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1.
Life Sci ; 242: 117225, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31881229

RESUMO

AIMS: Data concerning the influence of statin lipophilicity on the myotoxic and pleiotropic effects of statins is conflicting, and mechanistic head-to-head comparison studies evaluating this parameter are limited. In order to address the disparity, this mechanistic investigation aimed to assess the effects of two short-acting statins with different lipophilic indices on skeletal, cardiac and vascular smooth muscle physiology. MATERIALS AND METHODS: Young female Wistar rats were randomised to simvastatin (80 mg kg-1 day-1), pravastatin (160 mg kg-1 day-1) or control treatment groups. Changes in functional muscle performance were assessed, as well as mRNA levels of genes relating to atrophy, hypertrophy, mitochondrial function and/or oxidative stress. KEY FINDINGS: There were no significant differences in the mRNA profiles of isolated skeletal muscles amongst the treatment groups. In terms of skeleletal muscle performance, simvastatin reduced functionality but treatment with pravastatin significantly improved force production. Rodents given simvastatin demonstrated comparable myocardial integrity to the control group. Conversely, pravastatin reduced left ventricular action potential duration, diastolic stiffness and Mhc-ß expression. Pravastatin improved endothelium-dependent relaxation, particularly in muscular arteries, but this effect was absent in the simvastatin-treated rats. The responsiveness of isolated blood vessels to noradrenaline also differed between the statin groups. The findings of this study support that the effects of statins on skeletal, cardiac and vascular smooth muscle vary with their lipophilic indices. SIGNIFICANCE: The results of this work have important implications for elucidating the mechanisms responsible for the myotoxic and pleiotropic effects of statins.


Assuntos
Coração/efeitos dos fármacos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Músculo Esquelético/efeitos dos fármacos , Músculo Liso Vascular/efeitos dos fármacos , Pravastatina/farmacologia , Sinvastatina/farmacologia , Animais , Feminino , Microeletrodos , Contração Muscular/efeitos dos fármacos , Músculo Esquelético/metabolismo , Músculo Liso Vascular/metabolismo , Miocárdio/metabolismo , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transcriptoma/efeitos dos fármacos , Função Ventricular Esquerda/efeitos dos fármacos
2.
Cell Physiol Biochem ; 53(6): 961-981, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31820856

RESUMO

BACKGROUND/AIMS: We assessed the effects of ticagrelor, aspirin and prasugrel, started 7days after myocardial ischemia-reperfusion injury on remodeling, inflammation and fibrosis in the rat. We examined whether ticagrelor can affect the number of progenitor cells in the border zone. Ticagrelor, started 24h after myocardial ischemia-reperfusion injury, attenuates the decrease in heart function and adverse remodeling, an effect which is blocked by aspirin. METHODS: Rats underwent 40min ischemia followed by reperfusion. Oral dosing with vehicle, ticagrelor (300mg/kg/d), aspirin (20mg/kg/d), their combination or prasugrel (15mg/kg/d) started 7days after infarction. Echocardiography was used to assess systolic function. Heart tissue were analyzed by rt-PCR, immunoblotting, ELISA and immunohistochemistry 2weeks after infarction. RESULTS: Both ticagrelor and aspirin attenuated the decrease in systolic function and remodeling, an effect that was blocked by their combination. Ticagrelor and aspirin attenuated the increase in ANP, BNP, collagen-I and collagen-III. Again, the effect was blocked by their combination. Ticagrelor increased c-Kit, Sca-1, Ki-67, CD34, attenuated the decrease in CD105 mRNA levels, and attenuated the increase in CD31, whereas aspirin increased Ki-67, suppressed the increase in CD31 and attenuated the decrease in CD105 mRNA levels. Prasugrel did not display any effects. CONCLUSION: Ticagrelor attenuated adverse remodeling and deterioration of left ventricular systolic function despite starting treatment after the myocardial ischemia-reperfusion injury is completed. Aspirin had similar effects; however, when combined with ticagrelor, the protective effects were significantly attenuated. Ticagrelor increased the levels of several markers of stem cells and regeneration, suggesting cardiac healing by recruiting regenerative cells into the infarct.


Assuntos
Apoptose/efeitos dos fármacos , Infarto do Miocárdio/patologia , Inibidores da Agregação de Plaquetas/farmacologia , Ticagrelor/farmacologia , Remodelação Ventricular/efeitos dos fármacos , Animais , Aspirina/farmacologia , Aspirina/uso terapêutico , Fator Natriurético Atrial/genética , Fator Natriurético Atrial/metabolismo , Modelos Animais de Doenças , Quimioterapia Combinada , Endoglina/genética , Endoglina/metabolismo , Fibrose , Regulação da Expressão Gênica/efeitos dos fármacos , Infarto do Miocárdio/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Inibidores da Agregação de Plaquetas/uso terapêutico , Cloridrato de Prasugrel/farmacologia , Cloridrato de Prasugrel/uso terapêutico , Proteínas Proto-Oncogênicas c-kit/genética , Proteínas Proto-Oncogênicas c-kit/metabolismo , Ratos , Ratos Sprague-Dawley , Células-Tronco/citologia , Células-Tronco/efeitos dos fármacos , Células-Tronco/metabolismo , Ticagrelor/uso terapêutico , Função Ventricular Esquerda/efeitos dos fármacos
3.
Vasc Health Risk Manag ; 15: 539-550, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31827327

