Sustained sympathetic activity in altitude acclimatizing lowlanders and high-altitude natives.

Combined results from different independent studies suggest that acclimatization to high altitude induces a slowly developing sympathetic activation, even at levels of hypoxia that cause no acute chemoreflex-mediated sympathoexcitation. We here provide direct neurophysiological evidence for this phenomenon. In eight Danish lowlanders, we quantified mean arterial blood pressure (MAP), heart rate (HR), and muscle sympathetic nerve activity (MSNA), twice at sea level (normoxia and with acute hypoxic exposure to 12.6% O2 ) and twice at high altitude (after 10 and 50 days of exposure to 4100 m). Measurements were also obtained in eight Bolivian highlanders on one occasion at high altitude. Acute hypoxic exposure caused no increase in MSNA (15 ± 2 vs 16 ± 2 bursts per min, respectively, and also MAP and HR remained stable). In contrast, from sea level to 10 and 50 days in high-altitude increases were observed in MAP: 72 ± 2 vs 78 ± 2 and 75 ± 2 mm Hg; HR: 54 ± 3 vs 67 ± 3 and 65 ± 3 beats per min; MSNA: 15 ± 2 vs 42 ± 5 and 42 ± 5 bursts per min, all P < .05. Bolivian subjects had high levels of MSNA: 34 ± 4 bursts per min. The simultaneous increase in MAP, HR, and MSNA suggests high altitude-induced sympathetic activity, which is sustained in well-acclimatized lowlanders. The high MSNA levels in the Bolivian highlanders suggest lifelong sympathetic activation at high altitude.

The lactate paradox revisited in lowlanders during acclimatization to 4100 m and in high-altitude natives.

Chronic hypoxia has been proposed to induce a closer coupling in human skeletal muscle between ATP utilization and production in both lowlanders (LN) acclimatizing to high altitude and high-altitude natives (HAN), linked with an improved match between pyruvate availability and its use in mitochondrial respiration. This should result in less lactate being formed during exercise in spite of the hypoxaemia. To test this hypothesis six LN (22-31 years old) were studied during 15 min warm up followed by an incremental bicycle exercise to exhaustion at sea level, during acute hypoxia and after 2 and 8 weeks at 4100 m above sea level (El Alto, Bolivia). In addition, eight HAN (26-37 years old) were studied with a similar exercise protocol at altitude. The leg net lactate release, and the arterial and muscle lactate concentrations were elevated during the exercise in LN in acute hypoxia and remained at this higher level during the acclimatization period. HAN had similar high values; however, at the moment of exhaustion their muscle lactate, ADP and IMP content and Cr/PCr ratio were higher than in LN. In conclusion, sea-level residents in the course of acclimatization to high altitude did not exhibit a reduced capacity for the active muscle to produce lactate. Thus, the lactate paradox concept could not be demonstrated. High-altitude natives from the Andes actually exhibit a higher anaerobic energy production than lowlanders after 8 weeks of acclimatization reflected by an increased muscle lactate accumulation and enhanced adenine nucleotide breakdown.

Similar carbohydrate but enhanced lactate utilization during exercise after 9 wk of acclimatization to 5,620 m.

We hypothesized that reliance on lactate as a means of energy distribution is higher after a prolonged period of acclimatization (9 wk) than it is at sea level due to a higher lactate Ra and disposal from active skeletal muscle. To evaluate this hypothesis, six Danish lowlanders (25 +/- 2 yr) were studied at rest and during 20 min of bicycle exercise at 146 W at sea level (SL) and after 9 wk of acclimatization to 5,260 m (Alt). Whole body glucose Ra was similar at SL and Alt at rest and during exercise. Lactate Ra was also similar for the two conditions at rest; however, during exercise, lactate Ra was substantially lower at SL (65 micro mol. min(-1). kg body wt(-1)) than it was at Alt (150 micro mol. min(-1). kg body wt(-1)) at the same exercise intensity. During exercise, net lactate release was approximately 6-fold at Alt compared with SL, and related to this, tracer-calculated leg lactate uptake and release were both 3- or 4-fold higher at Alt compared with SL. The contribution of the two legs to glucose disposal was similar at SL and Alt; however, the contribution of the two legs to lactate Ra was significantly lower at rest and during exercise at SL (27 and 81%) than it was at Alt (45 and 123%). In conclusion, at rest and during exercise at the same absolute workload, CHO and blood glucose utilization were similar at SL and at Alt. Leg net lactate release was severalfold higher, and the contribution of leg lactate release to whole body lactate Ra was higher at Alt compared with SL. During exercise, the relative contribution of lactate oxidation to whole body CHO oxidation was substantially higher at Alt compared with SL as a result of increased uptake and subsequent oxidation of lactate by the active skeletal muscles.