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1.
J Assoc Physicians India ; 68(11): 46-50, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33187037

RESUMO

Diabetes Mellitus (DM) is a global heath burden and the leading cause for cardiovascular (CV) disease. The differential presentation of CV disease in DM is related to the metabolic derangements leading to deterioration of myocardial cell function and its serious consequences. Therefore, there is a need for early and effective treatment intervention for this myocardial cell metabolic dysfunction. DM and myocardial ischemia (MI) share a common metabolic dysregulation mediated via increased fatty acid oxidation that makes the diabetic heart susceptible to myocardial ischemia and reduced myocardial performance during ischemia compared to non-diabetic heart. Modulation of myocardial free fatty acid metabolism should be the key target for metabolic interventions in patients with Diabetic CV complications. Trimetazidine, a fatty acid metabolic modulator, has shown to improve CV outcomes in diabetes. The present review summarizes the clinical evidence and relevance of trimetazidine as an anti-anginal and antiischemic agent in patients with DM. Evidence suggested that trimetazidine could significantly improve clinical outcomes in patients with angina or heart failure and diabetes. Administering trimetazidine in patients with diabetes undergoing re-vascularization could also provide significant clinical benefits. Current clinical practice guidelines also recommend trimetazidine as a first-line agent for selected patients or as a second-line treatment option for angina patients.


Assuntos
Doença da Artéria Coronariana , Diabetes Mellitus , Isquemia Miocárdica , Trimetazidina , Diabetes Mellitus/tratamento farmacológico , Humanos , Isquemia Miocárdica/tratamento farmacológico , Trimetazidina/uso terapêutico , Vasodilatadores/uso terapêutico
2.
Kardiologiia ; 60(7): 115-124, 2020 Aug 11.
Artigo em Russo | MEDLINE | ID: mdl-33155950

RESUMO

The review focuses on upper gastrointestinal (GI) bleeding in patients with ischemic heart disease (IHD) receiving an antithrombotic therapy. Approaches to risk stratification for GI bleeding and correction of modifiable factors that determine the probability of such events are addressed in detail. Recommendations are provided for administration of stomach-protecting drugs. The interrelation of risk factors for thromboses and bleedings is stressed, and possible indications for a multicomponent antithrombotic therapy in patients with stable IHD are discussed.


Assuntos
Doença da Artéria Coronariana , Isquemia Miocárdica , Trombose , Anticoagulantes , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/tratamento farmacológico , Fibrinolíticos/efeitos adversos , Hemorragia Gastrointestinal/induzido quimicamente , Hemorragia Gastrointestinal/prevenção & controle , Humanos , Isquemia Miocárdica/complicações , Isquemia Miocárdica/tratamento farmacológico , Inibidores da Agregação de Plaquetas/efeitos adversos , Fatores de Risco , Trombose/tratamento farmacológico
3.
J Pharmacol Sci ; 144(4): 218-228, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33070841

RESUMO

Myocardial ischemia initiates a chain of pathological conditions leading to cardiomyocyte death. Therefore, pharmacological treatment to stop ischemia-induced damage is necessary. Fibrates, have been reported to decrease inflammatory markers and to modulate the renin-angiotensin system (RAS). Our aim was to explore if clofibrate treatment, administered one week after myocardial event, decreases MI-induced cardiac damage. Wistar rats were assigned to: 1. Sham or 2. Coronary artery ligation (MI). Seven days after, rats were subdivided to receive vehicle (V) or clofibrate [100 mg/kg (C)] daily for 7 days. Blood samples and left ventricle were analyzed. RAS components [angiotensin II, angiotensin converting enzyme (ACE), and AT1-receptor] decreased in MI-C compared to MI-V, while [Ang-(1-7), bradykinin, ACE-2, and AT2-receptor] raised in response to clofibrate treatment. Oxidative stress markers increased in MI-V rats, a profile reverted in MI-C rats. Nitric oxide (NO) pathway (Akt, eNOS, and NO) exhibits a lower participation in MI-V, but clofibrate raised NO-pathway components and its production. MI-induced fibrosis and structural damage was also improved by clofibrate-treatment. In conclusion, clofibrate administration to 7 days MI-rats exerts an antioxidant, pro-vasodilator expression profile, and anti-fibrotic effect suggesting that PPARα activation can be considered a therapeutic target to improve cardiac condition posterior to ischemia.


Assuntos
Clofibrato/administração & dosagem , Clofibrato/farmacologia , Ventrículos do Coração/metabolismo , Isquemia Miocárdica/tratamento farmacológico , Isquemia Miocárdica/metabolismo , Miocárdio/patologia , Óxido Nítrico/metabolismo , Sistema Renina-Angiotensina/efeitos dos fármacos , Angiotensina II/metabolismo , Animais , Fibrose , Ventrículos do Coração/patologia , Masculino , Isquemia Miocárdica/patologia , Estresse Oxidativo/efeitos dos fármacos , Peptidil Dipeptidase A/metabolismo , Ratos Wistar , Receptor Tipo 1 de Angiotensina/metabolismo , Fatores de Tempo
4.
Vasc Health Risk Manag ; 16: 353-365, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32982263

RESUMO

Among the vast number of noncommunicable diseases encountered worldwide, cardiovascular diseases accounted for about 17.8 million deaths in 2017 and ischemic heart disease (IHD) remains the single-largest cause of death in countries across all income groups. Because conventional medications are not without shortcomings and patients still refractory to these medications, scientific investigation is ongoing to advance the management of IHD, and shows a great promise for better treatment modalities, but additional research can warrant improvement in terms of the quality of life of patients. Metabolic modulation is one promising strategy for the treatment of IHD, because alterations in energy metabolism are involved in progression of the disease. Therefore, the purpose of this review was to strengthen attention toward the use of metabolic modulators and to review the current level of knowledge on cardiac energy metabolic pathways.


