Non-invasive evaluation of the capillary recruitment in the human muscle during exercise in hypoxia
Introduction
Factors limiting maximal oxygen consumption ( 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 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 correlation has been found between 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 peak increases more slowly. This suggests that mitochondrial capacity is a minor limiting step of peak, at least in untrained subjects (di Prampero, 1985, di Prampero, 1992, di Prampero and Ferretti, 1990). In humans exercising at heavy intensities, venous blood oxygen saturations between 15 and 30% have been reported (Rowell et al., 1986, Richardson et al., 1993) suggesting a diffusive limitation of oxygen transport (Roca et al., 1989). There seems to be a rapid fall in intramyocyte away from the capillary which sets a gradient over a short distance and thus a limited diffusion rate for O2 in the overall skeletal muscle (Honig et al., 1984, Roca et al., 1989). Finally, enhanced quadriceps peak resulting from training is largely due to the increase in O2 delivery and blood flow (Mourtzakis et al., 2004) which in turn suggests a convective limitation to whole body 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 maximum 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 capillaries are recruited as increases has recently been discussed in the literature (Clark et al., 2008, Poole et al., 2008). However, capillary recruitment is presently accepted by many authors to play a role in the decrease in diffusion distance and the increase in surface 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 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 at maximal exercise (Wagner, 1996, Chapman et al., 1999, Woorons et al., 2005, Woorons et al., 2007, Mollard et al., 2007b). In hypoxic conditions, both pulmonary and muscle O2 diffusive conductances are believed to be of considerable influence to peak (Wagner, 1996). In acute hypoxia, the importance of the convective limitation of blood transport is increased as arterial O2 content is drastically decreased (Romer et al., 2006). It has been shown that trained athletes have a lower arterial O2 saturation than sedentary subjects at heavy exercise intensities (Woorons et al., 2007). Acute hypoxia provokes a shift to the left of the O2–Hb binding curve which facilitates O2 capture at the pulmonary level but compromises O2 delivery at the muscular level, thus the O2 diffusion from blood to the consuming tissue may be altered. Finally, acute hypoxia does not alter the mitochondrial enzymes content, but rates of O2 consumption as high as in normoxia cannot be reached, due to limiting steps in the O2 transport.
Many previous studies investigated the control of microcirculation during exercise and/or hypoxia (Honig et al., 1982, Lindbom, 1983, Rattigan et al., 1997, Wei et al., 1998, Kalliokoski et al., 2001, Peltonen et al., 2007, Subudhi et al., 2007). Although animal preparations (anesthesia, surgery, etc.) required to access muscle blood flow data are of great interest, the heavy and restrictive experimental equipment used may alter the fragile structure of capillaries and/or change the very low in the skeletal muscle thus modifying the vasoconstriction/dilation balance (Poole et al., 2008). Non-invasive techniques investigating a whole muscle group (Kalliokoski et al., 2001) did not allow the subjects to reach peak. Finally, a non-invasive technique such as near infra-red spectroscopy (NIRS) (Peltonen et al., 2007, Subudhi et al., 2007) has the primary goal of monitoring the proportion of oxy/deoxyhemoglobin within the muscle microvessels. It must be remembered that the NIRS signal is only a relative measurement and not flow-based, as such, it is not adequate to speculate about local blood flow.
In light of the debate concerning capillary recruitment during exercise and the paucity of data about capillary recruitment in hypoxia, we hypothesized that hypoxia would increase capillary recruitment during exercise. To answer this question we introduced a new method to explore capillary recruitment. The method is essentially non-invasive and can be applied to any exercise intensity. Such an indicator of capillary recruitment would be helpful in the non-invasive follow-up of training for athletes as well as in the monitoring of diseases with possibly altered muscle oxygenation such as chronic obstructive pulmonary disease, type 2 diabetes or hypertensive patients with microvascular dysfunction (Saey et al., 2005, Clerk et al., 2007, de Jongh et al., 2007, Jansson, 2007).
Section snippets
Study design
Sixteen male subjects were divided into two groups: “sedentary” (n = 8; height: 1.80 ± 0.05 m; mass: 70 ± 7 kg; age: 25 ± 4 years) and “endurance trained” (n = 8; height: 1.80 ± 0.10 m; mass: 72 ± 8 kg; age: 31 ± 3 years). A written informed consent was obtained from the 16 volunteers who participated in this study. All procedures were approved by the ethics committee of Hôpital Necker, Paris.
