Methods

1. The Effect of Exercise on Peripheral Muscle in Emphysema: A Preliminary Investigation Anne K. Swisher, Stephen E. Alway, Rachel Yeater Presentation By: Brittany Smithson, DPT Student Abstract Methods Discussion Article #1 Evidence • Subjects: Male Syrian golden hamsters aged 7-9 weeks • Animals were randomly assigned to the emphysema or control groups • The emphysema group was injected with porcine elastase and the control group with sterile saline • Exercise was induced by selective tenotomy of the gastrocnemius and soleus muscles which places an overload stimulus on the remaining intact plantaris while walking • The left hindlimb of each animal served as the intact control limb • Animals were sacrificed at 1, 3 and 5 months following instillation • The plantaris muscle was removed from each hindlimb • Alveolar wall intercepts were counted for 3 lung sections from the lung of each animal and summed for each section • Muscle section images were analyzed to determine the number of type I, IIA and IIB fibers present in each muscle section • The capillary-to-fiber ratio was determined for each muscle section by dividing the sum of capillaries by the sum of fibers in each section • Statistical Analysis • Analysis of variance procedures were used to determine differences in fiber type composition, CFR and alveolar wall intercepts and the effect of overload on disease-induced changes • The effect of emphysema was determined by comparing the intact control limb plantaris in the emphysema group to the same limb in the control group • The influence of overload on disease-related muscle changes was determined by comparing the overloaded plantaris muscle in the emphysema group to the same limb in the control group Emphysema has been associated with loss of aerobic muscle fibers and decreased blood supply. However, when these changes begin and whether exercise can prevent these changes is unknown. The purpose of this study was to examine peripheral muscle at different time points during the development of emphysema and to determine the additional effects of muscle activity. In a series of 3 experiments, emphysema was induced in hamsters. Exercise was simulated through surgical overload (OV) of the plantaris muscle of one leg. Animals were sacrificed at 1, 3, and 5 months following emphysema induction. Fiber type composition and capillary-to-fiber ratio (CFR) were determined. There were no significant changes in fiber type composition in the 1-month group. A significant increase in type IIA fiber composition (mean 72.0 vs. 54.5%) and decrease in type IIB fiber (mean 13.3 vs. 28.1%) was seen in the non-overloaded muscles following 3 months. In the 5-month group, there was a significant decrease in percentage of type I fibers (mean 14.7 vs. 28.0%). There were no significant differences in fiber type composition in the OV limb, regardless of duration. The CFR was significantly lower in the OV limb after 5-months of emphysema (mean 0.92 vs. 1.55 cap/fiber). Muscle overload prevented emphysema-associated changes in fiber type composition, but not in CFR. Peripheral muscle is affected early in the course of emphysema and chronic overload may play an important role in preserving normal muscle composition. • Mattson J, Poole D. Pulmonary emphysema decreases hamster skeletal muscle oxidative enzyme capacity. Journal Of Applied Physiology (Bethesda, Md.: 1985) [serial online]. July 1998;85(1):210-214. Available from: MEDLINE, Ipswich, MA. Accessed October 19, 2011. • This article supports the original article by showing that oxidative enzyme capacity is decreased in the skeletal muscles of hamsters with emphysema • Activity of citrate synthase, an enzyme in the oxidation process, was measured in the hindlimbs and diaphragms of hamsters 6 months after being injected with emphysema • Citrate synthase activity in the gastrocnemius and vastuslateralis was reduced in the hamsters with emphysema • These results show that emphysema reduces oxidative capacity in certain skeletal muscles and can lead to exercise limitations in hamsters with emphysema • Most Important Findings • Emphysema resulted in peripheral muscle fiber composition changes beginning as early as 3 months after induction of emphysema • Overload prevented peripheral muscle effects of emphysema regardless of disease duration • Overload decreased the capillary-to-fiber ratio in peripheral muscles of animals with long duration disease • Fiber Type Changes Due to Emphysema • Results show evidence of alveolar destruction 1 month following disease induction but changes in muscle fiber composition were not seen until 3 months • The shift of fiber type from IIB to IIA seen at 3 months suggests that peripheral muscles may be adapting to preserve oxidative capacity • Animals exposed to emphysema for 5 months showed a decrease in the percentage of type I fibers which may indicate impaired muscle oxidative capacity • Effect of