Inhibition of glutaminolysis alleviates myocardial fibrosis induced by angiotensin II / 生理学报

The present study was aimed to investigate the role and mechanism of glutaminolysis of cardiac fibroblasts (CFs) in hypertension-induced myocardial fibrosis. C57BL/6J mice were administered with a chronic infusion of angiotensin II (Ang II, 1.6 mg/kg per d) with a micro-osmotic pump to induce myocardial fibrosis. Masson staining was used to evaluate myocardial fibrosis. The mice were intraperitoneally injected with BPTES (12.5 mg/kg), a glutaminase 1 (GLS1)-specific inhibitor, to inhibit glutaminolysis simultaneously. Immunohistochemistry and Western blot were used to detect protein expression levels of GLS1, Collagen I and Collagen III in cardiac tissue. Neonatal Sprague-Dawley (SD) rat CFs were treated with 4 mmol/L glutamine (Gln) or BPTES (5 μmol/L) with or without Ang II (0.4 μmol/L) stimulation. The CFs were also treated with 2 mmol/L α-ketoglutarate (α-KG) under the stimulation of Ang II and BPTES. Wound healing test and CCK-8 were used to detect CFs migration and proliferation respectively. RT-qPCR and Western blot were used to detect mRNA and protein expression levels of GLS1, Collagen I and Collagen III. The results showed that blood pressure, heart weight and myocardial fibrosis were increased in Ang II-treated mice, and GLS1 expression in cardiac tissue was also significantly up-regulated. Gln significantly promoted the proliferation, migration, mRNA and protein expression of GLS1, Collagen I and Collagen III in the CFs with or without Ang II stimulation, whereas BPTES significantly decreased the above indices in the CFs. α-KG supplementation reversed the inhibitory effect of BPTES on the CFs under Ang II stimulation. Furthermore, in vivo intraperitoneal injection of BPTES alleviated cardiac fibrosis of Ang II-treated mice. In conclusion, glutaminolysis plays an important role in the process of cardiac fibrosis induced by Ang II. Targeted inhibition of glutaminolysis may be a new strategy for the treatment of myocardial fibrosis.

Prognostic significance of T2 mapping in evaluating myocardium alterations in patients with ST segment elevation myocardial infarction / 中华危重病急救医学

OBJECTIVE@#To investigate the value of T2 mapping in the assessment of myocardial changes and prognosis in patients with acute ST segment elevation myocardial infarction (STEMI).@*METHODS@#A retrospective study was conducted. A total of 30 patients with acute STEMI admitted to Tianjin First Central Hospital from January 2021 to March 2022 were enrolled as the experimental group. At the same time, 30 age- and sex-matched healthy volunteers and outpatients with non-specific chest pain with no abnormalities in cardiac magnetic resonance (CMR) examination were selected as the control group. CMR was performed within 2 weeks after the diagnosis of STEMI, as the initial reference. A plain CMR review was performed 6 months later (chronic myocardial infarction, CMI). Plain scanning includes film sequence (CINE), T2 weighted short tau inversion recovery (T2-STIR), native-T1 mapping, and T2 mapping. Enhanced scanning includes first-pass perfusion, late gadolinium enhancement (LGE), and post-contrast T1 mapping. Quantitative myocardial parameters were compared between the two groups, before and after STEMI myocardial infarction. The receiver operator characteristic curve (ROC curve) was used to evaluate the diagnostic efficacy of native-T1 before myocardial contrast enhancement and T2 values in differentiating STEMI and CMI after 6 months.@*RESULTS@#There were no statistically significant differences in age, gender, heart rate and body mass index (BMI) between the two groups, which were comparable. The native-T1 value, T2 value and extracellular volume (ECV) were significantly higher than those in the control group [native-T1 value (ms): 1 434.5±165.3 vs. 1 237.0±102.5, T2 value (ms): 48.3±15.6 vs. 21.8±13.1, ECV: (39.6±13.8)% vs. (22.8±5.0)%, all P < 0.05]. In the experimental group, 12 patients were re-examined by plain CMR scan 6 months later. After 6 months, the high signal intensity on T2-STIR was still visible, but the range was smaller than that in the acute phase, and the native-T1 and T2 values were significantly lower than those in the acute phase [native-T1 value (ms): 1 271.0±26.9 vs. 1 434.5±165.3, T2 value (ms): 34.2±11.2 vs. 48.3±15.6, both P < 0.05]. ROC curve analysis showed that the area under the ROC curve (AUC) of native-T1 and T2 values in differentiating acute STEMI from CMI was 0.71 and 0.80, respectively. When native-T1 cut-off value was 1 316.0 ms, the specificity was 100% and the sensitivity was 53.3%; when T2 cut-off value was 46.7 ms, the specificity was 100% and the sensitivity was 73.8%.@*CONCLUSIONS@#The T2 mapping is a non-invasive method for the diagnosis of myocardial changes in patients with acute STEMI myocardial infarction, and can be used to to evaluate the clinical prognosis of patients.

