Fatigue and recovery at altitude

Fatigue and recovery at altitude

During exercise fatigue is defined as a reversible reduction in force/power generating capacity and can be elicited by ‘central’ and/or ‘peripheral’ mechanisms. During skeletal muscle contractions both aspects of fatigue may develop independent of alterations in convective O2 delivery, however, reductions in O2 supply exacerbate and increases attenuate the rate of accumulation. In this regard, peripheral fatigue development is mediated via the O2 dependent rate of accumulation of metabolic byproducts (e.g. inorganic phosphate) and their interference with excitation-contraction coupling within the myocyte. In contrast, the development of O2-dependent central fatigue is elicited a) by interference with the development of central command and/or b) via inhibitory feedback on central motor drive secondary to the peripheral effects of low convective O2 transport. Changes in convective O2 delivery in the healthy human can result from modifications in arterial O2 content, blood flow, or a combination of both and can be induced via heavy exercise at sea level; these changes are exacerbated during acute and chronic exposure to altitude. With acute hypoxia arterial O2 content (CaO2) and PaO2 are reduced. Homeostatic responses cause an elevation of resting cardiac output, which is mainly mediated by an elevation of resting heart rate.

To avoid hypotension due to hypoxia-induced vasodilation sympathetic nerve activity is increased. With acclimatization sympathetic nerve activity remains elevated, despite normalization of CaO2 and so does mean arterial pressure. The elevation of mean arterial pressure is not caused by the increase in haematocrit, since it persists after isovolemic and hypervolemic haemodilution. However, it is partly reversed by hyperoxia, suggesting and involvement of the preripheral chemoreceptors. During submaximal exercise in acute and chronic hypoxia at the same absolute exercise intensity, systemic O2 delivery and pulmonary ventilation are similar to that observed at sea level, and so is VO2. However, compared to normoxia, pulmonary ventilation is higher, a factor by itself that could lead to reduced endurance at altitude. After acclimatization, endurance in dramatically improved thanks to the elevation in blood hemoglobin concentration, which allows to achieve a similar O2 delivery as at sea level with similar cardiac output and leg blood flows. Nevertheless, pulmonary ventilation remains elevated. The latter may be a contributing factor to fatigue during prolonged exercise at altitude. Altitude acclimatization causes some degree of haemoconcentration which may also limit heat dissipation, meaning that hyperthermia could develop more easily during exercise at altitude in warm and humid environments. During maximal exercise in severe acute and chronic hypoxia maximal cardiac output (Qmax) and peak leg blood flow are reduced (this effect is not observed below 4000m).

With a lower Qmax, maximal systemic oxygen delivery is also reduced in hypoxia and hence, VO2max and exercise capacity. The reduction in Qmax is associated with a lower peak heart rate (HRpeak), particularly in chronic hypoxia. However, increasing HRpeak to normoxic values with glycopyrrolate (a muscarinic antagonist) did not increase cardiac output above the value observed during maximal exercise in chronic hypoxia. Lowering the 29 Edita: www.altorendimiento.net 31 afterload by isovolemic haemodilution or by peripheral vasodilation (intraarterial ATP infusion at peak exercise) had almost no influence on maximal exercise Q or leg blood flow. Although blood volume is reduced during the first 2-3 months of residence at altitude, plasma volume expansion with 1 litre of 6% dextran did not cause changes in peak exercise capacity nor Qmax. Structural changes at the level of the myocardium can be excluded since sea level values of Qmax can be achieved in chronic hypoxia with hyperoxia.

Thus, a major component of the lowered maximal exercise capacity at altitude is the reduction in maximal cardiac output and, hence, systemic O2 delivery. We have proposed that the reduction of Qmax in chronic hypoxia is caused by a neural mechanism that senses PaO2 (or CaO2) and downregulates the maximal pumping capacity of the heart. In agreement, we have observed that during submaximal exercise in acute hypoxia (FiO2=0.11, 100 W) cardiac output is barely increased to counteract the effect of adenosine-induced hypotension (mean arterial pressure ~72 mmHg), despite the fact that an increase of exercise Q to a value 85-90% of Qmax would have allowed for a preserved mean arterial pressure. Interestingly, during exercise in severe acute hypoxia (FIO2 0.105) peak exercise cardiac output is reduced only when the exercise is performed with a large muscle mass, but not when the exercise recruits only one leg. Due to the very low PaO2 observed during whole body exercise with severe acute hypoxia (~34 mmHg) pulmonary ventilation is strongly stimulated leading to very low PaCO2 values (~25 mmHg, i.e. 8 mmHg less than during peak exercise in normoxia). Cerebral blood flow drops between 2 and 3% per each 1 mmHg drop in PaCO2 when PO2 remains close to 100 mmHg and even if the effect of low PaCO2 on CBF may be attenuated by severe hypoxia, the vasoconstricting effect of hypocapnia predominates on the vasodilatory action of hypoxia.

The latter combined with the reduction in CaO2 causes brain deoxygenation, which is more accentuated during intense exercise. The situation is further complicated by the very low PaO2, which may lead to PtiO2 (interstitial cerebral PO2) values close or below 10 mmHg in some areas of the brain. Strong support for the role of low brain oxygenation in fatigue during exercise in severe acute hypoxia has been provided by the fact that, at peak exercise acute re-oxygenation relieves the presumably central limitation to exercise (i.e. central fatigue) almost instantaneously. With altitude acclimatization peak exercise cerebral oxygenation is restored to sea level values due to higher cerebral blood flow, PaO2 and CaO2. Thus, it is unlikely that insufficient brain oxygenation contributes to cause central fatigue during exercise at moderate altitude in acclimatized humans. However, at extreme altitudes the low PaO2, may cause a low PtiO2 and by this mechanism in fact limit O2 diffusion in some regions of the CNS even in the altitude acclimatized human. The hypothesis that insufficient brain oxygenation contributes to fatigue during maximal exercise in chronic hypoxia is supported by the fact that in well acclimatized humans at 5000-5260 m acute re-oxygenation at peak exercise enables the subjects to continue the exercise and even to increase workload. Is central command affected by hypoxia? The ability to generate maximal power as well as maximal force during brief efforts is preserved in severe acute as well as chronic hypoxia. Similarly, there is no evidence of central mechanisms limiting small muscle mass exercise in hypoxia. More recently it has been reported that during severe acute hypoxia (FIO2 0.10) handgrip MVC force is reduced, while maximal finger-typing frequency is not affected.