Maximal force is unaffected by emphysema-induced atrophy in extensor digitorium longus.

Patients with chronic obstructive pulmonary disease (COPD) demonstrate a limited exercise capacity. It is unknown whether muscle fiber atrophy and subsequent decrease in force production contributes to this functional limitation. Therefore, the purpose of this investigation was to determine whether emphysema-induced muscle fiber atrophy leads to a reduction in locomotory muscle force production. Maximal muscle force production and fiber cross-sectional area were measured in the almost exclusively fast-twitch extensor digitorium longus muscles at 4 and 8 months following saline (control, n=8/time period) or elastase (emphysema, n=15/time period) instillation in the lungs of hamsters. Excised lung volume increased 145 and 161% with emphysema at 4 and 8 months, respectively (both P<0.01). Muscle mass, maximal force, and fiber cross-section were unaltered at 4 months. However, absolute mass (-15%) and fiber cross-sectional area (-18%) were reduced at 8 months (both P<0.01). Surprisingly, maximal force was preserved in emphysema animals. These data demonstrate that maximal muscle force may be preserved in the face of emphysema-induced fiber atrophy.

Differential effects of emphysema on skeletal muscle fibre atrophy in hamsters.

Patients afflicted with emphysema demonstrate altered peripheral skeletal muscle fibre composition and atrophy. It is unknown whether these alterations are general to all skeletal muscles independent of function, phenotype or oxidative capacity. Therefore, the purpose of this investigation was to determine whether emphysema induces alterations in muscle fibre composition or atrophy in respiratory and locomotory muscles with diverse fibre types and metabolic profiles. Fibre composition and cross-sectional area were measured in selected hindlimb muscles and diaphragm of hamsters following saline (control, n=7) or elastase (emphysema, n=15) instillation. Excised lung volume increased 145% with emphysema. Fibre composition was largely unaltered, with the exception of a 13% reduction in IIB fibres in the tibialis anterior muscle of emphysema animals. Type I fibre size was also mainly unaltered, except for a diminished cross-sectional area in plantaris muscle. However, fibre cross-sectional area of fast-twitch types IIA, IIX and/or IIB fibres was reduced in the caudal biceps femoris, vastus lateralis, tibialis anterior, gastrocnemius and plantaris muscles of emphysema animals. In contrast, there was a trend for emphysema to increase the cross-sectional area of type IIA fibres in the diaphragm. These data demonstrate that emphysema-induced atrophy primarily affects locomotory muscles, independent of phenotype or oxidative capacity.

Induction of mitochondrial stress proteins following treadmill running.

PURPOSE: The purpose of this investigation was to examine the relationship between the expression of HSP60 and GRP75 and the oxidative potential of skeletal muscle as assessed by the citrate synthase activity following endurance training to sedentary controls. METHODS: Female Wistar rats were assigned to one of two groups: sedentary controls (N = 8) or endurance trained (N = 9). Endurance trained rats were run 60 min x d(-1) at 27 m x min(-1) up a 10% incline 6 d x wk(-1) for 8 wk on a motor-driven treadmill. RESULTS: Training produced a 47% increase in citrate synthase activity along with a 103% increase in the expression of HSP60 and a 105% increase in the expression of GRP75 in plantaris muscle. In addition, there was a significant correlation between the citrate synthase activity and expression of HSP60 found in plantaris muscle. CONCLUSIONS: These findings are consistent with the hypothesis that the adaptive response to treadmill running may require elevations in the expression of HSP60 and GRP75 to support protein import and folding.

Pulmonary emphysema decreases hamster skeletal muscle oxidative enzyme capacity.

Skeletal muscle oxidative enzyme capacity is impaired in patients suffering from emphysema and chronic obstructive pulmonary disease. This effect may result as a consequence of the physiological derangements because of the emphysema condition or, alternatively, as a consequence of the reduced physical activity level in these patients. To explore this issue, citrate synthase (CS) activity was measured in selected hindlimb muscles and the diaphragm of Syrian Golden hamsters 6 mo after intratracheal instillation of either saline (Con, n = 7) or elastase [emphysema (Emp); 25 units/100 g body weight, n = 8]. Activity level was monitored, and no difference between groups was found. Excised lung volume increased with emphysema (Con, 1.5 +/- 0.3 g; Emp, 3.0 +/- 0.3 g, P < 0.002). Emphysema significantly reduced CS activity in the gastrocnemius (Con, 45.1 +/- 2.0; Emp, 39.2 +/- 0.8 micromol . min-1 . g wet wt-1, P < 0.05) and vastus lateralis (Con, 48.5 +/- 1.5; Emp, 44.9 +/- 0.8 micromol . min-1 . g wet wt-1, P < 0.05) but not in the plantaris (Con, 47.4 +/- 3.9; Emp, 48.0 +/- 2.1 micromol . min-1 . g wet wt-1, P < 0.05) muscle. In contrast, CS activity increased in the costal (Con, 61.1 +/- 1.8; Emp, 65.1 +/- 1.5 micromol . min-1 . g wet wt-1, P < 0.05) and crural (Con, 58.5 +/- 2.0; Emp, 65.7 +/- 2.2 micromol . min-1 . g wet wt-1, P < 0.05) regions of the diaphragm. These data indicate that emphysema per se can induce decrements in the oxidative capacity of certain nonventilatory skeletal muscles that may contribute to exercise limitations in the emphysematous patient.

