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BACKGROUND: This study evaluated the effects of concurrent isolated training (T) or training combined with the antioxidant N-acetylcysteine (NAC) on cardiac remodeling and oxidative stress in spontaneously hypertensive rats (SHR). METHODS: Six-month-old male SHR were divided into sedentary (S, n = 12), concurrent training (T, n = 13), sedentary supplemented with NAC (SNAC, n = 13), and concurrent training with NAC supplementation (TNAC, n = 14) groups. T and TNAC rats were trained three times a week on a treadmill and ladder; NAC supplemented groups received 120 mg/kg/day NAC in rat chow for eight weeks. Myocardial antioxidant enzyme activity and lipid hydroperoxide concentration were assessed by spectrophotometry. Gene expression of NADPH oxidase subunits Nox2, Nox4, p22 phox, and p47 phox was evaluated by real time RT-PCR. Statistical analysis was performed using ANOVA and Bonferroni or Kruskal-Wallis and Dunn. RESULTS: Echocardiogram showed concentric remodeling in TNAC, characterized by increased relative wall thickness (S 0.40 ± 0.04; T 0.39 ± 0.03; SNAC 0.40 ± 0.04; TNAC 0.43 ± 0.04 *; * p < 0.05 vs T and SNAC) and diastolic posterior wall thickness (S 1.50 ± 0.12; T 1.52 ± 0.10; SNAC 1.56 ± 0.12; TNAC 1.62 ± 0.14 * mm; * p < 0.05 vs T), with improved contractile function (posterior wall shortening velocity: S 39.4 ± 5.01; T 36.4 ± 2.96; SNAC 39.7 ± 3.44; TNAC 41.6 ± 3.57 * mm/s; * p < 0.05 vs T). Myocardial lipid hydroperoxide concentration was lower in NAC treated groups (S 210 ± 48; T 182 ± 43; SNAC 159 ± 33 *; TNAC 110 ± 23 *# nmol/g tissue; * p < 0.05 vs S, # p < 0.05 vs T and SNAC). Nox 2 and p22 phox expression was higher and p47 phox lower in T than S [S 1.37 (0.66-1.66); T 0.78 (0.61-1.04) *; SNAC 1.07 (1.01-1.38); TNAC 1.06 (1.01-1.15) arbitrary units; * p < 0.05 vs S]. NADPH oxidase subunits did not differ between TNAC, SNAC, and S groups. CONCLUSION: N-acetylcysteine supplementation alone reduces oxidative stress in untreated spontaneously hypertensive rats. The combination of N-acetylcysteine and concurrent exercise further decreases oxidative stress. However, the lower oxidative stress does not translate into improved cardiac remodeling and function in untreated spontaneously hypertensive rats.
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Acetilcisteína , Hipertensão , NADPH Oxidases , Estresse Oxidativo , Ratos Endogâmicos SHR , Remodelação Ventricular , Animais , Masculino , Estresse Oxidativo/efeitos dos fármacos , Acetilcisteína/farmacologia , Remodelação Ventricular/efeitos dos fármacos , Hipertensão/fisiopatologia , Hipertensão/tratamento farmacológico , Hipertensão/metabolismo , NADPH Oxidases/metabolismo , NADPH Oxidases/genética , Ratos , Antioxidantes/farmacologia , Condicionamento Físico Animal , Modelos Animais de Doenças , NADPH Oxidase 2/metabolismo , NADPH Oxidase 2/genética , NADPH Oxidase 4/metabolismo , NADPH Oxidase 4/genética , Glicoproteínas de Membrana/metabolismo , Glicoproteínas de Membrana/genética , Miocárdio/metabolismo , Miocárdio/patologia , Peróxidos Lipídicos/metabolismo , Função Ventricular Esquerda/efeitos dos fármacos , Suplementos Nutricionais , Hipertrofia Ventricular Esquerda/fisiopatologia , Hipertrofia Ventricular Esquerda/prevenção & controle , Hipertrofia Ventricular Esquerda/metabolismoRESUMO
Sodium overload during childhood impairs baroreflex sensitivity and increases arterial blood pressure and heart rate in adulthood; these effects persist even after high-salt diet (HSD) withdrawal. However, the literature lacks details on the effects of HSD during postnatal phases on cardiac ischemia/reperfusion responses in adulthood. The current study aimed to elucidate the impact of HSD during infancy adolescence on isolated heart function and cardiac ischemia/reperfusion responses in adulthood. Male 21-day-old Wistar rats were treated for 60 days with hypertonic saline solution (NaCl; 0.3M; experimental group) or tap water (control group). Subsequently, both groups were maintained on a normal sodium diet for 30 days. Subsequently, the rats were euthanized, and their hearts were isolated and perfused according to the Langendorff technique. After 30 min of the basal period, the hearts were subjected to 20 min of anoxia, followed by 20 min of reperfusion. The basal contractile function was unaffected by HSD. However, HSD elevated the left ventricular end-diastolic pressure during reperfusion (23.1 ± 5.2 mmHg vs. 11.6 ± 1.4 mmHg; p < 0.05) and increased ectopic incidence period during reperfusion (208.8 ± 32.9s vs. 75.0 ± 7.8s; p < 0.05). In conclusion, sodium overload compromises cardiac function after reperfusion events, diminishes ventricular relaxation, and increases the severity of arrhythmias, suggesting a possible arrhythmogenic effect of HSD in the postnatal phases.
