HTK), St. Thomas-1(STH-1) e Celsior (CEL). Após a estabilização com KHB a 37ºC, valores basais (controle) foram coletados para frequência cardíaca (FC), pressão sistólica do ventrículo esquerdo (PSVE), derivada máxima de aumento da pressão ventricular esquerda (+dP/dt), derivada máxima de queda da pressão ventricular esquerda (-dP/dt) e fluxo coronariano (FCo). Os corações foram então perfundidos a 10ºC por 5 min e mantidos por 2 h em isquemia estática a 20ºC em cada solução cardioprotetora. Avaliação dos dados foi por análise de variância inteiramente casualizados em One-Way ANOVA e teste de Tukey para comparações múltiplas. O nível de significância estatística escolhido foi P<0,05. RESULTADOS: Houve recuperação da FC com todas as soluções utilizadas. A avaliação da contratilidade ventricular esquerda (PSVE, +dP/dt e -dP/dt) demonstrou que o tratamento com a solução CEL foi melhor em comparação às outras soluções. Ao analisar o CF, a solução HTK indicou melhor proteção contra edema. CONCLUSÃO: Apesar das soluções cristaloides cardioprotetoras estudadas não serem capazes de suprimir os efeitos deletérios da isquemia e reperfusão no coração de ratos, a solução CEL apresentou resultado superior seguido por HTK>KHB>STH-1.

Animals , Male , Rats , Cardioplegic Solutions/pharmacology , Edema, Cardiac/pathology , Heart Transplantation , Heart Conduction System/drug effects , Isotonic Solutions/pharmacology , Myocardial Contraction/drug effects , Ventricular Function, Left/drug effects , Analysis of Variance , Bicarbonates/pharmacology , Calcium Chloride/pharmacology , Disaccharides/pharmacology , Electrolytes/pharmacology , Glucose/pharmacology , Glutamates/pharmacology , Glutathione/pharmacology , Heart Arrest, Induced/methods , Hemodynamics/drug effects , Histidine/pharmacology , Models, Animal , Magnesium/pharmacology , Mannitol/pharmacology , Myocardial Reperfusion Injury/prevention & control , Organ Preservation/methods , Potassium Chloride/pharmacology , Procaine/pharmacology , Random Allocation , Rats, Wistar , Sodium Chloride/pharmacology , Tromethamine/pharmacology
Arq. bras. endocrinol. metab ; 55(7): 460-467, out. 2011. graf, tab
Article in English | LILACS | ID: lil-607492


OBJECTIVE: To evaluate the effects of levothyroxine (L-T4) replacement in echocardiographic parameters of middle-aged women with subclinical hypothyroidism (SH). SUBJECTS AND METHODS: This was a randomized, double-blind, placebo-controlled study. Echocardiographic evaluation was carried out at baseline and one year after restoration of euthyroidism. Thirty-three women with SH were assigned to one of two groups (L-T4 or placebo). RESULTS: The two groups had similar basal characteristics. There was a significant deterioration of left ventricular Tei index after one year of placebo use, which differed from the effect of L-T4 replacement (+0.086 ± 0.092 vs. -0.014 ± 0.012; p = 0.047). There was also a slight reduction in cardiac output and cardiac index with placebo use, which was not different from L-T4 effect. CONCLUSION: Results suggest a positive impact of L-T4 replacement in cardiac function of middle-aged women with SH.

OBJETIVO: Avaliar os efeitos da reposição de levotiroxina (L-T4) nos parâmetros ecocardiográficos em mulheres de meia-idade com hipotireoidismo subclínico (HS). SUJEITOS E MÉTODOS: Realizado estudo duplo-cego, controlado com placebo com avaliação dos parâmetros ecocardiográficos no início e um ano após o restabelecimento do eutireoidismo. Trinta e três mulheres foram incluídas em dois grupos (uso de L-T4 ou placebo). RESULTADOS: Os dois grupos tinham características basais similares. Houve uma significativa piora do índice TEI do ventrículo esquerdo no grupo que usou placebo por um ano. Já no grupo em reposição com L-T4 observou-se uma leve melhora desse índice (+0,086 ± 0,092 vs. -0,014 ± 0,012; p = 0,047). Ocorreu também uma leve redução no débito cardíaco e no índice cardíaco com placebo, os quais não diferiram do efeito da reposição de L-T4. CONCLUSÃO: Os resultados sugerem um impacto positivo com a reposição de L-T4, na função cardíaca de mulheres de meia-idade, com HS.

