Downregulation of Tnf-α and Cat Expression in a Wistar Rat Diabetic Model during Diabetes Onset.

INTRODUCTION: Diabetes Mellitus (DM) is a metabolic disorder characterized by persistent hyperglycemia and/or insulin resistance. If left uncontrolled, it can lead to a combination of cardiac and renal alterations known as cardiorenal syndrome. Additionally, oxidative stress and inflammation contribute to tissue damage, thereby reducing the life expectancy of individuals with diabetes. AIM: The aim of this study was to identify early molecular markers associated with cardiorenal syndrome, oxidative stress, and inflammation, and to investigate their correlation with the duration of exposure to DM. METHODS: An experimental DM model was employed using Wistar rats. The rats were divided into four groups: diabetic rats at 7 days (DM7), diabetic rats at 30 days (DM30), control sham at 7 days (CS7), and control sham at 30 days (CS30). Blood and brain tissue from the brainstem region were collected at 7 and 30 days after confirming DM induction. Gene expression analysis of Bnp, Anp, Cat, Gpx, Sod, Tnf-α, and Il-6 was performed. RESULTS: The analysis revealed lower expression values of Cat in the brainstem tissue of the DM7 group compared to the NDS7 group. Moreover, diabetic animals exhibited statistically lower levels of Tnf-α in their peripheral blood compared to the control animals. CONCLUSION: This study concluded that DM alters the oxidative balance in the brainstem after 7 days of DM induction, resulting in lower Cat expression levels. Although some genes did not show statistical differences after 30 days of DM induction, other genes exhibited no expression values, indicating possible gene silencing. The study identified an imbalance in the studied pathways and concluded that the organism undergoes a compensatory state in response to the initial metabolic alterations caused by DM.

Prevalencia, caracterización y pronóstico de pacientes con sospecha de insuficiencia cardíaca en atención primaria de salud en Chile / Characterization and prognosis of patients with suspected heart failure at primary health care institutions in Chile

Introducción: La insuficiencia cardíaca (IC) tiene alta morbilidad y mortalidad. Su diagnóstico temprano en atención primaria de salud (APS) es un reto dada la baja especificidad de sus criterios clínicos y las limitaciones en acceso a técnicas diagnósticas. Objetivo: Analizar la prevalencia de IC, subtipos y pronóstico de pacientes con disnea y/o edema de extremidades inferiores que consultan en APS. Metodología: Se trata de un estudio prospectivo de 340 pacientes en APS, sin diagnóstico previo de IC. Se realizó una evaluación clínica, electrocardiograma, NT-proBNP "point-of-care", ecocardiografía con interpretación telemática por cardiólogos. Utilizando los algoritmos HFA-PEFF y H2FPEF se clasificaron los pacientes como :1) IC con fracción de eyección (FE) reducida (ICFER); 2) IC con FE preservada (ICFEP) y 3) pacientes sin diagnóstico de IC. Se efectuó un análisis de sobrevida de los diferentes grupos. Resultados: La prevalencia de ICFER fue 8%, ICFEP por HFA-PEFF 42% y por H2FPEF 8%. Los algoritmos sugieren efectuar un estudio complementario en el 47% con HFA-PEFF y 76% con H2FPEF (p<0.05). La sobrevida global a 36 meses fue 90±2% y cardiovascular 95±1%. Usando HFA-PEFF, los pacientes con IC tuvieron menor sobrevida que aquellos sin IC (HR 2.3, IC95% 1.14.9; p=0.029). No hubo diferencias de mortalidad con H2FPEF. Conclusiones: En pacientes de APS que consultan por disnea y/o edema de extremidades inferiores sometidos a evaluación con NT-proBNP y ecocardiografía, se observó una prevalencia de IC de hasta 50%, 8% de ICFER y 42% de ICFEP. La caracterización de IC utilizando HFA-PEFF está asociada al pronóstico vital.