Forensic Pathological Diagnosis of Acute and Old Myocardial Infarction Using Fourier Transform Infrared Spectroscopy / 法医学杂志

OBJECTIVES@#Fourier transform infrared spectroscopy (FTIR) was used to analyze myocardial infarction tissues at different stages of pathological change to achieve the forensic pathology diagnosis of acute and old myocardial infarction.@*METHODS@#FTIR spectra data of early ischemic myocardium, necrotic myocardium, and myocardial fibrous tissue in the left ventricular anterior wall of the sudden death group of atherosclerotic heart disease and the myocardium of the normal control group were collected using hematoxylin-eosin (HE) and immunohistochemistry (IHC) staining as a reference, and the data were analyzed using multivariate statistical analysis.@*RESULTS@#The mean normalized spectra of control myocardium, early ischemic myocardium and necrotic myocardium were relatively similar, but the mean second derivative spectra were significantly different. The peak intensity of secondary structure of proteins in early ischemic myocardium was significantly higher than in other types of myocardium, and the peak intensity of the α-helix in necrotic myocardium was the lowest. The peaks of amide Ⅰ and amide Ⅱ in the mean normalized spectra of myocardial fibrous tissue significantly shifted towards higher wave numbers, the peak intensities of amide Ⅱ and amide Ⅲ were higher than those of other types of myocardium, and the peak intensities at 1 338, 1 284, 1 238 and 1 204 cm-1 in the mean second derivative spectra were significantly enhanced. Principal component analysis (PCA) and partial least square-discriminant analysis (PLS-DA) showed that FTIR could distinguish different types of myocardium.@*CONCLUSIONS@#FTIR technique has the potential to diagnose acute and old myocardial infarction, and provides a new basis for the analysis of the causes of sudden cardiac death.

Nilotinib-loaded gelatin methacryloyl microneedles patch for the treatment of cardiac dysfunction after myocardial infarction / 生物医学工程学杂志

The study aimed to evaluate the therapeutic effect of nilotinib-loaded biocompatible gelatin methacryloyl (GelMA) microneedles patch on cardiac dysfunction after myocardial infarction(MI), and provide a new clinical perspective of myocardial fibrosis therapies. The GelMA microneedles patches were attached to the epicardial surface of the infarct and peri-infarct zone in order to deliver the anti-fibrosis drug nilotinib on the 10th day after MI, when the scar had matured. Cardiac function and left ventricular remodeling were assessed by such as echocardiography, BNP (brain natriuretic peptide) and the heart weight/body weight ratio (HW/BW). Myocardial hypertrophy and fibrosis were examined by WGA (wheat germ agglutinin) staining, HE (hematoxylin-eosin staining) staining and Sirius Red staining. The results showed that the nilotinib-loaded microneedles patch could effectively attenuate fibrosis expansion in the peri-infarct zone and myocardial hypertrophy, prevent adverse ventricular remodeling and finally improve cardiac function. This treatment strategy is a beneficial attempt to correct the cardiac dysfunction after myocardial infarction, which is expected to become a new strategy to correct the cardiac dysfunction after MI. This is of great clinical significance for improving the long-term prognosis of MI patients.

Effect and mechanism of Jiming Powder on myocardial fibrosis in mice with myocardial infarction / 中国中药杂志

