Respiratory Physiology & Neurobiology 165 (2009) 237–244 Contents lists available at ScienceDirect Respiratory Physiology & Neurobiology journal homepage: www.elsevier.com/locate/resphysiol Non-invasive evaluation of the capillary recruitment in the human muscle during exercise in hypoxia Nicolas Bourdillon a,∗ , Pascal Mollard a , Murielle Letournel b , Michèle Beaudry a , Jean-Paul Richalet a,b a Université Paris 13, Laboratoire «Réponses cellulaires et fonctionnelles à l’hypoxie» EA 2363, Bobigny, France b AP-HP Hôpital Avicenne, Service de Physiologie, Explorations Fonctionnelles et Médecine du sport, Bobigny, France article info Article history: Accepted 12 December 2008 Keywords: Capillary recruitment Hypoxia Exercise abstract This study proposes a non-invasive evaluation of capillary recruitment in human muscle from resting state to maximal exercise while under hypoxic conditions. Our work is based on the analysis of oxygen transport variables measured during incremental exercise in endurance-trained men (n = 8) and in their sedentary counterparts (n = 8). Maximal exercise tests were performed on a cycloergometer in normoxia and at three simulated normobaric levels of hypoxia (altitude equivalent to 1000, 2500 and 4500m). We made the assumption that the relationship between the oxygen diffusion coefficient (Kt) and cardiac output ( ˙ Qc) was: Kt = k ˙ Qc Nc where Nc is the capillary recruitment coefficient during exercise. Our results demonstrate that Nc increases with altitude and that the increase is greater in trained compared with untrained subjects at high altitude (4500 m). Moreover, the venous P O 2 threshold beyond which capillary recruitment increases is lower in trained men. Despite their greater increase in capillary recruitment, trained men are not able to compensate for their drastic drop in arterial oxygen content during exercise in acute hypoxia, which results in a greater drop in maximal oxygen consumption than in sedentary men. © 2008 Elsevier B.V. All rights reserved. 1. Introduction Factors limiting maximal oxygen consumption ( ˙ V O 2 peak) in humans have been questioned for decades (Roca et al., 1989; Ferretti and di Prampero, 1995; Wagner, 1996; Mortensen et al., 2005; Mollard et al., 2007b). Factors which may play a role on ˙ V O 2 peak limitation are: (i) a convective limitation of blood transport, (ii) a diffusive limitation from blood to the consuming tissue and (iii) the specific activity of mitochondrial enzymes in the Krebs’ cycle and (iv) maximal activity of the electron transport chain. A correla- tion has been found between ˙ V O 2 peak and the maximum activity of key enzymes of highly stimulated muscle (Blomstrand et al., 1997). Moreover, endurance exercise training leads to an increase in the mitochondrial volume of up to 50% in a few weeks (Hoppeler and Fluck, 2003), even though ˙ V O 2 peak increases more slowly. This sug- gests that mitochondrial capacity is a minor limiting step of ˙ V O 2 peak, at least in untrained subjects (di Prampero, 1985, 1992; di Prampero and Ferretti, 1990). In humans exercising at heavy inten- sities, venous blood oxygen saturations between 15 and 30% have been reported (Rowell et al., 1986; Richardson et al., 1993) suggest- ing a diffusive limitation of oxygen transport (Roca et al., 1989). ∗ Corresponding author at: Laboratoire de physiologie, Université Paris 13, 74 rue Marcel Cachin, 93017 Bobigny, France. Tel.: +33 1 48 38 88 76; fax: +33 1 48 38 89 24. E-mail address: nicolas.bourdillon@gmail.com (N. Bourdillon). There seems to be a rapid fall in intramyocyte P O 2 away from the capillary which sets a P O 2 gradient over a short distance and thus a limited diffusion rate for O 2 in the overall skeletal muscle (Honig et al., 1984; Roca et al., 1989). Finally, enhanced quadriceps ˙ V O 2 peak resulting from training is largely due to the increase in O 2 delivery and blood flow (Mourtzakis et al., 2004) which in turn sug- gests a convective limitation to whole body ˙ V O 2 peak. Moreover, Mourtzakis et al., concluded that the increase in local blood flow with training was a result of local adaptation in the tested muscle as supported by the increase in local vascular conductance. The max- imum distance that oxygen can diffuse from a blood microvessel to the working skeletal muscle decreases as oxygen demand increases (McGuire and Secomb, 2001). In the exercising skeletal muscle, the increase in blood flow is due to vasodilation. Whether more capil- laries are recruited as ˙ V O 2 increases has recently been discussed in the literature (Clark et al., 2008; Poole et al., 2008). However, cap- illary recruitment is presently accepted by many authors to play a role in the decrease in diffusion distance and the increase in sur- face area for oxygen diffusion. Capillary recruitment seems a key feature to allow adequate muscle oxygenation during exercise. It directly acts both on convective and diffusive limitations and may then allow a higher level of activity of mitochondrial enzymes. Acute exposure to hypoxia results in a reduction in ˙ V O 2 peak from sea level values (Martin and O’Kroy, 1993; Ferretti et al., 1997). This decline in physical performance is associated with a decrease in arterial oxygen saturation (Sa O 2 ) at maximal exercise (Wagner, 1996; Chapman et al., 1999; Woorons et al., 2005, 2007; Mollard 1569-9048/$ – see front matter © 2008 Elsevier B.V. All rights reserved. doi:10.1016/j.resp.2008.12.007