Background: Heart failure (HF) is a condition associated with high morbidity and mortality. Its early diagnosis in primary health care (PHC) represents a substantial challenge, considering its non-specific clinical manifestations and the limitations on timely access to diagnostic techniques. Objective: To evaluate the prevalence of HF, characterize subtypes and determine the prognosis of patients consulting in PHC for dyspnea Edema of the lower extremities. Methods: Prospective study in 340 patients who consulted in PHC, without previous diagnosis of HF. Clinical evaluation, electrocardiogram, NT-proBNP point-ofcare and echocardiography with telematic interpretation by cardiologists were performed. Using the HFA-PEFF and H2FPEF algorithms patients were classified as: 1) HF with reduced ejection fraction (HFREF); 2) HF with preserved ejection fraction (HFPEF) and 3) No HF. Actuarial survival analyses were performed. Results: We observed a prevalence of HFREF of 8%, high probability of HFPEF by HFA-PEFF in 42% and by H2FPEF in 8%. Intermediate probability of HFPEF, requiring complementary study, was observed in 47% of patients with HFA-PEFF and 76% of patients with H2FPEF (p<0.05). Overall survival at 36 months was 90±2% and cardiovascular survival at 36 months was 95±1%. Using HFA-PEFF, patients with HF presented lower overall survival compared to patients with no HF (HR 2.3, 95%CI 1.1-4.9; p=0.029). We did not observe mortality differences with H2FPEF. Conclusions: In patients consulting for dyspnea and/or lower extremity edema at PHC and undergoing evaluation with NT-proBNP and echocardiography, we observed a HF prevalence of 50%. HF classification through HFA-PEFF was associated with lower survival rates.

B-type natriuretic peptide and N-terminal Pro-B-type natriuretic peptide in severe aortic stenosis: a comprehensive literature review.

B-type natriuretic peptide (BNP) and N-terminal pro-BNP (NT-pro BNP) are cardiac biomarkers that are released in response to increased ventricular and atrial wall stress. Aortic stenosis (AS) leads to hemodynamic changes and left ventricular hypertrophy and may be associated with natriuretic peptide levels. Several studies have shown that increased natriuretic peptide levels are correlated with AS severity and can predict the need for intervention. It can be useful in risk stratification, monitoring follow-up, and predicting cardiovascular outcomes of patients with severe AS. This paper aims to summarize the evidence of the role of BNP and NT-pro BNP in AS, before and after intervention.

El difícil camino de los péptidos natriuréticos en la insuficiencia cardiaca

Esta es una revisión sobre el papel de los péptidos natriuréticos y los intentos de utilizarlos como diana terapéutica a medida que se iba comprendiendo mejor su papel en la fisiopatología de la insuficiencia cardíaca con función sistólica deprimida. Se hace un recuento de su participación en sucesivos estudios fallidos y se explican los motivos de sus fracasos, hasta lograr el éxito deseado con la combinación del sacubitrilo/valsartan, lo que produjo un cambio de paradigma en el manejo de la insuficiencia cardíaca.

This review is conducted on the role of natriuretic peptides and the attempts to use them as a treatment as their role in the pathophysiology of heart failure with depressed systolic function was better understood. A recount of their participation in successive failed studies is provided, explaining the reasons for their failures, until achieving the desired success with the combination of sacubitril/valsartan. This produced a paradigm shift in the management of heart failure.

PPAR Alpha Activation by Clofibrate Alleviates Ischemia/Reperfusion Injury in Metabolic Syndrome Rats by Decreasing Cardiac Inflammation and Remodeling and by Regulating the Atrial Natriuretic Peptide Compensatory Response.

Metabolic syndrome (MetS) is a cluster of factors that increase the risk of developing diabetes, stroke, and heart failure. The pathophysiology of injury by ischemia/reperfusion (I/R) is highly complex and the inflammatory condition plays an important role by increasing matrix remodeling and cardiac apoptosis. Natriuretic peptides (NPs) are cardiac hormones with numerous beneficial effects mainly mediated by a cell surface receptor named atrial natriuretic peptide receptor (ANPr). Although NPs are powerful clinical markers of cardiac failure, their role in I/R is still controversial. Peroxisome proliferator-activated receptor α agonists exert cardiovascular therapeutic actions; however, their effect on the NPs' signaling pathway has not been extensively studied. Our study provides important insight into the regulation of both ANP and ANPr in the hearts of MetS rats and their association with the inflammatory conditions caused by damage from I/R. Moreover, we show that pre-treatment with clofibrate was able to decrease the inflammatory response that, in turn, decreases myocardial fibrosis, the expression of metalloprotease 2 and apoptosis. Treatment with clofibrate is also associated with a decrease in ANP and ANPr expression.

