Cannon 2012 Abstract IOC68

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Cannon DT, Oudiz R, Casaburi R, Rossiter HB (2012) The effects of exercise training on skeletal muscle mitochondrial function in patients with primary pulmonary arterial hypertension. MiPNet17.08.

Link: MiPNet17.08 IOC68

Cannon DT, Oudiz R, Casaburi R, Rossiter HB (2012)

Event: IOC68

Primary pulmonary arterial hypertension (PAH) is a progressive disease of the pulmonary circulation resulting in increased pulmonary vascular resistance, right ventricular hypertrophy and right ventricular failure. PAH results in poor quality of life due to dyspnoea and exercise intolerance, and unsurprisingly, an increased mortality risk. Therefore, therapies to improve muscle metabolic function and exercise tolerance are crucial to preserve quality of life and patient prognosis. Numerous studies support the safety and efficacy of exercise training in patients with COPD, and early concerns about accelerating the rate of decline in patient health have mostly not been substantiated. Evidence for benefits with rehabilitative exercise training in PAH have recently been reported (Mereles et al 2006). While limited data are available for exercise training in PAH, none have examined mitochondrial function after exercise training. Recently, our group have demonstrated reduced maximum respiratory rate and Complex I dysfunction using high-resolution respirometry in an animal model of PAH (Wuest et al 2012). However, whether this mitochondrial dysfunction is reversible through exercise training or pharmacologic intervention (Piao et al 2010) remains to be determined.

Therefore, our study aims to exploit a multi-disciplinary exercise and education intervention study of PAH. This investigation will explore the efficacy of exercise training in mild and severe PAH. Control groups of mild and severe patients will receive health education and exercise training in a cross-over design. In conjunction with traditional measures of cardiorespiratory fitness, pulmonary function, muscle oxygenation during exercise, cardiac MR imaging, and quality-of-life assessment, knee-extensor muscle biopsies will be taken for measurement of mitochondrial function. This is to be done using a substrate-uncoupler-inhibitor-titration protocol of high-resolution respirometry. Additionally, biochemical analyses for respiratory enzymes and mitochondrial protein expression will be made.

References: Mereles D, Ehlken N, Kreuscher S, Ghofrani S, Hoeper MM, Halank M, Meyer FJ, Karger G, Buss J, Juenger J, Holzapfel N, Opitz C, Winkler J, Herth FF, Wilkens H, Katus HA, Olschewski H, Grunig E (2006) Exercise and respiratory training improve exercise capacity and quality of life in patients with severe chronic pulmonary hypertension. Circulation 114: 1482-1489.

Piao L, Marsboom G, Archer SL (2010) Mitochondrial metabolic adaptation in right ventricular hypertrophy and failure. J Mol Med 88: 1011-1020.

Wuest RC, Myers DS, Stones R, Benoist D, Robinson PA, Boyle JP, Peers C, White E, Rossiter HB (2012) Regional skeletal muscle remodeling and mitochondrial dysfunction in right ventricular heart failure. Am J Physiol Heart Circ Physiol 302: H402-H411.

Keywords: Exercise training, Respiration, Permeabilised fibres, Skeletal muscle

O2k-Network Lab: US CA Torrance Rossiter HB, US CA San Diego Cannon DT

Labels: Pathology: COPD 

Organism: Human  Tissue;cell: Skeletal muscle 

HRR: Oxygraph-2k