Relationship between pyroptosis and cardiovascular diseases and traditional Chinese medicine prevention and treatment research / 中国中药杂志

Pyroptosis is a programmed cell death initiated by the activation of caspases, which is involved in the development and progression of several cardiovascular diseases. The gasdermins, a protein family, are key executive proteins in the development of pyroptosis, which increase cell membrane permeability, mediate the release of inflammatory factors, and aggravate the inflammatory injury. Traditional Chinese medicine(TCM)has shown unique therapeutic advantages in cardiovascular diseases with multi-component and multi-target characteristics. Currently, the effective prevention and treatment of cardiovascular diseases based on the theory of pyroptosis become a new research hotspot in this field. Based on the theories of TCM and modern medicine, this study summarized the role of pyroptosis in cardiovascular diseases such as atherosclerosis, myocardial infarction, diabetic cardiomyopathy, hypertension, and myocarditis. The role of TCM, including active monomers, crude extracts, and compound preparations, in cardiovascular protection through the regulation of pyroptosis was also summarized, providing a theoretical basis for the clinical prevention and treatment of cardiovascular diseases by TCM.

Utilidad de la tomografía de coherencia óptica como guía en el tratamiento del síndrome coronario agudo: reporte de un caso / Utility of optical coherence tomography to guide treatment in acute coronary syndromes: case report / Utilidade da tomografia de coerência óptica como guia no tratamento da síndrome coronariana aguda: relato de um caso

La tomografía de coherencia óptica (OCT) es una técnica de imagen endovascular con elevada resolución espacial que permite evaluar las diferentes estructuras que componen la pared de las arterias coronarias, caracterizar morfológicamente la placa aterosclerótica y establecer el mecanismo fisiopatológico subyacente en los síndromes coronarios agudos (SCA). Se presenta el caso clínico de un paciente con infarto agudo de miocardio, donde la OCT evidenció que la reducción de la luz arterial estaba determinada principalmente por la presencia de trombo, a la vez que demostró una disrupción endotelial (ruptura de placa) como mecanismo fisiopatológico subyacente. Se adoptó una estrategia invasivo-conservadora, donde finalmente no se implantó stent. La información surgida de la OCT en este caso particular fue fundamental en la toma de decisiones.

Optical coherence tomography (OCT) is an endovascular imaging technique with high spatial resolution. It allows to evaluate the different structures that compose coronary arteries' wall, morphologically characterize atherosclerotic plaques and establish the underlying pathophysiological mechanism in acute coronary syndromes (ACS). The case of a patient with acute myocardial infarction is presented, in which OCT showed that the reduction of arterial lumen was determined mainly by the presence of thrombus, while also demonstrated endothelial disruption (plaque rupture) as the underlying pathophysiological mechanism. An invasive-conservative strategy was adopted and finally stent was not implanted. The information that emerged from the OCT in this particular case was fundamental in decision-making.

A tomografia de coerência óptica (OCT) é uma técnica de imagem endovascular com alta resolução espacial que permite a avaliação das diferentes estruturas que compõem a parede das artérias coronárias, a caracterização morfológica da placa aterosclerótica e o estabelecimento do mecanismo fisiopatológico subjacente de síndrome coronariana aguda (SCA). Apresentamos o caso clínico de um paciente com enfarte agudo do miocárdio, onde a OCT mostrou que a redução do lúmen arterial foi determinada principalmente pela presença de trombo, ao mesmo tempo que demonstrou uma ruptura endotelial (ruptura da placa) como causa fisiopatológica subjacente. Adotou-se uma estratégia invasiva-conservadora, onde finalmente o stent não foi implantado. As informações obtidas da OCT neste caso específico foram fundamentais na tomada de decisão.

