RESUMO
SUMMARY: The main cause of mortality and disability globally is myocardial infarction (MI). Isoproterenol (ISO), a β-adrenoceptor agonist, has been used to induce rat myocardial necrosis. Whereas interleukin-37 (IL-37) has anti-inflammatory and cytoprotective properties. The study aimed to investigate the potential protective effects of IL-37 administration on cardiac architecture, oxidative stress, and inflammatory markers during ISO-induced MI in rats. Three groups of adult male rats were used in this study, the normal control group (n=8), ISO-induced MI group (n=8) that received isoproterenol hydrochloride (ISO) (100 mg/kg/day, SC, for the first 2 consecutive days), and IL-37-treated group (ISO+IL-37) (n=8) that received recombinant human IL-37 (40 µg/kg /day, intraperitoneally, for 2 weeks during and after ISO injections. Heart rate (HR.) and ECG changes were monitored. Some oxidative stress markers such as superoxide dismutase (SOD), nitric oxide (NOx), malondialdehyde (MDA), and glutathione (GSH) tissue levels in the tissue homogenate were assayed. Interleukin- 6 (IL-6), tumor necrosis factor- α (TNF-α), caspase-8, P53, and C- reactive protein (CRP) were among the inflammatory markers examined. In addition, serum levels of creatinine kinase (CK-MB) and lactate dehydrogenase (LDH) were analyzed to evaluate the myocardial injury. For histological analysis, tissues were sectioned, fixed in paraffin, and stained with hematoxylin and eosin (H&E), Masson Trichrome and, immunohistochemical against NF-kB, TNF-α, and Caspase-9. IL-37 improved ECG changes, cardiac enzyme markers, and some inflammatory markers of oxidative stress in ISO-induced MI. It also improved the histopathological and immunohistochemical changes in MI. In conclusion: IL-37 might be a promising therapeutic modality in myocardial infarction.
La principal causa de mortalidad y discapacidad a nivel mundial es el infarto de miocardio (IM). El isoproterenol (ISO), un agonista de los receptores adrenérgicos β, se ha utilizado para inducir necrosis miocárdica en ratas. Mientras que la interleucina-37 (IL-37) tiene propiedades antiinflamatorias y citoprotectoras. El estudio tuvo como objetivo investigar los posibles efectos protectores de la administración de IL-37 en la arquitectura cardíaca, el estrés oxidativo y los marcadores inflamatorios durante el infarto de miocardio inducido por ISO en ratas. En este estudio se utilizaron tres grupos de ratas macho adultas, el grupo control normal (n=8), el grupo con IM inducido por ISO (n=8) que recibió clorhidrato de isoproterenol (ISO) (100 mg/kg/día, SC, durante los primeros 2 días consecutivos) y el grupo tratado con IL-37 (ISO+IL- 37) (n=8) que recibió IL-37 humana recombinante (40 µg/kg/día, por vía intraperitoneal, durante 2 semanas durante y después de las inyecciones de ISO. Se monitorearon la frecuencia cardíaca (FC) y los cambios en el ECG. Se analizaron algunos marcadores de estrés oxidativo como la superóxido dismutasa (SOD), el óxido nítrico (NOx), el malondialdehído (MDA) y los niveles tisulares de glutatión (GSH) en el homogeneizado de tejido. La interleucina-6 (IL-6), el factor de necrosis tumoral-α (TNF-α), la caspasa-8, la P53 y la proteína C reactiva (CRP) se encontraban entre los marcadores inflamatorios examinados. Se analizaron los niveles de creatinoquinasa (CK-MB) y lactato deshidrogenasa (LDH) para evaluar la lesión miocárdica; para el análisis histológico se seccionaron los tejidos, se fijaron en parafina y se tiñeron con hematoxilina y eosina (H&E), Tricromo de Masson e inmunohistoquímica contra NF-kB, TNF-α y Caspasa-9. IL-37 mejoró los cambios de ECG, los marcadores de enzimas cardíacas y algunos marcadores inflamatorios de estrés oxidativo en el IM inducido por ISO. Además mejoró los cambios histopatológicos e inmunohistoquímicos en MI. En conclusión: la IL-37 podría ser una modalidad terapéutica prometedora en el infarto de miocardio.