Assuntos
Fármacos Cardiovasculares/uso terapêutico , Metabolismo Energético/efeitos dos fármacos , Mitocôndrias Cardíacas/efeitos dos fármacos , Isquemia Miocárdica/tratamento farmacológico , Miócitos Cardíacos/efeitos dos fármacos , Animais , Humanos , Mitocôndrias Cardíacas/metabolismo , Terapia de Alvo Molecular , Isquemia Miocárdica/metabolismo , Isquemia Miocárdica/fisiopatologia , Miócitos Cardíacos/metabolismo
5.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 36(6): 513-519, 2020 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-32696741

RESUMO

Objective To study the protective effect and mechanism of daphnetin (DAP) against myocardial ischemia-reperfusion injury in rats. Methods Seventy-five SD rats were randomly divided into five groups: control group, model group, (30, 60, 90) mg/kg DAP-treated groups. The model of myocardial ischemia in rats was established by isoproterenol (85 mg/kg) through subcutaneous injection for 2 consecutive days. DAP was administered by gavage for 7 consecutive days to observe the protective effect of DAP on the injury of rat myocardium. The electrocardiographic changes of each group of experimental rats were measured with electrocardiographic measuring device. The activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) in the sera were detected with spectrophotometry. The serum levels of creatine kinase isoenzyme, muscle b (CK-MB), lactate dehydrogenase (LDH) and creatine phosphokinase (CPK), and the content of interleukin 1ß (IL-1ß), tumor necrosis factor α (TNF-α), IL-6 in the homogenate of myocardial tissue were measured by ELISA. The injury and fibrosis of cardiomyocytes were observed by HE staining and Masson staining, the mRNA levels of JNK and NF-κB were detected by real-time quantitative PCR, and the phosphorylation of JNK and NF-κB were determined by Western blot analysis. Results DAP increased the activities of SOD, CAT, GSH-Px, decreased MDA, inhibited the levels of CK-MB, LDH, CPK, TNF-α and IL-ß in the sera, decreased myocardial fibrosis, depressed the expression and phosphorylation of JNK and NF-κBp65. Conclusion DAP can inhibit the activation of JNK/NF-κB signal pathway and myocardial apoptosis and fibrosis induced by myocardial ischemia-reperfusion.


Assuntos
Isquemia Miocárdica , Animais , Isquemia Miocárdica/tratamento farmacológico , Isquemia Miocárdica/metabolismo , Miocárdio/metabolismo , NF-kappa B/genética , NF-kappa B/metabolismo , Estresse Oxidativo , Ratos , Ratos Sprague-Dawley , Umbeliferonas
6.
Life Sci ; 257: 118004, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32621918

RESUMO

BACKGROUND: Patients undergoing cardiopulmonary bypass (CPB) often develop acute kidney injury (AKI) caused by myocardial ischemia reperfusion (MI/R), and this renal injury can be resolved notably by dexmedetomidine. Endoplasmic reticulum (ER) stress was reported to get involved in organ injury including AKI. OBJECTIVES: The current study aimed to address the correlation between MI/R induced AKI with ER stress and to assess the effects of dexmedetomidine pretreatment on AKI protection. METHOD: Patients selected for heart valve replacement surgery were randomly assigned to NS group (pre-anesthesia with 0.9% NaCl) and DEX group (pre-anesthesia with dexmedetomidine). Rat MI/R model was induced by occluding coronary artery for 30 min followed by 48-hour reperfusion. Rats were randomized into Sham (0.9% NaCl), I/R (MI/R + 0.9% NaCl) and I/R + DEX (MI/R + dexmedetomidine). Organ function and ER stress condition were evaluated by blood chemistry, pathology, and molecular test. RESULTS: Clinical data indicated dexmedetomidine pretreatment attenuated AKI and oxidative stress as well as postischemic myocardial injury in patients. Accordingly animal results suggested dexmedetomidine reduced cellular injury and improved postischemic myocardial and renal function. Dexmedetomidine also reduced myocardial and renal cells apoptosis and down-regulated ER stress. CONCLUSIONS: These results suggested that dexmedetomidine pretreatment attenuates MI/R injury-induced AKI by relieving the ER stress.