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Arritmias Cardíacas , Traumatismo por Reperfusão Miocárdica , Ratos Wistar , Animais , Ratos , Arritmias Cardíacas/etiologia , Arritmias Cardíacas/fisiopatologia , Masculino , Traumatismo por Reperfusão Miocárdica/etiologia , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Diástole/fisiologia , Cloreto de Sódio na Dieta/efeitos adversos , Frequência Cardíaca/fisiologiaRESUMO
INTRODUCTION: High sucrose intake is linked to cardiovascular disease, a major global cause of mortality worldwide. Calcium mishandling and inflammation play crucial roles in cardiac disease pathophysiology. OBJECTIVE: Evaluate if sucrose-induced obesity is related to deterioration of myocardial function due to alterations in the calcium-handling proteins in association with proinflammatory cytokines. METHODS: Wistar rats were divided into control and sucrose groups. Over eight weeks, Sucrose group received 30% sucrose water. Cardiac function was determined in vivo using echocardiography and in vitro using papillary muscle assay. Western blotting was used to detect calcium handling protein; ELISA assay was used to assess TNF-α and IL-6 levels. RESULTS: Sucrose led to cardiac dysfunction. RYR2, SERCA2, NCX, pPBL Ser16 and L-type calcium channels were unchanged. However, pPBL-Thr17, and TNF-α levels were elevated in the S group. CONCLUSION: Sucrose induced cardiac dysfunction and decreased myocardial contractility in association with altered pPBL-Thr17 and elevated cardiac pro-inflammatory TNF-α.
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Proteínas de Ligação ao Cálcio , Ratos Wistar , Fator de Necrose Tumoral alfa , Animais , Masculino , Ratos , Proteínas de Ligação ao Cálcio/metabolismo , Interleucina-6/metabolismo , Contração Miocárdica/efeitos dos fármacos , Miocárdio/metabolismo , Miocárdio/patologia , Fosforilação/efeitos dos fármacos , Sacarose/farmacologia , Fator de Necrose Tumoral alfa/metabolismoRESUMO
OBJECTIVE: The objective of this study was to investigate the impact of Doxorubicin, Epirubicin, and Liposomal Doxorubicin (Anthracycline) on cardiac function in osteosarcoma patients and analyze the factors influencing this effect. METHODS: A retrospective study was conducted on 165 osteosarcoma patients admitted to our hospital from January 2020 to December 2022. Based on the chemotherapy regimen, the patients were divided into two groups: the control group (n = 62) treated with Cisplatin and cyclophosphamide, and the observation group (n = 103) treated with Doxorubicin, Epirubicin, and Liposomal Doxorubicin (Anthracycline). The general records of both groups were analyzed, and left ventricular ejection fraction (LVEF) was evaluated through echocardiography before and after chemotherapy. Blood cTnT and CK-MB levels were measured using immunoluminescence. The incidence of adverse reactions during chemotherapy was also analyzed. Univariate analysis was performed to identify patients with cardiotoxic events, and multiple logistic regression analysis was done to study the effects of Doxorubicin, Epirubicin, Liposomal Doxorubicin, and their dosages on cardiotoxicity in patients. RESULTS: The general records between the two groups showed no significant differences (P > 0.05). However, at the fourth cycle of chemotherapy, the observation group exhibited a lower LVEF (P < 0.05), and a higher percentage of LVEF decrease compared to the control group (P < 0.05). Moreover, the observation group had higher levels of blood cTnT and CK-MB (P < 0.05). The incidence of cardiotoxicity in the observation group was also higher (P < 0.05), but no significant differences were seen in other adverse reaction rates (P > 0.05). The occurrence of cardiotoxicity was found to be related to the choice and dosage of chemotherapy drugs (P < 0.05), but not significantly correlated with age, sex, and mediastinal irradiation in patients (P > 0.05). Furthermore, the use of Doxorubicin, Epirubicin, and Liposomal Doxorubicin in chemotherapy, as well as an increase in their dosages, was found to elevate the risk of cardiotoxicity in osteosarcoma patients (P < 0.05). However, age, sex, and mediastinal radiation were not significantly associated with cardiotoxicity in osteosarcoma patients (P > 0.05). CONCLUSION: We demonstrated that Doxorubicin, Epirubicin, Liposomal Doxorubicin (Anthracycline), and other drugs adversely affected cardiac function in osteosarcoma patients, increasing the risk of cardiac toxicity. Therefore, close monitoring of cardiac function during chemotherapy is crucial, and timely adjustments to the chemotherapy regimen are necessary. In addition, rational control of drug selection and dosage is essential to minimize the occurrence of cardiac toxicity.