Uso de NT-proBNP en el seguimiento ambulatorio de pacientes con insuficiencia cardiaca con fracción de eyección del ventrículo izquierdo reducida en una unidad multidisciplinaria de insuficiencia cardiaca

Introducción: La insuficiencia cardíaca (IC) es un síndrome clínico prevalente a nivel mundial, que se beneficia del abordaje multidisciplinario, pero su seguimiento ambulatorio sigue siendo un reto. La utilidad diagnóstica y pronóstica del NT-proBNP está apoyada en la evidencia actual; pero su uso en el seguimiento aún no ha sido definido. En el presente estudio se busca determinar si la variación en el tiempo del valor de NT-proBNP se relacionó con modificación en el tratamiento farmacológico de pacientes ambulatorios con IC y fracción de eyección del ventrículo izquierdo reducida (FEVI ≤ 40%) de una unidad multidisciplinaria de insuficiencia cardíaca (UMIC). Metodología: Estudio cohorte retrospectivo, de pacientes que cumplieron con los criterios de inclusión: 2 o más cuantificaciones de NT-proBNP en 12 meses y un seguimiento mínimo de 2 años entre los años 2013 y 2017. Resultados: De un total de 566 sujetos integrantes de cohorte activa de UMIC se incluyeron 107 que cumplieron criterios de inclusión; la mayoría hombres (58%), edad mediana de 63 años (Q1;Q3: 55,9;71,2 años), la principal comorbilidad fue hipertensión arterial (71%). En 56% de la población la etiología de IC fue no isquémica y el 50% tenía una clase funcional - NYHA I. La mediana de NT-proBNP basal fue de 698 pg/ml (Q1;Q3: (218;1564 pg/ml), con FEVI basal mediana de 30% (Q1;Q3: 27%;40%). En 55% de los pacientes la variación del valor de NT-proBNP durante el seguimiento se relacionó con modificaciones en el tratamiento farmacológico. Conclusiones: En la mitad de la población de nuestra cohorte se evidenció que los valores de NT-proBNP se relacionaron con cambios en el tratamiento farmacológico, independientemente de la situación clínica.

Introduction: Heart failure (HF) is a prevalent clinical syndrome worldwide, which benefits from a multidisciplinary approach, but its outpatient follow-up remains a challenge. The diagnostic and prognostic utility of NT-proBNP is supported by current evidence, but its use in monitoring has not yet been defined. The present study sought to determine whether the variation over time in the value of NT-proBNP was related to changes in the pharmacological treatment of outpatients with HF and reduced left ventricular ejection fraction (LVEF ≤ 40%) in a multidisciplinary heart failure unit. (MHFU). Methodology: Retrospective cohort study of patients, who met the inclusion criteria: 2 or more quantifications of NT-proBNP in 12 months and a minimum follow-up of 2 years between 2013 and 2017. Results: Of 566 members of the MHFU active cohort, 107 met the inclusion criteria; most men (58%), median age 63 years (Q1;Q3: 55.9;71.2), the main comorbidity was arterial hypertension (71%). The etiology of HF was non-ischemic in 56% of the population, and 50% had a functional class - NYHA I. Median baseline NT-proBNP was 698 pg/ml (Q1;Q3: (218;1564), with median baseline LVEF of 30% (Q1;Q3: 27;40). In 55% of the patients, the variation in the NT-proBNP value during follow-up was related to changes in pharmacological treatment. Conclusions: In half of the population of our cohort, it was shown that NT-proBNP values were related to changes in pharmacological treatment, regardless of the clinical situation.