Adult , Female , Humans , Middle Aged , Heart/drug effects , Hormone Replacement Therapy/adverse effects , Hypothyroidism/physiopathology , Thyroxine/adverse effects , Cardiac Output/drug effects , Cardiac Output/physiology , Double-Blind Method , Diastole/drug effects , Heart/physiopathology , Hypothyroidism/drug therapy , Hypothyroidism , Statistics, Nonparametric , Systole/drug effects , Treatment Outcome , Thyroxine/therapeutic use , Ventricular Function, Left/drug effects
Indian J Biochem Biophys ; 2011 Feb; 48(1): 22-28
Article in English | IMSEAR | ID: sea-135296


The cardioprotective potential of Inula racemosa root hydroalcoholic extract against isoproterenol-induced myocardial infarction was investigated in rats. The rats treated with isoproterenol (85 mg/kg, s.c.) exhibited myocardial infarction, as evidenced by significant (P<0.05) decrease in mean arterial pressure, heart rate, contractility, relaxation along with increased left ventricular end diastolic pressure, as well as decreased endogenous myocardial enzymatic and non-enzymatic antioxidants. Isoproterenol also significantly (P<0.05) induced lipid peroxidation and increased leakage of myocyte injury marker enzymes. Pretreatment with I. racemosa extract (50, 100 or 200 mg/kg per day, p.o.) for 21 consecutive days, followed by isoproterenol injections on days 19th and 20th significantly (P<0.05) improved cardiac function by increasing the heart rate, mean arterial pressure, contractility and relaxation along with decreasing left ventricular end diastolic pressure. Pretreatment with I. racemosa also significantly (P<0.05) restored the reduced form of glutathione and endogenous antioxidant enzymes superoxide dismutase, catalase, glutathione peroxidase from the heart, which were depleted after isoproterenol administration. In addition to restoration of antioxidants, I. racemosa significantly (P<0.05) inhibited lipid peroxidation and prevented the leakage of myocytes specific marker enzymes creatine phosphokinase-MB and lactate dehydrogenase from the heart. Thus, it is concluded that I. racemosa protects heart from isoproterenol-induced myocardial injury by reducing oxidative stress and modulating hemodynamic and ventricular functions of the heart. Present study findings demonstrate the cardioprotective effect of I. racemosa and support the pharmacological relevance of its use and cardioprotection mechanism in ischemic heart disease as well as substantiate its traditional claim

Animals , Catalase/drug effects , Catalase/metabolism , Creatine Kinase, MB Form/drug effects , Creatine Kinase, MB Form/metabolism , Glutathione/drug effects , Glutathione/metabolism , Glutathione Peroxidase/drug effects , Glutathione Peroxidase/metabolism , Heart Rate/drug effects , Hemodynamics/drug effects , Inula , Isoproterenol , L-Lactate Dehydrogenase/drug effects , L-Lactate Dehydrogenase/metabolism , Lipid Peroxidation/drug effects , Male , Myocardial Infarction/chemically induced , Myocardial Infarction/drug therapy , Oxidative Stress/drug effects , Phytotherapy/methods , Plant Extracts/pharmacology , Plant Roots/metabolism , Rats , Rats, Wistar , Superoxide Dismutase/drug effects , Superoxide Dismutase/metabolism , Ventricular Function, Left/drug effects
Clinics ; 66(5): 777-784, 2011. ilus, graf, tab
Article in English | LILACS | ID: lil-593840