Jiming Powder is a traditional ancient prescription with good therapeutic effect in the treatment of heart failure, but its mechanism lacks further exploration. In this study, a mouse model of coronary artery ligation was used to evaluate the effect and mechanism of Jiming Powder on myocardial fibrosis in mice with myocardial infarction. The study constructed a mouse model of heart failure after myocardial infarction using the method of left anterior descending coronary artery ligation. The efficacy of Jiming Powder was evaluated from multiple angles, including ultrasound imaging, hematoxylin-eosin(HE) staining, Masson staining, Sirius Red staining, and serum myocardial enzyme spectrum detection. Western blot analysis was performed to detect key proteins involved in ventricular remodeling, including transforming growth factor-β1(TGF-β1), α-smooth muscle actin(α-SMA), wingless-type MMTV integration site family member 3a(Wnt3a), β-catenin, matrix metallopeptidase 2(MMP2), matrix metallopeptidase 3(MMP3), TIMP metallopeptidase inhibitor 1(TIMP1), and TIMP metallopeptidase inhibitor 2(TIMP2). The results showed that compared with the model group, the high and low-dose Jiming Powder significantly reduced the left ventricular internal diameter in systole(LVID;s) and diastole(LVID;d), increased the left ventricular ejection fraction(LVEF) and left ventricular fractional shortening(LVFS), effectively improved cardiac function in mice after myocardial infarction, and effectively reduced the levels of myocardial injury markers such as creatine kinase(CK), creatine kinase isoenzyme(CK-MB), and lactic dehydrogenase(LDH), thus protecting ischemic myocardium. HE staining showed that Jiming Powder could attenuate myocardial inflammatory cell infiltration after myocardial infarction. Masson and Sirius Red staining demonstrated that Jiming Powder effectively inhibited myocardial fibrosis, reduced the collagen Ⅰ/Ⅲ ratio in myocardial tissues, and improved collagen remodeling after myocardial infarction. Western blot results showed that Jiming Powder reduced the expression of TGF-β1, α-SMA, Wnt3a, and β-catenin, decreased the levels of MMP2, MMP3, and TIMP2, and increased the level of TIMP1, suggesting its role in inhibiting cardiac fibroblast transformation, reducing extracellular matrix metabolism in myocardial cells, and lowering collagen Ⅰ and α-SMA content, thus exerting an anti-myocardial fibrosis effect after myocardial infarction. This study revealed the role of Jiming Powder in improving ventricular remodeling and treating myocardial infarction, laying the foundation for further research on the pharmacological effect of Jiming Powder.

Shexiang Tongxin Dropping Pill Allieviates Heart Failure via Extracellula Matrix-Receptor Interaction Pathways Based on RNA-Seq Transcriptomics and Experimental Studies / 中国结合医学杂志

OBJECTIVE@#To investigate the protective mechanisms of Chinese medicine Shexiang Tongxin Dropping Pills (STDP) on heart failure (HF).@*METHODS@#Isoproterenol (ISO)-induced HF rat model and angiotensin II (Ang II)-induced neonatal rat cardiac fibroblast (CFs) model were used in the present study. HF rats were treated with and without STDP (3 g/kg). RNA-seq was performed to identify differentially expressed genes (DEGs). Cardiac function was evaluated by echocardiography. Hematoxylin and eosin and Masson's stainings were taken to assess cardiac fibrosis. The levels of collagen I (Col I) and collagen III (Col III) were detected by immunohistochemical staining. CCK8 kit and transwell assay were implemented to test the CFs' proliferative and migratory activity, respectively. The protein expressions of α-smooth muscle actin (α-SMA), matrix metalloproteinase-2 (MMP-2), MMP-9, Col I, and Col III were detected by Western blotting.@*RESULTS@#The results of RNA-seq analysis showed that STDP exerted its pharmacological effects on HF via multiple signaling pathways, such as the extracellular matrix (ECM)-receptor interaction, cell cycle, and B cell receptor interaction. Results from in vivo experiments demonstrated that STDP treatment reversed declines in cardiac function, inhibiting myocardial fibrosis, and reversing increases in Col I and Col III expression levels in the hearts of HF rats. Moreover, STDP (6, 9 mg/mL) inhibited the proliferation and migration of CFs exposed to Ang II in vitro (P<0.05). The activation of collagen synthesis and myofibroblast generation were markedly suppressed by STDP, also the synthesis of MMP-2 and MMP-9, as well as ECM components Col I, Col III, and α-SMA were decreased in Ang II-induced neonatal rats' CFs.@*CONCLUSIONS@#STDP had anti-fibrotic effects in HF, which might be caused by the modulation of ECM-receptor interaction pathways. Through the management of cardiac fibrosis, STDP may be a compelling candidate for improving prognosis of HF.

Involvement of Interleukin-1 β/Insulin-Like Growth Factor 1 in Ameliorating Effects of Electroacupuncture on Myocardial Fibrosis Induced by Essential Hypertension / 中国结合医学杂志