Assuntos
Dexmedetomidina/farmacologia , Isquemia Miocárdica/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Lesão Renal Aguda/metabolismo , Lesão Renal Aguda/prevenção & controle , Idoso , Animais , Apoptose/efeitos dos fármacos , China , Dexmedetomidina/metabolismo , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Estresse do Retículo Endoplasmático/fisiologia , Feminino , Humanos , Isquemia/metabolismo , Rim/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/metabolismo , Reperfusão Miocárdica/métodos , Traumatismo por Reperfusão Miocárdica/patologia , Miocárdio/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Estudos Prospectivos , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/metabolismo , Transdução de Sinais/efeitos dos fármacos
7.
Life Sci ; 259: 118162, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32730836

RESUMO

OBJECTIVE: The inhaled sevoflurane (sevo) is known to protect against myocardial ischemia/reperfusion (I/R) injury (MIRI), in which the functions of microRNAs (miRNAs) have been uncovered. However, the effect of sevo regulating miR-204 on this disease remains unknown. This research aims to explore the roles of sevo and miR-204 in the progression of MIRI. METHODS: The MIRI mice models induced by coronary artery ligation were treated by sevo, miR-204 mimics or silenced coactosin-like protein-1 (Cotl1). The pathology of mice myocardial tissues, apoptosis and ultrastructure of cardiomyocytes were observed. The expression of miR-204, Cotl1, Bax and Bcl-2 was determined. The contents of oxidative stress-related factors and inflammatory factors in mouse myocardial tissues were assessed, and the serum levels of indicators that correlated with myocardial infarction were determined as well. The target relation between miR-204 and Cotl1 was confirmed. RESULTS: MiR-204 was down-regulated, and Cotl1 was up-regulated in myocardial tissues of MIRI mice, and Cotl1 was targeted by miR-204. Sevo, elevated miR-204 and inhibited Cotl1 could promote cardiac function of MIRI mice, and protect myocardial tissue against MIRI by repressing the cardiomyocyte apoptosis, oxidative stress and inflammation reaction in MIRI mice. CONCLUSION: We found that sevo could up-regulate miR-204 to ameliorate MIRI in mice by inhibiting Cotl1 expression, which may provide candidates for the MIRI treatment.


Assuntos
Anestésicos Inalatórios/farmacologia , MicroRNAs/biossíntese , Proteínas dos Microfilamentos/antagonistas & inibidores , Isquemia Miocárdica/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Sevoflurano/farmacologia , Animais , Progressão da Doença , Hemodinâmica/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Isquemia Miocárdica/patologia , Traumatismo por Reperfusão Miocárdica/patologia , Miocárdio/patologia , Miócitos Cardíacos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos
8.
Acta Cir Bras ; 35(3): e202000306, 2020 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-32692797

RESUMO

PURPOSE: To evaluate whether the attenuation of mitochondrial Ca2+ overload produced by pharmacological blockade of mitochondrial Ca2+ uniporter (MCU) protects the myocardium against injuries caused by cardiac ischemia and reperfusion (CIR). METHODS: CIR was induced in adult male Wistar rats (300-350 g) by occlusion of the left anterior descendent coronary artery (10 min), followed by reperfusion (120 min). Rats were treated with different doses of MCU blocker ruthenium red (RuR), administered 5 min before ischemia or reperfusion. RESULTS: In untreated rats, the incidences of ventricular arrhythmias (VA), atrioventricular block (AVB) and the lethality (LET) induced by CIR were 85%, 79% and 70%, respectively. In rats treated with RuR before ischemia, the incidences of VA, AVB and LET were significantly reduced to 62%, 25% and 25%, respectively. In rats treated with RuR after ischemia, the incidences of VA, AVB and LET were significantly reduced to 50%, 25% and 25%, respectively. CONCLUSION: The significant reduction of the incidence of CIR-induced VA, AVB and LET produced by the treatment with RuR indicates that the attenuation of mitochondrial Ca2+ overload produced by pharmacological blockade of MCU can protect the myocardium against injuries caused by CIR.


Assuntos
Canais de Cálcio , Isquemia Miocárdica , Traumatismo por Reperfusão Miocárdica , Animais , Cálcio , Canais de Cálcio/efeitos dos fármacos , Masculino , Isquemia Miocárdica/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Ratos , Ratos Wistar
9.
Arch Med Res ; 51(6): 515-523, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32487324

RESUMO

BACKGROUND: Platelet hyper adhesiveness orchestrates with inflammation and vascular muscle proliferation leading to atheroma formation and endothelial dysfunction. OBJECTIVES: The current study aims to compare the prophylactic role of Aspirin and Clopidogrel therapy against isoproterenol-induced acute myocardial infarction (AMI), in mice on high-fat, cholesterol-rich diet (HFD-C). METHODS: The animals received HFD-C with Aspirin or Clopidogrel for 8 weeks and were subjected to AMI by isoproterenol. The blood lipids, inflammatory cytokines, myocardial enzymes, redox state, long pentraxin (PTX3), and matrix metalloproteinases (MMP-2 and MMP-9) activities were investigated. RESULTS: Antiplatelet therapy moderated the hyperlipidemia induced by HFD-C in the current study. Essentially, the total cholesterol and LDL-C levels were lower with Aspirin than with Clopidogrel therapy. Yet Aspirin and Clopidogrel each comparably lowered CK-MB, AST, MMP-2, MMP-9, and the lipid peroxidation product malondialdehyde (MDA) in the hyperlipidemic animals exposed to AMI. However, the decline in cTn-T, LDH and PTX3 levels was greater after Clopidogrel than Aspirin administration. Therefore, Clopidogrel provides greater protection against AMI than Aspirin in the hyperlipidemic mice. This could be explained by the suppression of the proinflammatory cytokines IL-6, TNF-α, TGF-1ß and stabilization of the extracellular matrix through the inhibition of MMP-2 and MMP-9 activities. Furthermore, Clopidogrel demonstrated significant antioxidative action in the AMI animals, resulting in diminished MDA production and preserved CAT activity. CONCLUSION: Beside its therapeutic role in the thrombotic vascular events, Clopidogrel confers significant protection against ischemic myocardial injury by counteracting the platelet-mediated inflammation and oxidative stress associated with HFD-C consumption in animals.