Assuntos
Animais , Masculino , Ratos , Interleucinas/administração & dosagem , Coração/efeitos dos fármacos , Infarto do Miocárdio/induzido quimicamente , Infarto do Miocárdio/prevenção & controle , Imuno-Histoquímica , Ratos Wistar , Estresse Oxidativo/efeitos dos fármacos , Inflamação , Isoproterenol/efeitos adversosRESUMO
Alpinia zerumbet is a plant popularly used to treat hypertension and anxiety. Studies with Alpinia zerumbet demonstrate antihypertensive and vasodilator effects, among others. The objective of this study was to analyze the effect of essential oil of Alpinia zerumbet (EOAz) on cardiovascular and autonomic function in rats with isoproterenol-induced myocardial infarction. Male Wistar rats (n=32) were equally allocated into four groups: Control, ISO (150mg/kg, subcutaneous), EOAz (100mg/kg by gavage), ISO+EOAz. The rats were evaluated for cardiovascular and, autonomic parameters, electrocardiogram, and infarct size. EOAz was not able to reduce the electrocardiographic variations induced by ISO. Heart rate variability showed a decrease in sympathetic modulation on the heart in the groups treated with EOAz. The cardiopulmonary reflex induced by serotonin invoked a superior blood pressure variation at the 2 µg/kg dose in the EOAz treated groups, while the heart rate variation was significantly higher at the 16 µg/kg dose, when compared to other doses, in all groups, except EOAz+ISO. The sympathetic vagal index was higher in ISO group than in control. EOAz did not reduce the infarct size. We conclude that pretreatment with EOAz does not reverse the hemodynamic and electrocardiographic damage caused by isoproterenol but does reduce sympathetic modulation.
Assuntos
Alpinia , Infarto do Miocárdio , Óleos Voláteis , Ratos , Animais , Óleos Voláteis/farmacologia , Óleos Voláteis/uso terapêutico , Isoproterenol , Ratos Wistar , Folhas de Planta , Infarto do Miocárdio/induzido quimicamente , Infarto do Miocárdio/tratamento farmacológicoRESUMO
Aloysia polystachya is a plant species that is widely used in Brazilian folk medicine for the treatment of different disorders that affect the cardiovascular system. The aim of the study was to investigate the cardioprotective effects of an ethanol-soluble fraction of A. polystachya (ESAP) on isoproterenol-induced myocardial infarction in rats. Different groups of rats (n = 8) were orally treated with ESAP (30, 100, and 300 mg/kg), carvedilol (10 mg/kg), or vehicle (filtered water; 1 mL/100 g) for 7 days. Naive rats received no treatment. On the morning of day 6, acute myocardial infarction was induced by the acute oral administration of isoproterenol (100 mg/kg). On the morning of day 8, all rats underwent electrocardiography and transthoracic echocardiography. Blood samples were then collected, and serum levels of creatine kinase-MB fraction (CK-MB) and cardiac troponin T (cTNT) were quantified. ESAP significantly reduced electrocardiographic changes, improved the ventricular ejection fraction, and reduced serum levels of CK-MB and cTNT in infarcted rats. The cardioprotective effects of ESAP could be exploited as an effective tool against isoproterenol-induced myocardial infarction in rats.
Assuntos
Infarto do Miocárdio , Verbenaceae , Animais , Ratos , Etanol , Isoproterenol , Infarto do Miocárdio/induzido quimicamente , Infarto do Miocárdio/tratamento farmacológico , Miocárdio , Ratos WistarRESUMO
ABSTRACT Herein, we examined the protective effect of metoprolol combined with atractylenolide I (Atr I) in acute myocardial infarction (AMI) by regulating the SIRT3 (silent information regulator 3)/ß-catenin/peroxisome proliferator-activated receptor gamma (PPAR-γ) signaling pathway. Briefly, 50 rats were randomly divided into the sham operation, model, metoprolol, Atr I, and combination metoprolol with Atr I groups (combined treatment group). The AMI model was established by ligating the left anterior descending coronary artery. After treatment, infarct size, histopathological changes, and cell apoptosis were examined using 2,3,5-triphenyltetrazolium chloride staining, hematoxylin-eosin staining, and the TUNEL assay. The left ventricular ejection fraction (LVEF), left ventricular fraction shortening (LVFS), and left ventricular mass index (LVMI) were detected by echocardiography. Endothelin-1 (ET-1), nitric oxide (NO), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) levels were detected using enzyme-linked immunosorbent assays. Furthermore, we measured lactate dehydrogenase (LDH), creatine kinase (CK) isoenzyme (CK-MB), and CK levels. Western blotting was performed to determine the expression of SIRT3, ß-catenin, and PPAR-γ. Herein, the combined treatment group exhibited increased levels of LVEF, LVFS, and NO, whereas LVMI, ET-1, TNF-α, IL-6, LDH, CK-MB, and CK levels were decreased. Importantly, the underlying mechanism may afford protection against AMI by increasing the expression levels of SIRT3, ß-catenin, and PPAR-γ