OBJECTIVE@#To investigate the effect of electroacupuncture (EA) at Neiguan (PC 6) on myocardial fibrosis in spontaneously hypertensive rats (SHRs), and to explore the contribution of interleukin-1 β (IL-1 β), insulin-like growth factor 1 (IGF-1), and transforming growth factor β 1 (TGF- β 1) to the effects.@*METHODS@#Nine 12-weeks-old Wistar Kyoto (WKY) male rats were employed as the normal group. Twenty-seven SHRs were equally randomized into SHR, SHR+EA, and SHR + sham groups. EA was applied at bilateral PC 6 once a day 30 min per day in 8 consecutive weeks. After 8-weeks EA treatment at PC 6, histopathologic changes of collagen type I (Col I), collagen type 1 (Col 1) and the levels of IGF-1, 1L-1 β, TGF- β 1, matrix metalloproteinase (MMP)-2 and MMP-9 were examined in myocardial tissure respectively.@*RESULTS@#After 8-weeks EA treatment at PC 6, the enhanced myocardial fibrosis in SHRs were characterized by the increased mean fluorescence intensity of Col I and Col 1 in myocardium tissue (P<0.01). All these abnormal alterations above in SHR + EA group was significantly lower compared with the SHR group (P<0.01). Meanwhile, the increased levels of IL-1 β, IGF-1, TGF-β 1 in serum or myocardial tissue of SHRs, diminished MMP 9 mRNA expression in SHRs were also markedly inhibited after 8 weeks of EA treatment (P<0.05 or P<0.01). Furthermore, the contents of IL-1 β, IGF-1, TGF-β 1 in myocardial tissue were positively correlated with the systolic blood pressure and hydroxyproline respectively (P<0.01).@*CONCLUSION@#EA at bilateral PC 6 could ameliorate cardiac fibrosis in SHRs, which might be mediated by regulation of 1L-1 β/IGF-1-TGF- β 1-MMP9 pathway.

Myocardial biopsy of Liwen procedure: representability and etiological diagnostic value of cardiac samples obtained by a novel technique in patients with hypertrophic cardiomyopathy / 中华心血管病杂志

Objective: To investigate the representability and etiological diagnostic value of myocardium samples obtained from patients with hypertrophic cardiomyopathy (HCM) by transthoracic echocardiography-guided percutaneous intramyocardial septal biopsy (myocardial biopsy of Liwen procedure). Methods: This study was a retrospective case-series analysis. Patients with HCM, who underwent myocardial biopsy of Liwen procedure and radiofrequency ablation in Xijing Hospital, Air Force Military Medical University from July to December 2019, were included. Demographic data (age, sex), echocardiographic data and complications were collected through electronic medical record system. The histological and echocardiographic features, pathological characteristics of the biopsied myocardium of the patients were analyzed. Results: A total of 21 patients (aged (51.2±14.5) years and 13 males (61.9%)) were enrolled. The thickness of ventricular septum was (23.3±4.5)mm and the left ventricular outflow tract gradient was (78.8±42.6)mmHg (1 mmHg=0.133 kPa). Eight patients (38.1%) were complicated with hypertension, 1 patient (4.8%) had diabetes, and 2 patients (9.5%) had atrial fibrillation. Hematoxylin-eosin staining of myocardial samples of HCM patients before radiofrequency ablation evidenced myocytes hypertrophy, myocytes disarray, nuclear hyperchromatism, hypertrophy, atypia, coronary microvessel abnormalities, adipocyte infiltration, inflammatory cell infiltration, cytoplasmic vacuoles, lipofuscin deposition. Interstitial fibrosis and replacement fibrosis were detected in Masson stained biopsy samples. Hematoxylin-eosin staining of myocardial samples of HCM patients after radiofrequency ablation showed significantly reduced myocytes, cracked nuclear in myocytes, coagulative necrosis, border disappearance and nuclear fragmentation. Quantitative analysis of myocardial specimens of HCM patients before radiofrequency ablation showed that there were 9 cases (42.9%) with mild myocardial hypertrophy and 12 cases (57.1%) with severe myocardial hypertrophy. Mild, moderate and severe fibrosis were 5 (23.8%), 9 (42.9%) and 7 (33.3%), respectively. Six cases (28.6%) had myocytes disarray. There were 11 cases (52.4%) of coronary microvessel abnormalities, 4 cases (19.0%) of adipocyte infiltration, 2 cases (9.5%) of inflammatory cell infiltration,6 cases (28.5%) of cytoplasmic vacuole, 16 cases (76.2%) of lipofuscin deposition. The diameter of cardiac myocytes was (25.2±2.8)μm, and the percentage of collagen fiber area was 5.2%(3.0%, 14.6%). One patient had severe replacement fibrosis in the myocardium, with a fibrotic area of 67.0%. The rest of the patients had interstitial fibrosis. The myocardial specimens of 13 patients were examined by transmission electron microscopy. All showed increased myofibrils, and 9 cases had disorder of myofibrils. All patients had irregular shape of myocardial nucleus, partial depression, mild mitochondrial swelling, fracture and reduction of mitochondrial crest, and local aggregation of myofibrillary interfascicles. One patient had hypertrophy of cardiomyocytes, but the arrangement of muscle fibers was roughly normal. There were vacuoles in the cytoplasm, and Periodic acid-Schiff staining was positive. Transmission electron microscopy showed large range of glycogen deposition in the cytoplasm, with occasional double membrane surround, which was highly indicative of glycogen storage disease. No deposition of glycolipid substance in lysozyme was observed under transmission electron microscope in all myocardial specimens, which could basically eliminate Fabry disease. No apple green substance was found under polarized light after Congo red staining, which could basically exclude cardiac amyloidosis. Conclusion: Myocardium biopsied samples obtained by Liwen procedure of HCM patients are representative and helpful for the etiological diagnosis of HCM.

