Central and peripheral responses to exercise: the role of muscle synergy, central command and age.

Background and goals. In 1870, Fick, A. provided a mathematical means of oxygen uptake, arguing that cardiac output (CO) is equivalent to the oxygen consumed by aerobic metabolism divided by the arterial venous oxygen difference. In the last 140 years exercise-physiologists, being interested in the determinants of VO2 limiting factors. Physiology researches are commonly very specific, this cause lack of knowledge in translational studies, as for the interaction between neuromuscular coordination and cardiovascular, or metabolic exercise-factors. Moreover, is not clear the roles of central-command on the central and peripheral hemodynamic response. Exercise-physiologist usually describes physiological phenomena with models, because many influencing-factors can modify the result. This concept can be also applied to one of the most intriguing and ancestral question: what is the secret of longevity? The human-model of centenarians could be considered the best example of successful aging, however at this moment no studies have investigated maximal exercise capacity in centenarians. Therefore three different studies were performed to analyze these relationships reported above: I- the cardio-pulmonary responses during maximal exercise in centenarians; II- the contribution of muscular synergy to central and peripherals VO2 factors; III- the role of central command on hemodynamic response to passive-leg movement in subjects without afferent feedback. Methods: I- 8 centenarians (98 – 102yrs) and 8 young females (18 – 22yrs) were recruited for the 1st study. Subjects were evaluated for health history and physical evaluation, lung function, and anthropometric measures. Both groups performed oxygen uptake measurements by incremental maximal test on cycle ergometer at absolute and relative workloads. II- 8 right-legged healthy male participated at the 2nd study (26.4±5.1 yr; height 174.2±4.1 cm; weight 73.3±5.0 kg). After the practice sessions, each subject performed a constant workload exercise (20W ∼40% of maximal workload) in 2 different modalities: with dominant leg (1DL), non-dominant leg (1NDL). III- In 9 spinal cord injury humans (last study), we compared central and peripheral hemodynamic and ventilatory responses to one-leg passive knee extension with and without visual feedback, and with only the perception of movement. Ventilation, oxygen uptake, cardiac output, heart rate, stroke volume, mean arterial pressure, and leg arterial blood flow were evaluated during the 3 experimental protocols. Results: In the 1st study, instead of a sufficient health status, centenarians showed a dramatically reduction in lung function FEV1 (0.68±0.12 Vs 3.23±0.50l), and FVC (1.22±0.10 Vs 3.45±0.62l). The old women hypo-ventilate during exercise, VE was significantly lower at 45% of maximal exercise, and the strategy used to increase the ventilation was different compared to adult women. In the centenarians group the oxygen saturation decrease during the exercise (83±2 Vs 98±3%). At the same absolute exercise workload, centenarians showed an improved metabolic-efficiency, VO2max was significantly lower from 10 to 35w. However the heart rate response during the exercise at the same absolute workload was similar between the groups. The 2nd study showed that higher muscle synergy (quadriceps contraction/relaxation time) and mean leg force were associated to dominant limb, ∼30% and ∼50% of difference respectively, while similar limb work (p = 0.8) was maintained for all the modalities. At the same power output, the more coordinated limb showed better efficiency +25%, reduced cardiovascular responses -8%, higher blood flow (+0.45 l∙min-1) but reduced HHb (-38%), which explains the difference between a dominant and non-dominant limb. In the 3rd study VE was significantly increased from baseline to maximal response during movement with visual feedback (47 ± 12%); movement without visual feedback (34 ± 10%) and only the perception of passive movement (20 ± 9%). These increases were not different between protocols (p = 0.8), and were equally increased from baseline (∼33%; p < 0.05), but VE/VO2 was not different from baseline. Central hemodynamics (cardiac output ∼7%; heart rate ∼7%; stroke volume ∼4%; and mean arterial pressure ∼3%) were unchanged from baseline during the three different protocols. Leg blood flow increased significantly by 126 ± 18 ml⋅min-1, and 109 ± 23 ml⋅min-1 in movement with and without visual feedback, respectively, but was unchanged from baseline in the only perception of passive movement experiment (33 ± 21 ml⋅min-1; p = 0.8). The change in leg blood flow was significantly lower during this protocol compared to passive movement with and without visual feedback. Discussion: The overall results of these researches can facilitate in clarifying the role of different mechanisms, i.e. muscular synergy, central command and ageing, on central and peripheral oxygen uptake limiting factors. Especially these results demonstrate that the O2 delivery and utilization are clearly influenced by the intra and inter muscular synergies, in SCI individuals characterized by a complete spinal block, central command significantly contributes to the ventilatory response to passive movement, but has no effect on central or peripheral hemodynamics. Moreover, the cardio-pulmonary responses during exercise demonstrated that centenarians pulmonary function is very limited, but an incremented metabolic-efficiency, probably related to the markedly fibres type adaptation, maintain a sufficient maximal exercise capacity. Future development: Future developments for this study will be addressed to examine the molecular dimension of the above mentioned mechanism and it could be focused on the evaluation by a biopsy of the fibre type, capillarization, mitochondrial respiration in centenarian-quadriceps muscle, and on the analysis of the centenarians maximal exercise capacity during hyperoxia. Analyze the effect of different coordination pattern in specific “human-models”, (post-poliomyelitis subjects) on oxygen uptake central and peripheral factors, and evaluate on SCI subjects, the effect of passive leg movement on central and peripheral hemodynamic factors executed in different position: seated or supine.