Changes in skeletal muscle biochemistry and histology relative to fiber type in rats with heart failure.

One of the primary consequences of left ventricular dysfunction (LVD) after myocardial infarction is a decrement in exercise capacity. Several factors have been hypothesized to account for this decrement, including alterations in skeletal muscle metabolism and aerobic capacity. The purpose of this study was to determine whether LVD-induced alterations in skeletal muscle enzyme activities, fiber composition, and fiber size are 1) generalized in muscles or specific to muscles composed primarily of a given fiber type and 2) related to the severity of the LVD. Female Wistar rats were divided into three groups: sham-operated controls (n = 13) and rats with moderate (n = 10) and severe (n = 7) LVD. LVD was surgically induced by ligating the left main coronary artery and resulted in elevations (P < 0.05) in left ventricular end-diastolic pressure (sham, 5 +/- 1 mmHg; moderate LVD, 11 +/- 1 mmHg; severe LVD, 25 +/- 1 mmHg). Moderate LVD decreased the activities of phosphofructokinase (PFK) and citrate synthase in one muscle composed of type IIB fibers but did not modify fiber composition or size of any muscle studied. However, severe LVD diminished the activity of enzymes involved in terminal and beta-oxidation in muscles composed primarily of type I fibers, type IIA fibers, and type IIB fibers. In addition, severe LVD induced a reduction in the activity of PFK in type IIB muscle, a 10% reduction in the percentage of type IID/X fibers, and a corresponding increase in the portion of type IIB fibers. Atrophy of type I fibers, type IIA fibers, and/or type IIB fibers occurred in soleus and plantaris muscles of rats with severe LVD. These data indicate that rats with severe LVD after myocardial infarction exhibit 1) decrements in mitochondrial enzyme activities independent of muscle fiber composition, 2) a reduction in PFK activity in type IIB muscle, 3) transformation of type IID/X to type IIB fibers, and 4) atrophy of type I, IIA, and IIB fibers.

Decreased [3H]ouabain binding sites in skeletal muscle of rats with chronic heart failure.

Abnormalities intrinsic to skeletal muscle are thought to contribute to decrements in exercise capacity found in individuals with chronic heart failure (CHF). Na+-K+-adenosinetriphosphatase (the Na+ pump) is essential for maintaining muscle excitability and contractility. Therefore, we investigated the possibility that the number and affinity of Na+ pumps in locomotor muscles of rats with CHF are decreased. Myocardial infarction (MI) was induced in 8 rats, and a sham operation was performed in 12 rats. The degree of CHF was assessed approximately 180 days after surgery. Soleus and plantaris muscles were harvested, and Na+ pumps were quantified by using a [3H]ouabain binding assay. At the time of muscle harvest, MI and sham-operated rats were similar in age (458 +/- 54 vs. 447 +/- 34 days old, respectively). Compared with their sham-operated counterparts, MI rats had a significant amount of heart failure, right ventricular-to-body weight ratio was greater (48%), and the presence of pulmonary congestion was suggested by an elevated lung-to-body weight ratio (29%). Left ventricular end-diastolic pressure was significantly increased in the MI rats (11 +/- 1 mmHg) compared with the sham-operated controls (1 +/- 1 mmHg). In addition, mean arterial blood pressure was lower in the MI rats compared with their control counterparts. [3H]ouabain binding sites were reduced 18% in soleus muscle (136 +/- 12 vs. 175 +/- 13 pmol/g wet wt, MI vs. sham, respectively) and 22% in plantaris muscle (119 +/- 12 vs. 147 +/- 8 pmol/g wet wt, MI vs. sham, respectively). The affinity of these [3H]ouabain binding sites was similar for the two groups. The relationship between the reduction in Na+ pump number and the reduced exercise capacity in individuals with CHF remains to be determined.