Counterpoint: There is not capillary recruitment in active skeletal muscle during exercise
2008; American Physiological Society; Volume: 104; Issue: 3 Linguagem: Inglês
10.1152/japplphysiol.00779.2007a
ISSN8750-7587
AutoresDavid C. Poole, Margaret D. Brown, O Hudlická,
Tópico(s)Muscle metabolism and nutrition
ResumoPOINT-COUNTERPOINTCounterpoint: There is not capillary recruitment in active skeletal muscle during exerciseDavid C. Poole, Margaret D. Brown, and Olga HudlickaDavid C. Poole, Margaret D. Brown, and Olga HudlickaPublished Online:01 Mar 2008https://doi.org/10.1152/japplphysiol.00779.2007aMoreSectionsPDF (53 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations The notion that a substantial proportion of capillaries do not contain moving red blood cells (RBCs) in muscle at rest but are “recruited,” i.e., begin flowing with RBCs during contractions, is one basis for our present understanding of blood-muscle exchange during exercise (20, 28). This concept emanates, in part, from August Krogh, who showed that many capillaries in resting muscle did not contain India ink after high pressure perfusion (19). Despite Krogh himself recognizing that India ink particles clumped together, more likely to prevent complete perfusion of the capillary bed at rest than during exercise, these experiments, and Krogh's O2 diffusion model based on them, are still cited by researchers invoking capillary recruitment (e.g., Refs. 22). Today capillary recruitment during exercise is accepted by many to explain important physiological phenomena, including: 1) greater blood-muscle delivery and extraction of O2, free fatty acids, and glucose and 2) reduced capillary-to-mitochondrial diffusion distances. It makes great sense that, if there were a reserve of capillaries at rest, during exercise when the muscle demands for O2 may increase up to 100-fold, all—or at least most—capillaries would contribute to meet that demand.Why, therefore, choose to oppose the concept of capillary recruitment during exercise? In Britain, the motto of The Royal Society is “Nullius in Verba” (Take nobody's word for it, see it for yourself). However, the majority of research papers invoking capillary recruitment have not visualized the capillary bed (e.g., Refs. 3, 7, 25). In his letter to the editor of The American Journal of Physiology, the eminent microcirculation expert, Professor Eugene Renkin (26) criticized Dr. Bentzer for entitling his paper “Capillary filtration coefficient is independent of number of perfused capillaries in skeletal muscle”(4) on the basis that “… its title is misleading. No direct measurements of [RBC-flowing] capillary number were made. …” The same criticism could be leveled at almost all papers that include the words capillary recruitment in their titles. Evidence that most capillaries already sustain flow in resting muscle would preclude the possibility that recruitment of previously nonperfused capillaries occurs to any great extent during contractions.Direct evidence for RBC flow in most capillaries in resting muscle.In resting muscle, intravital light microscopy shows that over 80% of capillaries support RBC flow, e.g., in rat spinotrapezius (14, 17, 24), diaphragm (15), and extensor digitorum longus (1), hamster cremaster and sartorius (8), cat sartorius (6), rabbit tenuissimus (30). However, animals in these experiments were anesthetized to facilitate muscle exteriorization and viewing of the capillary beds. To address this, Bailey and colleagues (2) employed minimally invasive techniques to measure blood flow (radioactive microspheres) and microvascular oxygen partial pressure in muscle in situ and neither criterion was altered by exteriorization. Moreover, the dynamic matching of increased O2 delivery and V̇o2 during contractions in situ was preserved in the exteriorized muscle. It is difficult to conceive how anesthesia might affect arteriolar smooth muscle function at rest (to produce a falsely high %RBC-perfused capillaries) and yet muscles increase their blood