RESUMO

Background: Left ventricular hypertrophy (LVH), as assessed by measurement of left ventricular mass (LVM), is one of the most important cardiovascular risk factors. It is commonly present in patients with ischemic heart disease (IHD), irrespective of the level of blood pressure; recently, oxidative stress has been shown to be an important factor in its development. The question then arises: can this risk factor be modified by antioxidant treatment (e.g., with allopurinol, a xanthine oxidase inhibitor)? Methods: This is an observational study with a cross-sectional design which explored the association between long-term (>12 months) allopurinol therapy and LV mass index (LVMI) as well as geometry in patients generally receiving standard treatments for IHD. The primary endpoint was LVMI measurement (by 2D-echocardiography) and secondary endpoints included the association of allopurinol use with LV function (ejection fraction), blood pressure, glycemic control, and lipid profile. Results: Ninety-six patients on standard anti-ischemic drug treatment (control group) and 96 patients who were additionally taking allopurinol (minimum dose 100 mg/day) were enrolled. Both groups were matched for age, sex, height, and co-morbidities, but poorer kidney function in the allopurinol group required further sub-group analysis based on renal function. Allopurinol treatment was associated with the lowest LVMI in the patients with normal serum creatinine (median LVMI; 70.5 g/m2): corresponding values were 76.0 and 87.0 in the control group with, respectively, normal and elevated serum creatinine, and 89.5 in the allopurinol group with elevated serum creatinine (P=0.027). In addition, allopurinol was associated with better glycemic control (HbA1c) with a difference of 0.8% (95% CI; 1.3, 0.2) (P=0.004) as compared with control patients. Conclusion: In our population, treatment with allopurinol (presumably because of its anti-oxidant properties) has shown a tendency to be associated with smaller LVM in IHD patients with normal serum creatinine, along with better glycemic control.


Assuntos
Alopurinol/uso terapêutico , Antioxidantes/uso terapêutico , Hipertrofia Ventricular Esquerda/tratamento farmacológico , Isquemia Miocárdica/tratamento farmacológico , Função Ventricular Esquerda/efeitos dos fármacos , Remodelação Ventricular/efeitos dos fármacos , Idoso , Idoso de 80 Anos ou mais , Alopurinol/efeitos adversos , Antioxidantes/efeitos adversos , Biomarcadores/sangue , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Estudos de Casos e Controles , Creatinina/sangue , Estudos Transversais , Feminino , Hemoglobina A Glicada/metabolismo , Humanos , Hipertrofia Ventricular Esquerda/sangue , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Hipertrofia Ventricular Esquerda/fisiopatologia , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/sangue , Isquemia Miocárdica/diagnóstico por imagem , Isquemia Miocárdica/fisiopatologia , Fatores de Tempo , Resultado do Tratamento
4.
Cell Physiol Biochem ; 53(2): 388-399, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31403269

RESUMO

BACKGROUND/AIMS: Doxorubicin, a chemotherapy drug used successfully for years, could induce cardiotoxicity. Euterpe oleracea Mart. (açai) is a fruit high in antioxidant properties. The aim of this study was to evaluate doxorubicin-induced cardiotoxicity prevention after açai administration. METHODS: A total of 64 male Wistar rats were allocated into 4 groups: control (C), açai (A), doxorubicin (D) and açai-doxorubicin (DA). Rats received regular chow (C and D groups) or chow supplemented with açai 5% (A and DA groups) for 4 weeks. Subsequently, rats received doxorubicin 20 mg/kg (D and DA groups) or saline (C and A groups). Euthanasia was performed 48 hours after doxorubicin injection. Left ventricular function was evaluated by echocardiography in vivo and by isolated heart study ex vivo. Oxidative stress, myocardial metabolism and nitric oxide metabolite were evaluated by spectrophotometry, MMP-2 activity by zymography and caspase-3 and Bcl-2 protein expression by Western blot. RESULTS: Doxorubicin induced decreases in body weight, food and water ingestion. We observed decreases in left ventricular fractional shortening in rats treated with doxorubicin. Additionally, the same rats showed lower +dP/dt and -dP/dt during isolated heart study than those who did not receive doxorubicin. Doxorubicin injection increased caspase-3 protein expression, myocardium lipid hydroperoxide concentration, MMP-2 activity, phosphofructokinase and lactate dehydrogenase activity, and decreased ß-hydroxyacyl-CoA dehydrogenase, pyruvate dehydrogenase, citrate synthase, complex I, complex II and ATP synthase activity in myocardium. Açai supplementation improved left ventricular fractional shortening, decreased myocardium lipid hydroperoxide concentration, MMP-2 activity, and improved ß-hydroxyacyl-CoA dehydrogenase, phosphofructokinase, citrate synthase, complex II and ATP synthase enzymatic activities. We did not observe differences in nitric oxide metabolite concentrations between groups. CONCLUSION: Doxorubicin induced left ventricular dysfunction, increases in oxidative stress, changes in myocardium metabolism and MMP-2 activation. Açai supplementation was able to prevent these alterations.


Assuntos
Doxorrubicina/toxicidade , Euterpe/química , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Animais , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Suplementos Nutricionais , Ecocardiografia , Euterpe/metabolismo , Cardiopatias/etiologia , Cardiopatias/prevenção & controle , Técnicas In Vitro , L-Lactato Desidrogenase/metabolismo , Masculino , Metaloproteinase 2 da Matriz/metabolismo , Miocárdio/metabolismo , Óxido Nítrico/sangue , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Ratos Wistar , Função Ventricular Esquerda/efeitos dos fármacos
5.
Int J Mol Sci ; 20(16)2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31443187

