Bengt Saltin

Effect of blood haemoglobin concentration on V̇O2,max and cardiovascular function in lowlanders acclimatised to 5260 m

The principal aim of this investigation was to determine the influence of blood haemoglobin concentration ([Hb]) on maximal exercise capacity and maximal O2 consumption (V̇O2,max) in healthy subjects acclimatised to high altitude. Secondarily, we examined the effects of [Hb] on the regulation of cardiac output (CO), blood pressure and muscular blood flow (LBF) during exercise. Eight Danish lowlanders (three females and five males; 24 ± 0.6 years, mean ±s.e.m.) performed submaximal and maximal exercise on a cycle ergometer after 9 weeks at an altitude of 5260 m (Mt Chacaltaya, Bolivia). This was done first with the high [Hb] resulting from acclimatisation and again 2‐4 days later, 1 h after isovolaemic haemodilution with Dextran 70 to near sea level [Hb]. After measurements at maximal exercise while breathing air at each [Hb], subjects were switched to hyperoxia (55 % O2 in N2) and the measurements were repeated, increasing the work rate as tolerated. Hyperoxia increased maximal power output and leg V̇O2,max, showing that breathing ambient air at 5260 m, V̇O2,max is limited by the availability of O2 rather than by muscular oxidative capacity. Altitude increased [Hb] by 36 % from 136 ± 5 to 185 ± 5 g l−1 (P < 0.001), while haemodilution (replacing 1 l of blood with 1 l of 6 % Dextran) lowered [Hb] by 24 % to 142 ± 6 g l−1 (P < 0.001). Haemodilution had no effect on maximal pulmonary or leg V̇O2,max, or power output. Despite higher LBF, leg O2 delivery was reduced and maximal V̇O2 was thus maintained by higher O2 extraction. While CO increased linearly with work rate irrespective of [Hb] or inspired oxygen fraction (FI,O2), both LBF and leg vascular conductance were systematically higher when [Hb] was low. Close and significant relationships were seen between LBF (and CO) and both plasma noradrenaline and K+ concentrations, independently of [Hb] and FI,O2. In summary, under conditions where O2 supply limits maximal exercise, the increase in [Hb] with altitude acclimatisation does not improve maximal exercise capacity or V̇O2,max, and does not alter peak CO. However, LBF and vascular conductance are higher at altitude when [Hb] is lowered to sea level values, with both relating closely to catecholamine and potassium concentrations. This suggests that the lack of effect of [Hb] on V̇O2,max may involve reciprocal changes in LBF via local metabolic control of the muscle vasculature.

Low-intensity training increases peak arm VO2 by enhancing both convective and diffusive O2 delivery

It is an ongoing discussion the extent to which oxygen delivery and oxygen extraction contribute to an increased muscle oxygen uptake during dynamic exercise. It has been proposed that local muscle factors including the capillary bed and mitochondrial oxidative capacity play a large role in prolonged low‐intensity training of a small muscle group when the cardiac output capacity is not directly limiting. The purpose of this study was to investigate the relative roles of circulatory and muscle metabolic mechanisms by which prolonged low‐intensity exercise training alters regional muscle VO2.

Exercise physiology and human performance: systems biology before systems biology!

In this edition of The Journal of Physiology we focus on issues related to how humans (and animals) meet the acute physiological demands of exercise and also on the factors that govern some of the long-terms adaptations to physical activity and exercise training. The fact that 2008 is an Olympic year was a stimulus for this general topic. Additionally, some of the most cited papers in the history of The Journal of Physiology have direct relevance to exercise, and many questions first raised over 100 years ago remain both unanswered and relevant today. Finally, the scientific basis of human performance and studies of how both athletes and ‘normal’ subjects respond to exercise is of interest to the general public and public policy makers. In this context, the field of ‘exercise’ is enormous and touches on every conceivable organ system and every level of biological organization. Thus, reviews in all of the key areas were not sought. Instead we sought to focus on areas with direct relevance to human athletic performance (fatigue, , world records, thermoregulation and ageing) and several newer or underappreciated areas (neural adaptations, genetics and evolution, and connective tissue). n nSince ‘fatigue’ is a key feature of athletic performance, this topic is reviewed by Enoka & Duchateau (2008). is covered by Levine (2008) in the context of what limits and also the continued relevance (or irrelevance) of this measure as an index of ‘maximal’ capacity. What world records and elite endurance performance tell us about integrative physiology is covered by Joyner & Coyle (2008). Since the Summer Olympic games are frequently associated with warm weather Gonzalez-Alonso et al. (2008) discuss how thermoregulation and dehydration can affect performance. Tanaka & Seals (2008) cover issues related to ageing and performance and especially what the older athlete tells us about successful physiological ageing. n nIn an effort to expand beyond the ‘traditional’ areas of ‘exercise physiology’ we asked Nielsen & Cohen (2008) to discuss the neural adaptations to exercise and how the brain and spinal cord adapt to facilitate skill acquisition with practice. Magnusson et al. (2008) also present new ideas on connective tissues showing that in a variety of settings these tissues are far more dynamic than generally appreciated. Finally, much of exercise is about oxygen transport and Koch & Britton (2008) consider this question at levels of integration ranging from geophysics to evolution to disease. n nOne general conclusion from all of the reviews and papers is that the main regulatory and adaptive responses to acute and chronic exercise defy simple reductionist explanations. A more provocative conclusion is that before the reductionist community naively concluded they needed to reinvent and rename physiology in the guise of ‘systems biology’, investigators interested in exercise were already committed to understanding the interactions of key biological responses at multiple levels of organization and integration. An even more provocative conclusion is that the systems biologists have much to learn from the successes of investigators interested in exercise and even more to learn from their continuing questions.

Chronic hypoxia increases arterial blood pressure and reduces adenosine and ATP induced vasodilatation in skeletal muscle in healthy humans

To determine the role played by adenosine, ATP and chemoreflex activation on the regulation of vascular conductance in chronic hypoxia.

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.