Estrategia fármaco-invasiva en el manejo del infarto agudo al miocardio con supradesnivel del ST / Pharmaco-invasive approach in the management of acute myocardial infarction. Analysis of 144 cases

BACKGROUND: In those patients who do not have timely access to primary angioplasty, the pharmaco-invasive approach, that is, the use of thrombolysis as a bridging measure prior to the coronary angiography, is a safe alternative. AIM: To describe the features of patients with an acute ST-elevation myocardial infarction (STEMI) treated with a pharmaco-invasive strategy. MATERIAL AND METHODS: Descriptive observational study of 144 patients with mean age of 46 years with STEMI who received a dose of thrombolytic prior to their referral for primary angioplasty at a public hospital between 2018 and 2021. RESULTS: There were no differences the clinical presentation according to the Killip score at admission between thrombolyzed and non-thrombolyzed patients (p = ns). Fifty-three percent of non-thrombolyzed patients were admitted with an occluded vessel (TIMI 0) compared with 27% of thrombolyzed patients (p < 0.001). The thrombolyzed group required significantly less use of thromboaspiration (3.5 and 8.4% respectively; p = 0.014). Despite this, 91 and 92% of non-thrombolyzed and thrombolyzed patients achieved a post-angioplasty TIMI 3 flow. Long-term survival was 91 and 86% in thrombolyzed and non-thrombolyzed patients, respectively (p = ns). CONCLUSIONS: The pharmaco-invasive strategy is a safe alternative when compared to primary angioplasty in centers that don't have timely access to Interventional Cardiology.

Consumption of mate Ilex paraguariensis: a folk beverage with antioxidant power against myocardial ischemic injury

The effects of the aqueous extract of Ilex paraguariensis (Ip)and the flavonoid quercetin were tested during the induction of in vivomyocardial ischemia/ reperfusion in Rattus norvegicus. The antioxidant power of the extract and quercetin were chemically determined. The experimental groups were: control, ischemia/reperfusion induction, Iporal treatment, Iporal treatment and ischemia /reperfusion, quercetin oral treatment, and quercetin oral treatment and ischemia/reperfusion. Rats were anesthetized with sodium thiopental and xylazine via intraperitoneal injection and subsequently underwent 15 minutes of ischemia followed by 15 minutes of reperfusion. Ischemia was promoted by tying the left anterior descending coronary artery. Areas of risk and infarction were stained by intravenous Evans blue and triphenyl tetrazolium chloride. Reactive oxygen species (ROS), antioxidant capacity against peroxylradicals, and lipid peroxidation of the myocardium were quantified. A significant reduction in areas of risk and infarction was detected in the ischemic myocardium treated with Ipand quercetin; ROS generation and lipid peroxidation were significantly reduced, and the antioxidant capacity was elevated. Oral administration of Ippromoted antioxidant benefits in the myocardium during ischemia and reperfusion, which reduced infarction. We suggest that Mate (a hot drink made from steeped dried leaves of Ip) consumption is a potential cardioprotective habit of indigenous people from southern South American countries, which must be better understood scientifically and ethnographically.

Jatrorrhizine reduces myocardial infarction-induced apoptosis and fibrosis through inhibiting p53 and TGF-ß1/Smad2/3 pathways in mice

Purpose: To explore the mechanism of jatrorrhizine on apoptosis and fibrosis induced by myocardial infarction (MI) in an animal model. Methods: The left anterior descending branch of coronary artery was surgically ligated to duplicate the mouse model of MI. The sham and infarcted mice were treated with normal saline once a day, while mice in experimental groups received low-dose (LD) and high-dose (HD) jatrorrhizine once a day respectively. Two weeks later, cardiac function was detected by echocardiography, and histopathological examination was performed using hematoxylin and eosin (H&E) and Masson staining. The expressions of p53, TGF-ß1, Smad/2/3, Bax, Bcl-2, collagen I and collagen III were quantified using qRT-PCR and western blot assays. Results: Jatrorrhizine significantly improved left ventricular ejection fraction (LVEF) and left ventricle end-systolic (LVES) in mice. Histopathological, administration of jatrorrhizine weakened infiltration of inflammatory cells and cardiac fibrosis in myocardium of mice caused by MI. Additionally, jatrorrhizine suppressed cardiomyocyte apoptosis exhibited as its capability to reverse changes of Bax and Bcl-2 levels in myocardium caused by MI. Jatrorrhizine statistically significantly downregulated expression of collagen I and collagen III, as well as TGF-ß1, Smad2/3 and p53. Conclusions: Jatrorrhizine reduce cardiomyocyte apoptosis and fibrosis through inhibiting p53/Bax/Bcl-2 and TGF-ß1/Smad2/3 signaling pathways.