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Neoplasias Ósseas , Cardiotoxicidade , Doxorrubicina , Epirubicina , Osteossarcoma , Humanos , Osteossarcoma/tratamento farmacológico , Epirubicina/efeitos adversos , Epirubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Doxorrubicina/análogos & derivados , Feminino , Masculino , Estudos Retrospectivos , Adulto , Adulto Jovem , Neoplasias Ósseas/tratamento farmacológico , Cardiotoxicidade/etiologia , Adolescente , Volume Sistólico/efeitos dos fármacos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Função Ventricular Esquerda/efeitos dos fármacos , Antibióticos Antineoplásicos/efeitos adversos , Antibióticos Antineoplásicos/uso terapêutico , Ecocardiografia , Troponina T/sangue , Creatina Quinase Forma MB/sangue , Ciclofosfamida/efeitos adversos , Ciclofosfamida/administração & dosagem , Criança , Cisplatino/efeitos adversos , Cisplatino/administração & dosagem , PolietilenoglicóisRESUMO
To evaluate milrinone's impact on pediatric cardiac function, focusing on its specific role as an inotrope and lusitrope, while considering its systemic and pulmonary vasodilatory effects. Search of PubMed, EMBASE, and the Cochrane Library up to August 2023. We included all studies that evaluated milrinone in children under 18 years old in neonatal, pediatric, or cardiac intensive care units. We excluded case reports, studies that did not provide tabular information on milrinone's outcomes, and studies focused on non-intensive care populations. We extracted data on the research design, objectives, study sample, and results of each study, including the impact of milrinone and any associated factors. We screened a total of 9423 abstracts and 41 studies were ultimately included. Milrinone significantly improved left ventricular ejection fraction (WMD 3.41 [95% CI 0.61 - 6.21]), left ventricle shortening fraction (WMD 4.25 [95% CI 3.43 - 5.08]), cardiac index (WMD 0.50 [95% CI 0.32 to 0.68]), left ventricle output (WMD 55.81 [95% CI 4.91 to 106.72]), serum lactate (WMD -0.59 [95% CI -1.15 to -0.02]), and stroke volume index (WMD 2.95 [95% CI 0.09 - 5.82]). However, milrinone was not associated with improvements in ventricular myocardial performance index (WMD -0.01 [95% CI -0.06 to 0.04]) and ventricular longitudinal strain (WMD -2.14 [95% CI -4.56 to 0.28]). Furthermore, milrinone was not associated with isovolumetric relaxation time reduction (WMD -8.87 [95% CI -21.40 to 3.66]). CONCLUSION: Our meta-analysis suggests potential clinical benefits of milrinone by improving cardiac function, likely driven by its systemic vasodilatory effects. However, questions arise about its inotropic influence and the presence of a lusitropic effect. Moreover, milrinone's pulmonary vasodilatory effect appears relatively weaker compared to its systemic actions. Further research is needed to elucidate milrinone's precise mechanisms and refine its clinical applications in pediatric practice. WHAT IS KNOWN: ⢠Milrinone is a phosphodiesterase III inhibitor that has been used to treat a variety of pediatric and neonatal conditions. ⢠Milrinone is believed to exert its therapeutic effects by enhancing cardiac contractility and promoting vascular relaxation. WHAT IS NEW: ⢠Milrinone may not have a significant inotropic effect. ⢠Milrinone's pulmonary vasodilatory effect is less robust than its systemic vasodilatory effect.
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Insuficiência Cardíaca , Hipertensão Pulmonar , Adolescente , Criança , Humanos , Recém-Nascido , Cardiotônicos/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Hipertensão Pulmonar/tratamento farmacológico , Milrinona/uso terapêutico , Volume Sistólico , Função Ventricular Esquerda , Lactente , Pré-EscolarRESUMO
In addition to their well-known classical effects, cannabinoid CB1 and CB2 receptors have also been involvement in both deleterious and protective actions on the heart under various pathological conditions. While the potential therapeutic applications of the endocannabinoid system in the context of cardiovascular function are indeed a viable prospect, significant debate exists within the literature regarding whether CB1, CB2, or a combination of both receptors exert a favorable influence on cardiac function. Hence, the aim of this study was to investigate the effects of CB1 + CB2 or CB2 agonists on cardiac excitation-contraction (E-C) coupling, utilizing fish (Brycon amazonicus) as an experimental model. The CB2 agonist elicited marked positive inotropic and lusitropic responses in isolated ventricular myocardium, induced cyclic adenosine 3',5'-monophosphate (cAMP) production, and upregulated critical Ca2+ handling proteins, such as sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) and Na+/Ca2+ exchanger (NCX). Our current study demonstrated, for the first time, that CB2 receptor activation-induced effects improved the efficiency of Ca2+ cycling, excitation-contraction coupling (E-C coupling), and cardiac performance in under physiological conditions. Hence, CB2 receptors could be considered a potential therapeutic target for modulating cardiac contractile dysfunctions.
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Canabinoides , Caraciformes , Animais , Receptores de Canabinoides/metabolismo , Miocárdio/metabolismo , Coração , Acoplamento Excitação-Contração , Agonistas de Receptores de Canabinoides/metabolismo , Agonistas de Receptores de Canabinoides/farmacologia , Receptor CB2 de Canabinoide/metabolismo , Receptor CB1 de Canabinoide/metabolismoRESUMO
Surprisingly, the impacts of environmental changes on the physiology of tropical/subtropical marine fishes have received limited attention. Given that (i) temperature is considered to be a key factor controlling the biology of fishes; (ii) no published data are available on the swimming performance, metabolic capacity or cardiac function of any of the ~165 grouper species worldwide; and (iii) the Nassau grouper is an endangered species of great ecological and socioeconomic significance in The Bahamas, we investigated how current summer/early fall (30°C) and winter (22°C) temperatures in South Eleuthera affected the aerobic metabolism and heart function of wild Nassau grouper when swum to exhaustion (i.e. to their critical swimming speed, Ucrit). The Nassau grouper had a very low Ucrit at 30°C (i.e. <1 body lengths s-1), and a 30% lower swimming performance during the winter (at 22°C), and this was that was indicative of a reduced absolute aerobic scope (~185 vs. 290 mg O2 kg-1 h-1) and values of maximum heart rate ([Formula: see text]HMax) and scope for [Formula: see text]H that were only one-half of that achieved at 30°C (~60 vs. 120 and 29 vs. 61 beats min-1, respectively). Overall, these data reveal that the Nassau grouper's aerobic and swimming capacity are well below values reported for other tropical/subtropical fishes and suggest that, despite a compensatory (~30-40%) increase in stroke volume, constraints on [Formula: see text]H near this species' lower thermal limit negatively affect its cardiac output and swimming performance. These findings have considerable ecological implications as Bahamian grouper populations migrate over long distances to spawn during the winter months, and given the predicted increase in temperature variability with climate change.