RESUMO

Background: New treatments are needed to reduce myocardial infarct size (MI) and prevent heart failure (HF) following acute myocardial infarction (AMI), which are the leading causes of death and disability worldwide. Studies in rodent AMI models showed that genetic and pharmacological inhibition of mitochondrial fission, induced by acute ischemia and reperfusion, reduced MI size. Whether targeting mitochondrial fission at the onset of reperfusion is also cardioprotective in a clinically-relevant large animal AMI model remains to be determined. Methods: Adult pigs (30-40 kg) were subjected to closed-chest 90-min left anterior descending artery ischemia followed by 72 h of reperfusion and were randomized to receive an intracoronary bolus of either mdivi-1 (1.2 mg/kg, a small molecule inhibitor of the mitochondrial fission protein, Drp1) or vehicle control, 10-min prior to reperfusion. The left ventricular (LV) size and function were both assessed by transthoracic echocardiography prior to AMI and after 72 h of reperfusion. MI size and the area-at-risk (AAR) were determined using dual staining with Tetrazolium and Evans blue. Heart samples were collected for histological determination of fibrosis and for electron microscopic analysis of mitochondrial morphology. Results: A total of 14 pigs underwent the treatment protocols (eight control and six mdivi-1). Administration of mdivi-1 immediately prior to the onset of reperfusion did not reduce MI size (MI size as % of AAR: Control 49.2 ± 8.6 vs. mdivi-1 50.5 ± 11.4; p = 0.815) or preserve LV systolic function (LV ejection fraction %: Control 67.5 ± 0.4 vs. mdivi-1 59.6 ± 0.6; p = 0.420), when compared to vehicle control. Similarly, there were no differences in mitochondrial morphology or myocardial fibrosis between mdivi-1 and vehicle control groups. Conclusion: Our pilot study has shown that treatment with mdivi-1 (1.2 mg/kg) at the onset of reperfusion did not reduce MI size or preserve LV function in the clinically-relevant closed-chest pig AMI model. A larger study, testing different doses of mdivi-1 or using a more specific Drp1 inhibitor are required to confirm these findings.


Assuntos
Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/metabolismo , Quinazolinonas/uso terapêutico , Animais , Modelos Animais de Doenças , Ecocardiografia , Feminino , Dinâmica Mitocondrial/efeitos dos fármacos , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/metabolismo , Projetos Piloto , Suínos , Função Ventricular Esquerda/efeitos dos fármacos
6.
BMC Cancer ; 19(1): 778, 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31391011

RESUMO

BACKGROUND: Adjunct testosterone therapy improves lean body mass, quality of life, and physical activity in patients with advanced cancers; however, the effects of testosterone on cardiac morphology and function are unknown. Accordingly, as an ancillary analysis of a randomized, placebo-controlled trial investigating the efficacy of testosterone supplementation on body composition in men and women with advanced cancers, we explored whether testosterone supplementation could prevent or reverse left ventricular (LV) atrophy and dysfunction. METHODS: Men and women recently diagnosed with late stage (≥IIB) or recurrent head and neck or cervical cancer who were scheduled to receive standard of care chemotherapy or concurrent chemoradiation were administered an adjunct 7 week treatment of weekly intramuscular injections of either 100 mg testosterone (T, n = 1 M/5F) or placebo (P, n = 6 M/4F) in a double-blinded randomized fashion. LV morphology (wall thickness), systolic function (ejection fraction, EF), diastolic function (E/A; E'/E), arterial elastance (Ea), end-systolic elastance (Ees), and ventricular-arterial coupling (Ea/Ees) were assessed. RESULTS: No significant differences were observed in LV posterior wall thickness in placebo (pre: 1.10 ± 0.1 cm; post: 1.16 ± 0.2 cm; p = 0.11) or testosterone groups (pre: 0.99 ± 0.1 cm; post: 1.14 ± 0.20 cm; p = 0.22). Compared with placebo, testosterone significantly improved LVEF (placebo: - 1.8 ± 4.3%; testosterone: + 6.2 ± 4.3%; p < 0.05), Ea (placebo: 0.0 ± 0.2 mmHg/mL; testosterone: - 0.3 ± 0.2 mmHg/mL; p < 0.05), and Ea/Ees (placebo: 0.0 ± 0.1; testosterone: - 0.2 ± 0.1; p < 0.05). CONCLUSIONS: In patients with advanced cancers, testosterone was associated with favorable changes in left ventricular systolic function, arterial elastance, and ventricular-arterial coupling. Given the small sample size, the promising multisystem benefits of testosterone warrants further evaluation in a definitive randomized trial. TRIAL REGISTRATION: This study was prospectively registered on ClinicalTrials.gov (NCT00878995; date of registration: April 9, 2009).


Assuntos
Coração/efeitos dos fármacos , Neoplasias/fisiopatologia , Testosterona/uso terapêutico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Ecocardiografia , Feminino , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/etiologia , Frequência Cardíaca/efeitos dos fármacos , Ventrículos do Coração/efeitos dos fármacos , Ventrículos do Coração/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Qualidade de Vida , Testosterona/administração & dosagem , Testosterona/efeitos adversos , Resultado do Tratamento , Função Ventricular Esquerda/efeitos dos fármacos
7.
Int Heart J ; 60(4): 899-909, 2019 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-31308326

RESUMO

To systematically review and conduct a meta-analysis of the ivabradine-induced improvement in cardiopulmonary function, exercise capacity, and primary composite endpoints in patients with chronic heart failure (CHF).This study was a systematic review and meta-analysis.Databases, including PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Clinical Trials and European Union Clinical Trials, were searched for randomized placebo-controlled trials. The efficacy and safety of ivabradine treatment in patients with CHF were assessed and compared to those of the standard anti-heart failure treatment. Review Manager 5.3 software was used to analyze the relative risk (RR) for dichotomous data and the mean difference (MD) for continuous data.In total, 22 studies with 24,562 patients were included. Cardiopulmonary function analysis showed that treatment with added ivabradine reduced the heart rate (MD = -17.30, 95% confidence interval (CI): 19.52--15.08, P < 0.00001), significantly increased the left ventricular ejection fraction (LVEF) (MD = 3.90, 95% CI: 0.40-7.40, P < 0.0001), and led to a better New York Heart Association (NYHA) classification. Ivabradine significantly reduced the minute ventilation/carbon dioxide production (VE/VCO2) (MD = -2.68, 95% CI: -4.81--0.55, P = 0.01) and improved the peak VO2 (MD = 2.80, 95% CI: 1.05-4.55, P = 0.002) and the exercise capacity, including the exercise duration with a submaximal load (MD = 7.82, 95% CI: -2.57--18.21, P < 0.00001) and the 6-minute walk distance. The RR of cardiovascular death or worsening heart failure was significantly decreased (RR = 0.93, 95% CI: 0.87--0.98, P = 0.01) in the patients treated with ivabradine. Additionally, the RRs of heart failure and hospitalization also decreased (RR = 0.91, 95% CI: 0.85--0.97, P = 0.006; RR = 0.86, 95% CI: 0.79--0.93, P = 0.0002). Safety analysis showed no significant difference in the RR of severe adverse events between the ivabradine group and the standard anti-heart failure treatment group (P = 0.40). However, ivabradine significantly increased the RR of visual symptoms in CHF patients (RR = 3.82, 95% CI: 1.80--8.13, P = 0.0005).Existing evidence showed that adding ivabradine treatment significantly improved the cardiopulmonary function and increased the exercise capacity of patients with CHF. Adding ivabradine to the standard anti-heart failure treatment reduced the mortality and hospitalization risk and improved the quality of life. Finally, ivabradine significantly increased the RR of visual symptoms in CHF patients.This is the first systematic review and meta-analysis to focus on the efficacy of ivabradine, which improved the cardiac function and increased the exercise capacity in patients with chronic heart failure (CHF). Therefore, this study will help evaluate the quality of life after adding ivabradine to the treatment of patients with CHF, even though there are differences in the standard for resting heart rate, left ventricular ejection fraction (LVEF), and New York Heart Association (NYHA) class in the included studies. This hybrid effect might be smaller when analyzed separately but might have a higher heterogeneity when analyzed in multiple studies.