Salidroside induced repair of myocardial infarction through Nrf2/HO-1

Abstract Salidroside (SAL) has been confirmed to have some protective effects against inflammatory injury. However, little information was established as to the mechanism of these protective effects. To this effect, we designed this study to explore the protective effects and mechanisms of SAL against myocardial infarction (MI). A rat MI model was established and divided into five groups (n = 6): sham, MI, MI+SAL, MI+ LY294002 (PI3K inhibitor), and MI+SAL+ LY294002. The cardiac function and histological pathology were analyzed with a color Doppler ultrasonic diagnostic instrument. Anti-oxidative enzyme activities and the production of inflammatory media were assayed by biochemical kits and ELISA. MI size and fibrosis were assayed by Masson's trichrome staining while Bax/Bcl-2 and PI3K/Akt/Nrf2/HO-1 were assayed by Western blotting and immunofluorescence. The results showed that SAL significantly improved the left ventricle ejection fraction and fractional shortening, decreased the MI size and fibrosis, inhibited apoptosis and promoted blood vessel formation. SAL promoted anti-oxidative and anti-inflammatory abilities. Moreover, SAL enhanced PI3K/ Akt/Nrf2/HO-1 expression. To this effect, we designed this study suggested that SAL induced repair of MI via PI3K/A kt/ Nrf2/HO-1.

Pterostilbeno Reduz o Estresse Oxidativo no Pulmão e no Ventrículo Direito Induzido por Infarto do Miocárdio Experimental / Pterostilbene Reduces Experimental Myocardial Infarction-Induced Oxidative Stress in Lung and Right Ventricle

Resumo Fundamento O pterostilbeno (PS), um composto polifenólico natural e antioxidante, surge como uma intervenção promissora para minimizar danos do infarto agudo do miocárdio (IAM). Objetivo Este estudo teve como objetivo avaliar o desempenho do PS na promoção da homeostase redox nos pulmões e no ventrículo direito (VD) de animais infartados. Métodos Ratos Wistar machos (60 dias de idade) foram randomizados em três grupos: SHAM, IAM (infarto) e IAM+PS (IAM + pterostilbeno). Sete dias após o procedimento de IAM, os ratos foram tratados com PS (100 mg/kg/dia) por gavagem por oito dias. Os animais foram depois sacrificados e os pulmões e VD foram coletados para análise do balanço redox (diferenças foram consideradas significativas quando p<0,05). Resultados Nossos resultados mostram que o IAM desencadeia a interrupção redox no VD e nos pulmões, o que pode contribuir para danos induzido pelo IAM nesses órgãos. Consistentemente, o PS mitigou o estresse oxidativo e restaurou as defesas antioxidantes (Glutationa - GSH nos pulmões: SHAM = 0,79 ± 0,07; IAM = 0,67 ± 0,05; IAM + PS = 0,86 ± 0,14; p<0,05), indicando seu papel protetor neste cenário. Conclusão Nosso trabalho evidencia o potencial do uso de PS como abordagem terapêutica adjuvante após IAM para proteção dos tecidos pulmonares e cardíacos direitos.

Abstract Background Pterostilbene (PS), a natural and antioxidant polyphenolic compound emerges as a promising intervention in improving the myocardial infarction (MI) damages. Objetives This study aimed to evaluate PS actions in promoting redox homeostasis in lungs and right ventricle (RV) of infarcted animals. Methods Male Wistar rats (60 day-old) were randomized into three groups: SHAM, MI (infarcted), and MI+PS (MI+pterostilbene). Seven days after MI procedure, rats were treated with PS (100 mg/kg/day) via gavage for eight days. Animals were euthanized and the lungs and RV were harvested for analyses of redox balance (Differences were considered significant when p<0.05). Results Our results show that MI triggers a redox disruption scenario in RV and lungs, which can contribute to MI-induced damage on these organs. Consistently, PS mitigated oxidative stress and restored antioxidant defenses (GSH in lungs: SHAM= 0.79±0.07; MI=0.67±0.05; MI+PS=0.86±0.14; p<0.05), indicating its protective role in this scenario. Conclusions Our work evidences the PS potential use as an adjuvant therapeutic approach after MI focusing on protecting pulmonary and right-sided heart tissues.