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BACKGROUND: Angiotensin converting enzyme 2 (ACE2) plays a crucial role in the infection cycle of SARS-CoV-2 responsible for formation of COVID-19 pandemic. In the cardiovascular system, the virus enters the cells by binding to the transmembrane form of ACE2 causing detrimental effects especially in individuals with developed hypertension or heart disease. Zofenopril, a H2S-releasing angiotensin-converting enzyme inhibitor (ACEI), has been shown to be effective in the treatment of patients with essential hypertension; however, in conditions of ACE2 inhibition its potential beneficial effect has not been investigated yet. Therefore, the aim of the study was to determine the effect of zofenopril on the cardiovascular system of spontaneously hypertensive rats, an animal model of human essential hypertension and heart failure, under conditions of ACE2 inhibition induced by the administration of the specific inhibitor MLN-4760 (MLN). RESULTS: Zofenopril reduced MLN-increased visceral fat to body weight ratio although no changes in systolic blood pressure were recorded. Zofenopril administration resulted in a favorable increase in left ventricle ejection fraction and improvement of diastolic function regardless of ACE2 inhibition, which was associated with increased H2S levels in plasma and heart tissue. Similarly, the acute hypotensive responses induced by acetylcholine, L-NAME (NOsynthase inhibitor) and captopril (ACEI) were comparable after zofenopril administration independently from ACE2 inhibition. Although simultaneous treatment with zofenopril and MLN led to increased thoracic aorta vasorelaxation, zofenopril increased the NO component equally regardless of MLN treatment, which was associated with increased NO-synthase activity in aorta and left ventricle. Moreover, unlike in control rats, the endogenous H2S participated in maintaining of aortic endothelial function in MLN-treated rats and the treatment with zofenopril had no impact on this effect. CONCLUSIONS: Zofenopril treatment reduced MLN-induced adiposity and improved cardiac function regardless of ACE2 inhibition. Although the concomitant MLN and zofenopril treatment increased thoracic aorta vasorelaxation capacity, zofenopril increased the participation of H2S and NO in the maintenance of endothelial function independently from ACE2 inhibition. Our results confirmed that the beneficial effects of zofenopril were not affected by ACE2 inhibition, moreover, we assume that ACE2 inhibition itself can lead to the activation of cardiovascular compensatory mechanisms associated with Mas receptor, nitrous and sulfide signaling.
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Captopril , Sistema Cardiovascular , Humanos , Ratos , Animais , Captopril/farmacologia , Ratos Endogâmicos SHR , Enzima de Conversão de Angiotensina 2/farmacologia , Pandemias , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Pressão Sanguínea , Hipertensão EssencialRESUMO
Cardiovascular disease is a leading cause of death worldwide. Heart failure is a cardiovascular disease with high prevalence, morbidity, and mortality. Several natural compounds have been studied for attenuating pathological cardiac remodeling. Orange juice has been associated with cardiovascular disease prevention by attenuating oxidative stress. However, most studies have evaluated isolated phytochemicals rather than whole orange juice and usually under pathological conditions. In this study, we evaluated plasma metabolomics in healthy rats receiving Pera or Moro orange juice to identify possible metabolic pathways and their effects on the heart. METHODS: Sixty male Wistar rats were allocated into 3 groups: control (C), Pera orange juice (PO), and Moro orange juice (MO). PO and MO groups received Pera orange juice or Moro orange juice, respectively, and C received water with maltodextrin (100 g/L). Echocardiogram and euthanasia were performed after 4 weeks. Plasma metabolomic analysis was performed by high-resolution mass spectrometry. Type I collagen was evaluated in picrosirius red-stained slides and matrix metalloproteinase (MMP)-2 activity by zymography. MMP-9, tissue inhibitor of metalloproteinase (TIMP)-2, TIMP-4, type I collagen, and TNF-α protein expression were evaluated by Western blotting. RESULTS: We differentially identified three metabolites in PO (N-docosahexaenoyl-phenylalanine, diglyceride, and phosphatidylethanolamine) and six in MO (N-formylmaleamic acid, N2-acetyl-L-ornithine, casegravol isovalerate, abscisic alcohol 11-glucoside, cyclic phosphatidic acid, and torvoside C), compared to controls, which are recognized for their possible roles in cardiac remodeling, such as extracellular matrix regulation, inflammation, oxidative stress, and membrane integrity. Cardiac function, collagen level, MMP-2 activity, and MMP-9, TIMP-2, TIMP-4, type I collagen, and TNF-α protein expression did not differ between groups. CONCLUSION: Ingestion of Pera and Moro orange juice induces changes in plasma metabolites related to the regulation of extracellular matrix, inflammation, oxidative stress, and membrane integrity in healthy rats. Moro orange juice induces a larger number of differentially expressed metabolites than Pera orange juice. Alterations in plasma metabolomics induced by both orange juice are not associated with modifications in cardiac extracellular matrix components. Our results allow us to postulate that orange juice may have beneficial effects on pathological cardiac remodeling.