Assuntos
Tolerância ao Exercício/efeitos dos fármacos , Insuficiência Cardíaca/tratamento farmacológico , Ivabradina/uso terapêutico , Volume Sistólico/fisiologia , Função Ventricular Esquerda/fisiologia , Fármacos Cardiovasculares/uso terapêutico , Insuficiência Cardíaca/fisiopatologia , Humanos , Volume Sistólico/efeitos dos fármacos , Função Ventricular Esquerda/efeitos dos fármacos
8.
Mayo Clin Proc ; 94(7): 1210-1220, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31272569

RESUMO

OBJECTIVE: To assess the association of nitrate use with cardiovascular events in patients with heart failure with preserved ejection fraction (HFpEF). PATIENTS AND METHODS: Patient data were collected from the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist trial, which had been conducted at 233 sites in 6 countries from August 10, 2006, through January 31, 2012. The primary outcome was the occurrence of a major adverse cardiovascular event (cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke) or heart failure hospitalization. The association between nitrate use and cardiovascular risk was evaluated using Cox proportional hazards analysis. In addition, we verified the results using propensity score-matched patients. RESULTS: A total of 3417 patients with HFpEF were evaluated over a mean follow-up of 3.1 years, and 778 experienced a primary outcome event. The risk of primary outcome events was significantly higher in patients taking nitrates than in those not taking nitrates (hazard ratio [HR], 1.21; 95% CI, 1.01-1.46, P=.04). The risk of major adverse cardiovascular events was significantly higher in patients taking nitrates than in those not taking nitrates (HR, 1.32; 95% CI, 1.05-1.66, P=.01). Furthermore, the risk of hospitalization for heart failure was higher in patients taking nitrates (HR, 1.25; 95% CI, 0.99-1.60, P=.06), with propensity score-matched analyses revealing similar findings. In addition, a similar association was observed in various subgroups. CONCLUSION: This study reported that nitrate use in patients with HFpEF was associated with a significantly increased risk of cardiovascular events.


Assuntos
Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/fisiopatologia , Nitratos/uso terapêutico , Volume Sistólico/efeitos dos fármacos , Função Ventricular Esquerda/efeitos dos fármacos , Idoso , Feminino , Humanos , Masculino , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Infarto do Miocárdio/complicações , Nitratos/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Espironolactona/uso terapêutico , Acidente Vascular Cerebral/complicações
9.
Medicine (Baltimore) ; 98(27): e16143, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31277114

RESUMO

Ischemia/reperfusion (I/R) injury is associated with primary percutaneous coronary intervention (PPCI). The current study was performed to compare the effect of tirofiban and recombinant human pro-urokinase (rh-proUK) on the improvement of coronary slow blood after PPCI.Sixty-five ST elevation myocardial infarction (STEMI) patients treated with rh-proUK and an equal number treated with tirofiban after PPCI were employed in the current study. The clinicopathological information regarding the biochemical parameters, thrombolysis in myocardial infarction (TIMI) grade, hemodynamics parameters, thrombus core (TS), sum-STR, left ventricular ejection fraction (LVEF), blood routine parameters, high-sensitivity C-reactive protein (CRP) level, uric acid, hepatorenal function, electrocardiogram (ECG), and echocardiography before and after the interventions were collected. The differences in those parameters between the 2 groups then compared with assess the treatment effect and side effects associated with the both therapies.The results showed that the TIMI level post-intervention (P = .03), the proportion of TIMI myocardial perfusion grade level III (P = .04), the changes in thrombus score (P < .001) in rh-proUK group were significantly higher than those in tirofiban group while the corrected TIMI Frame Count (CTFC) (P = .02), the incidence of slow flow (P = .02), the thrombus score post-intervention (P < .001), the stent length (P = .02), and the number of receiving administration of sodium nitroprusside (P = .01) were significantly lower than those in tirofiban group. Moreover, the levels of CK (P < .001), CK-MB (P = .01), and NT-proBNP 24-hour post-intervention (P < .02) were significantly lower in rh-proUK group than those in tirofiban group and the sum-STR right after the intervention (P < .03) of rh-proUK group was significantly higher than that of tirofiban group. No significant difference was detected between the 2 therapies regarding major adverse cardiac events (MACE).The findings outlined in the current study showed that the improvement effect of rh-proUK on blood flow condition was stronger right after the intervention and the therapy had a similar safety when compared with tirofiban during a 30-day follow-up.


