glycogen and Peripheral-Vascular-Diseases

To better understand the association between skeletal muscle and exercise intolerance in peripheral arterial disease (PAD), we assessed treadmill-walking performance and gastrocnemius muscle phenotype in healthy control subjects and in patients with PAD. We hypothesized that gastrocnemius muscle characteristics would be altered in PAD compared with control subjects and that exercise tolerance in patients PAD would be related to muscle phenotype.. Sixteen patients with PAD and intermittent claudication and 13 healthy controls of the same age participated. Each subject completed a graded treadmill-walking test and underwent a resting muscle biopsy. Muscle biopsy samples were obtained from the medial gastrocnemius muscle of the most ischemic limb in PAD and a limb chosen at random in controls. Samples were analyzed for fiber type and cross-sectional area, capillary-to-fiber ratio, the number of capillaries in contact with each fiber type, and the optical density of glycogen within each fiber by using histochemical procedures. Total muscle glycogen content was determined biochemically.. Exercise capacity measured on the incremental walking test in the PAD group was only 30% to 40% of that observed in controls. The PAD group had a lower proportion of type I muscle fibers (P < .05), fewer capillaries per muscle fiber (P < .05), and tended to have smaller fiber areas (P = .08). The relative area of type I fibers, the capillary-to-fiber ratio, capillary contacts with type I and IIa fibers, and the optical density of glycogen in type I fibers were all positively correlated with exercise tolerance in the PAD group (P < .05) but not controls.. These data suggest that muscle phenotype is altered in PAD and that such alterations are associated with the exercise intolerance in these patients. In light of these findings, therapies such as resistance training or electrical stimulation that target skeletal muscle in PAD may prove beneficial, and further investigation of such therapies is warranted.

Topics: Biopsy, Needle; Exercise Test; Exercise Tolerance; Female; Follow-Up Studies; Glycogen; Humans; Leg; Male; Middle Aged; Muscle Fibers, Fast-Twitch; Muscle Fibers, Slow-Twitch; Muscle, Skeletal; Peripheral Vascular Diseases; Phenotype; Walking

1. We set out to define abnormalities of oxidative ATP synthesis, cellular proton efflux and the efficiency of ATP usage in gastrocnemius muscle of patients with claudication due to peripheral vascular disease, using data obtained by 31P magnetic resonance spectroscopy during aerobic exercise and recovery. 2. Eleven patients with moderate claudication were studied and results were compared with 25 age-matched control subjects. Changes in pH and phosphocreatine concentration during recovery were used to calculate the maximum rate of oxidative ATP synthesis (Qmax.) and the capacity of net proton efflux. Changes in pH and phosphocreatine concentration were used to estimate rates of non-oxidative and (indirectly) oxidative ATP synthesis throughout exercise, taking account of abnormalities in proton efflux during exercise. 3. In patients with claudication, slow post-exercise phosphocreatine recovery showed a 42 +/- 9% decrease in Qmax., and the slow ADP recovery was consistent with this. pH recovery was slow, showing a 77 +/- 9% decrease in the capacity for proton efflux. Both abnormalities are compatible with a substantial reduction in muscle blood flow. 4. During exercise, increased phosphocreatine depletion and intracellular acidification were a consequence of impaired oxidative ATP synthesis and the consequent increase in non-oxidative ATP synthesis, compounded by reduced proton efflux. The acidification prevented an increase in ADP concentration which could otherwise partially compensate for the oxidative defect. All these abnormalities are compatible with a reduced muscle blood flow. 5. In addition, initial-exercise changes in pH and phosphocreatine concentration implied a 44 +/- 5% reduction in 'effective muscle mass', necessitating an ATP turnover (per litre of muscle water) twice as high for given power output as in control muscle. Some of this is probably due to a localized loss of muscle fibres, but the rest appears to reflect reduced metabolic efficiency of the muscle. This is not a direct consequence of reduced blood flow, and may be related to change in muscle fibre type.

Topics: Adenosine Triphosphate; Adult; Aged; Aged, 80 and over; Case-Control Studies; Female; Glycogen; Humans; Intermittent Claudication; Magnetic Resonance Spectroscopy; Male; Middle Aged; Mitochondria, Muscle; Muscle, Skeletal; Peripheral Vascular Diseases; Phosphorus Radioisotopes