flow and V̇o2 at a ratio of ∼6:1 (11), which is precisely that seen in intact voluntary exercising animals and humans (23).Another valid concern about intravital microscopy is that there are non-RBC containing capillaries at rest that cannot be seen because of their translucency. However, neither observation of contracting (17) nor vasodilated (16) muscles revealed a significant number of such vessels (see also Refs. 8, 14). The technical requirements necessary to observe capillaries within living muscle restrict the procedure to a limited selection of animal muscles so that one question to ask is: How representative of other muscles in the animals' body and in humans are these? In anesthetized and conscious animals, Snyder et al. (29) used systemic indicator injections and demonstrated that essentially all capillaries in each muscle examined (vastus lateralis, diaphragm, soleus) were perfused within 3–7 s.Indirect evidence for RBC flow in most capillaries in resting human muscle.Noninvasive near-infrared spectroscopy (NIRS) measures muscle hemoglobin concentration ([Hb]). If there were significant recruitment of previously non-RBC containing capillaries during exercise, say from 20 to 90%, [Hb] would be expected to increase several-fold. However, the rest-to-exercise [Hb] increase is less than onefold (e.g., 10) and can be accounted for by increased capillary hematocrit (18). Thus, as in animal muscles, there is little room for substantial capillary recruitment in human muscle.Against the evidence for capillary recruitment during exercise.The literature that purports to demonstrate capillary recruitment deserves to be evaluated on its own merits, but the following must be considered as possible explanations for reports of many non-RBC flowing capillaries in resting muscle. 1) Capillaries are fragile structures, subject to damage by blunt trauma, surgery, and/or manipulations such as stretching (24). 2) Po2 within resting muscle is normally very low and raising this will cause arteriolar constriction and capillary flow stoppage (22). 3) Anesthetized preparations are often hypovolemic and hypotensive, which provokes reflex vasoconstriction.In addition, misinterpretation of histological techniques has supported the notion of capillary recruitment. The conclusion that a RBC in the muscle capillary cross-section indicates RBC flow, whereas its absence supports no flow is erroneous (e.g., Ref. 13). In resting animal muscle observed in vivo, RBC movement in flowing capillaries varies over time, appearing either continuous or stop-start (9). Muscle contractions result in more continuously flowing vessels with higher RBC velocities (5). Hargreaves et al. (12) used thioflavine S (a plasma marker) to show that, since all capillaries were perfused, during contractions the increase in muscle blood flow (microspheres) could be accounted for by the increased velocity rather than capillary recruitment. Reduced flow heterogeneity and hence augmented capillary hematocrit from rest to exercise decreases the length of inter-RBC plasma gaps and increases the probability that an RBC will appear in cross section.Is the concept that most capillaries support RBC flow in resting muscle mathematically possible?In a typical 70-kg human with 31.5 kg of muscle (45% body mass), resting muscle blood flow is estimated as ∼1 l/min (or 5.4 × 1012 RBCs/min; Refs. 20, 28). Accepting a mean value for capillary density and length of 300/mm2 and 1,000 μm, respectively, if 80% of the 8.9 × 109 capillaries support RBC flow at rest, as in the rat (14, 17, 24), this would be ∼12 RBCs per capillary per second—very close to the 15–20 RBCs per capillary/s actually measured in rat muscle (17). Whereas such calculations are certainly not proof that most skeletal muscle capillaries have RBC flow in humans at rest, they support that it is feasible.Why is it crucial that we question the dogma of capillary recruitment?If most capillaries support RBC flow at rest and are not recruited at exercise onset, increased