Physical exercise and electrical stimulation in the management of metabolic, cardiovascular and skeletal-muscle alterations in people with tetraplegia

Abstract: Interruption of the spinal cord at the cervical level leads to permanent extensive motor paralysis, serious autonomic regulation deficits and profound short term and long term metabolic disorders The defects play a decisive role for the tetraplegic individuals future function and health. The aims of the present thesis were ( I ) to assess the physical endurance capacity and the trainability of recently spinal cord injured patients, with a special emphasis on tetraplegic persons, (2) to investigate the autonomic regulatory defects during arm ergometry in chronic tetraplegic individuals, (3) to study skeletal muscle metabolic and morphologic consequences of long standing tetraplegia, and (4) to investigate the effects of electrically stimulated leg cycle training (ESLC training) on oxygen uptake, body composition, skeletal muscle glucose metabolism, and skeletal muscle morphology. To address the aims, peak VO2 was measured by conventional methods. Blood pressure was recorded by an intra-arterial method. Arterial concentrations of catecholamines were analysed by a single isotope radio-enzymatic method. Body composition was recorded by the DEXA method. Whole body peripheral insulin mediated glucose uptake was investigated by the hyperinsulinemic euglycemic clamp method. An open muscle biopsy technique combined with in vitro incubation of isolated muscle strips was used to study glucose transport in the decentralised vastus lateralis skeletal muscle. Protein expression of the glucose transporter protein (GLUT4), hexokinase (HKII), glycogen synthase (GS), and phosphpofructokinase (PFK) was assessed before and after ESLC training using Western blot analysis. Corresponding enzyrnatic activities plus citrate synthase activity were also determined. Muscle fiber type distribution was determined by the ATP-ase staining method, capillary supply by the PAS method, and glycogen by an enzymatic method. Peak VO2 in tetraplegic subjects was very low due to limited volatile arm muscles and weak sympathetic exercise response. Arm ergometry training did not improve the metabolic indicator of aerobic capacity, peak V02, in tetraplegic persons. ESLC training increased peak VO2 by 70%, and led to further improvements in body composition. Whole body insulin mediated glucose uptake was increased by 30% in tetraplegic persons after ESLC training. The improvement in glucose uptake occurred concomitant with a two-fold increase in basal and insulin-stimulated in vitro muscle glucose transport and an increase in lean body mass. ESLC training increased muscle glycogen stores by 68%, and induced profound overexpression of GLUT4, HKII, and GS in all the tetraplegic subjects, whereas PFK expression was increased in four of five persons following training. Taken together, the results provide the first evidence for a direct connection between overexpression of key enzymes in glucose metabolism through exercise (ESLC) to enhanced glucose transport and metabolism in human skeletal muscle. Muscle biopsies from tetraplegic individuals demonstrated extensive muscle fiber atrophy, increased connective tissue and large dominance of type llb fibers Following 8 wks of ESLC training, the histological profile of the muscle fibers was not significantly altered. Furthermore training did not lead to increases in the fiber cross sectional area However, type llb fiber dominance was reduced. In four of five tetraplegic persons, an increased proportion of type lla fibers and a small increase in type I fibers was noted following training. In conclusion, cervical spinal cord injury leads to physical inactivity, which accounts for profound changes in metabolism and morphology, which may increase the risk for long-terrn complications such as non-insulin dependent diabetes mellitus or cardiovascular disease. ESLC training activates large decentralised muscle groups, and thereby normalises the metabolic disturbances associated with spinal injury Thus, ESLC training is highly recommended for both the early and late stages after spinal cord injuries.