Abnormal skeletal muscle blood flow, contractile mechanics and fibre morphology in a rat model of obese-HFpEF.

KEY POINTS: Heart failure is characterised by limb and respiratory muscle impairments that limit functional capacity and quality of life. However, compared with heart failure with reduced ejection fraction (HFrEF), skeletal muscle alterations induced by heart failure with preserved ejection fraction (HFpEF) remain poorly explored. Here we report that obese-HFpEF induces multiple skeletal muscle alterations in the rat hindlimb, including impaired muscle mechanics related to shortening velocity, fibre atrophy, capillary loss, and an impaired blood flow response to contractions that implies a perfusive oxygen delivery limitation. We also demonstrate that obese-HFpEF is characterised by diaphragmatic alterations similar to those caused by denervation - atrophy in Type IIb/IIx (fast/glycolytic) fibres and hypertrophy in Type I (slow/oxidative) fibres. These findings extend current knowledge in HFpEF skeletal muscle physiology, potentially underlying exercise intolerance, which may facilitate future therapeutic approaches. ABSTRACT: Peripheral skeletal muscle and vascular alterations induced by heart failure with preserved ejection fraction (HFpEF) remain poorly identified, with limited therapeutic targets. This study used a cardiometabolic obese-HFpEF rat model to comprehensively phenotype skeletal muscle mechanics, blood flow, microvasculature and fibre atrophy. Lean (n = 8) and obese-HFpEF (n = 8) ZSF1 rats were compared. Skeletal muscles (soleus and diaphragm) were assessed for in vitro contractility (isometric and isotonic properties) alongside indices of fibre-type cross-sectional area, myosin isoform, and capillarity, and estimated muscle PO2 . In situ extensor digitorum longus (EDL) contractility and femoral blood flow were assessed. HFpEF soleus demonstrated lower absolute maximal force by 22%, fibre atrophy by 24%, a fibre-type shift from I to IIa, and a 17% lower capillary-to-fibre ratio despite increased capillary density (all P < 0.05) with preserved muscle PO2 (P = 0.115) and isometric specific force (P > 0.05). Soleus isotonic properties (shortening velocity and power) were impaired by up to 17 and 22%, respectively (P < 0.05), while the magnitude of the exercise hyperaemia was attenuated by 73% (P = 0.012) in line with higher muscle fatigue by 26% (P = 0.079). Diaphragm alterations (P < 0.05) included Type IIx fibre atrophy despite Type I/IIa fibre hypertrophy, with increased indices of capillarity alongside preserved contractile properties during isometric, isotonic, and cyclical contractions. In conclusion, obese-HFpEF rats demonstrated blunted skeletal muscle blood flow during contractions in parallel to microvascular structural remodelling, fibre atrophy, and isotonic contractile dysfunction in the locomotor muscles. In contrast, diaphragm phenotype remained well preserved. This study identifies numerous muscle-specific impairments that could exacerbate exercise intolerance in obese-HFpEF.

Impaired skeletal muscle regeneration in diabetes: From cellular and molecular mechanisms to novel treatments.

Diabetes represents a major public health concern with a considerable impact on human life and healthcare expenditures. It is now well established that diabetes is characterized by a severe skeletal muscle pathology that limits functional capacity and quality of life. Increasing evidence indicates that diabetes is also one of the most prevalent disorders characterized by impaired skeletal muscle regeneration, yet underlying mechanisms and therapeutic treatments remain poorly established. In this review, we describe the cellular and molecular alterations currently known to occur during skeletal muscle regeneration in people with diabetes and animal models of diabetes, including its associated comorbidities, e.g., obesity, hyperinsulinemia, and insulin resistance. We describe the role of myogenic and non-myogenic cell types on muscle regeneration in conditions with or without diabetes. Therapies for skeletal muscle regeneration and gaps in our knowledge are also discussed, while proposing future directions for the field.

Caloric Restriction Rejuvenates Skeletal Muscle Growth in Heart Failure With Preserved Ejection Fraction.

Heart failure with preserved ejection fraction (HFpEF) is a major clinical problem, with limited treatments. HFpEF is characterized by a distinct, but poorly understood, skeletal muscle pathology, which could offer an alternative therapeutic target. In a rat model, we identified impaired myonuclear accretion as a mechanism for low myofiber growth in HFpEF following resistance exercise. Acute caloric restriction rescued skeletal muscle pathology in HFpEF, whereas cardiac therapies had no effect. Mechanisms regulating myonuclear accretion were dysregulated in patients with HFpEF. Overall, these findings may have widespread implications in HFpEF, indicating combined dietary with exercise interventions as a beneficial approach to overcome skeletal muscle pathology.