Introdução: A insuficiência cardíaca (IC) é uma síndrome clínica prevalente em todo o mundo, que se beneficia de uma abordagem multidisciplinar, mas seu acompanhamento ambulatorial continua sendo um desafio. A utilidade diagnóstica e prognóstica do NT-proBNP é suportada pelas evidências atuais, mas seu uso no monitoramento ainda não foi definido. O presente estudo procurou determinar se a variação ao longo do tempo no valor do NT-proBNP estava relacionada a mudanças no tratamento farmacológico de pacientes ambulatoriais com IC e fração de ejeção do ventrículo esquerdo (FEVE ≤ 40%) reduzida em uma unidade multidisciplinar de insuficiência cardíaca. (UMIC). Metodologia: Estudo de coorte retrospectivo de pacientes que preencheram os critérios de inclusão: 2 ou mais quantificações de NT-proBNP em 12 meses e seguimento mínimo de 2 anos entre 2013 e 2017. Resultados: Dos 566 membros da coorte ativa do UMIC, 107 preencheram os critérios de inclusão; maioria dos homens (58%), idade mediana 63 anos (Q1;Q3: 55,9;71,2), a principal comorbidade foi hipertensão arterial (71%). A etiologia da IC foi não-isquêmica em 56% da população, e 50% tinham classe funcional - NYHA I. A mediana basal do NT-proBNP foi de 698 pg/ml (Q1;Q3: (218;1564), com mediana basal FEVE de 30% (Q1;Q3: 27;40). Em 55% dos pacientes, a variação do valor de NT-proBNP durante o seguimento esteve relacionada a mudanças no tratamento farmacológico. Conclusões: Em metade da população do nosso coorte, foi demonstrado que os valores de NT-proBNP estavam relacionados a mudanças no tratamento farmacológico, independentemente da situação clínica.

The MAGGIC risk score in the prediction of death or hospitalization in patients with heart failure: Comparison with natriuretic peptides.

BACKGROUND: The MAGGIC risk score has been validated to predict mortality in patients with heart failure (HF). OBJECTIVES: To assess the score ability to predict hospitalization and death and to compare with natriuretic peptides. METHODS: Ninety-three consecutive patients (mean age 62±10 years) with chronic HF and left ventricular ejection fraction (EF) <50% were studied. The MAGGIC score was applied at baseline and the patients were followed for 219±86 days. MAGGIC score was compared with NT-proBNP in the prediction of events. The primary end point was the time to the first event, which was defined as cardiovascular death or hospitalization for HF. RESULTS: There were 23 (24.7%) events (3 deaths and 20 hospitalizations). The median score in patients with and without events was, respectively, 20 [interquartile range 14.2-22] vs. 15.5 [11/21], p=0.16. A ROC curve was performed and a cutoff point of 12 points showed a sensitivity of 87% and specificity of 37% with an area under the curve of 0.59 (95% CI 0.48-0.69) which was lower than that of NT-proBNP (AUC 0.67; 95% CI 0.56-0.76). The mean event-free survival time for patients above and below this cutpoint was 248.8±13 vs. 290±13.7 days (log rank test with p=0.044). Using the COX proportional hazard model, age (p=0.004), NT-proBNP >1000 pg/mL (p=0.014) and the MAGGIC score (p=0.025) were independently associated with the primary outcome. CONCLUSION: The MAGGIC risk score was an independent predictor of events, including heart failure hospitalization. The addition of biomarkers improved the accuracy of the score.

Análise Crítica e Limitações do Diagnóstico de Insuficiência Cardíaca com Fração de Ejeção Preservada (ICFEp) / Critical Analysis and Limitations of the Diagnosis of Heart Failure with Preserved Ejection Fraction (HFpEF)

Resumo Com o aumento da expectativa de vida da população e a maior frequência de fatores de risco como obesidade, hipertensão arterial e diabetes, espera-se um aumento na prevalência de insuficiência cardíaca com fração de ejeção preservada (ICFEp). Entretanto, no momento, o diagnóstico e o tratamento de pacientes com ICFEp permanecem desafiadores. O diagnóstico sindrômico de ICFEp inclui diversas etiologias e doenças com tratamentos específicos, mas que apresentam pontos em comum em relação à apresentação clínica e à avaliação laboratorial no que diz respeito aos biomarcadores como BNP e NT-ProBNP, à avaliação ecocardiográfica do remodelamento cardíaco e às pressões de enchimento diastólico ventricular esquerdo. Extensos ensaios clínicos randomizados envolvendo a terapia nesta síndrome falharam na demonstração de benefícios para o paciente, fazendo-se necessária uma reflexão acerca do diagnóstico, dos mecanismos de morbidade, da taxa de mortalidade e da reversibilidade. Na revisão, serão abordados os conceitos atuais, as controvérsias e, especialmente, os desafios no diagnóstico da ICFEp através de uma análise crítica do escore da European Heart Failure Association.