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Background: Adipokines are associated with cardiovascular disease; in chronic kidney disease (CKD) patients adipokines could be useful prognostic factors. Objectives: To explore whether leptin and adiponectin in kidney replacement therapy (KRT) children could have a role on their cardiac function, in the long-term. Design: Prospective cohort study was performed with pediatric KRT patients, aged 8 to 17 years who were undergoing hemodialysis or peritoneal dialysis. At enrollment, lipid profile, adipokines (leptin, leptin receptor, free leptin, and adiponectin), anthropometric measurements and cardiological evaluation were determined. At two-year follow-up, a new cardiological evaluation was performed. Statistical analysis: Quantitative data are presented as median and interquartile range (IQR). Mann-Whitney U test and Chi-squared were used for the between-group comparison. Multivariate analyzes were performed to determine the association of adipokines levels with ventricular ejection fraction (LEVF). Results: We included 56 patients, with a median age of 12.5 years. In the first cardiological evaluation, median LVEF was 70.0% (IQR 61%, 76%), 20 patients (35.7%) had some cardiovascular condition, and 10 (17.8%) altered LVEF. At 24-month follow-up, the median LVEF was 70.5% (IQR 65.1%, 77%), while the delta-LVEF values was 3% (IQR -6.5%, 7%). Delta-LVEF were correlated with baseline adipokines serum levels, and the only positive correlation found was with free leptin (r=0.303, p=0.025). In multivariate analysis, levels of free leptin (Coef. 0.12, p<0.036) and leptin (coef. 1.72, p=0.049), as well as baseline LVEF (Coef. -0.65, p<0.001) were associated with delta-LVEF. Conclusions: Free leptin, leptin and LVEF at the beginning of follow-up were associated with the LVEF decrease at the 24-month follow-up in KRT children.
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Doenças Cardiovasculares , Insuficiência Renal Crônica , Humanos , Criança , Adipocinas , Leptina , Adiponectina , Estudos Prospectivos , Insuficiência Renal Crônica/terapia , Doenças Cardiovasculares/diagnósticoRESUMO
BACKGROUND: Heart Failure with Preserved Ejection Fraction (HFpEF) is a syndrome characterized by different degrees of exercise intolerance, which leads to poor quality of life and prognosis. Recently, the European score (HFA-PEFF) was proposed to standardize the diagnosis of HFpEF. Even though Global Longitudinal Strain (GLS) is a component of HFA-PEFF, the role of other strain parameters, such as Mechanical Dispersion (MD), has yet to be studied. In this study, we aimed to compare MD and other features from the HFA-PEFF according to their association with exercise capacity in an outpatient population of subjects at risk or suspected HFpEF. METHODS: This is a single-center cross-sectional study performed in an outpatient population of 144 subjects with a median age of 57 years, 58% females, referred to the Echocardiography and Cardiopulmonary Exercise Test to investigate HFpEF. RESULTS: MD had a higher correlation to Peak VO2 (r=-0.43) when compared to GLS (r=-0.26), MD presented a significant correlation to Ventilatory Anaerobic Threshold (VAT) (r=-0.20; p = 0.04), while GLS showed no correlation (r=-0.14; p = 0.15). Neither MD nor GLS showed a correlation with the time to recover VO2 after exercise (T1/2). In Receiver Operator Characteristic (ROC) analysis, MD presented superior performance to GLS to predict Peak VO2 (AUC: 0.77 vs. 0.62), VAT (AUC: 0.61 vs. 0.57), and T1/2 (AUC: 0.64 vs. 0.57). Adding MD to HFA-PEFF improved the model performance (AUC from 0.77 to 0.81). CONCLUSION: MD presented a higher association with Peak VO2 when compared to GLS and most features from the HFA-PEFF. Adding MD to the HFA-PEFF improved the model performance.
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Insuficiência Cardíaca , Feminino , Humanos , Pessoa de Meia-Idade , Masculino , Insuficiência Cardíaca/diagnóstico por imagem , Volume Sistólico , Estudos Transversais , Tolerância ao Exercício , Qualidade de Vida , Valor Preditivo dos Testes , Ecocardiografia , Função Ventricular EsquerdaRESUMO
AIMS: This network meta-analysis aimed to compare the effect of different types of physical exercise [endurance training, endurance/resistance training, and high-intensity interval training (HIIT)] on exercise capacity and cardiac function parameters in patients with heart failure with preserved ejection fraction. METHODS AND RESULTS: A systematic search of the MEDLINE (via PubMed), Scopus, and Web of Science databases was conducted to identify experimental studies addressing the effect of different physical exercise training programmes on exercise capacity and cardiac function in heart failure with preserved ejection fraction. Comparative evaluation of the effect of exercise training type was performed by conducting a standard pairwise meta-analysis and a network meta-analysis for direct and indirect comparisons between exercise training types and controls/non-interventions. Eleven studies were included in the analysis showing that endurance training improves the main exercise capacity parameters (VO2peak, workload, exercise time, peak heart rate, VO2, and 6 min walk distance). Additionally, endurance/resistance training showed a significant effect on VO2peak, workload, early mitral annulus velocity, and early mitral/mitral annulus velocity ratio. Finally, HIIT showed a significant effect on VO2peak, VO2, and the early mitral/mitral annulus velocity ratio. CONCLUSION: Our findings support the effect of three different types of physical exercise on exercise capacity, mainly VO2peak. Additionally, endurance/resistance training and HIIT could reverse left ventricular remodelling in patients with heart failure with preserved ejection fraction. REGISTRATION: PROSPERO: CRD42021276111.