Chronic heart failure with diabetes mellitus is characterized by a severe skeletal muscle pathology.

BACKGROUND: Patients with coexistent chronic heart failure (CHF) and diabetes mellitus (DM) demonstrate greater exercise limitation and worse prognosis compared with CHF patients without DM, even when corrected for cardiac dysfunction. Understanding the origins of symptoms in this subgroup may facilitate development of targeted treatments. We therefore characterized the skeletal muscle phenotype and its relationship to exercise limitation in patients with diabetic heart failure (D-HF). METHODS: In one of the largest muscle sampling studies in a CHF population, pectoralis major biopsies were taken from age-matched controls (n = 25), DM (n = 10), CHF (n = 52), and D-HF (n = 28) patients. In situ mitochondrial function and reactive oxygen species, fibre morphology, capillarity, and gene expression analyses were performed and correlated to whole-body exercise capacity. RESULTS: Mitochondrial respiration, content, coupling efficiency, and intrinsic function were lower in D-HF patients compared with other groups (P < 0.05). A unique mitochondrial complex I dysfunction was present in D-HF patients only (P < 0.05), which strongly correlated to exercise capacity (R2 = 0.64; P < 0.001). Mitochondrial impairments in D-HF corresponded to higher levels of mitochondrial reactive oxygen species (P < 0.05) and lower gene expression of anti-oxidative enzyme superoxide dismutase 2 (P < 0.05) and complex I subunit NDUFS1 (P < 0.05). D-HF was also associated with severe fibre atrophy (P < 0.05) and reduced local fibre capillarity (P < 0.05). CONCLUSIONS: Patients with D-HF develop a specific skeletal muscle pathology, characterized by mitochondrial impairments, fibre atrophy, and derangements in the capillary network that are linked to exercise intolerance. These novel preliminary data support skeletal muscle as a potential therapeutic target for treating patients with D-HF.

[EFFECTS OF INGESTING CARBOHYDRATE-PROTEIN SUPPLEMENTS DURING EXERCISE ON ENDURANCE PERFORMANCE: A SYSTEMATIC REVIEW]. / EFECTOS EN EL RENDIMIENTO FÍSICO DE LA INGESTA DE SUPLEMENTOS CON CARBOHIDRATOS Y PROTEÍNA DURANTE EL EJERCICIO: REVISIÓN SISTEMÁTICA.

INTRODUCTION: sports drinks aid to improve physical performance significantly because of its content of carbohydrate, electrolytes and water. However, in recent decades it has been found that drinking a sports drink with protein during exercise improves endurance performance, produces lower losses of body weight induced by dehydration and helps to reduce post-exercise muscle damage compared to a drink only with carbohydrate and electrolytes. PURPOSE: the aim of this study was to analyze the main studies about the effectiveness of a supplement intake with carbohydrate, protein and electrolytes during exercise. METHODS: studies were identified by searching Google Scholar, EBSCO, PubMed and Scopus using the following search terms: Carbohydrate-protein and performance and Added protein and sports drink. The methodological quality of the trials was evaluated, and It was considered that the intake of the supplement has been during exercise. RESULTS: twenty articles were included in this study. Thirteen obtained results were the intake of sports drinks with protein produced significant improvements on endurance performance compared to beverages with carbohydrates and electrolytes alone, or a placebo. DISCUSSION: increase the caloric content of sports drinks to add protein was probably a better strategy than reduce the carbohydrate content to match the amount of calories. CONCLUSIONS: protein intake during exercise demonstrated an ergogenic effect on endurance performance when assessed by time to exhaustion. However, we need more evidence to prove this possible ergogenic effect of protein.

