Rebuttal from Drs. Clark, Rattigan, Barrett, and Vincent

Abstract

POINT-COUNTERPOINTRebuttal from Drs. Clark, Rattigan, Barrett, and VincentPublished Online:01 Mar 2008https://doi.org/10.1152/japplphysiol.00779.2007bMoreSectionsPDF (39 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInEmailWeChat We congratulate David Poole and his associates for a clear and thoughtful argument (6). The accompanying intravital microscopy video of the spinotrapezius muscle is equally instructive where over 80% of the capillaries are supporting RBC flow at rest.However, the data are only as good as the techniques used to acquire them, and the authors themselves (6) acknowledge some of the problems associated with exposing a muscle such as the spinotrapezius for viewing under a microscope. These problems, which could alter the extent of capillary recruitment, include the effect of manipulations required to expose the muscle; the question of whether the thin muscles that can be exposed are representative of the cylindrical load-bearing muscles; the effects of anesthesia; and the superfusion Po2. Since the weight of argument against exercise-mediated capillary recruitment is based on studies using intravital microscopy it is essential that the findings from this system can be extrapolated to in vivo. Not least among the problems is the superfusion Po2 where suffusate buffer for intravital microscopy of isolated muscles is invariably gassed with 5% CO2 in 95% N2 [e.g. tenuissimus (4); spinotrapezius (3); cremaster (2)]. Comparison with a suffusate Po2 dose curve (7) suggests this could have a marked impact to increase the number of capillaries perfused at rest.In contrast, our endeavours in this field have focused on noninvasive estimations of microvascular perfusion in bulk load-bearing muscle in vivo that has not been manipulated nor perturbed by invasive conditions. Ultrasound imaging of a region of interest comprising ∼15 g of human forearm muscle of conscious healthy humans has indicated capillary recruitment to occur in response to insulin infusion under euglycemic conditions, to a mixed meal, and to exercise (8), and that the insulin response is impaired in obese insulin-resistant patients (1).Finally, despite the differences in our two approaches, an impaired blood-muscle exchange has been identified in animal models of type 2 diabetes (5, 9). The percentage of RBC-perfused capillaries is decreased in the Goto-Kakizaki rat (5) and we find that the obese Zucker rat has impaired insulin-mediated capillary recruitment (9). Future experiments may reveal that the vascular dysfunction that is responsible for the impaired insulin response in vivo (9) is also that which prevents capillary recruitment when the muscle is exposed, irrigated with N2 buffer, and viewed microscopically (5). “The voyage of discovery is not in seeking new landscapes but in having new eyes.”—Marcel ProustREFERENCES1 Clerk LH, Vincent MA, Jahn LA, Liu Z, Lindner JR, Barrett EJ. Obesity blunts insulin-mediated microvascular recruitment in human forearm muscle. Diabetes 55: 1436–1442, 2006.Crossref | PubMed | ISI | Google Scholar2 Gorczynski RJ, Klitzman B, Duling BR. Interrelations between contracting striated muscle and precapillary microvessels. Am J Physiol Heart Circ Physiol 235: H494–H504, 1978.Link | ISI | Google Scholar3 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 Scholar4 Lindbom L. Microvascular blood flow distribution in skeletal muscle. Acta Physiol Scand Suppl 525: 1–40, 1983.PubMed | Google Scholar5 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 Scholar6 Poole DC, Brown MD, Hudlicka O.Counterpoint: There is not capillary recruitment in active skeletal muscle during exercise. J Appl Physiol; doi:10.1152/japplphysiol.00779.2007a.Link | ISI | Google Scholar7 Shibata M, Ichioka S, Togawa T, Kamiya A. Arterioles' contribution to oxygen supply to the skeletal muscles at rest. Eur J Appl Physiol 97: 327–331, 2006.Crossref | PubMed | ISI | Google Scholar8 Vincent MA, Clerk LH, Lindner JR, Price WJ, Jahn LA, Leong-Poi H, Barrett EJ. Mixed meal and light exercise each recruit muscle capillaries in healthy humans. Am J Physiol Endocrinol Metab 290: E1191–E1197, 2006.Link | ISI | Google Scholar9 Wallis MG, Wheatley CM, Rattigan S, Barrett EJ, Clark ADH, Clark MG. Insulin-mediated hemodynamic changes are impaired in muscle of Zucker obese rats. Diabetes 51: 3492–3498, 2002.Crossref | PubMed | ISI | Google Scholar Download PDF Previous Back to Top Next FiguresReferencesRelatedInformation More from this issue > Volume 104Issue 3March 2008Pages 893-893 Copyright & PermissionsCopyright © 2008 the American Physiological Societyhttps://doi.org/10.1152/japplphysiol.00779.2007bHistory Published online 1 March 2008 Published in print 1 March 2008 Metrics Downloaded 133 times