Each subject underwent four peak tests, the first of which was performed in normoxia , the others were
Results
As expected, workload at maximal exercise and peak decreased with increasing altitude (Table 1, p < 0.05). Moreover, there was a significant interaction between training and hypoxia which demonstrated that the effects of hypoxia on peak depend on the training status. The decrease in peak was greater in endurance-trained athletes (Table 1, p < 0.05). Cardiac output increased linearly with work rate and was higher in trained than in untrained subjects (Table 1, p < 0.05). Additionally,
Discussion
The main finding of this study is the observation of a linear relationship between and (Fig. 2). It validates the hypothesis we formulated through Eq. defining an index of capillary recruitment in exercising humans. Our method gives one value of Nc per exercise test per subject, allowing the evaluation of the effect of altitude and training on exercise induced capillary recruitment. The aim is to compare specific populations (such as athletes or patients) to healthy
Conclusion
This study proposes a non-invasive evaluation of capillary recruitment in the human muscle from rest to maximal exercise. The computations demonstrate that endurance-trained athletes have a higher recruitment coefficient than their sedentary counterparts. A decrease in blood subsequent to environmental hypoxia provokes an increase in capillary recruitment in both populations, the increase being greater in athletes. Moreover, the threshold beyond which capillary recruitment increases is at a
References (58)
- et al.
Réponses du réseau capillaire du muscle squelettique à l’entraînement
Sci. Sport
(2003) An analysis of the factors limiting maximal oxygen consumption in healthy subjects
Chest
(1992)- et al.
A theoretical analysis of intracellular oxygen diffusion
J. Theor. Biol.
(1995) - et al.
Factors limiting maximal O2 consumption: effects of acute changes in ventilation
Respir. Physiol.
(1995) - et al.
Cerebral and muscle tissue oxygenation in acute hypoxic ventilatory response test
Respir. Physiol. Neurobiol.
(2007) - et al.
Skeletal muscle capillary geometry: adaptation to chronic hypoxia
Respir. Physiol.
(1989) A theoretical analysis of factors determining at sea level and altitude
Respir. Physiol.
(1996)- et al.
Alterations in cerebral autoregulation and cerebral blood flow velocity during acute hypoxia: rest and exercise
Am. J. Physiol. Heart Circ. Physiol.
(2007) - et al.
HIF-independent regulation of VEGF and angiogenesis by the transcriptional coactivator PGC-1 alpha
Nature
(2008) - et al.
Influence of hypoxic ventilatory response on arterial O2 saturation during maximal exercise in acute hypoxia
Eur. J. Appl. Physiol. Occup. Physiol.
(1995)
Maximum rate of oxygen uptake by human skeletal muscle in relation to maximal activities of enzymes in the Krebs cycle
J. Physiol.
Angiogenic and cell survival functions of vascular endothelial growth factor (VEGF)
J. Cell. Mol. Med.
Cardiac output and leg and arm blood flow during incremental exercise to exhaustion on the cycle ergometer
J. Appl. Physiol.
Degree of arterial desaturation in normoxia influences decline in mild hypoxia
Med. Sci. Sports Exerc.
Enhancement of microvessel tortuosity in the vastus lateralis muscle of old men in response to endurance training
J. Physiol.
A new impedance cardiograph device for the non-invasive evaluation of cardiac output at rest and during exercise: comparison with the “direct” Fick method
Eur. J. Appl. Physiol.
Point:counterpoint: there is/is not capillary recruitment in active skeletal muscle during exercise
J. Appl. Physiol.
Skeletal muscle capillary responses to insulin are abnormal in late-stage diabetes and are restored by angiotensin-converting enzyme inhibition
Am. J. Physiol. Endocrinol. Metab.
Improvement of by cardiac output and oxygen extraction adaptation during intermittent versus continuous endurance training
Eur. J. Appl. Physiol.
Microvascular function: a potential link between salt sensitivity, insulin resistance and hypertension
J. Hypertens.
Metabolic and circulatory limitations to at the whole animal level
J. Exp. Biol.
Factors limiting maximal oxygen consumption in humans
Respir. Physiol.
The decrease of maximal oxygen consumption during hypoxia in man: a mirror image of the oxygen equilibrium curve
J. Physiol.
Muscle O2 gradients from hemoglobin to cytochrome: new concepts, new complexities
Adv. Exp. Med. Biol.
Active and passive capillary control in red muscle at rest and in exercise
Am. J. Physiol.
Plasticity of skeletal muscle mitochondria: structure and function
Med. Sci. Sports Exerc.
Endothelial dysfunction in insulin resistance and type 2 diabetes
J. Intern. Med.
Enhanced oxygen extraction and reduced flow heterogeneity in exercising muscle in endurance-trained men
Am. J. Physiol. Endocrinol. Metab.
Microvascular blood flow distribution in skeletal muscle, an intravital microscopic study in the rabbit
Acta Physiol. Scand. Suppl.
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