J Appl Physiol 104: 563-564, 2008;
doi:10.1152/japplphysiol.00694.2007c
8750-7587/08 $8.00
POINT-COUNTERPOINT
Rebuttal from Drs. Richard, Zoll, Mettauer, Piquard, and Geny
First, even if surprising to the readers, we will agree with many of Dr. Andreassen's statements (1). Particularly knowing that his team demonstrated that "peripheral factors, such as vasoreactivity and increased minimal resistance, are related to exercise performance after heart transplantation" (6), we congratulate him for his well documented position supporting that cardiac denervation does play a role in exercise limitation after heart transplantation. In addition to nicely describing the cardiovascular adjustments during exercise, Dr. Andreassen also brought to the forefront of this debate that cardiac denervation should not be viewed only through its repercussion on heart rate but also through its effects on cardiac inotropy.
Nevertheless, Htx patients generally present with a normal systolic cardiac function that still improves during exercise, and this argument should be considered as secondary. Indeed, administration of Dobutamine failed to enhance peak aerobic capacity despite an immediate rise in cardiac output during exercise (8).
Similarly, although the heart rate response to exercise has been shown to be related with exercise capacity (1), improving the heart rate reserve by exercise training or L-arginine supplementation failed to improve patients' exercise capacity (2, 4). Accordingly, a controlled trial of exercise rehabilitation after heart transplantation demonstrated that exercise capacity improvement occurred only in the training group, whereas exercise-induced heart rate increase was similar in both the exercising and the control groups (7). This should apply to Htx, since, even in case of documented sinus node denervation, their resting heart rate can be decreased by endogenous sympathoinhibitory factors (5), thus likely allowing an increased heart rate span during exercise. Taken together, these data strongly support that peripheral limitations are major compared with central limitations when considering exercise capacity after heart transplantation.
Of course, other organ transplanted patients, including renal transplant recipients, might demonstrate muscular limitations (9), mainly related to physical deconditioning, immunosuppressive therapy, and/or to endothelial dysfunction. Such muscular impairments better explain the reduced peak heart rate during exercise. Indeed, it is well known that cardiac output does adapt to the metabolic demand (i.e., muscular demand) rather than the opposite. The main driving mechanism of the cardiac response to exercise relies on peripheral metabolic need (3), which is likely to be reduced in Htx. A potential cardiac limitation can thus only be unmasked when Htx patients perform exercise of very high intensity or duration.
In conclusion, peripheral factors do generally play a major role in exercise limitation after heart transplantation, with an exception that confirms the rule: "For gold, heart rate matters" (10).
REFERENCES
- Andreassen AK. Point: Cardiac denervation does play a role in exercise limitation after heart transplantation. J Appl Physiol; doi:10.1152/japplphysiol.00694.2007.
- Doutreleau S, Mettauer B, Piquard F, Schaefer A, Lonsdorfer E, Richard R, Geny B. Chronic but not acute oral L-arginine supplementation delays the ventilatory threshold during exercise in heart failure patients. Can J Appl Physiol 30: 419–432, 2005.[Medline]
- Dufour SP, Doutreleau S, Lonsdorfer-Wolf E, Lampert E, Hirth C, Piquard F, Lonsdorfer J, Geny B, Mettauer B, Richard R. Deciphering the metabolic and mechanical contributions to the exercise-induced circulatory response: insights from eccentric cycling. Am J Physiol Regul Integr Comp Physiol 292: R1641–R648, 2007.[Abstract/Free Full Text]
- Geny B, Saini J, Mettauer B, Lampert E, Piquard F, Follenius M, Epailly E, Schnedecker B, Eisenmann B, Haberey P, Lonsdorfer J. Effect of short term endurance training on exercise capacity, hemodynamics and atrial natriuretic peptide secretion in heart transplant recipients. Eur J Appl Physiol 73: 259–266, 1996.[CrossRef][Web of Science]
- Geny B, Charloux A, Brandenberger G, Piquard F. Despite cardiac denervation, atrial natriuretic peptides possess a cardiac sympathoinhibitory effect after heart transplantation. J Thorac Cardiovasc Surg 131: 1417–1418, 2006.[Free Full Text]
- Hognestad A, Holm T, Simonsen S, Kjekshus J, Andreassen AK. Serial measurements of peripheral vascular reactivity and exercise capacity in congestive heart failure and after heart transplantation. J Card Fail 6: 447–454, 2005.
- Kobashigawa JA, Leaf DA, Lee N, Gleeson MP, Liu H, Hamilton MA, Moriguchi JD, Kawata N, Einhorn K, Herlihy E, Laks H. A controlled trial of exercise rehabilitation after heart transplantation. N Engl J Med 340: 272–277, 1999.[Abstract/Free Full Text]
- Maskin CS, Kugler J, Sonnenblick EH, LeJemtel TH. Acute inotropic stimulation with dopamine in severe congestive heart failure: beneficial hemodynamic effect at rest but not during maximal exercise. Am J Cardiol 52: 1028–1032, 1983.[CrossRef][Medline]
- Richard R, Verdier JC, Doutreleau S, Piquard F, Geny B, Rieu M. Exercise limitation in trained heart and kidney transplant recipients: central and peripheral limitations. J Heart Lung Transplant 24: 1774–1780, 2005.[CrossRef][Medline]
- Surmely JF, Mohacsi P, Schmid JP, Carrel T, Delacretaz E. For gold, heart rate matters. J Heart Lung Transplant 24: 1171–1173, 2005.[CrossRef][Medline]
Copyright © 2008 by the American Physiological Society.