substrate delivery must occur within already flowing capillaries. Accordingly, is the recruitment of more surface area along the length of already flowing capillaries, rather than de novo flow in previously stagnant capillaries, key to increased blood-myocyte exchange? Diabetes (21), heart failure (27), and chronic ischemia (5) decrease the proportion of RBC-perfused capillaries in resting muscle. If we do not recognize that most capillaries may support RBC flow at rest in healthy muscle, our ability to appreciate the mechanisms for impaired blood-muscle exchange, which may be pathognomonic to these and other diseases, is crippled.Nullius in verba! The online version of this article contains supplemental data showing intravital microscopy recordings demonstrating RBC flow in almost all capillaries in healthy resting spinotrapezius muscle (first video, Refs. 24, 27) and diaphragm (third video, Ref. 15). The second video demonstrates the effects of chronic heart failure (CHF; left coronary artery ligation, Ref. 27) on capillary perfusion in spinotrapezius muscle. Note, in the CHF condition, the presence of stopped RBCs in central capillaries and other capillaries that have intermittent RBC flow and/or very low/sporadic RBC flux. Adherence to the misconception that many capillaries do not flow in healthy resting muscle (i.e., capillary recruitment notion) would confound identification of the effects of this disease on capillary hemodynamics and therefore O2 delivery and substrate exchange. GRANTSThis work was supported, in part, by grants from National Heart, Lung, and Blood Institute, HLBI-17731 and -50306, and grants-in-aid from the American Heart Association, Heartland Affiliate.We thank Professors Timothy I. Musch and George A. Brooks for facilitating presentation of the capillary recruitment debate at the American College of Sports Medicine's Integrative Physiology of Exercise meeting in Indianapolis in September 2006.REFERENCES1 Anderson SI,Hudlicka O, Brown MD. Capillary red blood cell flow and activation of white blood cells in chronic muscle ischemia in the rat. Am J Physiol Heart Circ Physiol 272: H2757–H2764, 1997.Link | ISI | Google Scholar2 Bailey JK, Kindig CA, Behnke BJ, Musch TI, Schmid-Schoenbein GW, Poole DC. Spinotrapezius muscle microcirculatory function: effects of surgical exteriorization. Am J Physiol Heart Circ Physiol 279: H1331–H1337, 2000.Google Scholar3 Baron AD, Tarshoby M, Hook G, Lazaridis EN, Cronin J, Johnson A, Steinberg HO. Interaction between insulin sensitivity and muscle perfusion on glucose uptake in human skeletal muscle: evidence for capillary recruitment. Diabetes 49: 768–774, 2000.Crossref | PubMed | ISI | Google Scholar4 Bentzer P, Kongstad L, Grande PO. Capillary filtration coefficient is independent of number of perfused capillaries in cat skeletal muscle. Am J Physiol Heart Circ Physiol 280:H2697–H2706, 2001.Link | ISI | Google Scholar5 Brown MD, Kelsall CJ, Milkiewicz M, Anderson S, Hudlicka O. A new model of peripheral arterial disease: sustained impairment of nutritive microcirculation and its recovery by chronic electrical stimulation. Microcirculation 12: 373–381, 2005.Crossref | PubMed | ISI | Google Scholar6 Burton KS, Johnson PC. Reactive hyperemia in individual capillaries of skeletal muscle. Am J Physiol 223: 517–524, 1972.Link | ISI | Google Scholar7 Clark ADH, Barrett EJ, Rattigan S, Wallis MG, Clark MG. Insulin stimulates laser Doppler signal by rat muscle which is consistent with nutritive flow recruitment. Clin Sci 100: 283–290, 2001.Crossref | PubMed | ISI | Google Scholar8 Damon DH, Duling BR. Distribution of capillary blood flow in the microcirculation of the hamster: an in vivo study using epifluorescent microscopy. Microvasc Res 27: 81–95, 1984.Crossref | PubMed | ISI | Google Scholar9 Dawson JM, Tyler KR, Hudlicka O. A comparison of the microcirculation in rat fast glycolytic and slow oxidative muscles at rest and during contractions. Microvasc Res 33: 167–182, 1987.Crossref | PubMed | ISI | Google