Journal of Applied Physiology Millar Instruments
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

J Appl Physiol 104: 562-563, 2008; doi:10.1152/japplphysiol.00694.2007b
8750-7587/08 $8.00
This Article
Right arrow Full Text (PDF) Free
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Search for Related Content

POINT-COUNTERPOINT

Rebuttal from Dr. Andreassen

Richard, Zoll, Mettauer, Piquard, and Geny focus on the periphery in their discussion—are their arguments and references central in explaining the diminished exercise capacity among HTx recipients? I think not and will address the evidence for the four main arguments put forward.
  1. While correlation may not necessarily translate into causation, the larger referred studies have sufficient power to allow robust statistical analysis (2, 3, 6). Multiple regression analysis in each of these studies confirms that peak heart rate and heart rate increase are powerful independent predictors of exercise capacity. Furthermore, invasive studies show that a reduced heart rate response is not compensated by an increase in stroke volume during exercise in HTx recipients (4), underlining that denervation may lead to both chronotropic and inotropic incompetence.
  2. Braith et al. (1) demonstrated a higher peak heart rate with a parallel significant improvement of peak VO2 of 22% in HTx recipients receiving chronotropic support with a rate-responsive pacemaker. Pacing of the allograft in synchrony with the intrinsic depolarization rate of the native SA node may not be coupled to the dynamic metabolic demands of exercise, perhaps explaining why another study could not confirm the same benefit (9). In the absence of larger trials using chronotropic support, the issue of possible beneficial effects of exercise capacity by artificial enhancement of heart rate may seem unanswered.
  3. I am grateful to my opponents' contribution to improving my citation index, but other vasoactive studies should also be mentioned in search of evidence for endothelial dysfunction in HTx recipients. Sinoway et al. (8) described a delayed reversal of impaired vasodilation after HTx and Kubo et al. (5) found normal forearm blood flow responses to an endothelium-dependent agent within 4 mo. Thus no consensus exists on maintained impaired endothelium-dependent vasodilation after HTx. In fact, postoperative normalization is described in studies where well established methods for evaluation of vasodilator responses have been used. Also, I am unaware of any studies assessing the effect of training on peripheral blood flow.
  4. After describing various skeletal muscle metabolic abnormalities, Richard et al. (7) state that these limitations are reversible after training to levels comparable with controls. Considering that peripheral structural microangiopathy and minimal vascular resistance do gradually normalize within the first year (10), which peripheral factors could then explain why most HTx recipients with or without training, continue to demonstrate subnormal exercise capacity, if not taking central factors as denervation into account?

REFERENCES

  1. Braith RW, Clapp L, Brown T, Brown C, Schofield R, Mills RM, Hill JA. Rate-responsive pacing improves exercise tolerance in heart transplant recipients: a pilot study. J Cardiopulm Rehabil 20: 377–382, 2000.[CrossRef][Medline]
  2. Givertz MM, Hartley LH, Colucci WS. Long-term sequential changes in exercise capacity and chronotropic responsiveness after cardiac transplantation. Circulation 96: 232–237, 1997.[Abstract/Free Full Text]
  3. Gullestad L, Haywood G, Ross H, Bjørnerheim R, Geiran O, Kjekshus J, Simonsen S, Fowler M. Exercise capacity of heart transplant recipients: the importance of chronotropic incompetence. J Heart Lung Transplant 15: 1075–1083, 1996.[Web of Science][Medline]
  4. Kao AC, Van Trigt P, Shaeffer-McCall GS, Shaw JP, Kuzil BB, Page RD, Higginbottam MB. Central and peripheral limitations to upright exercise in untrained cardiac transplant recipients. Circulation 89: 2605–2615, 1994.[Abstract/Free Full Text]
  5. Kubo SH, Rector TS, Bank AJ, Tschumperlin LK, Raij L, Brunsvold N, Kraemer MD. Effects of cardiac transplantation on endothelium-dependent dilation of the peripheral vasculature in congestive heart failure. Am J Cardiol 71: 88–93, 1993.[CrossRef][Web of Science][Medline]
  6. Leung TC, Ballman KV, Allison TG, Wagner JA, Olson LJ, Frantz RP, Edwards BS, Dearani JA, Daly RC, McGregor CG, Rodeheffer RJ. Clinical predictors of exercise capacity 1 year after cardiac transplantation. J Heart Lung Transplant 22: 16–27, 2003.[CrossRef][Medline]
  7. Richard R, Zoll J, Mettauer B, Piquard F, Geny B. Counterpoint: Cardiac denervation does not play a major role in exercise limitation after heart transplantation. J Appl Physiol; doi:10.1152/japplphysiol.00694.2007.
  8. Sinoway LI, Minolti JR, Davis D, Pennock JL, Burg JE, Musch TI, Zelis R. Delayed reversal of impaired vasodilation in congestive heart failure after heart transplantation. Am J Cardiol 61: 1076–1071, 1988.[CrossRef][Web of Science][Medline]
  9. Volker H, Sigmund M, Desch U, Silny J, Schondube Hanrath P. Benefits of rate adaptive pacemakers on cardiac transplant patients. Z Kardiol 82: 775–780, 1993.[Medline]
  10. Wroblewski H, Sindrup JH, Nørgaard T, Haunsø S, Kastrup J. Effect of orthotopic cardiac transplantation on structural microangiopathy and abnormal hemodynamics in idiopathic dilated cardiomyopathy. Am J Cardiol 77: 281–285, 1996.[CrossRef][Web of Science][Medline]




This Article
Right arrow Full Text (PDF) Free
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Search for Related Content

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online
Copyright © 2008 by the American Physiological Society.