2026-06-07T23:41:42Zhttps://docta.ucm.es/rest/oai/request
oai:docta.ucm.es:20.500.14352/1236502025-09-04T00:14:04Zcom_20.500.14352_14col_20.500.14352_15
Docta Complutense author Santos Lozano, Alejandro author Boraita, Araceli author Valenzuela, Pedro L. author Santalla, Alfredo author Villareal Salazar, Mónica author Bustos, Asunción author Brea Alejo, Lidia author Barranco Gil, David author Millán Parlanti, Daniela author López Ortiz, Susana author Peñín Grandes, Saúl author Naranjo Orellana, José author Fiuza Luces, Carmen author González Gálvez, Beatriz author García Fernández, Miguel Ángel author Pinós, Tomàs author Lucia, Alejandro 2025-09-03T11:54:39Z 2025-09-03T11:54:39Z 2024 Santos-Lozano A, Boraita A, Valenzuela PL, Santalla A, Villarreal-Salazar M, Bustos A, et al. Exercise intolerance in mcardle disease: a role for cardiac impairment? A preliminary study in humans and mice. Medicine & Science in Sports & Exercise [Internet]. diciembre de 2024 [citado 19 de junio de 2025];56(12):2241-55. Disponible en: https://journals.lww.com/10.1249/MSS.0000000000003529 10.1249/MSS.0000000000003529 https://hdl.handle.net/20.500.14352/123650 https://dx.doi.org/10.1249/MSS.0000000000003529 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-min 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 ventricular global longitudinal strain (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. eng Attribution-NonCommercial-NoDerivatives 4.0 International Exercise Intolerance in McArdle Disease: A Role for Cardiac Impairment? A Preliminary Study in Humans and Mice. journal article 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