Scholar10 Ferreira LF, Lutjemeier BJ, Townsend DK, Barstow TJ. Effects of pedal frequency on estimated muscle microvascular O2 extraction. Eur J Appl Physiol 96: 558–563, 2006.Crossref | ISI | Google Scholar11 Ferreira LF, McDonough P, Behnke BJ, Musch TI, Poole DC. Blood flow and O2 extraction as a function of O2 uptake in muscles composed of different fiber type. Respir Physiol Neurobiol 153: 237–249, 2006.Crossref | PubMed | ISI | Google Scholar12 Hargreaves D, Egginton S, Hudlicka O. Changes in capillary perfusion induced by different patterns of activity in rat skeletal muscle. Microvasc Res 40: 14–28, 1990.Crossref | PubMed | ISI | Google Scholar13 Honig CR, Odoroff CL, Frierson JL. Capillary recruitment in exercise: rate, extent, uniformity, and relation to blood flow. Am J Physiol Heart Circ Physiol 238: H31–H42, 1980.Link | ISI | Google Scholar14 Hudlicka O, Zweifach BW, Tyler KR. Capillary recruitment and flow velocity in skeletal muscle after contractions. Microvasc Res 23: 201–213, 1982.Crossref | PubMed | ISI | Google Scholar15 Kindig CA, Poole DC. A comparison of the microcirculation in the rat spinotrapezius and diaphragm muscles. Microvasc Res 55: 249–259, 1998.Crossref | PubMed | ISI | Google Scholar16 Kindig CA, Poole DC. Sarcomere length-induced alterations of capillary hemodynamics in rat spinotrapezius muscle: vasoactive vs passive control. Microvasc Res 61: 64–74, 2001.Crossref | PubMed | ISI | Google Scholar17 Kindig CA, Richardson TE, Poole DC. Skeletal muscle capillary hemodynamics from rest to contractions: implications for oxygen transfer. J Appl Physiol 92: 2513–2520, 2002.Link | ISI | Google Scholar18 Klitzman B, Duling BR. Microvascular hematocrit and red cell flow in resting and contracting striated muscle. Am J Physiol Heart Circ Physiol 237: H481–H490, 1979.Link | ISI | Google Scholar19 Krogh A. The number and distribution of capillaries in muscles with calculations of the oxygen pressure head necessary for supplying the tissue. J Physiol 52: 409–415, 1919.Crossref | PubMed | Google Scholar20 McArdle WD, Katch FI, Katch VL. Exercise Physiology: Energy, Nutrition and Human Performance (6th ed.). London: Lippincott Williams & Wilkins, 2007, p. 319–344.Google Scholar21 Padilla DJ, McDonough P, Behnke BJ, Kano Y, Hageman KS, Musch TI, Poole DC. Effects of Type II diabetes on capillary hemodynamics in skeletal muscle. Am J Physiol Heart Circ Physiol 291: H2439–H2444, 2006.Link | ISI | Google Scholar22 Parthasarathi K, Lipowsky HH. Capillary recruitment in response to tissue hypoxia and its dependence on red blood cell deformability. Am J Physiol Heart Circ Physiol 277: H2145–H2157, 1999.Link | ISI | Google Scholar23 Poole DC. Influence of exercise training on skeletal muscle oxygen delivery and utilization. In: The Lung: Scientific Foundations, edited by Crystal RG, West JB, Weibel ER, Barnes PJ. New York: Raven, 1997, p. 1957–1967.Google Scholar24 Poole DC, Musch TI, Kindig CA. In vivo microvascular structural and functional consequences of muscle length changes. Am J Physiol Heart Circ Physiol 272: H2107–H2114, 1997.Link | ISI | Google Scholar25 Rattigan S, Clark MG, Barrett EJ. Hemodynamic actions of insulin in rat skeletal muscle: evidence for capillary recruitment. Diabetes 46: 1381–1388, 1997.Crossref | PubMed | ISI | Google Scholar26 Renkin EM. Evaluation of capillary perfusion. Am J Physiol Heart Circ Physiol 282: H1172–H1173, 2002.Link | ISI | Google Scholar27 Richardson TS, Kindig CA, Musch TI, Poole DC. Effects of chronic heart failure on skeletal muscle capillary hemodynamics at rest and during contractions. J Appl Physiol 95: 1055–1062, 2003.Link | ISI | Google Scholar28 Rowell LB. Human Cardiovascular Control. Oxford: Oxford University Press, 1993, p. 294.Google Scholar29 Snyder GK, Farrelly C, Coelho JR. Capillary perfusion in skeletal muscle. Am J Physiol Heart Circ Physiol 262: H828–H832, 1992.Link | ISI | Google Scholar30 Vrielink HH, Slaaf DW, Tangelder GJ, Reneman RS. 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