Abstract With the increase in the population's life expectancy and the higher frequency of risk factors such as obesity, hypertension and diabetes, an increase in the prevalence of heart failure with preserved ejection fraction (HFpEF) is expected. However, to date, the diagnosis and treatment of patients with HFpEF remain challenging. The syndromic diagnosis of HFpEF includes several etiologies and diseases with specific treatments but has points in common regarding the clinical presentation, laboratory evaluation related to biomarkers, such as BNP and NT-ProBNP, and echocardiographic evaluation of cardiac remodeling and left ventricular diastolic filling pressures. Extensive randomized clinical trials involving the treatment of this condition have failed to demonstrate benefits to the patient, making it necessary to reflect on the diagnosis, mechanisms of morbidity, mortality and reversibility in this syndrome. In this review, the current concepts, controversies and challenges, especially regarding diagnosis, will be addressed, critically analyzing the European Heart Failure Association score for the diagnosis of HFpEF.

NT-proBNP as a predictor of death and cardiovascular events in patients with type 2 diabetes.

Existing risk prediction scores based on clinical and laboratory variables have been considered inaccurate in patients with Type 2 Diabetes Mellitus (T2DM). Circulating concentrations of natriuretic peptides have been used to aid in the diagnosis and to predict outcomes in heart failure. However, there is a growing body of evidence for the use of natriuretic peptides measurements, mainly N-terminal pro-B-type natriuretic peptide (NT-proBNP), as a tool in risk stratification for individuals with T2DM. Studies have demonstrated the ability of NT-proBNP to improve outcomes prediction when incorporated into multivariate models. More recently, evidence has emerged of the discriminatory power of NT-proBNP, demonstrating, as a single variable, a similar and even superior ability to multivariate risk models for the prediction of death and cardiovascular events in individuals with T2DM. Natriuretic peptides are synthesized and released from the myocardium as a counter-regulatory response to increased cardiac wall stress, sympathetic tone, and vasoconstriction, acting on various systems and affecting different biological processes. In this article, we present a review of the accumulated knowledge about these biomarkers, underscoring the strength of the evidence of their predictive ability for fatal and non-fatal outcomes. It is likely that, by influencing the functioning of many organs, these biomarkers integrate information from different systems. Although not yet recommended by guidelines, measurement of natriuretic peptides, and particularly NT-proBNP, should be strongly considered in the risk stratification of individuals with T2DM.

Natriuretic peptides to differentiate constrictive pericarditis and restrictive cardiomyopathy: A systematic review and meta-analysis.

Previous studies have shown that natriuretic peptide levels are increased in patients with restrictive cardiomyopathy (RCM) but not in constrictive pericarditis (CP). We performed a systematic review and meta-analysis to evaluate the diagnostic utility of B-type natriuretic peptide (BNP) and N-terminal pro-brain natriuretic peptide (NT-proBNP) to differentiate CP and RCM. We searched electronic databases from inception to January 07, 2021. Studies involving adult patients that assessed the utility of natriuretic peptides to differentiate CP and RCM were included. All meta-analyses were performed using a random-effects model. Seven studies (four case-control and three cohorts) involving 204 patients were included. The mean age ranged between 25.7 and 64.1 years and 77% of patients were men. BNP levels were significantly lower (standardized median difference [SMD], -1.48; 95% confidence interval [CI], -2.33 to -0.63) in patients with CP compared to RCM. The pooled area under the curve (AUC) of the BNP level was 0.81 (95% CI, 0.70-0.92). NT-proBNP (SMD, -0.86; 95% CI, -1.38 to -0.33) and log NT-proBNP (SMD, -1.89; 95% CI, -2.59 to -1.20) levels were significantly lower in patients with CP compared to RCM. Our review shows that BNP and NT-proBNP levels were significantly lower in patients with CP compared to RCM. The pooled AUC of BNP level showed a good diagnostic accuracy to differentiate both conditions.