Assuntos
Aspirina/uso terapêutico , Clopidogrel/uso terapêutico , Hipercolesterolemia/tratamento farmacológico , Hiperlipidemias/tratamento farmacológico , Inflamação/tratamento farmacológico , Isquemia Miocárdica/tratamento farmacológico , Inibidores da Agregação de Plaquetas/uso terapêutico , Animais , Modelos Animais de Doenças , Humanos , Masculino , Camundongos
10.
Radiología (Madr., Ed. impr.) ; 62(3): 213-221, mayo-jun. 2020. ilus, tab, graf
Artigo em Espanhol | IBECS | ID: ibc-194219

RESUMO

OBJETIVO: Describir la seguridad del regadenosón como fármaco vasodilatador en estudios de resonancia magnética cardíaca (RMC) de estrés realizados para detectar isquemia miocárdica. MATERIAL Y MÉTODOS: Se analizaron de manera retrospectiva los estudios de 120 pacientes (88 varones, edad media 67 ±11,6 años) con sospecha de cardiopatía isquémica o con enfermedad coronaria conocida e indicación clínica para RMC de estrés. Los estudios se realizaron en un equipo de 1,5 Tesla (MAGNETOM Aera, Siemens Healthineers) empleando regadenosón (5ml, 0,4mg) como agente vasodilatador. En todos los pacientes se recogieron los factores de riesgo cardiovascular, fármacos que tomaban e indicación de la prueba, además de las constantes vitales en situación de reposo y bajo estrés y los síntomas y efectos adversos inducidos por el fármaco. RESULTADOS: El 52,6% de los pacientes permanecieron asintomáticos. Los síntomas más frecuentes fueron la opresión centrotorácica (25%) y la disnea (12%). Durante el pico de estrés, el incremento medio de la frecuencia cardíaca fue de 23,9±11,4 lpm y el descenso medio de la presión arterial sistólica y diastólica de 7,1±18,8mmHg y 5,3±9,2mmHg, respectivamente (p < 0,001). En pacientes obesos y diabéticos se objetivó menor respuesta hemodinámica al regadenosón, mientras que los pacientes sintomáticos presentaron mayor incremento de la frecuencia cardíaca (27,4±11,2 lpm frente a 20,6±10,7 lpm, p = 0,001). No se evidenció ningún efecto adverso grave. CONCLUSIÓN: El regadenosón es un fármaco bien tolerado que se puede utilizar con seguridad en RMC de estrés


OBJECTIVE: To determine the safety of regadenoson for vasodilation in cardiac MRI stress tests to detect myocardial ischemia. MATERIAL AND METHODS: We retrospectively analyzed cardiac MRI studies done in 120 patients (mean age, 67±11.6 years; 88 men) with suspected ischemic heart disease or known coronary disease who had clinical indications for cardiac MRI stress tests. All studies were done on a 1.5 T scanner (MAGNETOM Aera, Siemens Healthineers) using regadenoson (5ml, 0.4mg) for vasodilation. We recorded cardiovascular risk factors, medications, and indications for the test as well as vital signs at rest and under stress and the symptoms and adverse effects induced by the drug. RESULTS: No symptoms developed in 52.6% of patients. The most common symptoms were central chest pain (25%) and dyspnea (12%). At peak stress, the mean increase in heart rate was 23.9±11.4 beats per minute and the mean decreases in systolic and diastolic blood pressure were 7.1±18.8mmHg and 5.3±9.2mmHg, respectively (p <0.001). The response to regadenoson was less pronounced in obese and diabetic patients. The increase in heart rate was greater in symptomatic patients (27.4±11.2 bpm vs. 20.6±10.7 bpm in asymptomatic patients, p = 0.001). No severe adverse effects were observed. CONCLUSION: Regadenoson is well tolerated and can be safely used for cardiac MRI stress tests


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Vasodilatadores/administração & dosagem , Imagem por Ressonância Magnética , Isquemia Miocárdica/diagnóstico por imagem , Isquemia Miocárdica/tratamento farmacológico , Estudos Retrospectivos , Doença das Coronárias/diagnóstico por imagem , Fatores de Risco , Gadolínio/administração & dosagem , Administração Intravenosa
11.
Cardiovasc Ther ; 2020: 3480276, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32565909