BACKGROUND: A limited number of studies have used Tissue Doppler Imaging (TDI) to evaluate the effect of statin therapy on left ventricular dysfunction in patients with chronic heart failure. In this work, we aimed to determine whether statin administration influenced prognosis, inflammatory activation and myocardial performance evaluated by Tissue Doppler Imaging in subjects enrolled in the Daunia Heart Failure Registry, a local registry of patients with chronic heart failure. METHODS: This study retrospectively analyzed 353 consecutive outpatients with chronic heart failure (mean follow-up 384 days), based on whether statin therapy was used. In all patients, several Tissue Doppler Imaging parameters were measured; circulating levels of interleukin (IL)-6, IL-10 and C-reactive protein were also assayed. RESULTS: Statin administration in 128 subjects with ischemic heart disease was associated with a lower incidence of adverse events (rehospitalization for HF 15 percent vs. 46 percent, p<0.001; ventricular arrhythmias 5 percent vs. 21 percent, p<0.01; cardiac death 1 percent vs. 8 percent, p<0.05), lower circulating levels of IL-6 (p<0.05) and IL-10 (p<0.01), lower rates of chronic heart failure (p<0.001) and better Tissue Doppler Imaging performance (E/E' ratio 12.82 + 5.42 vs. 19.85 + 9.14, p<0.001; ET: 260.62+ 44.16 vs. 227.11 +37.58 ms, p<0.05; TP: 176.79 + 49.93 vs. 136.7 + 37.78 ms, p<0.05 and St: 352.35 + 43.17 vs. 310.67 + 66.46 + 37.78 ms, p<0.05). CONCLUSIONS: Chronic ischemic heart failure outpatients undergoing statin treatment had fewer readmissions for adverse events, blunted inflammatory activation and improved left ventricular performance assessed by Tissue Doppler Imaging.

Aged , Female , Humans , Male , Middle Aged , Heart Failure/drug therapy , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Myocardial Ischemia/drug therapy , Biomarkers/blood , Chronic Disease , Cytokines/blood , Echocardiography, Doppler , Heart Failure/blood , Myocardial Ischemia/complications , Prognosis , Retrospective Studies , Ventricular Function, Left/drug effects
Article in English | WPRIM | ID: wpr-46542


BACKGROUND/AIMS: The aim of this study was to identify changes in left ventricular (LV) performance in patients with a myocardial bridge (MB) in the left anterior descending coronary artery during resting and in an inotropic state. METHODS: Myocardial strain measurement by speckle-tracking echocardiography and conventional LV wall-motion scoring was performed in 18 patients with MB (mean age, 48.1 +/- 1.7 years, eight female) during resting and intravenous dobutamine challenge (10 and 20 microg/kg/min). RESULTS: Conventional LV wall-motion scoring was normal in all patients during resting and in an inotropic state. Peak regional circumferential strain increased dose dependently upon dobutamine challenge. Longitudinal strains of the anterior and anteroseptal segments were, however, reduced at 20 microg/kg/min and showed a dyssynchronous pattern at 20 microg/kg/min. Although there were no significant differences in radial strain and displacement of all segments at rest compared with under 10 microg/kg/min challenge, radial strain and displacement of anterior segments at 20 microg/kg/min were significantly reduced compared with posterior segments at the papillary muscle level (44.8 +/- 14.9% vs. 78.4 +/- 20.1% and 5.3 +/- 2.3 mm vs. 8.5 +/- 1.8 mm, respectively; all p < 0.001), and showed plateau (40%) or biphasic (62%) patterns. CONCLUSIONS: Reduced LV strain of patients with MB after inotropic stimulation was identified. Speckle-tracking strain echocardiography identified a LV myocardial dyssynchrony that was not demonstrated by conventional echocardiography in patients with MB.

Adult , Aged , Female , Humans , Male , Middle Aged , Adrenergic beta-1 Receptor Agonists , Chest Pain , Coronary Angiography , Diastole , Dobutamine , Echocardiography, Stress/instrumentation , Myocardial Contraction , Myocardium , Physical Exertion , Systole , Ventricular Dysfunction, Left , Ventricular Function, Left/drug effects