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INTRODUCTION: Whether cardiac impairment can be fully discarded in McArdle disease-the paradigm of 'exercise intolerance', caused by inherited deficiency of the skeletal muscle-specific glycogen phosphorylase isoform ('myophosphorylase')-remains to be determined. METHODS: Eight patients with McArdle disease and seven age/sex-matched controls performed a 15-minute moderate, constant-load cycle-ergometer exercise bout followed by a maximal ramp test. Electrocardiographic and two-dimensional transthoracic (for cardiac dimension's assessment) and speckle tracking [for left-ventricle global longitudinal (GLS) assessments] echocardiographic evaluations were performed at baseline. Electrocardiographic and GLS assessments were also performed during constant-load exercise and immediately upon maximal exertion. Four human heart biopsies were obtained in individuals without McArdle disease, and in-depth histological/molecular analyses were performed in McArdle and wild-type mouse hearts. RESULTS: Exercise intolerance was confirmed in patients ('second wind' during constant-load exercise, -55% peak power output vs controls). As opposed to controls, patients showed a decrease in GLS during constant-load exercise, especially upon second wind occurrence, but with no other between-group difference in cardiac structure/function. Human cardiac biopsies showed that all three glycogen phosphorylase-myophosphorylase, but also liver and especially brain-isoforms are expressed in the normal adult heart, thereby theoretically compensating for eventual myophosphorylase deficiency. No overall histological (including glycogen depots), cytoskeleton, metabolic or mitochondrial (morphology/network/distribution) differences were found between McArdle and wild-type mouse hearts, except for lower levels of pyruvate kinase M2 and translocase of outer membrane 20 kDa subunit in the former. CONCLUSIONS: This study provides preliminary evidence that cardiac structure and function seem to be preserved in patients with McArdle disease. However, the role for an impaired cardiac contractility associated with the second wind phenomenon should be further explored.
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BACKGROUND & AIMS: Ketone supplementation is gaining popularity. Yet, its effects on exercise performance when muscle glycogen cannot be used remain to be determined. McArdle disease can provide insight into this question, as these patients are unable to obtain energy from muscle glycogen, presenting a severely impaired physical capacity. We therefore aimed to assess the effects of acute ketone supplementation in the absence of muscle glycogen utilization (McArdle disease). METHODS: In a randomized cross-over design, patients with an inherited block in muscle glycogen breakdown (i.e., McArdle disease, n = 8) and healthy controls (n = 7) underwent a submaximal (constant-load) test that was followed by a maximal ramp test, after the ingestion of a placebo or an exogenous ketone ester supplement (30 g of D-beta hydroxybutyrate/D 1,3 butanediol monoester). Patients were also assessed after carbohydrate (75 g) ingestion, which is currently considered best clinical practice in McArdle disease. RESULTS: Ketone supplementation induced ketosis in all participants (blood [ketones] = 3.7 ± 0.9 mM) and modified some gas-exchange responses (notably increasing respiratory exchange ratio, especially in patients). Patients showed an impaired exercise capacity (-65 % peak power output (PPO) compared to controls, p < 0.001) and ketone supplementation resulted in a further impairment (-11.6 % vs. placebo, p = 0.001), with no effects in controls (p = 0.268). In patients, carbohydrate supplementation resulted in a higher PPO compared to ketones (+21.5 %, p = 0.001) and a similar response was observed vs. placebo (+12.6 %, p = 0.057). CONCLUSIONS: In individuals who cannot utilize muscle glycogen but have a preserved ability to oxidize blood-borne glucose and fat (McArdle disease), acute ketone supplementation impairs exercise capacity, whereas carbohydrate ingestion exerts the opposite, beneficial effect.
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Enfermedad del Almacenamiento de Glucógeno Tipo V , Glucógeno , Humanos , Glucemia , Suplementos Dietéticos , Cetonas , Músculos , Estudios CruzadosRESUMEN
Introducción: Diversas publicaciones han teorizado sobre los desencadenantes de la fatiga relativa al cáncer, uno de losefectos secundarios de la enfermedad y sus tratamientos que más estresa a los supervivientes de esa enfermedad. Por otrolado, el ejercicio físico ha sido analizado como terapia para reducir el impacto de esta secuela, y diversas instituciones apoyansu inclusión dentro de los programas de cuidado para población oncológica. No obstante, la fatiga en cáncer y el papel queel entrenamiento tiene para su control, se ha expuesto sin realizar una valoración global que muestre su complejidad y porqué el ejercicio físico resulta de tanto valor para reducirla.Objetivos: El objetivo de este trabajo fue revisar la evidencia existente sobre los desencadenantes de fatiga en cáncer, paraexponer en qué modo el ejercicio físico actúa sobre cada uno de ellos para controlar su sintomatología y conseguir un efectoterapéutico integral.Material y método: Se realizaron diversas búsquedas bibliográficas que permitieran conocer cuáles eran los desencadenantesde fatiga propuestos por la investigación, cómo se desarrollan y afectan al paciente oncológico y, por último, en qué gradoel ejercicio físico sería una herramienta viable para controlar sus efectos.Resultados: Expuestos más de una veintena de desencadenantes y agravantes de la fatiga relativa al cáncer, encontramosque la mayoría de ellos podrían ser prevenidos o al menos controlados a través del ejercicio físico.Conclusiones: Resulta imposible aislar unos desencadenantes de otros, existiendo, además, algunos de ellos que son inevita-bles al ser parte del tratamiento médico de la enfermedad. Entender las relaciones que se producen entre desencadenantes yconocer los efectos positivos del ejercicio físico sobre cada uno de ellos, es claramente útil para controlar este efecto secundario.(AU)
Introduction: Several publications have theorized about the triggers of cancer-related fatigue, one of the side effects ofthe disease and its treatments that most stress cancer survivors. On the other hand, physical exercise has been analyzedas a therapy to reduce the impact of this sequel, and several institutions support its inclusion within care programs for theoncological population. However, cancer fatigue and the role that exercise plays in its control has been exposed without anoverall assessment that shows its complexity and why physical exercise is so valuable to reducing it.Objectives: The objective of this work was to review the existing evidence about triggers of fatigue in cancer, to expose howphysical exercise acts on each of them to control their symptoms and achieve a comprehensive therapeutic effect.Material and method: Several bibliographic searches were carried out to find out which were the triggers of fatigue proposedby the research, how they develop and affect the oncological patient and, finally, to what extent physical exercise would bea viable tool to control its effects.Results: Exposed to more than twenty triggers and aggravating factors of cancer-related fatigue, we found that most of themcould be prevented or at least controlled through physical exercise.Conclusions: It is impossible to isolate some triggers from others, and some of them are inevitable as they are part of themedical treatment of the disease. Understanding the relationships between triggers and knowing the positive effects ofphysical exercise on each one of them is clearly useful to control this side effect.(AU)