Assuntos
Animais , Masculino , Feminino , Ratos , Sirtuína 3/farmacologia , Metoprolol/agonistas , Infarto do Miocárdio/induzido quimicamente , Ecocardiografia/instrumentação , Creatina Quinase/classificação , Cateninas/efeitos adversosRESUMO
BACKGROUND: Despite lipid-lowering and antiplatelet therapy, the pattern of residual lipoproteins seems relevant to long-term cardiovascular outcomes. This study aims to evaluate the effects of combined therapies, commonly used in subjects with acute myocardial infarction, in the quality of low-density lipoprotein (LDL) particles. METHODS: Prospective, open-label trial, included patients with acute myocardial infarction. Patients were randomized to antiplatelet treatment (ticagrelor or clopidogrel) and subsequently to lipid-lowering therapy (rosuvastatin or simvastatin/ezetimibe) and were followed up for six months. Nonlinear optical properties of LDL samples were examined by Gaussian laser beam (Z-scan) to verify the oxidative state of these lipoproteins, small angle X-ray scattering (SAXS) to analyze structural changes on these particles, dynamic light scattering (DLS) to estimate the particle size distribution, ultra violet (UV)-visible spectroscopy to evaluate the absorbance at wavelength 484 nm (typical from carotenoids), and polyacrylamide gel electrophoresis (Lipoprint) to analyze the LDL subfractions. RESULTS: Simvastatin/ezetimibe with either clopidogrel or ticagrelor was associated with less oxidized LDL, and simvastatin/ezetimibe with ticagrelor to lower cholesterol content in the atherogenic subfractions of LDL, while rosuvastatin with ticagrelor was the only combination associated with increase in LDL size. CONCLUSIONS: The quality of LDL particles was influenced by the antiplatelet/lipid-lowering strategy, with ticagrelor being associated with the best performance with both lipid-lowering therapies. Trial registration: NCT02428374.
Assuntos
Anticolesterolemiantes , Inibidores de Hidroximetilglutaril-CoA Redutases , Infarto do Miocárdio , Anticolesterolemiantes/efeitos adversos , Clopidogrel , Ezetimiba/uso terapêutico , Humanos , Lipoproteínas , Infarto do Miocárdio/induzido quimicamente , Infarto do Miocárdio/tratamento farmacológico , Estudos Prospectivos , Rosuvastatina Cálcica/uso terapêutico , Espalhamento a Baixo Ângulo , Sinvastatina/uso terapêutico , Ticagrelor , Difração de Raios XRESUMO
BACKGROUND: Myocardial infarction (MI) is associated with high mortality rates, despite the fact that there are therapies available. Importantly, excessive oxidative stress may contribute to ischemia/reperfusion injury leading to death related to MI. In this scenario, naturally occurring antioxidant compounds are an important source of possible therapeutic intervention. Thus, this study sought to elucidate the mechanisms of cardioprotection of s-limonene in an isoproterenol-induced MI animal model. METHODS: Wistar rats were treated with 1 mg/kg s-limonene (SL) or 100 mg/kg N-acetylcysteine (NAC, positive control) once, 30 min after isoproterenol-induced MI (applied in two doses with a 24 h interval). The protective effects of SL in the heart were examined via the serum level of creatine kinase myocardial band (CK-MB), electrocardiographic profile, infarct size and histological parameters. Using isolated cardiomyocytes, we also assessed calcium transient amplitude, cytosolic and mitochondrial oxidative stress and the expression of proteins related to oxidative stress. RESULTS: SL at a concentration of 1 mg/kg attenuated isoproterenol-induced MI injury, by preventing ST-segment elevation and QTc prolongation in the ECG. SL reduced the infarct size and collagen content in cardiac tissue. At the cellular level, SL prevented increased Ca2+, associated with attenuation of cytosolic and mitochondrial oxidative stress. These changes resulted in a reduction of the oxidized form of Ca2+ Calmodulin-Dependent Kinase II (CaMKII) and restored superoxide dismutase and glutathione peroxidase activity. CONCLUSION: Our data show that s-limonene promotes cardioprotection against MI injury, probably through inhibition of increased Ca2+ and attenuation of oxidative stress via CaMKII.