A young patient with recurrent myocardial infarction within a half month / 中南大学学报(医学版)

In this study, we reported a young male patient with acute chest pain who was diagnosed as myocardial infarction. The regular medication was performed following coronary intervention. Under such condition, this patient had 3 times myocardial infarction within a half month. The laboratory results showed that there might be a state of hypercoagulability. Aspirin combined with clopidogrel and other treatment were administrated. Meanwhile, the examination demonstrated that there was aspirin-resistant in the patient. The antiplatelet drug and extended anticoagulation therapy were carried out. There was no further myocardial infarction, and no coronary arteries stenosis was found in the re-examination angiography. Aspirin resistance and hypercoagulability should be considered when patients occurred the repeated myocardial infarction after regular medication and coronary intervention. Replacement of the antiplatelet treatment or combination with anticoagulant therapy is necessary in similar patient to avoid the sever consequence.

Identification of traditional Chinese drugs containing active ingredients for treating myocardial infarction and analysis of their therapeutic mechanisms by network pharmacology and molecular docking / 南方医科大学学报

OBJECTIVE@#To identify traditional Chinese drugs that contain active ingredients for treatment of myocardial infarction (MI) and explore their therapeutic mechanisms using network pharmacology and molecular docking technology.@*METHODS@#The TCMSP database was used for screening the traditional Chinese drugs containing active ingredients for treating MI, and the related targets of MI and the candidate drugs were obtained from Genecards, OMIM, PharmGkb and PharmMapper databases. The common target network of the drug targets and disease targets was established using Venny2.1.0 software. GO and KEGG signal pathway enrichment analysis of the common targets was performed, and the protein-protein interaction (PPI) network was constructed for the targets. The targets in the PPI network were analyzed to identify the key targets, for which GO and KEGG pathway enrichment analyses were performed. Molecular docking was performed for the candidate ingredients and the key targets, and a total score ≥6 was used as the criteria for screening the therapeutic ingredients and their docking binding with key targets was verified. A human umbilical vein endothelial cell (HUVEC) model of oxygen-glucose deprivation (OGD) was used to validate the candidate ingredients and the key therapeutic targets for MI by Western blotting.@*RESULTS@#Our analysis identified Salvia miltiorrhiza and Dalbergiae odoriferae as the candidate drugs rich in active ingredients for treatment of MI. These ingredients involved 16 key therapeutic targets for MI, which participated in such biological processes as inflammatory response, angiogenesis, energy metabolism and oxidative stress and the pathways including HIF-1, VEGF, and TNF pathways. Sclareol and PTGS2 in Salvia miltiorrhiza and formononetin and KDR in Dalbergiae odoriferae all had high docking total scores. Western blotting showed that at medium and high doses, sclareol significantly inhibited PTGS2 expression and formononetin promoted KDR expressions in the cell models in a dose-dependent manner (P < 0.05).@*CONCLUSION@#Both Salvia miltiorrhiza and Dalbergiae odoriferae have good therapeutic effects on MI. Sclareol in Salvia miltiorrhiza and formononetin in Dalbergiae odoriferae regulate the expressions of KDR and PTGS2, respectively, to modulate the inflammatory response, angiogenesis, oxidative stress and energy metabolism and thus produce myocardial protective effects.