Increased N-terminal Pro-B-Type Natriuretic Peptide during Extracorporeal Life Support Is Associated with Poor Outcome in Neonates with Congenital Diaphragmatic Hernia.

OBJECTIVES: To evaluate the prognostic information derived from the daily measurements of N-terminal pro-B-type natriuretic peptide (proBNP) in neonates with congenital diaphragmatic hernia undergoing extracorporeal life support (ECLS). STUDY DESIGN: Plasma proBNP was prospectively measured daily during the first week of ECLS using an electrochemiluminescence immunoassay. Patients (n = 63) were allocated according to outcome: survivors (group 1, n = 35); nonsurvivors with successful weaning (defined as survival for >12 hours after ECLS discontinuation) (group 2, n = 16); nonsurvivors with unsuccessful weaning (group 3, n = 12). ProBNP kinetics were compared using Kruskal-Wallis testing and correlated with pulmonary hypertension and cardiac dysfunction on echocardiography using the Spearman correlation coefficient. RESULTS: Infants in group 3 presented significantly higher proBNP values from day 3 to day 6 compared with group 1 and 2. Overall mortality among patients with the highest proBNP values on day 1 was 30.6% compared with 63% in those patients with at least 1 higher value on day 2 to day 7. In patients with a late increase (day 4 to day 7) in proBNP the mortality was 70%, compared with 32.6% in those with proBNP below the value on day 1. Weaning failure was 35% in patients with a late increase and 11.6% in those without a late increase. ProBNP correlated significantly with pulmonary hypertension and cardiac dysfunction before and during ECLS. CONCLUSIONS: Absolute proBNP values are associated with weaning failure but not overall mortality in neonates with congenital diaphragmatic hernia undergoing ECLS. Echocardiographic findings correlate well with proBNP values.

Role of natriuretic peptides in the cardiovascular-adipose communication: a tale of two organs.

Natriuretic peptides have long been known for their cardiovascular function. However, a growing body of evidence emphasizes the role of natriuretic peptides in the energy metabolism of several substrates in humans and animals, thus interrelating the heart, as an endocrine organ, with various insulin-sensitive tissues and organs such as adipose tissue, muscle skeletal, and liver. Adipose tissue dysfunction is associated with altered regulation of the natriuretic peptide system, also indicated as a natriuretic disability. Evidence points to a contribution of this natriuretic disability to the development of obesity, type 2 diabetes mellitus, and cardiometabolic complications; although the causal relationship is not fully understood at present. However, targeting the natriuretic peptide pathway may improve metabolic health in obesity and type 2 diabetes mellitus. This review will focus on the current literature on the metabolic functions of natriuretic peptides with emphasis on lipid metabolism and insulin sensitivity. Natriuretic peptide system alterations could be proposed as one of the linking mechanisms between adipose tissue dysfunction and cardiovascular disease.

Effects of different stimulators of cGMP synthesis on lipid content in bovine oocytes matured in vitro.

Bovine oocytes and blastocysts produced in vitro are frequently of lower quality and less cryotolerant than those produced in vivo, and greater accumulation of lipids in the cytoplasm has been pointed out as one of the reasons. In human adipocytes cGMP signaling through the activation of PKG appears to be involved in lipid metabolism, and components of this pathway have been detected in bovine cumulus-oocyte complexes (COCs). The aim of this study was to investigate the influence of this pathway on the lipid content in oocytes and expression of PLIN2 (a lipid metabolism-related gene) in cumulus cells. COCs were matured in vitro for 24 h with different stimulators of cGMP synthesis. The activation of soluble guanylyl cyclase (sGC) by Protoporphyrin IX reduced lipid content (22.7 FI) compared to control oocytes (36.45 FI; P <0.05). Stimulation of membrane guanylyl cyclase (mGC) with natriuretic peptides precursors A and C (NPPA and NPPC) had no effect (36.5 FI; P>0.05). When the PKG inhibitor KT5823 was associated with Protoporphyrin IX, its effect was reversed and lipid contents increased (52.71 FI; P<0.05). None of the stimulators of cGMP synthesis affected the expression of PLIN2 in cumulus cells. In conclusion, stimulation of sGC for cGMP synthesis promotes lipolytic activities in bovine oocytes matured in vitro and such effect is mediated by PKG. However, such effect may vary depending on the stimulus received and/or which synthesis enzyme was activated, as stimulation of mGC had no effects.