Assuntos
Traumatismos Cardíacos , Infarto do Miocárdio , Animais , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Traumatismos Cardíacos/metabolismo , Isoproterenol/toxicidade , Limoneno/metabolismo , Limoneno/farmacologia , Limoneno/uso terapêutico , Modelos Teóricos , Infarto do Miocárdio/induzido quimicamente , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/prevenção & controle , Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo , Estresse Oxidativo , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismoAssuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Adulto Jovem , Doenças Cardiovasculares/induzido quimicamente , Acidente Vascular Cerebral/induzido quimicamente , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Insuficiência Cardíaca , Metformina/efeitos adversos , Infarto do Miocárdio/induzido quimicamente , Sódio/uso terapêutico , Estados Unidos , Doenças Cardiovasculares/prevenção & controle , Doenças Cardiovasculares/epidemiologia , Medicare , Acidente Vascular Cerebral/prevenção & controle , Acidente Vascular Cerebral/epidemiologia , Glucose/uso terapêutico , Hipoglicemiantes/efeitos adversos , Infarto do Miocárdio/prevenção & controle , Infarto do Miocárdio/epidemiologiaRESUMO
Myocardial infarction (MI) is the irreversible injury of the myocardium caused by prolonged myocardial ischemia and is a major cause of heart failure and eventual death among ischemic patients. The present study assessed the protective potentials of andrographolide against isoproterenol-induced myocardial infarction in rats. Animals were randomly divided into four groups: Control (Ctr) group received 0.9% saline solution once daily for 21 days, Isoproterenol (Iso) group received 0.9% saline solution once daily for 19 days followed by 80 mg/kg/day of isoproterenol hydrochloride solution on day 20 and 21, Andrographolide (Andro) group received 20 mg/kg/day of andrographolide for 21 days, and Andrographolide plus Isoproterenol (Andro + Iso) group received 20 mg/kg/day of andrographolide for 21 days with co-administration of 80 mg/kg/day of isoproterenol hydrochloride solution on day 20 and 21. After all treatments, cardiac-specific parameters that define cardiac health and early subacute MI were measured in all groups using both biophysical and pharmacological assay methods. Isoproterenol administration significantly (P < 0.05) increased cardiac mass indexes, systemic cardiac biomarkers, infarct size and caused cardiac histological alterations; significantly (P < 0.05) increased heart rate, QRS & QTc intervals and caused ST-segment elevation; significantly (P < 0.05) increased myocytes shortening, action potential duration (APD), L-type Ca2+ current (ICa,L) density and significantly (P < 0.05) decreased transient outward K+ current (Ito) density typical of the early subacute MI. Interestingly, pretreatment with andrographolide prevented and or minimized these anomalies, notably, by reducing ICa,L density and increasing Ito density significantly. Therefore, andrographolide could be seen as a promising therapeutic agent capable of making the heart resistant to early subacute infarction and it could be used as template for the development of semisynthetic drug(s) for cardiac protection against MI.
Assuntos
Bloqueadores dos Canais de Cálcio/farmacologia , Cardiotônicos/farmacologia , Diterpenos/farmacologia , Infarto do Miocárdio/prevenção & controle , Canais de Potássio/agonistas , Potenciais de Ação/efeitos dos fármacos , Animais , Bloqueadores dos Canais de Cálcio/uso terapêutico , Canais de Cálcio Tipo L/metabolismo , Cardiotônicos/uso terapêutico , Modelos Animais de Doenças , Diterpenos/uso terapêutico , Eletrocardiografia/efeitos dos fármacos , Humanos , Isoproterenol/administração & dosagem , Isoproterenol/toxicidade , Masculino , Infarto do Miocárdio/induzido quimicamente , Infarto do Miocárdio/diagnóstico , Canais de Potássio/metabolismo , RatosRESUMO
INTRODUCTION: Iron deficiency anaemia in orthopaedic surgery is common and there is increased risk of blood transfusion and associated adverse reactions. The management involves administration of iron (oral or intravenous) and erythropoietin stimulating agents. MATERIAL AND METHODS: We searched for PubMed, Embase, Google Scholar and Cochrane database to identify the studies from inception to April 2021. Randomized controlled trials with adult patients undergoing orthopedic surgery were included. The metanalysis compared patients who were administered combination of erythropoietin stimulating agents and iron in one group and iron alone. The primary outcome was the rate of blood transfusion and the secondary outcome studied were postoperative hemoglobin concentration, after treatment hemoglobin levels, and complications like mortality, stroke, myocardial infarction, deep vein thrombosis, pulmonary embolism and renal dysfunction. RESULTS: Eleven studies were included. The combination of ESA and iron decreased number of patients who required blood transfusion in comparison to patients treated with iron therapy alone (RR, 0.73; 95% CI, 0.59 to 0.91, I. CONCLUSION: 2 = 65%; p = 0.005). In subgroup analysis with oral and intravenous iron, the difference was not statistically significant (p = 0.24). Administration of erythropoietin either in high ( 80,000 IU) or low dose ( 80,000 IU) resulted in lower blood transfusion rates (p = 0.0007) with no significant difference between groups. The risk of mortality, myocardial infarction, stroke, deep vein thrombosis or pulmonary embolism did not significantly increase. Combined administration of ESA and iron versus iron only reduces the number of red blood cell transfusions in the postoperative period in orthopedic procedures with minimal risk of complications.