O Pré-Condicionamento com Dexmedetomidina Reduz a Lesão de Isquemia-Reperfusão do Miocárdio em Ratos, Inibindo a Via PERK / Dexmedetomidine Preconditioning Reduces Myocardial Ischemia-Reperfusion Injury in Rats by Inhibiting the PERK Pathway

Resumo Fundamento A cardiopatia isquêmica atraiu muito atenção devido às altas taxas de mortalidade, custos do tratamento e a crescente morbidade na população jovem. Estratégias de reperfusão reduziram a mortalidade. Porém, a reperfusão pode levar à morte do cardiomiócito e subsequente dano irreversível ao miocárdio. No momento, não há um tratamento eficiente e direcionado para a lesão de isquemia-reperfusão (I/R). Objetivos Avaliar se a dexmedetomidina (DEX) tem efeito protetivo na I/R do miocárdio e explorar os possíveis mecanismos por trás dela. Métodos Corações de ratos foram perfundidos com o sistema de perfusão de Langendorff e aleatoriamente distribuídos em cinco grupos: grupo controle, perfundido com solução de Krebs-Henseleit (K-H) por 205 minutos sem isquemia; e quatro grupos de teste que foram submetidos a 40 minutos de isquemia global e 120 minutos de reperfusão. O Grupo DEX, o grupo ioimbina (IO) e o grupo DEX + IO foram perfundidos com DEX (10 nM), IO (1 μM) ou a combinação de DEX e IO antes da reperfusão, respectivamente. A hemodinâmica cardíaca, o tamanho do infarto do miocárdio e a histologia do miocárdio foram avaliados. A expressão da proteína-78 regulada pela glicose (GRP78), a proteína quinase do retículo endoplasmático (PERK), a PERK fosforilada, o fator de iniciação eucariótico 2α (eIF2α), eIF2α fosforilado, o fator de transcrição 4 (TCF-4) e a proteína homóloga à proteína ligadora do acentuador CCAAT (CHOP) foram avaliados. P< 0,05 foi considerado para indicar a diferença estatisticamente significativa. Resultados O pré-condicionamento com DEX melhorou a função cardíaca nos corações com I/R, reduziu o infarto do miocárdio, a apoptose do miocárdio e a expressão de GRP78, p-PERK, eIF2α, p-eIF2α, TCF-4 e CHOP. Conclusões O pré-tratamento com DEX reduziu a lesão de I/R no miocárdio ao suprimir a apoptose, o que foi induzido pela via PERK.

Abstract Background Ischemic heart disease has attracted much attention due to its high mortality rates, treatment costs and the increasing morbidity in the young population. Strategies for reperfusion have reduced mortality. However, reperfusion can lead to cardiomyocyte death and subsequent irreversible myocardial damage. At present, the timely and targeted treatment of ischemia-reperfusion (I/R) injury is often lacking. Objectives To evaluate if dexmedetomidine (DEX) has a protective effect in myocardiual I/R and explore the possible mechanism behind it. Methods Rat hearts were perfused with a Langendorff perfusion system, and randomly assigned to five groups: control group, perfused with Krebs-Henseleit (K-H) solution for 205 minutes without ischemia; and four test groups that underwent 40 minutes of global ischemia and 120 min of reperfusion. The DEX group, the yohimbine (YOH) group and the DEX + YOH group were perfused with DEX (10 nM), YOH (1 μM) or the combination of DEX and YOH prior to reperfusion, respectively. Cardiac hemodynamics, myocardial infarct size, and myocardial histology were evaluated. The expression of glucose-related protein 78 (GRP78), protein kinase R-like ER kinase (PERK), phosphorylated PERK, eukaryotic initiation factor 2α (eIF2α), phosphorylated eIF2α, activating transcription factor 4 (ATF4), and CCAAT/enhancer-binding protein homologous protein (CHOP) were assessed. P<0.05 was considered to indicate a statistically significant difference. Results DEX preconditioning improved the cardiac function of I/R hearts, reduced myocardial infarction, myocardial apoptosis, and the expression of GRP78, p-PERK, eIF2α, p-eIF2α, ATF4 and CHOP. Conclusions DEX pretreatment reduced myocardial I/R injury by suppressing apoptosis, which was induced by the PERK pathway.