Rol de los péptidos natriuréticos en insuficiencia cardíaca: El fino equilibrio entre la medicina de precisión y la optimización de los recursos

La insuficiencia cardíaca constituye la fase final de la mayoría de las patologías cardiovasculares. Si bien el interrogatorio, el conocimiento de los antecedentes personales y familiares del paciente, sumados al examen físico detallado, contribuyen en sobremanera al diagnóstico; muchas veces el diagnóstico diferencial del síndrome de insuficiencia cardíaca no nos permite diferenciar entre los cuadros compensados de aquellos portadores de insuficiencia cardíaca en las primeras fases de la descompensación o nos llevan a la duda entre diagnósticos diferenciales. La falta de disponibilidad de camas de hospitalización, problemas de cobertura médica o incluso problemas sociales o psicológicos, obligan muchas veces a la determinación de altas precoces con el riesgo presente de descompensaciones e internaciones reiteradas. Evitar descompensaciones frecuentes es el trabajo silencioso que debe realizar el médico para tratar de detectar precozmente con la finalidad de enlentecer o detener el progreso de la enfermedad cardiovascular, evitando estudios e internaciones costosas. Entre el armamento necesario para cumplir con esta finalidad se encuentra el dosaje de péptidos natriuréticos. La presente revisión trata de resumir los datos disponibles que valoran el control de los niveles de péptidos natriuréticos en nuestra asistencia de los pacientes con insuficiencia cardíaca.

Heart failure constitutes the final stage of most cardiovascular diseases. Although the questioning, the knowledge of the patient s personal and family history, added to the detailed physical examination, greatly contribute to the diagnosis; Many times the differential diagnosis of heart failure syndrome does not allow us to differentiate between the compensated conditions of those with heart failure in the early stages of decompensation or leads us to doubt between differential diagnoses. The lack of availability of hospital beds, problems of medical coverage or even social or psychological problems, often force the determination of early discharges with the present risk of decompensation and repeated hospitalizations. Avoiding frequent decompensations is the silent work that the physician must do to try to detect it early in order to slow down or stop the progress of cardiovascular disease, avoiding expensive studies and hospitalizations. Among the weapons necessary to fulfill this purpose is the dosage of natriuretic peptides. This review attempts to summarize the available data that assess the control of natriuretic peptide levels in our care of patients with heart failure.

A insuficiência cardíaca constitui o estágio final da maioria das doenças cardiovasculares. Apesar do questionamento, o conhecimento da história pessoal e familiar do paciente, somado ao exame físico detalhado, contribuem muito para o diagnóstico; Muitas vezes, o diagnóstico diferencial da síndrome da insuficiência cardíaca não nos permite diferenciar as condições compensadas dos portadores de insuficiência cardíaca nos estágios iniciais de descompensação ou nos leva à dúvida entre os diagnósticos diferenciais. A falta de disponibilidade de leitos hospitalares, problemas de cobertura médica ou mesmo problemas sociais ou psicológicos, muitas vezes obrigam à determinação de altas precoces com o risco atual de descompensação e hospitalizações repetidas. Evitar descompensações frequentes é o trabalho silencioso que o médico deve fazer para tentar detectá-la precocemente, a fim de retardar ou interromper o progresso das doenças cardiovasculares, evitando estudos e internações dispendiosas. Entre as armas necessárias para cumprir esse propósito está a dosagem de peptídeos natriuréticos. Esta revisão tenta resumir os dados disponíveis que avaliam o controle dos níveis de peptídeo natriurético em nosso tratamento de pacientes com insuficiência cardíaca.

Prenatal Particulate Matter (PM) Exposure and Natriuretic Peptides in Newborns from Mexico City.