INTRODUCCIÓN: La anemia por deficiencia de hierro en la cirugía ortopédica es común y existe un mayor riesgo de transfusión de sangre y reacciones adversas asociadas. El tratamiento implica la administración de hierro (oral o intravenoso) y agentes estimulantes de la eritropoyetina. MATERIAL Y MÉTODOS: Se realizaron búsquedas en PubMed, Embase, Google Académico y la base de datos Cochrane para identificar los estudios desde su inicio hasta Abril de 2021. Se incluyeron ensayos controlados aleatorios con pacientes adultos sometidos a cirugía ortopédica. El metaanálisis comparó pacientes a los que se les administró una combinación de agentes estimulantes de la eritropoyetina y hierro en un grupo y hierro solo. El resultado primario fue la tasa de transfusión de sangre y el resultado secundario estudiado fue la concentración de hemoglobina postoperatoria, los niveles de hemoglobina después del tratamiento y complicaciones como mortalidad, accidente cerebrovascular, infarto de miocardio, trombosis venosa profunda, embolia pulmonar y disfunción renal. RESULTADOS: Se incluyeron 11 estudios. La combinación de AEE y hierro disminuyó el número de pacientes que requirieron transfusión de sangre en comparación con los pacientes tratados con tratamiento con hierro solo (RR, 0.73; IC del 95%, 0.59 a 0.91, I. CONCLUSIÓN: 2 = 65%; p = 0.005). En el análisis de subgrupos con hierro oral e intravenoso, la diferencia no fue estadísticamente significativa (p = 0.24). La administración de eritropoyetina en dosis altas ( 80,000 UI) o bajas ( 80,000 UI) dio lugar a tasas de transfusión de sangre más bajas (p = 0.0007) sin diferencias significativas entre los grupos. El riesgo de mortalidad, infarto de miocardio, accidente cerebrovascular, trombosis venosa profunda o embolia pulmonar no aumentó significativamente. La administración combinada de AEE y hierro frente al hierro solo reduce el número de transfusiones de glóbulos rojos en el período postoperatorio en procedimientos ortopédicos con un riesgo mínimo de complicaciones.
Assuntos
Eritropoetina , Ferro , Procedimentos Ortopédicos , Adulto , Combinação de Medicamentos , Eritropoetina/administração & dosagem , Hemoglobinas , Humanos , Ferro/administração & dosagem , Ferro/efeitos adversos , Infarto do Miocárdio/induzido quimicamente , Embolia Pulmonar/induzido quimicamente , Acidente Vascular Cerebral/induzido quimicamente , Trombose VenosaRESUMO
BACKGROUND Misuse of androgenic anabolic steroids (AAS) is a current practice associated with vigorous bodybuilding for muscular hypertrophy, especially among gym practitioners and bodybuilders, influenced by the culture of body image. In addition to liver, psychiatric, genital, urinary, dermatological, and musculoskeletal complications, AAS misuse reportedly can lead to development of cardiovascular complications, such as hypertension, dyslipidemia, cardiac hypertrophy, and early coronary disease, and potentially acute myocardial infarction (AMI) and sudden death. CASE REPORT A 26-year-old male farmer who was also an amateur bodybuilder developed an extensive Killip Class I AMI in the anterior wall while using AAS. A few days before the acute event, his lipid and hormone levels were measured and found to be significantly elevated. The patient was asymptomatic after left anterior descending branch angioplasty, but he had significant electrocardiographic sequelae and ventricular dysfunction. CONCLUSIONS We describe the case of a young male bodybuilder using AAS who presented with AMI and was treated with primary angioplasty. Documentation of high levels of lipids and hormones 1 week before the acute event suggests some relationship between AAS and cardiovascular disease. The main effects of using these steroids on the cardiovascular system are reviewed. It is time for a new global warning about the risks of misusing AAS to obtain muscle hypertrophy. Based on current medical knowledge, these hormones should not be prescribed without a clear indication for their use.