Introducción: las bebidas deportivas ayudan a mejorar el rendimiento físico de forma significativa debido a su aporte de carbohidratos, electrolitos y agua. Sin embargo, en las últimas décadas se ha encontrado que ingerir una bebida deportiva con proteína durante el ejercicio mejora el rendimiento físico, produce menores pérdidas de peso corporal inducidas por la deshidratación y ayuda a disminuir el daño muscular postejercicio en comparación con una bebida únicamente con carbohidratos y electrolitos. Objetivo: analizar los principales estudios sobre la efectividad de la ingesta de un suplemento con carbohidratos, proteína y electrolitos durante el ejercicio. Método: se realizó una búsqueda automatizada en Google académico, EBSCO, PubMEd y Scopus, utilizando las palabras clave: Carbohydrate-protein and performance y Added protein and sports drink. Se evaluó la calidad metodológica de los ensayos y se tomó en cuenta que la ingesta del suplemento fuera durante el ejercicio. Resultados: de los veinte artículos que se incluyeron, trece obtuvieron resultados en los que la ingesta de una bebida deportiva con proteína generó mejoras significativas en el rendimiento físico en comparación con una bebida únicamente con carbohidratos y electrolitos, o un placebo. Discusión: aumentar el contenido calórico de las bebidas deportivas al agregar proteína es probablemente una estrategia más efectiva en comparación con disminuir el contenido de carbohidratos para igualar la cantidad de energía. Conclusiones: el consumo de proteína durante el ejercicio posiblemente sirva como una ayuda ergogénica, retardando el tiempo hasta llegar al agotamiento. Sin embargo, hace falta más evidencia que así lo demuestre.

Efectos en el rendimiento físico de la ingesta de suplementos con carbohidratos y proteína durante el ejercicio: revisión sistemática / Effects of ingesting carbohydrate-protein supplements during exercise on endurance performance: a systematic review

Introducción: las bebidas deportivas ayudan a mejorar el rendimiento físico de forma significativa debido a su aporte de carbohidratos, electrolitos y agua. Sin embargo, en las últimas décadas se ha encontrado que ingerir una bebida deportiva con proteína durante el ejercicio mejora el rendimiento físico, produce menores pérdidas de peso corporal inducidas por la deshidratación y ayuda a disminuir el daño muscular post ejercicio en comparación con una bebida únicamente con carbohidratos y electrolitos. Objetivo: analizar los principales estudios sobre la efectividad de la ingesta de un suplemento con carbohidratos, proteína y electrolitos durante el ejercicio. Método: se realizó una búsqueda automatizada en Google académico, EBSCO, PubMEd y Scopus, utilizando las palabras clave: Carbohydrate-protein and performance y Added protein and sports drink. Se evaluó la calidad metodológica de los ensayos y se tomó en cuenta que la ingesta del suplemento fuera durante el ejercicio. Resultados: de los veinte artículos que se incluyeron, trece obtuvieron resultados en los que la ingesta de una bebida deportiva con proteína generó mejoras significativas en el rendimiento físico en comparación con una bebida únicamente con carbohidratos y electrolitos, o un placebo. Discusión: aumentar el contenido calórico de las bebidas deportivas al agregar proteína es probablemente una estrategia más efectiva en comparación con disminuir el contenido de carbohidratos para igualar la cantidad de energía. Conclusiones: el consumo de proteína durante el ejercicio posiblemente sirva como una ayuda ergogénica, retardando el tiempo hasta llegar al agotamiento. Sin embargo, hace falta más evidencia que así lo demuestre (AU)

Introduction: sports drinks aid to improve physical performance significantly because of its content of carbohydrate, electrolytes and water. However, in recent decades it has been found that drinking a sports drink with protein during exercise improves endurance performance, produces lower losses of body weight induced by dehydration and helps to reduce post-exercise muscle damage compared to a drink only with carbohydrate and electrolytes. Purpose: the aim of this study was to analyze the main studies about the effectiveness of a supplement intake with carbohydrate, protein and electrolytes during exercise. Methods: studies were identified by searching Google Scholar, EBSCO, PubMed and Scopus using the following search terms: Carbohydrate-protein and performance and Added protein and sports drink. The methodological quality of the trials was evaluated, and It was considered that the intake of the supplement has been during exercise. Results: twenty articles were included in this study. Thirteen obtained results were the intake of sports drinks with protein produced significant improvements on endurance performance compared to beverages with carbohydrates and electrolytes alone, or a placebo. Discussion: increase the caloric content of sports drinks to add protein was probably a better strategy than reduce the carbohydrate content to match the amount of calories. Conclusions: protein intake during exercise demonstrated an ergogenic effect on endurance performance when assessed by time to exhaustion. However, we need more evidence to prove this possible ergogenic effect of protein (AU)