RESUMO

Wenxin Keli (WXKL) is a traditional Chinese medicine drug approved for the treatment of cardiovascular diseases. This study aimed to identify WXKL-targeting genes involved in antiarrhythmic efficacy of WXKL. The Traditional Chinese Medicine Systems Pharmacology (TCMSP) technology platform was used to screen active compounds of WXKL and WXKL-targeting arrhythmia-related genes. A pig model of myocardial ischemia (MI) was established by balloon-expanding the endothelium of the left coronary artery. Pigs were divided into the model group and WXKL group (n = 6). MI, QT interval, heart rate, and arrhythmia were recorded, and the mRNA expression of target genes in myocardial tissues was detected by PCR. Eleven active ingredients of WXKL and eight WXKL-targeting arrhythmia-related genes were screened. Five pathways were enriched, and an "ingredient-gene-path" network was constructed. WXKL markedly decreased the incidence of arrhythmia in the MI pig model (P < 0.05). The QT interval was significantly shortened, and the heart rate was slowed down in the WXKL group compared with the model group (P < 0.05). In addition, the expression of sodium channel protein type 5 subunit alpha (SCN5A) and beta-2 adrenergic receptor (ADRB2) was downregulated, while muscarinic acetylcholine receptor M2 (CHRM2) was upregulated in the WXKL group (P < 0.05). In conclusion, WXKL may shorten the QT interval and slow down the heart rate by downregulating SCN5A and ADRB2 and upregulating CHRM2 during MI. These findings provide novel insight into molecular mechanisms of WXKL in reducing the incidence of ventricular arrhythmia.


Assuntos
Potenciais de Ação/efeitos dos fármacos , Antiarrítmicos/farmacologia , Arritmias Cardíacas/prevenção & controle , Medicamentos de Ervas Chinesas/farmacologia , Frequência Cardíaca/efeitos dos fármacos , Isquemia Miocárdica/tratamento farmacológico , Potenciais de Ação/genética , Animais , Arritmias Cardíacas/genética , Arritmias Cardíacas/metabolismo , Arritmias Cardíacas/fisiopatologia , Modelos Animais de Doenças , Regulação da Expressão Gênica , Redes Reguladoras de Genes , Frequência Cardíaca/genética , Masculino , Medicina Tradicional Chinesa , Isquemia Miocárdica/genética , Isquemia Miocárdica/metabolismo , Isquemia Miocárdica/fisiopatologia , Canal de Sódio Disparado por Voltagem NAV1.5/genética , Canal de Sódio Disparado por Voltagem NAV1.5/metabolismo , Mapas de Interação de Proteínas , Receptor Muscarínico M2/genética , Receptor Muscarínico M2/metabolismo , Receptores Adrenérgicos beta 2/genética , Receptores Adrenérgicos beta 2/metabolismo , Suínos , Porco Miniatura , Fatores de Tempo
12.
Cesk Patol ; 56(1): 13-17, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32393041

RESUMO

Several changes have occurred during last few years in diagnostics and treatment of the ischemic heart disease, especially due to introduction of so called high-sensitive troponins, implementation of new antiplatelet drugs, using of drug-eluting stents in percutaneous coronary interventions or novel definitions of acute myocardial infarction types. The European Society of Cardiology and Czech Society of Cardiology established new recommendations for management of both acute and chronic forms of the ischemic heart disease. Recently discovered inhibitors of the PCSK9 molecule that have been slowly introduced in the clinical practice represent a breakthrough in the treatment of dyslipidemia. Future research will certainly aim at detection of early forms of the atherosclerotic involvement of the coronary arteries.


Assuntos
Isquemia Miocárdica , Humanos , Isquemia Miocárdica/diagnóstico , Isquemia Miocárdica/tratamento farmacológico , Isquemia Miocárdica/genética , Pró-Proteína Convertase 9/efeitos dos fármacos
13.
PLoS One ; 15(5): e0233591, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32453773

RESUMO

The heart is critically dependent on mitochondrial respiration for energy supply. Ischemia decreases oxygen availability, with catastrophic consequences for cellular energy systems. After a few minutes of ischemia, the mitochondrial respiratory chain halts, ATP levels drop and ion gradients across cell membranes collapse. Activation of cellular proteases and generation of reactive oxygen species by mitochondria during ischemia alter mitochondrial membrane permeability, causing mitochondrial swelling and fragmentation and eventually cell death. The mitochondria, therefore, are important targets of cardioprotection against ischemic injury. We have previously shown that ixazomib (IXA), a proteasome inhibitor used for treating multiple myeloma, effectively reduced the size of the infarct produced by global ischemia in isolated rat hearts and prevented degradation of the sarcoplasmic reticulum calcium release channel RyR2. The aim of this work was to further characterize the protective effect of IXA by determining its effect on mitochondrial morphology and function after ischemia. We also quantified the effect of IXA on levels of mitofusin-2, a protein involved in maintaining mitochondrial morphology and mitochondria-SR communication. We found that mitochondria were significantly preserved and functional parameters such as oxygen consumption, the ability to generate a membrane potential, and glutathione content were improved in mitochondria isolated from hearts perfused with IXA prior to ischemia. IXA also blocked the release of cytochrome c observed in ischemia and significantly preserved mitofusin-2 integrity. These beneficial effects resulted in a significant decrease in the left ventricular end diastolic pressure upon reperfusion and a smaller infarct in isolated hearts.