Assuntos
Circulação Coronária/efeitos dos fármacos , Intervenção Coronária Percutânea/efeitos adversos , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia , Tirofibana/administração & dosagem , Ativador de Plasminogênio Tipo Uroquinase/administração & dosagem , Função Ventricular Esquerda/efeitos dos fármacos , Idoso , Feminino , Fibrinolíticos , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes/administração & dosagem , Estudos Retrospectivos
10.
Hum Exp Toxicol ; 38(10): 1183-1194, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31256679

RESUMO

Heart failure (HF) is a leading cause of hospitalization across the world and is known to cause ill-health and heavy economic losses. In the present study, a rat model of isoproterenol (ISO, 85 mg/kg subcutaneously for two subsequent days) induced HF was developed. ISO induces HF by its direct effect, that is, rise in left ventricular end-diastolic pressure (mechanical) and indirectly by altering the baroreflex (neural), electrocardiography (electrical), and development of oxidative stress and hyperlipidemia (chemical). Fenofibrate, a hypolipidemic drug, which ameliorates myocardial energy metabolism was seen to improve the both ISO-induced oxidative stress and lipid profile and consequently improved Baroreflex Sensitivity (BRS), partial ventricular functions, and cardiac hypertrophy. Therefore, our result suggests that fenofibrate treatment protected the heart by alleviating the ISO-induced effects, that is, neural, mechanical, electrical, and chemical alterations.


Assuntos
Barorreflexo/efeitos dos fármacos , Metabolismo Energético/efeitos dos fármacos , Fenofibrato/uso terapêutico , Insuficiência Cardíaca/prevenção & controle , Hipolipemiantes/farmacologia , Função Ventricular Esquerda/efeitos dos fármacos , Animais , Pressão Sanguínea/efeitos dos fármacos , Modelos Animais de Doenças , Eletrocardiografia/efeitos dos fármacos , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/fisiopatologia , Frequência Cardíaca/efeitos dos fármacos , Hipertrofia Ventricular Esquerda/metabolismo , Hipertrofia Ventricular Esquerda/fisiopatologia , Hipertrofia Ventricular Esquerda/prevenção & controle , Peroxidação de Lipídeos/efeitos dos fármacos , NADPH Oxidases/genética , Ratos Wistar
11.
Int Urol Nephrol ; 51(7): 1107-1112, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31165396

RESUMO

BACKGROUND: Androgen-deprivation therapy (ADT) is a treatment option for locally advanced and metastatic prostate cancer (PCA). The aim of the study was to evaluate the effect of ADT on left ventricular (LV) functions assessed by speckle-tracking echocardiography (STE) in prostate cancer (PCA) patients. METHODS: Forty-nine consecutive PCA patients (mean age 71.5 ± 6.7 years) who would be treated with radiotherapy and ADT and 32 consecutive PCA patients (mean age 71.9 ± 7.0 years) who would be treated with radical or partial prostatectomy and 42 age-matched healthy men (mean age 70.5 ± 9.1 years) were included in our study. The left ventricular functions were assessed by both conventional echocardiography and STE at baseline and 6 months later. RESULTS: There were not any significant difference in characteristics of the patients and controls. There were not any significant differences in conventional echocardiographic measures at baseline and at 6th month among the PCA patients and controls. Although there were not any significant differences in STE measures at baseline among the PCA patients and controls, the strain measures of the PCA patients receiving ADT decreased significantly at the 6th month and were significantly lower compared to strain measures of PCA patients undergoing prostatectomy and controls. There was not any statistically significant difference in baseline and 6th-month strain measures of the PCA patients undergoing prostatectomy. CONCLUSIONS: ADT might be associated with decrease in LV longitudinal, circumferential, and radial strain measures in patients with PCA. STE might be useful for early identification of LV subclinical impairment in PCA patients treated with ADT.


Assuntos
Antagonistas de Androgênios/efeitos adversos , Ecocardiografia , Neoplasias da Próstata , Disfunção Ventricular Esquerda , Função Ventricular Esquerda/efeitos dos fármacos , Idoso , Antagonistas de Androgênios/administração & dosagem , Ecocardiografia/métodos , Ecocardiografia/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prostatectomia/métodos , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologia , Neoplasias da Próstata/fisiopatologia , Neoplasias da Próstata/terapia , Radioterapia/métodos , Testosterona/sangue , Turquia , Disfunção Ventricular Esquerda/diagnóstico , Disfunção Ventricular Esquerda/etiologia , Disfunção Ventricular Esquerda/prevenção & controle
12.
Mol Med Rep ; 20(2): 1250-1258, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31173195

RESUMO

Post­resuscitation myocardial dysfunction (PRMD) is a severe complication that arises in patients after cardiac arrest (CA). However, there are no safe or effective treatment strategies that are currently available to treat these patients. In the present study, it was investigated whether resveratrol administration could inhibit myocardial nitrative stress to alleviate PRMD. CA was induced in Sprague­Dawley rats by trans­oesophageal alternating electrical stimulation, followed by cardiopulmonary resuscitation. Rats were then randomly divided into a preconditioning or a postconditioning group. Left ventricular function (+dP/dtmax and ­dP/dtmin) was recorded for 4 h after the return of spontaneous circulation (ROSC), after which the animals were euthanized. Myocardial nitrative stress was analysed using enzyme­linked immunosorbent assay, western blotting and immunohistochemistry. Wortmannin (a PI3K inhibitor) was used to investigate the involvement of the PI3k/Akt signalling pathway in the cardio­protective activity of resveratrol. After ROSC, resveratrol improved PRMD compared to the vehicle control; however, resveratrol administration significantly improved PRMD in the preconditioning group compared to the postconditioning group. Likewise, resveratrol preconditioning significantly decreased the expression of iNOS and nitrotyrosine in rat hearts but did not significantly ameliorate myocardial nitrative stress. Wortmannin partially inhibited the protective effect of resveratrol preconditioning and resulted in the deterioration of cardiac function and increase in iNOS and nitrotyrosine levels. Resveratrol preconditioning could alleviate PRMD by inhibiting myocardial nitrative stress. The PI3K/Akt signalling pathway may be partially involved in the process.