Effect and mechanism of leonurine on pressure overload-induced cardiac hypertrophy in rats / 中国中药杂志

To investigate the effects of leonurine(Leo) on abdominal aortic constriction(AAC)-induced cardiac hypertrophy in rats and its mechanism. A rat model of pressure overload-induced cardiac hypertrophy was established by AAC method. After 27-d intervention with high-dose(30 mg·kg~(-1)) and low-dose(15 mg·kg~(-1)) Leo or positive control drug losartan(5 mg·kg~(-1)), the cardiac function was evaluated by hemodynamic method, followed by the recording of left ventricular systolic pressure(LVSP), left ventricular end-diastolic pressure(LVESP), as well as the maximum rate of increase and decrease in left ventricular pressure(±dp/dt_(max)). The degree of left ventricular hypertrophy was assessed based on heart weight index(HWI) and left ventricular mass index(LVWI). Myocardial tissue changes and the myocardial cell diameter(MD) were measured after hematoxylin-eosin(HE) staining. The contents of angiotensin Ⅱ(AngⅡ) and angiotensin Ⅱ type 1 receptor(AT1 R) in myocardial tissue were detected by ELISA. The level of Ca~(2+) in myocardial tissue was determined by colorimetry. The protein expression levels of phospholipase C(PLC), inositol triphosphate(IP3), AngⅡ, and AT1 R were assayed by Western blot. Real-time quantitative PCR(qRT-PCR) was employed to determine the mRNA expression levels of β-myosin heavy chain(β-MHC), atrial natriuretic factor(ANF), AngⅡ, and AT1 R. Compared with the model group, Leo decreased the LVSP, LVEDP, HWI, LVWI and MD values, but increased ±dp/dt_(max) of the left ventricle. Meanwhile, it improved the pathological morphology of myocardial tissue, reduced cardiac hypertrophy, edema, and inflammatory cell infiltration, decreased the protein expression levels of PLC, IP3, AngⅡ, AT1 R, as well as the mRNA expression levels of β-MHC, ANF, AngⅡ, AT1 R, c-fos, and c-Myc in myocardial tissue. Leo inhibited AAC-induced cardiac hypertrophy possibly by influencing the RAS system.

Fatores associados a anormalidades na cintilografia de perfusão miocárdica de pacientes diabéticos / Factors associated with abnormalities on myocardial perfusion scintigraphy in diabetic patients

O diabetes melito é o maior fator de risco para doença arterial coronariana. Além da longa duração de diabetes, outros fatores, como presença de doença arterial periférica e tabagismo são fortes preditores para anormalidades na cintilografia de perfusão do miocárdio. O objetivo deste estudo foi avaliar o impacto dos fatores de risco de pacientes diabéticos nos resultados da cintilografia de perfusão do miocárdio e comparar com os resultados de pacientes não diabéticos em uma clínica de medicina nuclear. Foi realizado um estudo transversal retrospectivo por meio da análise de prontuários de pacientes que realizaram cintilografia miocárdica no período de 2010 a 2019. Foram avaliados 34.736 prontuários. Analisando a fase de estresse da cintilografia de perfusão do miocárdio, os portadores de diabetes melito precisaram receber estímulo farmacológico duas vezes mais que os não diabéticos para sua realização. Também foram avaliados fatores que tivessem impacto negativo no resultado da cintilografia de perfusão do miocárdio, e foi visto que o diabetes melito (33,6%), a insulinoterapia (18,1%), a hipertensão arterial sistêmica (69,9%), a dislipidemia (53%), o sedentarismo (83,1%), o uso de estresse farmacológico (50,6%), a dor torácica típica (8,5%) e a angina limitante durante o teste (1,7%) estiveram associados significativamente (p<0,001) a anormalidades neste exame. (AU)

Diabetes mellitus (DM) is the greatest risk factor for coronary artery disease. In addition to a long duration of diabetes, the presence of peripheral arterial disease and smoking are strong predictors of abnormalities on myocardial perfusion scintigraphy (MPS). This study aimed to assess the impact of risk factors in diabetic patients on MPS results and compare them with those of non-diabetic patients in a nuclear medicine clinic. A retrospective cross-sectional study was performed through the analysis of the medical records of patients who underwent MPS in 2010­2019. A total of 34,736 medical records were evaluated. Analyzing the stress phase of MPS, DM patients required two-fold more pharmacological stimulation than non-diabetic patients for MPS. Factors that negatively impact the MPS results were also evaluated, and DM (33.6%), insulin therapy (18.1%), systemic arterial hypertension (69.9%), dyslipidemia (53%), sedentary lifestyle (83.1%), use of pharmacological stress (50.6%), typical chest pain (8.5%), and limiting angina during the test (1.7%) were significantly associated (p < 0.001) with test abnormalities. (AU)

