Federico González-Aragoneses

Abnormal mitochondrial function in locomotor and respiratory muscles of COPD patients

Several cellular and molecular alterations have been described in skeletal and respiratory muscles of patients with chronic obstructive pulmonary disease (COPD), but information on potential abnormalities of mitochondrial function is scarce. The aim of the present study was to investigate mitochondrial function in the vastus lateralis (VL) and external intercostalis (EI) of COPD patients. Biopsies from VL and EI were obtained during surgery for lung cancer in 13 patients with mild to moderate COPD (age 68±6 yrs, forced expiratory volume in one second (FEV1) 66±15% predicted) and 19 control subjects (age 67±9 yrs, FEV1 95±18% pred). State 3 and 4 mitochondrial oxygen consumption (V′O2,m), ATP synthesis, citrate synthase, cytochrome oxidase (COX) and complex I–III activities, as well as reactive oxygen species (ROS) production, were determined. In COPD patients, in both muscles, COX activity (VL: COPD 3.0±0.8 versus control 2.0±0.8; EI: 3.7±1.6 versus 2.4±0.9 μmol·min−1·mg−1) and ROS production (VL: 1,643±290 versus 1,285±468; EI: 1,033±210 versus 848±288 arbitrary units) were increased, whereas state 3 V′O2,m was reduced (VL: 2.9±0.3 versus 3.6±0.4; EI: 3.6±0.3 versus 4.1±0.4 mmol·min−1·kg−1). Skeletal muscle mitochondria of patients with chronic obstructive pulmonary disease show electron transport chain blockade and excessive production of reactive oxygen species. The concurrent involvement of both vastus lateralis and external intercostalis suggests a systemic (rather than a local) mechanism(s) already occurring in relatively early stages (Global Initiative for Chronic Obstructive Lung Disease stage II) of the disease.

Site of Mitochondrial Reactive Oxygen Species Production in Skeletal Muscle of Chronic Obstructive Pulmonary Disease and Its Relationship with Exercise Oxidative Stress

Exercise triggers skeletal muscle oxidative stress in patients with chronic obstructive pulmonary disease (COPD). The objective of this research was to study the specific sites of reactive oxygen species (ROS) production in mitochondria isolated from skeletal muscle of patients with COPD and its relationship with local oxidative stress induced by exercise. Vastus lateralis biopsies were obtained in 16 patients with COPD (66 ± 10 yr; FEV(1), 54 ± 12% ref) and in 14 control subjects with normal lung function who required surgery because of lung cancer (65 ± 7 yr; FEV(1), 91 ± 14% ref) at rest and after exercise. In these biopsies we isolated mitochondria and mitochondrial membrane fragments and determined in vitro mitochondrial oxygen consumption (Mit

Lung cancer surgery in the elderly

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Tendencias en los factores pronósticos de los tumores pulmonares neuroendocrinos

o(2)) and ROS production before and after inhibition of complex I (rotenone), complex II (stigmatellin), and complex III (antimycin-A). We related the in vitro ROS production during state 3 respiration), which mostly corresponds to the mitochondria respiratory state during exercise, with skeletal muscle oxidative stress after exercise, as measured by thiobarbituric acid reactive substances.State 3 Mit

Ischaemic preconditioning prevents the liver inflammatory response to lung ischaemia/reperfusion in a swine lung autotransplant model †

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Análisis multicéntrico de supervivencia y factores pronósticos en el carcinoma no microcítico de pulmón en estadio I patológico según la nueva clasificación TNM de 2009

o(2) was similar in patients with COPD and control subjects (191 ± 27 versus 229 ± 46 nmol/min/mg; P = 0.058), whereas H(2)O(2) production was higher in the former (147 ± 39 versus 51 ± 8 pmol/mg/h; P < 0.001). The addition of complexI, II, and III inhibitors identify complex III as the main site of H(2)O(2) release by mitochondria in patients with COPD and in control subjects. The mitochondrial production of H(2)O(2) in state 3 respiration was related (r = 0.69; P < 0.001) to postexercise muscle thiobarbituric acid reactive substance levels. Our results show that complex III is the main site of the enhanced mitochondrial H(2)O(2) production that occurs in skeletal muscle of patients with COPD, and the latter appears to contribute to muscle oxidative damage.