Assuntos
Compostos de Boro/farmacologia , Glicina/análogos & derivados , Coração/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Isquemia Miocárdica/tratamento farmacológico , Animais , Quimotripsina/farmacologia , Modelos Animais de Doenças , Glutationa/genética , Glutationa/metabolismo , Glicina/farmacologia , Coração/fisiopatologia , Humanos , Potenciais da Membrana/efeitos dos fármacos , Mitocôndrias/genética , Isquemia Miocárdica/genética , Isquemia Miocárdica/fisiopatologia , Consumo de Oxigênio/genética , Complexo de Endopeptidases do Proteassoma/efeitos dos fármacos , Inibidores de Proteassoma/farmacologia , Ratos
14.
Int Heart J ; 61(3): 595-600, 2020 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-32418958

RESUMO

Cold ischemic injury in heart storage is an important issue pertaining to heart transplantation. This study aims to evaluate the addition of compound glycyrrhizin (CG) in histidine-tryptophan-ketoglutarate (HTK) solution on chronic isograft injury in comparison to traditional HTK solution.Hearts of mouse were stored for 8 h in 4°C cold preservation solution and then transplanted heterotopically into mouse. Five groups were evaluated: HTK, low dose of CG solution (LCG), medium dose of CG solution (MCG), high dose of CG solution (HCG), and hearts without cold ischemia (sham). Survival was assessed. Time to restoration of heartbeat and strength of the heartbeat was measured. Lactate dehydrogenase (LDH) and creatine kinase (CK) levels in the preservation solution were determined. The myocardial damage and interstitial fibrosis of transplanted hearts were evaluated. TGF-ß1 expression in the transplanted hearts was assessed.Addition of CG to HTK solution significantly attenuated cold ischemic injury during cold storage, as evidenced by the lower time to restoration of heartbeat, higher strength of the heartbeat, lower LDH, and CK leakage. After transplantation, hearts stored in HTK solution containing CG had decreased the myocardial damage and interstitial fibrosis, compared with those stored without CG. The percentage of TGF-ß1-positive cells and TGF-ß1 level in the transplanted hearts were also decreased when stored in CG-containing HTK solution.The addition of CG to HTK solution attenuates cold ischemic injury during cold storage.


Assuntos
Anti-Inflamatórios/uso terapêutico , Isquemia Fria/efeitos adversos , Ácido Glicirrízico/uso terapêutico , Transplante de Coração , Isquemia Miocárdica/tratamento farmacológico , Animais , Avaliação Pré-Clínica de Medicamentos , Glucose , Masculino , Manitol , Camundongos Endogâmicos C57BL , Isquemia Miocárdica/etiologia , Cloreto de Potássio , Procaína
15.
Int Heart J ; 61(3): 585-594, 2020 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-32418959

RESUMO

Ischemic heart disease (IHD) is one of the world's leading causes of human death. Kaempferol (Kae) was proved to have anti-inflammatory, antioxidant, and anticancer effects. Such properties suggested that it might play protective roles in IHD. In this study, we have attempted to disclose the potential regulating mechanisms of Kae in primary cardiomyocytes and H9c2 cells.Cells were first stimulated by oxygen-glucose deprivation (OGD) and then exposed to Kae. CCK-8 assay and flow cytometry were used to examine cell characteristics. Quantitative reverse-transcription polymerase chain reaction was utilized to test the expression levels of miR-15b and TLR4. Afterward, cell transfection, dual-luciferase activity assay, and western blot were used to explore the potential mechanisms.OGD treatment suppressed cell viability, whereas it enhanced cell apoptosis. Besides, OGD treatment enhanced the expression of apoptosis-associated proteins. Kae exposure, however, attenuated the effects that OGD-induced. Further experiments showed that Kae exposure promoted down-regulation of miR-15b, Bcl-2 and TLR4 were a target of miR-15b. Moreover, Kae enhanced the expression of key factors involved in PI3K/AKT and Wnt/ß-catenin pathways, whereas miR-15b mimic reversed the Kae-triggered effects.This investigation revealed that Kae diminished OGD-triggered cell damage through down-regulating miR-15b expression via activating PI3K/AKT and Wnt3a/ß-catenin pathways.


Assuntos
Quempferóis/uso terapêutico , MicroRNAs/metabolismo , Isquemia Miocárdica/tratamento farmacológico , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Receptor 4 Toll-Like/metabolismo , Animais , Linhagem Celular , Avaliação Pré-Clínica de Medicamentos , Quempferóis/farmacologia , Isquemia Miocárdica/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Ratos Wistar , Via de Sinalização Wnt , beta Catenina/metabolismo
16.
N Engl J Med ; 382(17): 1619-1628, 2020 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-32227754