Acurácia da redução do segmento-ST pós-trombólise como preditor de reperfusão adequada em estratégia fármaco-invasiva / Accuracy of post-thrombolysis ST-segment reduction as an adequate reperfusion predictor in the pharmaco-invasive aproach

Resumo Fundamento A intervenção coronária percutânea primária é considerada o "padrão-ouro" para reperfusão coronária. Entretanto, quando não disponível, a estratégia fármaco-invasiva é método alternativo, e o eletrocardiograma (ECG) tem sido utilizado para identificar sucesso na reperfusão. Objetivos Nosso estudo teve como objetivo examinar alterações no segmento-ST pós-lise e seu poder de prever a recanalização, usando os escores angiográficos TIMI e blush miocárdio (MBG) como critério de reperfusão ideal. Métodos Foram estudados 2.215 pacientes com infarto agudo do miocárdio com supra-ST submetidos à fibrinólise [(Tenecteplase)-TNK] e encaminhados para angiografia coronária em até 24 h pós-fibrinólise ou imediatamente encaminhados à terapia de resgate. O ECG foi realizado pré-TNK e 60 min-pós. Os pacientes foram categorizados em dois grupos: aqueles com reperfusão ideal (TIMI-3 e MBG-3) e aqueles com reperfusão inadequada (fluxo TIMI <3). Foi definido o critério de reperfusão do ECG pela redução do segmento ST >50%. Consideramos p-valor <0,05 para as análises, com testes bicaudais. Resultados O critério de reperfusão pelo ECG apresentou valor preditivo positivo de 56%; valor preditivo negativo de 66%; sensibilidade de 79%; e especificidade de 40%. Houve fraca correlação positiva entre a redução do segmento-ST e os dados angiográficos de reperfusão ideal (r = 0,21; p <0,001) e baixa precisão diagnóstica, com AUC de 0,60 (IC-95%; 0,57-0,62). Conclusão Em nossos resultados, a redução do segmento-ST não conseguiu identificar com precisão os pacientes com reperfusão angiográfica apropriada. Portanto, mesmo pacientes com reperfusão aparentemente bem-sucedida devem ser encaminhados à angiografia brevemente, a fim de garantir fluxo coronário macro e microvascular adequados.

Abstract Background Primary percutaneous coronary intervention is considered the "gold standard" for coronary reperfusion. However, when not available, the drug-invasive strategy is an alternative method and the electrocardiogram (ECG) has been used to identify reperfusion success. Objectives Our study aimed to assess ST-Segment changes in post-thrombolysis and their power to predict recanalization and using the angiographic scores TIMI-flow and Myocardial Blush Grade (MBG) as an ideal reperfusion criterion. Methods 2,215 patients with ST-Segment Elevation Myocardial Infarction (STEMI) undergoing fibrinolysis [(Tenecteplase)-TNK] and referred to coronary angiography within 24 h post-fibrinolysis or immediately referred to rescue therapy were studied. The ECG was performed pre- and 60 min-post-TNK. The patients were categorized into 2 groups: those with ideal reperfusion (TIMI-3 and MBG-3) and those with inadequate reperfusion (TIMI and MBG <3). The ECG reperfusion criterion was defined by the reduction of the ST-Segment >50%. A p-value <0.05 was considered for the analyses, with bicaudal tests. Results The ECG reperfusion criterion showed a positive predictive value of 56%; negative predictive value of 66%; sensitivity of 79%; and specificity of 40%. There was a weak positive correlation between ST-Segment reduction and ideal reperfusion angiographic data (r = 0.21; p <0.001) and low diagnostic accuracy, with an AUC of 0.60 (95%CI: 0.57-0.62). Conclusion The ST-Segment reduction was not able to accurately identify patients with adequate angiographic reperfusion. Therefore, even patients with apparently successful reperfusion should be referred to angiography soon, to ensure adequate macro and microvascular coronary flow.