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Tolerância ao Exercício , Insuficiência Cardíaca , Humanos , Terapia por Exercício/métodos , Metanálise em Rede , Exercício Físico , Insuficiência Cardíaca/terapia , Função Ventricular Esquerda , Volume SistólicoRESUMO
Previous studies have suggested that the Angiotensin-(1-7) [(Ang-(1-7)] can change cardiac function by modulating the autonomic nervous system. However, it is unknown whether the Ang-(1-7) can modulate the effect of acetylcholine (ACh) in ventricular contractility. Thus, this study aimed to investigate whether Ang-(1-7) modifies the amplitude of the cardiac cholinergic effects and if these effects are intrinsic to the heart. In anesthetized Wistar rats, Ang-(1-7) attenuated the effect of ACh in decreasing the left ventricular end-systolic pressure (LVESP), dP/dtmax, and dP/dtmin, but did not modify the hypotensive effect of ACh. Similarly, Ang-(1-7) attenuated the reduction of the LVESP, dP/dtmax, and dP/dtmin evoked by ACh in isolated hearts. These effects were blocked by the Mas receptor antagonist, A-779, but not by the adenylyl cyclase inhibitor MDL-12,330 A. Ang-(1-7) also attenuated the reduction in the maximum contraction and relaxation speeds and the shortening promoted by ACh in isolated cardiomyocytes. These data show that Ang-(1-7) acting through Mas receptor counter-regulates the myocardial contractile response to ACh in an arterial pressure and heart rate-independent manner.
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Acetilcolina , Contração Miocárdica , Ratos , Animais , Acetilcolina/farmacologia , Ratos Wistar , Coração , Miócitos Cardíacos , Angiotensina II/farmacologiaRESUMO
The aim of this study was to verify the effects of moderate-intensity continuous (MICT) and high-intensity interval (HIIT) aerobic training on cardiac morphology and function and the mechanical properties of single cardiomyocytes in spontaneously hypertensive rats (SHR) in the compensated phase of hypertension. Sixteen-week-old male SHR and normotensive Wistar (WIS) rats were allocated to six groups of six animals each: SHR CONT or WIS CONT (control); SHR MICT or WIS MICT (underwent MICT, 30 min/day, five days per week for eight weeks); and SHR HIIT or WIS HIIT (underwent HIIT, 30 min/day, five days per week for eight weeks). Total exercise time until fatigue and maximum running speed were determined using a maximal running test before and after the experimental period. Systolic (SAP), diastolic (DAP), and mean (MAP) blood pressures were measured using tail plethysmography before and after the experimental period. Echocardiographic evaluations were performed at the end of the experimental period. The rats were euthanized after in vivo assessments, and left ventricular myocytes were isolated to evaluate global intracellular Ca2+ transient ([Ca2+]i) and contractile function. Cellular measurements were performed at basal temperature (~37°C) at 3, 5, and 7 Hz. The results showed that both training programs increased total exercise time until fatigue and, consequently, maximum running speed. In hypertensive rats, MICT decreased SAP, DAP, MAP, interventricular septal thickness during systole and diastole, and the contraction amplitude at 5 Hz. HIIT increased heart weight and left ventricular wall thickness during systole and diastole and reduced SAP, MAP, and the time to peak [Ca2+]i at all pacing frequencies. In conclusion, both aerobic training protocols promoted beneficial adaptations to cardiac morphology, function, and mechanical properties of single cardiomyocytes in SHR.
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Hipertensão , Condicionamento Físico Animal , Masculino , Animais , Ratos , Ratos Endogâmicos SHR , Condicionamento Físico Animal/fisiologia , Ratos Wistar , Hipertensão/terapia , Miócitos Cardíacos/fisiologia , FadigaRESUMO
Cardiovascular diseases are the leading cause of death worldwide. Food-grade TiO2 (E171) is the most widely used additive in the food industry. Existing evidence shows TiO2 nanoparticles reach systemic circulation through biological barriers, penetrate cell membranes, accumulate in cells of different organs, and cause damage; however, their effects on cardiac cells and the development of heart diseases are still unexplored. Therefore, in this work, we tested E171 toxicity in rat cardiomyoblasts and hearts. E171 internalization and impact on cell viability, proliferation, mitochondria, lysosomes, F-actin distribution, and cell morphology were evaluated in H9c2 cells. Additionally, effects of E171 were measured on cardiac function in ex vivo rat hearts. E171 was uptaken by cells and translocated into the cytoplasm. E171 particles changed cell morphology reducing proliferation and metabolic activity. Higher caspase-3 and caspase-9 expression as well as Tunel-positive cells induced by E171 exposure indicate apoptotic death. Mitochondrial and lysosome alterations resulting from mitophagy were detected after 24 and 48 h exposure, respectively. Additionally, high E171 concentrations caused rearrangements of the F-actin cytoskeleton. Finally, hearts exposed to E171 showed impaired cardiac function. These results support E171 toxicity in cardiac cells in vitro altering cardiac function in an ex vivo model, indicating that consumption of this food additive could be toxic and may lead to the development of cardiovascular disease.