Acompanhamento a longo prazo de paciente do sexo masculino com fibroma cardíaco assintomático / Long-Term follow-up of an asymptomatic man with a cardiac fibroma

Descreve-se o caso de um homem de 19 anos assintomático com fibroma de ventrículo esquerdo em acompanhamento por 15 anos, sem tratamento.(AU)

Here we describe a case of a 19-year-old asymptomatic man with a left ventricular fibroma on follow-up for 15 years with no treatment required.(AU)

Deformação miocárdica (strain) e fibrose miocárdica na forma cardíaca leve da Doença de Chagas / Myocardial deformation (strain) and myocardial fibrosis in mild cardiac Chagas Disease

Fundamento: A identificação precoce do dano miocárdico parece ser importante na abordagem do paciente com doença de Chagas. A ecocardiografia com strain obtida por speckle tracking e a avaliação da fibrose miocárdica por meio da ressonância magnética cardíaca podem ser métodos diagnósticos promissores nesse sentido. Objetivo: Avaliar o acometimento miocárdico especificamente na forma crônica cardíaca leve da doença de Chagas por meio do strain por speckle tracking e da fibrose miocárdica pela ressonância magnética cardíaca, além de suas correlações. Método: Estudo de corte transversal que analisou portadores da forma cardíaca crônica leve da doença de Chagas (fração de ejeção preservada) submetidos à ecocardiografia com strain por speckle tracking e à ressonância magnética cardíaca. Resultados: Foram incluídos 21 participantes (mulheres: 62%; idade: 54 ± 5 anos). A prevalência de fibrose miocárdica por meio do realce tardio miocárdico foi de 50%. O strain longitudinal global encontrava-se diminuído em 17 pacientes (81%), com mediana de 14,1% (intervalo interquartil de 12,1 a 16,3). Os valores do mapa T1 encontravam-se, em média, elevados nos portadores de doença de Chagas (993 ± 163 ms). O mapa T1 foi significativamente correlacionado com o strain longitudinal global (r= 0,634; p = 0,015). Além disso, o índice de dispersão mecânica, obtido por strain, estava aumentado (> 55 ms) em 84%, com a maior área sob a curva Característica de Operação do Receptor (área sob a curva de 0,696; intervalo de confiança de 95% de 0,412-0,981) para discriminação de fibrose pelo realce tardio miocárdico. Conclusão: O strain miocárdico e o mapa T1 se comportam como marcadores precoces do dano miocárdico na cardiopatia chagásica crônica leve. O índice de dispersão mecânica estava elevado e foi o parâmetro que melhor se correlacionou com o realce tardio miocárdico. (AU)

Background: The early identification of myocardial damage seems important in the management of patients with Chagas disease. However, it is unknown whether speckle tracking echocardiography strain and cardiac magnetic resonance imaging are promising methods for assessing myocardial involvement and fibrosis, respectively. Objective: To evaluate myocardial involvement in the mild chronic cardiac form of Chagas disease using speckle tracking strain and myocardial fibrosis by cardiac magnetic resonance and assess their correlations. Method: This cross-sectional study analyzed patients with the mild chronic cardiac form of Chagas disease (preserved ejection fraction) using speckle tracking echocardiography and cardiac magnetic resonance. Results: The study included 21 participants (women: 62%; age: 54 ± 5 years). The prevalence of myocardial fibrosis was 50% on delayed myocardial enhancement. The median global longitudinal strain was decreased (14.1%; interquartile range, 12.1­16.3%) in 17 patients (81%). The mean T1 mapping value was high in patients with Chagas disease (993 ± 163 ms). The T1 map was significantly correlated with the global longitudinal strain (r = 0.634; p = 0.015). In addition, the mechanical dispersion index obtained by strain was increased (>55 ms) by 84%, with the largest area under the receiver operating characteristic curve (area under the curve, 0.696; 95% confidence interval, 0.412­0.981) for fibrosis discrimination by delayed myocardial enhancement. Conclusion: Myocardial strain and T1 mapping are early markers of myocardial damage in mild chronic Chagas heart disease. The mechanical dispersion index was high and the most closely correlated with delayed myocardial enhancement. (AU)