Muscle Overload on Disease-Induced Fiber Type Changes • Chronic overload was clearly able to prevent the loss of Type I fibers seen in longer durations of emphysema • Effects of Disease and Overload on Capillary-to-Fiber Ratio • The induction of emphysema alone had little effect on CFR in the plantaris • Since the plantaris muscle in the hamster is predominantly type IIA and IIB fibers, there may not have been a large enough change in fiber type composition to cause a significant increase in the whole muscle CFR • A significant decrease in the overloaded limbs of the emphysema group at 5 months suggests that the decrease may be due to chronic muscle overload or other factors Article #2 Evidence • Vogiatzis I, Terzis G, Zakynthinos S, et al. Effect of Pulmonary Rehabilitation on Peripheral Muscle Fiber Remodeling in Patients With COPD in GOLD Stages II to IV. CHEST [serial online]. September 2011;140(3):744-752. Available from: CINAHL with Full Text, Ipswich, MA. Accessed October 19, 2011. • This article supports the original article by showing that patients in the later GOLD stages of emphysema had significantly lower proportions of Type I fibers and higher proportions of Type II fibers compared to those in earlier stages of the disease and healthy individuals • Following pulmonary rehabilitation, there was no significant difference in the pattern of fiber type shifting across all stages of the disease • The improvement in peripheral muscle remodeling and exercise capacity in response to exercise training was independent of disease severity • Patients across all GOLD stages of emphysema had the same degree of improvement with regards to fiber type distribution, muscle capillarization and all muscle fiber cross sectional areas following pulmonary rehabilitation • The authors suggest that exercise training be performed by patients with emphysema as an effective treatment to moderately reverse irregular skeletal muscle changes. Purpose Results • To determine the effect of disease duration on peripheral skeletal muscle composition • To determine the influence of muscle activity on disease-related changes in muscle • Alveolar Wall Intercepts • Significantly less alveolar wall intercepts in the emphysema group indicating lung damage due to elastase instillation • Fiber Type Composition • 1-month: No significant difference in fiber type composition due to emphysema • 3-month: Significant increase in the percentage of type IIA fibers and concurrent decrease in type IIB fibers due to emphysema • 5-month experiment: Significantly lower percentage of type I fibers due to emphysema • The overloaded limb showed no difference in fiber type composition between the emphysema and control groups in all experiments • Capillary-to-Fiber Ratio • The intact control limb showed no significant changes in CFR between the emphysema and control groups in any of the experiments • The overloaded limb at 5 months duration had a significantly lower CFR in the emphysema group compared to the control group Clinical Significance Background • Exercise should be recommended to patients during the early stages of COPD to prevent changes in fiber type composition which decreases oxidative enzyme activity • Exercise may have the ability to combat decreases in exercise capacity that is often seen in patients with emphysema • Emphysema is a type of Chronic Obstructive Pulmonary Disease • This disease effects skeletal muscle and likely leads to an impaired exercise capacity by causing muscle atrophy, decreased fatigue-resistant type I fibers and decreased aerobic enzyme content • An animal model is used to study the effects of emphysema on skeletal muscles to control for extraneous variables such as inactivity, medication effects and malnutrition • Injecting the lungs of Syrian golden hamsters with elastase has been shown to produce similar detrimental effects as emphysema in humans • Exercise is recommended to patients with COPD to help combat the decrease in exercise capacity. However, these recommendations are often made in the later stages of the disease. • It may be possible to alter disease-related changes in peripheral muscles by beginning exercise training earlier in the disease process Summary Conclusions • Chronic emphysema causes a shift in the fiber type composition of skeletal muscles by decreasing the amount of Type I fibers and increasing the amount of Type II fibers • These muscular changes can lead to impaired exercise capacity by decreasing oxidative enzyme activity • Patients with emphysema should be advised to begin an exercise program during the early stages of the disease to reverse abnormal skeletal muscle changes • Peripheral muscle is affected during the early stages of emphysema that differ from those seen at later stages in the disease process • Chronic overload appears to be a powerful stimulus to prevent disease-related changes in fiber composition, but not capillary to fiber ratio.