RESUMO

BACKGROUND: In the ISCHEMIA-CKD trial, the primary analysis showed no significant difference in the risk of death or myocardial infarction with initial angiography and revascularization plus guideline-based medical therapy (invasive strategy) as compared with guideline-based medical therapy alone (conservative strategy) in participants with stable ischemic heart disease, moderate or severe ischemia, and advanced chronic kidney disease (an estimated glomerular filtration rate of <30 ml per minute per 1.73 m2 or receipt of dialysis). A secondary objective of the trial was to assess angina-related health status. METHODS: We assessed health status with the Seattle Angina Questionnaire (SAQ) before randomization and at 1.5, 3, and 6 months and every 6 months thereafter. The primary outcome of this analysis was the SAQ Summary score (ranging from 0 to 100, with higher scores indicating less frequent angina and better function and quality of life). Mixed-effects cumulative probability models within a Bayesian framework were used to estimate the treatment effect with the invasive strategy. RESULTS: Health status was assessed in 705 of 777 participants. Nearly half the participants (49%) had had no angina during the month before randomization. At 3 months, the estimated mean difference between the invasive-strategy group and the conservative-strategy group in the SAQ Summary score was 2.1 points (95% credible interval, -0.4 to 4.6), a result that favored the invasive strategy. The mean difference in score at 3 months was largest among participants with daily or weekly angina at baseline (10.1 points; 95% credible interval, 0.0 to 19.9), smaller among those with monthly angina at baseline (2.2 points; 95% credible interval, -2.0 to 6.2), and nearly absent among those without angina at baseline (0.6 points; 95% credible interval, -1.9 to 3.3). By 6 months, the between-group difference in the overall trial population was attenuated (0.5 points; 95% credible interval, -2.2 to 3.4). CONCLUSIONS: Participants with stable ischemic heart disease, moderate or severe ischemia, and advanced chronic kidney disease did not have substantial or sustained benefits with regard to angina-related health status with an initially invasive strategy as compared with a conservative strategy. (Funded by the National Heart, Lung, and Blood Institute; ISCHEMIA-CKD ClinicalTrials.gov number, NCT01985360.).


Assuntos
Angiografia Coronária , Ponte de Artéria Coronária , Nível de Saúde , Isquemia Miocárdica/tratamento farmacológico , Isquemia Miocárdica/cirurgia , Intervenção Coronária Percutânea , Insuficiência Renal Crônica/complicações , Idoso , Teste de Esforço , Feminino , Seguimentos , Estilo de Vida Saudável , Humanos , Análise de Intenção de Tratamento , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/complicações , Isquemia Miocárdica/mortalidade , Razão de Chances , Modelos de Riscos Proporcionais , Inquéritos e Questionários
17.
N Engl J Med ; 382(17): 1608-1618, 2020 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-32227756

RESUMO

BACKGROUND: Clinical trials that have assessed the effect of revascularization in patients with stable coronary disease have routinely excluded those with advanced chronic kidney disease. METHODS: We randomly assigned 777 patients with advanced kidney disease and moderate or severe ischemia on stress testing to be treated with an initial invasive strategy consisting of coronary angiography and revascularization (if appropriate) added to medical therapy or an initial conservative strategy consisting of medical therapy alone and angiography reserved for those in whom medical therapy had failed. The primary outcome was a composite of death or nonfatal myocardial infarction. A key secondary outcome was a composite of death, nonfatal myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. RESULTS: At a median follow-up of 2.2 years, a primary outcome event had occurred in 123 patients in the invasive-strategy group and in 129 patients in the conservative-strategy group (estimated 3-year event rate, 36.4% vs. 36.7%; adjusted hazard ratio, 1.01; 95% confidence interval [CI], 0.79 to 1.29; P = 0.95). Results for the key secondary outcome were similar (38.5% vs. 39.7%; hazard ratio, 1.01; 95% CI, 0.79 to 1.29). The invasive strategy was associated with a higher incidence of stroke than the conservative strategy (hazard ratio, 3.76; 95% CI, 1.52 to 9.32; P = 0.004) and with a higher incidence of death or initiation of dialysis (hazard ratio, 1.48; 95% CI, 1.04 to 2.11; P = 0.03). CONCLUSIONS: Among patients with stable coronary disease, advanced chronic kidney disease, and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of death or nonfatal myocardial infarction. (Funded by the National Heart, Lung, and Blood Institute and others; ISCHEMIA-CKD ClinicalTrials.gov number, NCT01985360.).


Assuntos
Angiografia Coronária , Ponte de Artéria Coronária , Isquemia Miocárdica/tratamento farmacológico , Isquemia Miocárdica/cirurgia , Intervenção Coronária Percutânea , Insuficiência Renal Crônica/complicações , Antagonistas Adrenérgicos beta/uso terapêutico , Idoso , Bloqueadores dos Canais de Cálcio/uso terapêutico , Teste de Esforço , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/prevenção & controle , Isquemia Miocárdica/complicações , Isquemia Miocárdica/mortalidade , Fatores de Risco
18.
J Pharmacol Sci ; 143(3): 156-164, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32278466

RESUMO

Safranal (SFR) is the major constituent of saffron. The purpose of this study was to observe the effect of SFR on myocardial ischemia induced by isoprenaline (ISO) and to explore its possible mechanism. The myocardial ischemia rat model was established by subcutaneous injection of ISO (85 mg/kg/d) on the 8th and 9th day of the experiment. Serum creatine kinase (CK), lactate dehydrogenase (LDH), malondialdehyde (MDA) and superoxide dismutase (SOD) were measured, as were changes in calcium concentration, reactive oxygen species (ROS) and cardiac morphology of the myocardial tissue. The effects of SFR on cell contraction, Ca2+ transient and L-type Ca2+ current (ICa-L) in isolated rat myocardial cells were measured using the Ion Optix detection system and the whole-cell patch-clamp technique. SFR can decrease the activity of serum CK, LDH and MDA, and increase the activity of serum SOD, reduce intracellular calcium concentration and the manufacture of ROS. In addition, SFR can improve changes in heart morphology. SFR can significantly inhibit contraction, Ca2+ transients and ICa-L in isolated ventricular myocytes. SFR has a cardioprotective role in ISO-induced MI rats, and the underling mechanism is related to the inhibition of oxidative stress, myocardial contractility, ICa-L and the regulation of Ca2+ homeostasis.