Comportamento dos critérios de uso apropriado da cintilografia de perfusão miocárdica na avaliação de assintomáticos de alto risco cardiovascular ou com doença coronária conhecida / Appropriate use of myocardial perfusion scintigraphy criteria for assessing asymptomatic patients with high cardiovascular risk or known coronary disease

Fundamentos: O papel da cintilografia de perfusão miocárdica em pacientes assintomáticos permanece restrito a situações clínicas muito específicas, muitas delas abordadas nos Critérios de Uso Apropriado (AUC) de Cintilografia de Perfusão Miocárdica. Objetivo: Realizar uma análise crítica da aplicação desses critérios nas indicações de exames realizados em pacientes assintomáticos do Instituto Dante Pazzanese de Cardiologia, cuja população é notadamente de alto risco cardiovascular. Métodos: Foram selecionados pacientes assintomáticos que realizaram cintilografia de perfusão miocárdica para pesquisa de isquemia. As indicações dos exames foram classificadas em apropriadas, inapropriadas ou incertas. Hipocaptação fixa, hipocaptação transitória ou dilatação isquêmica transitória foram consideradas exames alterados. Na análise estatística, buscou-se avaliar a correlação entre o grau de recomendação das indicações e a presença de exames alterados. Resultados: A partir de uma seleção inicial de 2.999 prontuários, 490 foram considerados assintomáticos e incluídos conforme critérios de inclusão estabelecidos previamente. Apenas 9,8% das indicações foram inapropriadas, enquanto que 61,4% foram apropriadas, e 28,8% foram incertas. A hipocaptação fixa do radiofármaco ocorreu em 43,5% dos casos e a hipocaptação transitória, em 16,1%. Solicitar o exame de maneira apropriada ou incerta foi fator preditor de exame com resultado alterado nesta população. Conclusão: O uso dos critérios de uso apropriado da cintilografia de perfusão miocárdica mostrou-se eficaz em predizer exames alterados em uma população assintomática de alto risco cardiovascular, especialmente no grupo de pacientes com indicação incerta, o que pode significar que algumas das indicações consideradas incertas talvez sejam apropriadas para uma população de alto risco cardiovascular. (AU)

The potential role of long non-coding RNA Dnm3os in the activation of cardiac fibroblasts / 生物医学工程学杂志

Long non-coding RNA (lncRNA) Dnm3os plays a critical role in peritendinous fibrosis and pulmonary fibrosis, but its role in the process of cardiac fibrosis is still unclear. Therefore, we carried out study by using the myocardial fibrotic tissues obtained by thoracic aortic constriction (TAC) in an early study of our group, and the

Testosterone activates glucose metabolism through AMPK and androgen signaling in cardiomyocyte hypertrophy

BACKGROUND: Testosterone regulates nutrient and energy balance to maintain protein synthesis and metabolism in cardiomyocytes, but supraphysiological concentrations induce cardiac hypertrophy. Previously, we determined that testosterone increased glucose uptake­via AMP-activated protein kinase (AMPK)­after acute treatment in cardiomyocytes. However, whether elevated glucose uptake is involved in long-term changes of glucose metabolism or is required during cardiomyocyte growth remained unknown. In this study, we hypothesized that glucose uptake and glycolysis increase in testosterone-treated cardiomyocytes through AMPK and androgen receptor (AR). METHODS: Cultured cardiomyocytes were stimulated with 100 nM testosterone for 24 h, and hypertrophy was verified by increased cell size and mRNA levels of ß-myosin heavy chain (ß-mhc). Glucose uptake was assessed by 2-NBDG. Glycolysis and glycolytic capacity were determined by measuring extracellular acidification rate (ECAR). RESULTS: Testosterone induced cardiomyocyte hypertrophy that was accompanied by increased glucose uptake, glycolysis enhancement and upregulated mRNA expression of hexokinase 2. In addition, testosterone increased AMPK phosphorylation (Thr172), while inhibition of both AMPK and AR blocked glycolysis and cardiomyocyte hypertrophy induced by testosterone. Moreover, testosterone supplementation in adult male rats by 5 weeks induced cardiac hypertrophy and upregulated ß-mhc, Hk2 and Pfk2 mRNA levels. CONCLUSION: These results indicate that testosterone stimulates glucose metabolism by activation of AMPK and AR signaling which are critical to induce cardiomyocyte hypertrophy.

