Cellular assessment of muscle in COPD: case studies of two males

Abstract

The objective of this paper is to provide an overview of the recent developments in muscle physiology and biochemistry in general, and with respect to chronic obstructive pulmonary disease (COPD) specifically. As a way of illustration, we have presented data on the remodeling that occurs in vastus lateralis in two patients with COPD (COPD #1, forced expiratory volume in one second/forced vital capacity [FEV1/FVC] = 63%; COPD #2, FEV1/FVC = 41%) exhibiting differences in muscle wasting as compared to healthy controls (CON; FEV1/FVC = 111 ± 2.2%, n = 4). Type I fibers percentages were lower in both COPD #1 (16.7) and COPD #2 (24.9) compared to CON (57.3 ± 5.2). Cross sectional area of the type I fibers of the patients ranged between 65%–68% of CON and for the type II subtypes (IIA, IIAX, IIX) between 74% and 89% (COPD #1) and 17%–32% (COPD #2). A lower number of capillary contacts were observed for all fiber types in COPD #1 but not COPD #2. Lower concentrations of adenosine triphosphate (ATP) (24%–26%) and phosphocreatine (18%–20%), but not lactate occurred in COPD. In contrast to COPD #1, who displayed normal glucose transporter content, GLUT1 and GLUT4 were only 71% and 54%, respectively of CON in COPD #2. Lower monocarboxylate contents were found for MCT1 in both COPD #1 (63%) and COPD #2 (41%) and for MCT4 (78%) in COPD #1. Maximal oxidative enzyme activities (Vmax) for COPD #2 ranged between 37% (succinic dehydrogenase) and 70% (cytochrome C oxidase) of CON. For the cytosolic enzymes, Vmax ranged between 89% (hexokinase) to 31% (pyruvate kinase) of CON. Depressions were also observed in Vmax of the Na+-K+-ATPase for COPD #1 (66% of CON) but not COPD #2 (92% of CON) while Vmax of the Ca2+-ATPase was near normal in COPD #1 (84% CON). It is concluded that disturbances can occur in muscle to a wide range of excitation, contraction and metabolic processes in COPD.

Effects of Gas Exchange on Acid‐Base Balance

“…Green and co-workers (97,98) have recently published a series of studies that examined the impact of COPD on the structural and biochemical remodeling of leg skeletal muscle in patients with moderate to severe COPD. In the vastus lateralis of these patients, exercise was associated with a reduced phosphorylation potential (reduced electron transport and fat oxidation), an increased potential of glucose phosphorylation and an elevated rate of glycolysis, and a possible impairment of glucose and lactate − transport (97,98). A consequence of these adaptations is an early onset of acidosis characterized by excessive lactate − production, a large increase in ventilatory demand and slowedVo 2 and VCO 2 kinetics (164,230).…”