Assuntos
Reanimação Cardiopulmonar/efeitos adversos , Coração/fisiopatologia , Fosfatidilinositol 3-Quinases/metabolismo , /fisiopatologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Resveratrol/farmacologia , Transdução de Sinais , Animais , Masculino , Óxido Nítrico Sintase Tipo II/metabolismo , Fosforilação/efeitos dos fármacos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Tirosina/análogos & derivados , Tirosina/metabolismo , Função Ventricular Esquerda/efeitos dos fármacos
13.
Int J Cardiovasc Imaging ; 35(11): 2085-2093, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31197526

RESUMO

Little is known about the comparison of multiple-gated acquisition (MUGA) scanning with cardiovascular magnetic resonance (CMR) for serial monitoring of HER2+ breast cancer patients receiving trastuzumab. The association of cardiac biomarkers with CMR left ventricular (LV) function and volume is also not well studied. Our objectives were to compare CMR and MUGA for left ventricular ejection fraction (LVEF) assessment, and to examine the association between changes in brain natriuretic peptide (NT-BNP) and troponin-I and changes in CMR LV function and volume. This prospective longitudinal two-centre cohort study recruited HER2+ breast cancer patients between January 2010 and December 2013. MUGA, CMR, NT-BNP and troponin-I were performed at baseline, 6, 12, and 18 months after trastuzumab initiation. In total, 41 patients (age 51.7 ± 10.8 years) were enrolled. LVEF comparison between MUGA and CMR demonstrated weak agreement (Lin's correlation coefficient r = 0.46, baseline; r = 0.29, 6 months; r = 0.42, 12 months; r = 0.39, 18 months; all p < 0.05). Bland-Altman plots demonstrated wide LVEF agreement limits (pooled agreement limits 3.0 ± 6.2). Both modalities demonstrated significant LVEF decline at 6 and 12 months from baseline, concomitant with increased LV volumes on CMR. Changes in NT-BNP correlated with changes in LV diastolic volume at 12 and 18 months (p < 0.05), and LV systolic volume at 18 months (p < 0.05). Changes in troponin-I did not correlate with changes in LV function or volume at any timepoint. In conclusion, CMR and MUGA LVEF are not interchangeable, warranting selection and utility of one modality for serial monitoring. CMR is useful due to less radiation exposure and accuracy of LV volume measurements. Changes in NT-BNP correlated with changes in LV volumes.


Assuntos
Antineoplásicos Imunológicos/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Imagem por Ressonância Magnética , Compostos Radiofarmacêuticos/administração & dosagem , Pertecnetato Tc 99m de Sódio/administração & dosagem , Volume Sistólico/efeitos dos fármacos , Tomografia Computadorizada de Emissão , Trastuzumab/efeitos adversos , Disfunção Ventricular Esquerda/diagnóstico por imagem , Função Ventricular Esquerda/efeitos dos fármacos , Adulto , Biomarcadores/sangue , Técnicas de Imagem de Sincronização Cardíaca , Cardiotoxicidade , Feminino , Humanos , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Valor Preditivo dos Testes , Estudos Prospectivos , Reprodutibilidade dos Testes , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Troponina I/sangue , Disfunção Ventricular Esquerda/induzido quimicamente , Disfunção Ventricular Esquerda/fisiopatologia
14.
Anticancer Res ; 39(6): 3255-3264, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31177176

RESUMO

BACKGROUND/AIM: Chemotherapy-induced cardiotoxicity may be observed during treatment or may cause severe cardiac failure as the main cause of death, even several years after therapy implementation. Herein, the aim was to establish the early diagnosis of cardiotoxicity through the periodic evaluation of the left ventricular (LV) and vascular remodeling parameters, in patients with acute lymphoblastic leukemia (ALL). MATERIALS AND METHODS: The study population included 35 patients diagnosed with ALL, evaluated before and 3 months after starting chemotherapy, measuring systolic and diastolic parameters of the LV and intima-media thickness (IMT), arterial stiffness aortic pulse wave velocity (PWVAo) and ankle-brachial index (ABI). RESULTS: After the first 2 cycles of chemotherapy, all patients experienced a drop in LV ejection fraction (LVEF) (p<0.001), and 12 patients suffered a decrease of LVEF<50%. The ABI (p<0.05) and the global longitudinal strain (GLS) (p<0.001) decreased, while IMT and PWVAo (p<0.001) increased, proving a subclinical deterioration of the LV function and vascular remodeling. CONCLUSION: Assessment of cardiovascular risk factors before chemotherapy initiation in ALL patients may be helpful for an early diagnosis of chemotherapy-induced cardiotoxicity, thus contributing to early treatment and a subsequent decrease of death caused by such cardiovascular complications.


Assuntos
Índice Tornozelo-Braço , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Doenças Cardiovasculares/diagnóstico , Ecocardiografia Doppler , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Adulto , Cardiotoxicidade , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/fisiopatologia , Diagnóstico Precoce , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Contração Miocárdica/efeitos dos fármacos , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Valor Preditivo dos Testes , Fatores de Risco , Volume Sistólico/efeitos dos fármacos , Fatores de Tempo , Resultado do Tratamento , Remodelação Vascular/efeitos dos fármacos , Rigidez Vascular/efeitos dos fármacos , Função Ventricular Esquerda/efeitos dos fármacos , Adulto Jovem
15.
Cardiovasc Diabetol ; 18(1): 55, 2019 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-31039778

