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 [FEV(1)/FVC] = 63%; COPD #2, FEV(1)/FVC = 41%) exhibiting differences in muscle wasting as compared to healthy controls (CON; FEV(1)/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 (V(max)) for COPD #2 ranged between 37% (succinic dehydrogenase) and 70% (cytochrome C oxidase) of CON. For the cytosolic enzymes, V(max) ranged between 89% (hexokinase) to 31% (pyruvate kinase) of CON. Depressions were also observed in V(max) of the Na(+)-K(+)-ATPase for COPD #1 (66% of CON) but not COPD #2 (92% of CON) while V(max) of the Ca(2+)-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.

Keywords: area; capillarization; enzymatic pathways; excitation-contraction processes; fiber types; glucose and monocarboxylate transporters; metabolism; vastus lateralis.

Figure 1

Fiber-specific histochemical properties in tissue obtained from vastus lateralis muscle in healthy volunteers and two patients with advanced chronic obstructive pulmonary disease. Notes: For CON, values are means ± SE (n = 4). Abbreviations: CON, control; COPD #1 and COPD #2, two chronic obstructive pulmonary disease patients; I, IIA, IIAX, IIX, fiber types and subtypes; CSA, cross-sectional area; capillary counts, number of capillaries ± around a fiber; capillary contacts/CSA, number of capillaries around a fiber divided by the CSA; SE, standard error.

Figure 2

Relative contents of glucose and monocarboxylate transporters in healthy volunteers and two patients with advanced chronic obstructive pulmonary disease. Notes: For CON, values are means ± SE. Abreviations: % Standard, percent change first calculated against a standard and then calculated as a relative change from 100% (CON); GLUT1 and GLUT4, glucose transporter isoforms, GLUT1 and GLUT4, respectively; MCT1 and MCT4, monocarboxylate isoforms, MCT1 and MCT4, respectively; SE, standard error.

Figure 3

Maximal activities of mitochondrial A) and cytosolic B) enzymes in vastus lateralis muscle of healthy volunteers and a patient with advanced chronic obstructive pulmonary disease. Notes: For CON, Values are means ± SE (n = 4). Abbreviations: CON, control; COPD #2, patient with chronic obstructive pulmonary disease. V_max, maximal enzymatic activity; CS, citrate synthase; SDH, succinic dehydrogenase; MDH, malate dehydrogenase; COX, cytochrome c oxidase; HADH, 3-hydroxyacyl-CoA dehydrogenase; HEX, hexokinase; PHOS, phosphorylase; PFK, phosphofructokinase; PK, pyruvate kinase; LDH, lactate dehydrogenase; CPK, creatine phosphokinase; SE, standard error.