Assuntos
Cálcio/metabolismo , Crocus/química , Cicloexenos/farmacologia , Cicloexenos/uso terapêutico , Isquemia Miocárdica/tratamento farmacológico , Isquemia Miocárdica/metabolismo , Miocárdio/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fitoterapia , Terpenos/farmacologia , Terpenos/uso terapêutico , Animais , Cardiotônicos , Células Cultivadas , Cicloexenos/isolamento & purificação , Modelos Animais de Doenças , Isoproterenol/efeitos adversos , Masculino , Malondialdeído/metabolismo , Contração Miocárdica/efeitos dos fármacos , Isquemia Miocárdica/induzido quimicamente , Ratos Sprague-Dawley , Superóxido Dismutase/metabolismo , Terpenos/isolamento & purificação
19.
Arch Med Res ; 51(5): 413-418, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32327292

RESUMO

INTRODUCTION: Stable ischemic heart disease (SIHD) is a condition that develops in subjects after myocardial infarction. Evidence suggests that optimal medical treatment (OMT) is not inferior to intervention (INT) using percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG). AIM: To compare clinical outcomes in subjects with SIHD who only received OMT and those who received INT+OMT. METHODS: We retrospectively examined subjects with SIHD who underwent myocardial perfusion study-SPECT/CT in a reference center in Mexico. We assigned two branches: INT+OMT (subjects with previous PCI or CABG) and OMT (subjects with antiplatelet drugs, ß-blockers, renin-angiotensin-system blockade, nitrates, calcium-channel blockers, and aggressive lipid-lowering therapy). Clinical outcomes at follow-up were angina relief, functional class improvement, hospitalization, myocardial reinfarction and death from any cause. RESULTS: We included 100 subjects; 51 with OMT and 49 with INT+OMT. 54 subjects had 1 affected vessel and 46 more than 2. INT+OMT group had up to 14 fold likelihood (95% CI: 3.38-63.35) of achieving angina relief and 2.2 fold likelihood (95% CI: 0.92-5.57, p = 0.077) for functional class improvement. No differences were found in hospitalization, myocardial infarction and death from any cause compared to OMT. CONCLUSIONS: Subjects with OMT have no higher risk of adverse clinical outcomes compared to INT+OMT. However, the INT+OMT provides angina relief and functional class improvement compared to OMT.


Assuntos
Isquemia Miocárdica/tratamento farmacológico , Idoso , Estudos de Coortes , Doença da Artéria Coronariana/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
20.
Am J Chin Med ; 48(2): 341-356, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32138537

RESUMO

MicroRNA 145 (miR-145) is a critical modulator of cardiovascular diseases. The downregulation of myocardial miR-145 is followed by an increase in disabled-2 (Dab2) expression in cardiomyocytes. (-)-epigallocatechin gallate (EGCG) is a flavonoid that has been evaluated extensively due to its diverse pharmacological properties including anti-inflammatory effects. The aim of this study was to investigate the cardioprotective effects of EGCG under hypoxia-induced stress in vitro and in vivo. The hypoxic insult led to the suppression of miR-145 expression in cultured rat cardiomyocytes in a concentration-dependent manner. Western blotting and real-time PCR were performed. In rat myocardial infarction study, in situ hybridization, and immunofluorescent analyses were adopted. The western blot and real-time PCR data revealed that hypoxic stress with 2.5% O2 suppressed the expression of miR-145 and Wnt3a/ß-catenin in cultured rat cardiomyocytes but augmented Dab2. Treatment with EGCG attenuated Dab2 expression, but increased Wnt3a and ß-catenin in hypoxic cultured cardiomyocytes. Following in vivo myocardial infarction (MI) study, the data revealed the myocardial infarct area reduced by 48.5%, 44.6%, and 48.5% in EGCG (50mg/kg) or miR-145 dominant or Dab2 siRNA groups after myocardial infarction for 28 days, respectively. This study demonstrated that EGCG increased miR-145, Wnt3a, and ß-catenin expression but attenuated Dab2 expression. Moreover, EGCG ameliorated myocardial ischemia in vivo. The novel suppressive effect was mediated through the miR-145 and Dab2/Wnt3a/ß-catenin pathways.


Assuntos
Proteínas Adaptadoras de Transporte Vesicular/genética , Proteínas Adaptadoras de Transporte Vesicular/metabolismo , Catequina/análogos & derivados , Expressão Gênica/efeitos dos fármacos , MicroRNAs/genética , MicroRNAs/metabolismo , Isquemia Miocárdica/tratamento farmacológico , Isquemia Miocárdica/genética , Miócitos Cardíacos/metabolismo , Fitoterapia , Proteína Wnt3A/genética , Proteína Wnt3A/metabolismo , beta Catenina/genética , beta Catenina/metabolismo , Animais , Catequina/farmacologia , Catequina/uso terapêutico , Células Cultivadas , Relação Dose-Resposta a Droga , Ratos
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