RESUMO

BACKGROUND: Liraglutide is an antidiabetic agent with cardioprotective effect. The purpose of this study is to test efficacy of liraglutide to improve diabetic cardiomyopathy in patients with diabetes mellitus type 2 (DM2) without cardiovascular disease. METHODS: Patients with DM2 were randomly assigned to receive liraglutide 1.8 mg/day or placebo in this double-blind trial of 26 weeks. Primary outcome measures were LV diastolic function (early (E) and late (A) transmitral peak flow rate, E/A ratio, early deceleration peak (Edec), early peak mitral annular septal tissue velocity (Ea) and estimated LV filling pressure (E/Ea), and systolic function (stroke volume, ejection fraction, cardiac output, cardiac index and peak ejection rate) assessed with CMR. Intention-to-treat analysis of between-group differences was performed using ANCOVA. Mean estimated treatment differences (95% confidence intervals) are reported. RESULTS: 23 patients were randomized to liraglutide and 26 to placebo. As compared with placebo, liraglutide significantly reduced E (- 56 mL/s (- 91 to - 21)), E/A ratio (- 0.17 (- 0.27 to - 0.06)), Edec (- 0.9 mL/s2 * 10-3 (- 1.3 to - 0.2)) and E/Ea (- 1.8 (- 3.0 to - 0.6)), without affecting A (3 mL/s (- 35 to 41)) and Ea (0.4 cm/s (- 0.9 to 1.4)). Liraglutide reduced stroke volume (- 9 mL (- 16 to - 2)) and ejection fraction (- 3% (- 6 to - 0.1)), but did not change cardiac output (- 0.4 L/min (- 0.9 to 0.2)), cardiac index (- 0.1 L/min/m2 (- 0.4 to 0.1)) and peak ejection rate (- 46 mL/s (- 95 to 3)). CONCLUSIONS: Liraglutide reduced early LV diastolic filling and LV filling pressure, thereby unloading the left ventricle. LV systolic function reduced and remained within normal range. Future studies are needed to investigate if liraglutide-induced left ventricular unloading slows progression of diabetic cardiomyopathy into symptomatic stages. Trial registration ClinicalTrials.gov: NCT01761318.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Cardiomiopatias Diabéticas/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Liraglutida/uso terapêutico , Volume Sistólico/efeitos dos fármacos , Disfunção Ventricular Esquerda/tratamento farmacológico , Função Ventricular Esquerda/efeitos dos fármacos , Pressão Ventricular/efeitos dos fármacos , Adolescente , Adulto , Idoso , Biomarcadores/sangue , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico por imagem , Diabetes Mellitus Tipo 2/fisiopatologia , Cardiomiopatias Diabéticas/sangue , Cardiomiopatias Diabéticas/diagnóstico por imagem , Cardiomiopatias Diabéticas/fisiopatologia , Método Duplo-Cego , Feminino , Humanos , Hipoglicemiantes/efeitos adversos , Liraglutida/efeitos adversos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Países Baixos , Recuperação de Função Fisiológica , Fatores de Tempo , Resultado do Tratamento , Disfunção Ventricular Esquerda/sangue , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/fisiopatologia , Adulto Jovem
16.
Biomed Pharmacother ; 116: 109003, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31125823

RESUMO

Trimetazidine (TMZ) has been shown to optimize myocardial energy metabolism and is a common anti-ischemic agent. Our trial (ChiCTR-TRC-13003298) aimed to explore whether TMZ has any preventive effect on high-altitude fatigue (HAF), cardiac function and cardiorespiratory fitness upon acute high-altitude exposure and how it works on HAF. Thirty-nine healthy young subjects were enrolled in a randomized double-blinded placebo-controlled trial and were randomized to take oral TMZ (n = 20) or placebo (n = 19), 20 mg tid, 14 days prior to departure until the end of study. The 2018 Lake Louise Score questionnaire, echocardiography, assessments of physical working capacity, circulating markers of myocardial energy metabolism and fatigue were performed both before departure and arrival at highland. At follow-up, TMZ significantly reduced the incidence of HAF (p = 0.038), reversed cardiorespiratory fitness impairment, decreased left ventricular end-systolic volume (LVESV, p = 0.032) and enhanced left ventricular ejection fraction (LVEF, p = 0.015) at highland. Relative to the placebo group, the TMZ group had significantly lower LDH (p = 0.025) and lactate levels before (p < 0.001) and after (p = 0.012) physical exercise after acute high-altitude exposure. Additionally, improved left ventricular systolic function might have contributed to ameliorating HAF during TMZ treatment (LVEF, OR = 0.859, 95% CI = 0.741-0.996, p = 0.044). In conclusion, our results demonstrated that TMZ could prevent HAF, cardiorespiratory fitness impairment and improves left ventricular systolic function during acute high-altitude exposure. This trial provides new insights into the effect of TMZ and novel evidence against HAF and cardiorespiratory fitness impairment at highland.


Assuntos
Altitude , Aptidão Cardiorrespiratória/fisiologia , Fadiga/tratamento farmacológico , Fadiga/fisiopatologia , Trimetazidina/uso terapêutico , Adolescente , Doença da Altitude/sangue , Doença da Altitude/tratamento farmacológico , Doença da Altitude/epidemiologia , Doença da Altitude/fisiopatologia , Método Duplo-Cego , Metabolismo Energético/efeitos dos fármacos , Fadiga/sangue , Testes de Função Cardíaca , Humanos , Incidência , L-Lactato Desidrogenase/sangue , Lactatos/sangue , Miocárdio/metabolismo , Placebos , Análise de Regressão , Sístole/efeitos dos fármacos , Trimetazidina/farmacologia , Função Ventricular Esquerda/efeitos dos fármacos , Adulto Jovem
18.
Expert Opin Drug Saf ; 18(5): 393-402, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31074301

RESUMO

INTRODUCTION: Heart failure with reduced ejection fraction (HFrEF) is associated with a worse outcome. Heart rate (HR) is related to outcome in HFrEF. Ivabradine selectively inhibits If (funny) channels in a concentration-dependent manner reducing HR. AREAS COVERED: The effects of ivabradine in HF were reviewed. The SHIFT trial results indicated that ivabradine improves chronic HFrEF outcomes, whereas published data suggest that amiodarone, digoxin, or verapamil may not be safe or the safety is controversial in HFrEF patients. In the CONSTATHE-DHF study, ivabradine reduced HR and improved left ventricular (LV) ejection fraction, LV diastolic functions, and right ventricle function in acute decompensated HF (ADHF). In chagasic patients, ivabradine reduced HR and a trend toward reduction in all-cause death was observed with ivabradine (p = 0.07). In children with HFrEF, ivabradine increased NYHA functional class. The most common side effects with ivabradine are bradycardia, atrial fibrillation, and phosphenes. Ivabradine was approved for HFrEF treatment by the EMA and FDA and seems to be cost-effective in HFrEF treatment. Ivabradine is indicated for HFrEF by the ESC HF Guidelines (IIa) and by the 2016 ACC/AHA/HFSA Guidelines (IIa-B-R). EXPERT OPINION: Published evidences demonstrate that ivabradine improves the outcome of chronic HFrEF and it seems to have a promising role in ADHF.