Efeitos Terapêuticos da Tripla Antiagregação Plaquetária em Pacientes Femininas Idosas com Diabetes e Infarto Agudo do Miocárdio / Therapeutic Effects of Triple Antiplatelet Therapy in Elderly Female Patients with Diabetes and Acute Myocardial Infarction

Resumo Fundamento A dupla antiagregação plaquetária (DAP) é o tratamento fundamental do infarto agudo do miocárdio (IAM). Objetivo O presente estudo visou investigar a eficácia e a segurança da tripla antiagregação plaquetária (TAP) em pacientes femininas idosas com diabetes e infarto agudo do miocárdio com supradesnível do segmento ST (IAMCSST), que foram submetidas à intervenção coronária percutânea ICP. Métodos Trata-se se de um estudo randomizado e mono-cego. O grupo controle A (97 pacientes idosos do sexo masculino com diabetes e STEMI, cujos escores CRUSADE foram < 30) recebeu aspirina, ticagrelor e tirofibana. Um total de 162 pacientes femininas idosas com diabetes e IAMCSST foram divididas aleatoriamente em dois grupos de acordo com o escore CRUSADE. O grupo B (69 pacientes com escore CRUSADE > 31) recebeu aspirina e ticagrelor. O grupo C (93 pacientes com escore CRUSADE < 30) recebeu aspirina, ticagrelor e tirofibana. Valores de p < 0,05 foram considerados estatisticamente significativos. Resultados Após a PCI, o fluxo sanguíneo grau 3 Thrombolysis in Myocardial Infarction (TIMI) e a perfusão miocárdica TIMI grau 3 foram significativamente menos prevalentes no grupo B, em comparação com o grupo A (p < 0,05). Quando comparada aos grupos A e C, a incidência de complicações adversas maiores foi significativamente maior no grupo B (p < 0,05). Conclusão A TAP pode efetivamente reduzir a incidência de complicações maiores em pacientes idosas com diabetes e IAMCSST. No entanto, atenção cuidadosa deve ser dada à hemorragia em pacientes que recebem TAP. (Arq Bras Cardiol. 2020; [online].ahead print, PP.0-0)

Abstract Background Dual antiplatelet therapy (DAPT) is the cornerstone treatment of acute myocardial infarction (AMI). Objective The present study aimed to investigate the efficacy and safety of triple antiplatelet therapy (TAPT) in elderly female patients with diabetes and ST segment elevation myocardial infarction (STEMI), who had undergone percutaneous coronary intervention (PCI). Methods We designed a randomized, single-blind study. Control group A (97 elderly male patients with diabetes and STEMI, whose CRUSADE scores were < 30) received aspirin, ticagrelor, and tirofiban. A total of 162 elderly female patients with diabetes and STEMI were randomly divided into two groups according to CRUSADE score. Group B (69 patients with CRUSADE score > 31) received aspirin and ticagrelor. Group C (93 patients with CRUSADE score < 30) received aspirin, ticagrelor and tirofiban. P values < 0.05 were considered statistically significant. Results Compared to the findings in group A, post-PCI Thrombolysis in Myocardial Infarction (TIMI) grade 3 blood flow and TIMI myocardial perfusion grade 3 were significantly less prevalent in group B (p < 0.05). When compared to groups A and C, the incidence of major adverse complications was significantly higher in group B (p < 0.05). Conclusion TAPT could effectively reduce the incidence of major complications in elderly female patients with diabetes and STEMI. However, close attention should be paid to hemorrhage in patients receiving TAPT. (Arq Bras Cardiol. 2020; [online].ahead print, PP.0-0)

Melatonin and the cardiovascular system in animals: systematic review and meta-analysis

Melatonin, a hormone released by the pineal gland, demonstrates several effects on the cardiovascular system. Herein, we performed a systematic review and meta-analysis to verify the effects of melatonin in an experimental model of myocardial infarction. We performed a systematic review according to PRISMA recommendations and reviewed MEDLINE, Embase, and Cochrane databases. Only articles in English were considered. A systematic review of the literature published between November 2008 and June 2019 was performed. The meta-analysis was conducted using the RevMan 5.3 program provided by the Cochrane Collaboration. In total, 858 articles were identified, of which 13 were included in this review. The main results of this study revealed that melatonin benefits the cardiovascular system by reducing infarct size, improving cardiac function according to echocardiographic and hemodynamic analyses, affords antioxidant effects, improves the rate of apoptosis, decreases lactate dehydrogenase activity, enhances biometric analyses, and improves protein levels, as analyzed by western blotting and quantitative PCR. In the meta-analysis, we observed a statistically significant decrease in infarct size (mean difference [MD], -20.37 [-23.56, -17.18]), no statistical difference in systolic pressure (MD, -1.75 [-5.47, 1.97]), a statistically significant decrease in lactate dehydrogenase in animals in the melatonin group (MD, -4.61 [-6.83, -2.40]), and a statistically significant improvement in the cardiac ejection fraction (MD, -8.12 [-9.56, -6.69]). On analyzing potential bias, we observed that most studies presented a low risk of bias; two parameters were not included in the analysis, and one parameter had a high risk of bias. Melatonin exerts several effects on the cardiovascular system and could be a useful therapeutic target to combat various cardiovascular diseases.