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Nanopartículas , Titânio , Animais , Sobrevivência Celular , Aditivos Alimentares/toxicidade , Nanopartículas/toxicidade , Ratos , Titânio/toxicidadeRESUMO
Clinical trials have shown that sodium glucose co-transporter 2 (SGLT2) inhibitors improve clinical outcomes in diabetes mellitus (DM) patients. As most studies were performed in Type 2 DM, the cardiovascular effects of SGLT2 inhibition still require clarification in Type 1 DM. We analyzed the effects of SGLT2 inhibitor dapagliflozin on cardiac remodeling in rats with streptozotocin-induced diabetes, an experimental model of Type 1 DM. Methods: Male Wistar rats were assigned into four groups: control (C, n = 14); control treated with dapagliflozin (C + DAPA, n = 14); diabetes (DM, n = 20); and diabetes treated with dapagliflozin (DM + DAPA, n = 20) for 8 weeks. Dapagliflozin dosage was 5 mg/kg/day. Statistical analyses: ANOVA and Tukey or Kruskal−Wallis and Dunn. Results: DM + DAPA presented decreased blood pressure and glycemia and increased body weight compared to DM (C 507 ± 52; C + DAPA 474 ± 50; DM 381 ± 52 *; DM + DAPA 430 ± 48 # g; * p < 0.05 vs. C; # p < 0.05 vs. C + DAPA and DM + DAPA). DM echocardiogram presented left ventricular and left atrium dilation with impaired systolic and diastolic function. Cardiac changes were attenuated by dapagliflozin. Myocardial hydroxyproline concentration and interstitial collagen fraction did not differ between groups. The expression of Type III collagen was lower in DM and DM + DAPA than their controls. Type I collagen expression and Type I-to-III collagen ratio were lower in DM + DAPA than C + DAPA. DM + DAPA had lower lipid hydroperoxide concentration (C 275 ± 42; C + DAPA 299 ± 50; DM 385 ± 54 *; DM + DAPA 304 ± 40 # nmol/g tissue; * p < 0.05 vs. C; # p < 0.05 vs. DM) and higher superoxide dismutase and glutathione peroxidase activity than DM. Advanced glycation end products did not differ between groups. Conclusion: Dapagliflozin is safe, increases body weight, decreases glycemia and oxidative stress, and attenuates cardiac remodeling in an experimental rat model of Type 1 diabetes mellitus.
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BACKGROUND: Heart failure (HF) associated with atrial fibrillation increases patients' physical inactivity, worsening their clinical condition and mortality. Exercise training is safe and has clear benefits in HF. However, little is known about the effects of exercise training on patients with HF with reduced ejection fraction and permanent atrial fibrillation (HFAF). OBJECTIVE: The purpose of this study was to test the hypothesis that exercise training improves functional capacity, cardiac function, and quality of life in patients with HFAF. METHODS: This randomized clinical trial was conducted at the Heart Institute. Patients with HFAF, left ventricular ejection fraction ≤40%, and resting heart rate (HR) ≤80 beats/min were included in the study. Cardiopulmonary testing, echocardiography, nervous system, and quality of life assessment were performed before and after the 12-week protocol period. RESULTS: Twenty-six patients (mean age 58 ± 1 years) were randomized to exercise training (HFAF-trained group; n = 13) or no training (HFAF-untrained group; n = 13). At baseline, no differences between the groups were found. Exercise improved peak oxygen consumption, slope of ventilation per minute/carbon dioxide production, and quality of life. The HFAF-trained group had significantly decreased resting HR (from 73 ± 2 to 69 ± 2 beats/min; P = .02) and recovery HR (from 148 ± 11 to 128 ± 9 beats/min; P = .001). Concomitantly, left ventricular ejection fraction increased (from 31% ± 1% to 36% ± 0.9%; P = .01), left atrial dimension decreased (from 52 ± 1.2 to 47 ± 1 mm; P = .03), and left ventricular end-systolic volume and left ventricular end-diastolic volume deceased (from 69 ± 2 to 64 ± 1.8 mL/m2 and from 99 ± 2.1 to 91 ± 2 mL/m2, respectively; P < .05). No changes were observed in the HFAF-untrained group. CONCLUSION: Exercise training can improve exercise capacity, quality of life, and cardiac function in patients with HF with reduced ejection fraction and permanent atrial fibrillation.