Assuntos
Fármacos Cardiovasculares/administração & dosagem , Insuficiência Cardíaca/tratamento farmacológico , Ivabradina/administração & dosagem , Animais , Fármacos Cardiovasculares/efeitos adversos , Fármacos Cardiovasculares/farmacologia , Relação Dose-Resposta a Droga , Insuficiência Cardíaca/fisiopatologia , Frequência Cardíaca/efeitos dos fármacos , Humanos , Ivabradina/efeitos adversos , Ivabradina/farmacologia , Guias de Prática Clínica como Assunto , Volume Sistólico/efeitos dos fármacos , Função Ventricular Esquerda/efeitos dos fármacos
19.
Mol Cell Biochem ; 458(1-2): 89-98, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30989474

RESUMO

The aim of the present study was to compare the cardiodynamic parameters in the isolated rat heart in animals chronically treated with cisplatin, platinum(IV) complex and its diamine ligand. Sixty Wistar albino rats (8 weeks old) were divided into five groups: three experimental and two control groups. Animals in all groups were treated with a dose of 4 mg/kg body weight once a week for 4 weeks with different substances; experimental groups received cisplatin, ligand and octahedral platinum(IV) complex, and control groups received saline and dimethyl sulfoxide. After sacrificing the animals, hearts were isolated and perfused according to the Langendorff technique at gradually increased coronary perfusion pressures (40-120 cmH2O). The following parameters of cardiac function were continuously recorded: maximum and minimum rate of change of pressure in the left ventricle, systolic and diastolic left ventricular pressure, heart rate and coronary flow. The results showed statistically significant differences between all experimental groups in maximum and minimum rate of pressure development as well as in systolic pressure of the left ventricle, whereas cisplatin, ligand and the platinum(IV) complex had effects on heart contractility without significant influences on coronary circulation. The findings of the present study could be important for a better understanding of anticancer drug cardiac side effects. Our results indicate that compared to cisplatin as a "gold standard", novel platinum complexes and ligands do not possess fewer negative effects on the heart, indicating insufficient safety for their usage in terms of affecting cardiac function, a result that can be of great interest for further investigations.


Assuntos
Pressão Sanguínea/efeitos dos fármacos , Cisplatino/efeitos adversos , Circulação Coronária/efeitos dos fármacos , Diaminas/efeitos adversos , Frequência Cardíaca/efeitos dos fármacos , Função Ventricular Esquerda/efeitos dos fármacos , Animais , Cisplatino/farmacologia , Diaminas/farmacologia , Masculino , Ratos , Ratos Wistar
20.
Cardiovasc Diabetol ; 18(1): 45, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30935417

RESUMO

BACKGROUND: Sodium glucose co-transporter 2 inhibitor (SGLT2i), a new class of anti-diabetic drugs acting on inhibiting glucose resorption by kidneys, is shown beneficial in reduction of heart failure hospitalization and cardiovascular mortality. The mechanisms remain unclear. We hypothesized that SGLT2i, empagliflozin can improve cardiac hemodynamics in non-diabetic hypertensive heart failure. METHODS AND RESULTS: The hypertensive heart failure model had been created by feeding spontaneous hypertensive rats (SHR) with high fat diet for 32 weeks (total n = 13). Half SHRs were randomized to be administered with SGLT2i, empagliflozin at 20 mg/kg/day for 12 weeks. After evaluation of electrocardiography and echocardiography, invasive hemodynamic study was performed and followed by blood sample collection and tissue analyses. Empagliflozin exhibited cardiac (improved atrial and ventricular remodeling) and renal protection, while plasma glucose level was not affected. Empagliflozin normalized both end-systolic and end-diastolic volume in SHR, in parallel with parameters in echocardiographic evaluation. Empagliflozin also normalized systolic dysfunction, in terms of the reduced maximal velocity of pressure incline and the slope of end-systolic pressure volume relationship in SHR. In histological analysis, empagliflozin significantly attenuated cardiac fibrosis in both atrial and ventricular tissues. The upregulation of atrial and ventricular expression of PPARα, ACADM, natriuretic peptides (NPPA and NPPB), and TNF-α in SHR, was all restored by treatment of empagliflozin. CONCLUSIONS: Empagliflozin improves hemodynamics in our hypertensive heart failure rat model, associated with renal protection, attenuated cardiac fibrosis, and normalization of HF genes. Our results contribute some understanding of the pleiotropic effects of empagliflozin on improving heart function.


Assuntos
Compostos Benzidrílicos/farmacologia , Glucosídeos/farmacologia , Insuficiência Cardíaca/tratamento farmacológico , Hemodinâmica/efeitos dos fármacos , Hipertensão/complicações , Miocárdio/patologia , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Função Ventricular Esquerda/efeitos dos fármacos , Remodelação Ventricular/efeitos dos fármacos , Animais , Função do Átrio Esquerdo/efeitos dos fármacos , Fator Natriurético Atrial/genética , Fator Natriurético Atrial/metabolismo , Dieta Hiperlipídica , Modelos Animais de Doenças , Ácidos Graxos/metabolismo , Fibrose , Regulação da Expressão Gênica , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/patologia , Insuficiência Cardíaca/fisiopatologia , Hipertensão/fisiopatologia , Masculino , Miocárdio/metabolismo , Peptídeo Natriurético Encefálico/genética , Peptídeo Natriurético Encefálico/metabolismo , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Recuperação de Função Fisiológica , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
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