Effect of neuregulin-1 on cardiac glucose metabolism in rats with experimental myocardial infarction / 中华心血管病杂志

Objective: To investigate the effect of neuregulin-1(NRG-1) on cardiac glucose metabolism in Sprague Dawley (SD) rats with experimental myocardial infarction (MI). Methods: Adult male SD rats were randomly divided into three groups: the sham-operated group, MI group, and MI+NRG1 group. The rat MI model was established via ligation of the left anterior descending coronary artery. Two weeks after operation, echocardiography was performed, MI rats with left ventricular ejection fraction (LVEF) between 0.3-0.5 were selected and randomly assigned to MI group and MI+NRG-1 group. Rats in MI+NRG-1 group were treated with recombinant human NRG-1β (100 μg/kg) via tail vein at 2 weeks after operation (twice per week for 6 weeks); while rats in sham-operated group and MI group received equal volume of physiological saline. By the end of administration, echocardiography and small animal positron emission tomography (PET) were performed to detect cardiac function and myocardial glucose uptake. Myocardial morphology and collagen volume fraction, cardiomyocyte apoptosis and reactive oxygen species (ROS) production were evaluated by histopathologic analysis. Myocardial pyruvate dehydrogenase (PDH) and citrate synthase (CS) activity, as well as ATP production were detected by commercial kits. The mRNA and protein expression levels of NRG-1, p-ErbB4, and key factors involved in glucose metabolism (including Glut-4, HK2, PDK4, PDH, CS) were detected by quantitative real-time PCR (qRT-PCR) and Western blot assay, respectively. Results: With the MI model successfully established, the left ventricular ejection fraction(LVEF) and left ventricular shortening fraction(LVFS) were significantly lower in MI group and MI+NRG-1 group than that in sham group (both P<0.01), while there was no significant difference between MI group and MI+NRG-1 group(all P>0.05). After 6 weeks of NRG-1β intervention, the LVEF and LVFS were significantly higher in MI+NRG-1 group than in MI group (both P<0.01). By the end of experiment, PET imaging showed that the mean standardized uptake value (SUVmean) were lower in MI+NRG-1 group than in the sham group (4.06±0.28 vs. 5.18±0.37, P<0.01), while significantly higher than that in MI group (4.06±0.28 vs.2.86±0.49, P<0.01). Histopathological analysis showed that compared with MI group, rats in MI+NRG-1 group exhibited significantly decreased left ventricle collagen volume fraction ((7.83±1.24) % vs. (18.31±3.58) %, P<0.01), cardiomyocyte apoptosis((37.98±4.26)% vs. (67.04±5.38)%, P<0.01), and DHE fluorescence intensity(0.057 28±0.007 06 vs. 0.076 94±0.008 46, P<0.01), indicating that NRG-1β could reduce ROS production. PDH activity, CS activity, and ATP production were significantly higher in MI+NRG-1 group than in MI group (all P<0.05). qRT-PCR demonstrated an upregulated Glut-4, HK2 and CS, but downregulated PDK4 mRNA expression in MI+NRG-1 group compared with MI group (all P<0.01). Western blot assay showed significantly higher protein expression of NRG-1, p-ErbB4, Glut-4, HK2, PDH, CS in MI+NRG-1 group than in MI group (all P<0.01). Conclusion: NRG-1 could improve glucose uptake and utilization in myocardium by activating phosphorylation of myocardial ErbB4 receptor in MI rats, thus providing a therapeutic option for improving energy metabolism after MI.