Alterações cardiorrespiratórias em indivíduos hemiparéticos crônicos pós-acidente vascular cerebral / Cardiorespiratory changes in chronic post-stroke hemiparetic patients

Objetivo: Analisar a função cardiorrespiratória em pacientes he- miparéticos crônicos pós-acidente vascular cerebral. Métodos: Estudo retrospectivo, por meio da análise de dados de prontuários de pacientes submetidos ao teste de caminhada de 6 minutos e manovacuometria em uma clínica de fisioterapia de um centro universitário. Foram analisados os dados de sete prontuários. Re- sultados: A média de metros percorridos pelos participantes no teste de caminhada de 6 minutos foi de 199,5. Os valores percentuais da manovacuometria foram de -41,34 na pressão inspiratória máxima e de 57,85 na pressão expiratória máxima. Conclusão: Os dados desta pesquisa sugerem que indivíduos hemiparéticos crônicos apresentam fadiga respiratória e muscular, diminuição da capacidade funcional durante a marcha e fraqueza dos músculos respiratórios.

Objective: To analyze the cardiorespiratory function in chronic post-stroke hemiparetic patients. Methods: This is a retrospective study, through data analysis of medical records from patients who underwent the 6-minute walk test and manovacuometry, in a physical therapy clinic of a university center. Results: The mean number of meters walked by participants in the 6-minut walk test was 199.5 meters. The percentage values of manovacuometry were -41,34 in the maximun inspiratory pressure and 57.85 in the maximun expiratory pressure. Conclusion: The data from this survey suggest that chronic hemiparetic individuals have respiratory and muscle fatigue, decreased functional capacity during gait, and respiratory muscle weakness.

Biomarcadores de Lesão Miocárdica e Complicações Cardíacas Associadas à Mortalidade em Pacientes com COVID-19 / Myocardial Injury Biomarkers and Cardiac Complications Associated with Mortality in Patients with COVID-19

Resumo Fundamento O SARS-CoV-2 é um vírus de RNA emergente associado à doença respiratória aguda grave conhecida como COVID-19. Embora a COVID-19 seja predominantemente uma doença pulmonar, alguns pacientes apresentam graves danos cardiovasculares. Realizamos uma síntese de evidências quantitativas de dados clínicos, biomarcadores de lesão miocárdica e complicações cardíacas associadas ao óbito hospitalar em pacientes com COVID-19. Métodos Buscamos nas bases de dados PubMed, Embase e Google Scholar para identificar estudos que comparassem dados clínicos, biomarcadores de lesão miocárdica e complicações cardíacas entre pacientes sobreviventes e não sobreviventes da COVID-19. Os tamanhos dos efeitos foram apresentados como diferença média ou diferença média padronizada para variáveis contínuas e razão de risco para variáveis dicotômicas, com intervalos de confiança de 95%. Foi utilizado um modelo de efeitos aleatórios para agrupar os resultados. Resultados Foram incluídos seis estudos retrospectivos que relataram dados de 1.141 pacientes (832 sobreviventes e 309 não sobreviventes). Verificamos que condições cardiovasculares subjacentes; elevação de troponina cardíaca I de alta sensibilidade; N-terminal do pró-hormônio do peptídeo natriurético do tipo B e creatina quinase-MB; e complicações cardíacas foram associadas ao aumento do risco de óbito em pacientes com infecção por SARS-CoV-2. Conclusões A confirmação de que condições cardiovasculares subjacentes, elevação de biomarcadores de lesão miocárdica durante a infecção por COVID-19 e descompensação cardiovascular aguda são preditores de mortalidade na infecção por SARS-CoV-2 deve incentivar novas pesquisas para esclarecer possíveis mecanismos e testar tratamentos adequados. (Arq Bras Cardiol. 2020; 115(2):273-277)

Abstract Background SARS-CoV-2 is an emerging RNA virus associated with a severe acute respiratory disease known as COVID-19. Although COVID-19 is predominantly a pulmonary disease, some patients have severe cardiovascular damage. We performed a quantitative evidence synthesis of clinical data, myocardial injury biomarkers, and cardiac complications associated with in-hospital death in patients with COVID-19. Methods We searched the databases PubMed, Embase, and Google Scholar to identify studies comparing clinical data, myocardial injury biomarkers, and cardiac complications between non-survivors and survivors of COVID-19. Effect sizes were reported as mean difference or standardized mean difference for continuous variables and risk ratio for dichotomous variables with 95% confidence intervals. A random effects model was used to pool the results. Results Six retrospective studies reporting data from 1,141 patients (832 survivors and 309 non-survivors) were included. We found that underlying cardiovascular conditions; elevation of high-sensitivity cardiac troponin I, N-terminal pro-B-type natriuretic peptide, and creatine kinase-MB; and cardiac complications were associated with increased risk of death for patients with SARS-CoV-2 infection. Conclusions The confirmation that underlying cardiovascular conditions, elevation of myocardial injury biomarkers during COVID-19 infection, and acute cardiovascular decompensation are predictors for mortality in SARS-CoV-2 infection must encourage new research to clarify potential mechanisms and test appropriate treatments. (Arq Bras Cardiol. 2020; 115(2):273-277)