(1) Background: The aim of this study was to assess associations between particulate matter (PM) exposure and natriuretic peptide concentrations in cord blood from newborns. (2) Methods: we conducted a cross-sectional study in Mexico City with 101 pregnant women from CIMIGEN Hospital. Atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP) and C-type natriuretic peptide (CNP) were measured in plasma from cord blood in 51 newborns by ELISA. We estimated PM exposure (PM2.5 and PM10) at first, second and third trimester of pregnancy. (3) Results: The median and interquartile range for ANP, BNP and CNP plasma concentrations were 66.71 (46.92-80.23), 98.23 (73.64-112.30) and 1129.11 (944.10-1452.02) pg/mL, respectively. PM2.5 and PM10 levels for the whole pregnancy period were 22.2 µg/m3 and 41.63 µg/m3, respectively. Employing multivariable linear regression models adjusted for maternal age, newborn sex, smoking before pregnancy, maternal occupation and newborns' length and height, we observed a 2.47 pg/mL (95%CI: -4.67, -0.27) decrease in BNP associated with PM2.5 exposure during second trimester. Adjusted for the same set of confounders, third trimester PM10 exposure was inversely associated with ANP concentrations (beta estimate: -0.90; 95% CI: -1.80, -0.03). Neither PM10 nor PM2.5 were associated with CNP at any trimester of pregnancy. (4) Conclusions: Prenatal exposure to particulate matter was associated with ANP and BNP decrease in newborns.

Cardiac Natriuretic Peptide Profiles in Chronic Hypertension by Single or Sequentially Combined Renovascular and DOCA-Salt Treatments.

The involvement of natriuretic peptides was studied during the hypertrophic remodeling transition mediated by sequential exposure to chronic hemodynamic overload. We induced hypertension in rats by pressure (renovascular) or volume overload (DOCA-salt) during 6 and 12 weeks of treatment. We also studied the consecutive combination of both models in inverse sequences: RV 6 weeks/DS 6 weeks and DS 6 weeks/RV 6 weeks. All treated groups developed hypertension. Cardiac hypertrophy and left ventricular ANP gene expression were more pronounced in single DS than in single RV groups. BNP gene expression was positively correlated with left ventricular hypertrophy only in RV groups, while ANP gene expression was positively correlated with left ventricular hypertrophy only in DS groups. Combined models exhibited intermediate values between those of single groups at 6 and 12 weeks. The latter stimulus associated to the second applied overload is less effective than the former to trigger cardiac hypertrophy and to increase ANP and BNP gene expression. In addition, we suggest a correlation of ANP synthesis with volume overload and of BNP synthesis with pressure overload-induced hypertrophy after a prolonged treatment. Volume and pressure overload may be two mechanisms, among others, involved in the differential regulation of ANP and BNP gene expression in hypertrophied left ventricles. Plasma ANP levels reflect a response to plasma volume increase and volume overload, while circulating BNP levels seem to be regulated by cardiac BNP synthesis and ventricular hypertrophy.

Effects of different stimulators of cGMP synthesis on lipid content in bovine oocytes matured in vitro

Bovine oocytes and blastocysts produced in vitro are frequently of lower quality and less cryotolerant than those produced in vivo, and greater accumulation of lipids in the cytoplasm has been pointed out as one of the reasons. In human adipocytes cGMP signaling through the activation of PKG appears to be involved in lipid metabolism, and components of this pathway have been detected in bovine cumulus-oocyte complexes (COCs). The aim of this study was to investigate the influence of this pathway on the lipid content in oocytes and expression of PLIN2 (a lipid metabolism-related gene) in cumulus cells. COCs were matured in vitro for 24 h with different stimulators of cGMP synthesis. The activation of soluble guanylyl cyclase (sGC) by Protoporphyrin IX reduced lipid content (22.7 FI) compared to control oocytes (36.45 FI; P <0.05). Stimulation of membrane guanylyl cyclase (mGC) with natriuretic peptides precursors A and C (NPPA and NPPC) had no effect (36.5 FI; P>0.05). When the PKG inhibitor KT5823 was associated with Protoporphyrin IX, its effect was reversed and lipid contents increased (52.71 FI; P<0.05). None of the stimulators of cGMP synthesis affected the expression of PLIN2 in cumulus cells. In conclusion, stimulation of sGC for cGMP synthesis promotes lipolytic activities in bovine oocytes matured in vitro and such effect is mediated by PKG. However, such effect may vary depending on the stimulus received and/or which synthesis enzyme was activated, as stimulation of mGC had no effects.(AU)