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Fibrilação Atrial , Insuficiência Cardíaca , Disfunção Ventricular Esquerda , Fibrilação Atrial/terapia , Exercício Físico , Teste de Esforço , Tolerância ao Exercício/fisiologia , Humanos , Pessoa de Meia-Idade , Consumo de Oxigênio/fisiologia , Qualidade de Vida , Volume Sistólico/fisiologia , Função Ventricular Esquerda/fisiologiaRESUMO
Chagas disease (CD), caused by Trypanosoma cruzi, affects approximately 6 to 7 million people in Latin America, with cardiomyopathy being the clinical manifestation most commonly associated with patient death during the acute phase. The etiological treatment of CD is restricted to benznidazole (Bz) and nifurtimox (Nif), which involve long periods of administration, frequent side effects, and low efficacy in the chronic phase. Thus, combined therapies emerge as an important tool in the treatment of CD, allowing the reduction of Bz dose and treatment duration. In this sense, amiodarone (AMD), the most efficient antiarrhythmic drug currently available and prescribed to CD patients, is a potential candidate for combined treatment due to its known trypanocidal activity. However, the efficacy of AMD during the acute phase of CD and its interaction with Bz or Nif are still unknown. In the present study, using a well-established murine model of the acute phase of CD, we observed that the Bz/AMD combination was more effective in reducing the peak parasitemia than both monotherapy treatments. Additionally, the Bz/AMD combination reduced (i) interleukin-6 (IL-6) levels in cardiac tissue, (ii) P-wave duration, and (iii) frequency of arrhythmia in infected animals and (iv) restored gap junction integrity in cardiac tissue. Therefore, our study validates AMD as a promising candidate for combined therapy with Bz, reinforcing the strategy of combined therapy for CD. IMPORTANCE Chagas disease affects approximately 6 to 7 million people worldwide, with cardiomyopathy being the clinical manifestation that most commonly leads to patient death. The etiological treatment of Chagas disease is limited to drugs (benznidazole and nifurtimox) with relatively high toxicity and therapeutic failures. In this sense, amiodarone, the most effective currently available antiarrhythmic drug prescribed to patients with Chagas disease, is a potential candidate for combined treatment due to its known trypanocidal effect. In the present study, we show that combined treatment with benznidazole and amiodarone improves the trypanocidal effect and reduces cardiac damage in acutely T. cruzi-infected mice.
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Amiodarona/uso terapêutico , Doença de Chagas/tratamento farmacológico , Nitroimidazóis/uso terapêutico , Trypanosoma cruzi/efeitos dos fármacos , Amiodarona/efeitos adversos , Amiodarona/farmacologia , Animais , Modelos Animais de Doenças , Quimioterapia Combinada/métodos , Coração/efeitos dos fármacos , Cardiopatias/induzido quimicamente , Cardiopatias/patologia , Testes de Função Cardíaca , Humanos , Masculino , Camundongos , Nitroimidazóis/efeitos adversos , Nitroimidazóis/farmacologia , Parasitemia/tratamento farmacológicoRESUMO
Approximately 12-18% of hypertensive patients are diagnosed with resistant hypertension (RH). The risk of having worse cardiovascular outcomes is twice higher in those patients. The low effectiveness of conventional antihypertensive drugs in RH emphasizes the need to evaluate complementary drug therapies to achieve blood pressure (BP) control. Previous studies have demonstrated that phosphodiesterase 5 (PDE-5) inhibitors improve hemodynamics and reduce BP on essential hypertension. So, the authors aimed to summarize current clinical trials-based evidence published concerning the use of PDE-5 inhibitors on BP, cardiovascular function, and hemodynamics of patients with RH. We searched MEDLINE, EMBASE, LILACS, ClinicalTrials.gov, and WHO International Clinical Trials Registry databases on May 15th, 2020 using pre-defined search terms. Two independent reviewers assessed and extracted data from clinical trials that evaluated the effect of PDE-5 inhibitors on BP. We have included five articles in this systematic review. Four of them developed a single-day protocol, while one has developed a 14-day study. The main findings indicate that PDE-5 inhibitors ameliorate BP, vascular hemodynamics, and diastolic function parameters. Some data demonstrated improvement of endothelial function, but it was not a consensus. The side effects seemed to be limited and well-tolerated. In brief, our systematic review highlights the potential of PDE-5 inhibitors as a therapeutic alternative in addition to the multiple-drug regime for RH. Larger studies are still needed to determine whether the beneficial effects of PDE-5 inhibitors on RH would be maintained with chronic administration.
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Hipertensão/tratamento farmacológico , Inibidores da Fosfodiesterase 5/farmacologia , Anti-Hipertensivos/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Doenças Cardiovasculares , Nucleotídeo Cíclico Fosfodiesterase do Tipo 5/metabolismo , Diástole/efeitos dos fármacos , Humanos , Hipertensão/fisiopatologia , Inibidores da Fosfodiesterase 5/metabolismoRESUMO
Chagas disease has a complex pathogenesis wherein the host immune response is essential for controlling its development. Suppressor of cytokine signaling(SOCS)2 is a crucial protein that regulates cytokine production. In this study, SOCS2 deficiency resulted in an initial imbalance of IL12- and IL-10-producing neutrophils and dendritic cells (DCs), which caused a long-lasting impact reducing inflammatory neutrophils and DCs, and tolerogenic DCs at the peak of acute disease. A reduced number of inflammatory and pro-resolving macrophages, and IL17A-producing CD4+ T cells, and increased lymphocyte apoptosis was found in SOCS2-deficient mice. Electrocardiogram analysis of chimeric mice showed that WT mice that received SOCS2 KO bone marrow transplantation presented increased heart dysfunction. Taken together, the results demonstrated that SOCS2 is a crucial regulator of the immune response during Trypanosoma cruzi infection, and suggest that a SOCS2 genetic polymorphism, or failure of its expression, may increase the susceptibility of cardiomyopathy development in Chagasic patients.