The hyperaemic response of the forearm is a widely used technique to assess the vascular reactivity. Little is known about the short-term reproducibility and the possible exhaustion of this response in normal or diseased states. As such, the current study was conducted to assess this phenomenon using a unique nuclear medicine- (NM-) based technique. 19 patients with coronary artery disease (CAD) undergoing NM exercise stress tests and 15 low risk (LR) participants completed 2 reactive hyperaemia tests, using a SPECT-based technique, separated by 15？ min. Analyses revealed that CAD patients had lower hyperaemic responses than LR participants ( ), and that there was a significant group × time interaction ( ), such that LR participants showed a larger decrease in the reactivity ( to ) than the CAD patients ( to ). These results suggest that there is a variability, due to disease states, in the reproducibility of the hypaeremic reactivity. This needs to be taken into account in short-term repeated measure studies. 1. Introduction Endothelial dysfunction is thought to be a major factor in the development and progression of coronary artery disease (CAD) [1]. Over the past several years, measures of endothelial function have become widely used in medical research. One such technique that has gained popularity is the occlusion-induced ischemia of the forearm using a blood pressure cuff. Release of the ischemia induces a hyperaemic reactivity measurable in the brachial artery [1, 2]. This assessment technique has been shown to have reasonable [2–5], though not perfect [6, 7], long-term reproducibility (e.g., day-to-day or month-to-month). However, little is known about the short-term (15？min) reproducibility of hyperaemic reactivity, or if this reproducibility is different between patients with CAD and healthy controls. Given the desirability of being able to conduct multiple tests over a short period of time for use in clinical trials and the assessment of acute exposures (e.g., exercise, acute psychological stress, pharmacological) such information would be important to be known. We previously compared hyperaemic reactivity in CAD patients and low risk participants using a nuclear medicine based forearm hyperaemic reactivity technique (FHR) [3]. This measure has very good discriminant properties and good day-to-day reproducibility. However, its short-term reproducibility is unknown and, as such, the objectives of the current study were to test this reproducibility in a sample of CAD patients and low risk controls. 2. Materials and Methods 2.1. Participants A
References
[1]
M. C. Corretti, T. J. Anderson, E. J. Benjamin et al., “Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery: a report of the international brachial artery reactivity task force,” Journal of the American College of Cardiology, vol. 39, no. 2, pp. 257–265, 2002.
[2]
D. S. Celermajer, K. E. Sorensen, V. M. Gooch et al., “Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis,” The Lancet, vol. 340, no. 8828, pp. 1111–1115, 1992.
[3]
J. Dupuis, A. Arsenault, B. Meloche, F. Harel, C. Staniloae, and J. Grégoire, “Quantitative hyperemic reactivity in opposed limbs during myocardial perfusion imaging: a new marker of coronary artery disease,” Journal of the American College of Cardiology, vol. 44, no. 7, pp. 1473–1477, 2004.
[4]
M. A. Welsch, J. D. Allen, and J. P. Geaghan, “Stability and reproducibility of brachial artery flow-mediated dilation,” Medicine and Science in Sports and Exercise, vol. 34, no. 6, pp. 960–965, 2002.
[5]
M. L. Hijmering, E. S. G. Stroes, G. Pasterkamp, M. Sierevogel, J. D. Banga, and T. J. Rabelink, “Variability of flow mediated dilation: consequences for clinical application,” Atherosclerosis, vol. 157, no. 2, pp. 369–373, 2001.
[6]
N. M. de Roos, M. L. Bots, E. G. Schouten, and M. B. Katan, “Within-subject variability of flow-mediated vasodilation of the brachial artery in healthy men and women: implications for experimental studies,” Ultrasound in Medicine and Biology, vol. 29, no. 3, pp. 401–406, 2003.
[7]
R. Brook, M. Grau, C. Kehrer, S. Dellegrottaglie, B. Khan, and S. Rajagopalan, “Intrasubject variability of radial artery flow-mediated dilatation in healthy subjects and implications for use in prospective clinical trials,” American Journal of Cardiology, vol. 96, no. 9, pp. 1345–1348, 2005.
[8]
A. Arsenault, S. L. Bacon, K. L. Lavoie, and B. Meloche, “RUR and EWRU, new markers of endothelial fucntion,” Psychosomatic Medicine, vol. 67, article A38, 2005.
[9]
B. Meloche, A. Arsenault, K. L. Lavoie, and S. L. Bacon, “Test-retest reliability of a new method to measure endothelial function,” Psychosomatic Medicine, vol. 67, article A54, 2005.
[10]
J. Veldhuijzen van Zanten, B. Meloche, S. L. Bacon, P. R. Stébenne, A. Arsenault, and K. L. Lavoie, “Inter-observer reliability of a new method to measure endothelial function,” Psychosomatic Medicine, vol. 68, article A36, 2006.
[11]
A. O. Karacalioglu, S. Demirkol, O. Emer et al., “Scintigraphic imaging of endothelium-dependent vasodilation in the forearm—a preliminary report,” Circulation Journal, vol. 70, no. 3, pp. 311–315, 2006.
[12]
S. Onkelinx, V. Cornelissen, K. Goetschalckx, T. Thomaes, P. Verhamme, and L. Vanhees, “Reproducibility of different methods to measure the endothelial function,” Vascular Medicine, vol. 17, no. 2, pp. 79–84, 2012.
[13]
M. Barton, A. T. Turner, K. J. Newens, C. M. Williams, and A. K. Thompson, “Minimum recovery time between reactive hyperemia stimulus in the repeated measurement of brachial flow-mediated dilatation,” Ultrasound in Medicine and Biology, vol. 37, no. 6, pp. 879–883, 2011.
[14]
M. H. Al-Shaer, N. E. Choueiri, M. L. G. Correia, C. A. Sinkey, T. A. Barenz, and W. G. Haynes, “Effects of aging and atherosclerosis on endothelial and vascular smooth muscle function in humans,” International Journal of Cardiology, vol. 109, no. 2, pp. 201–206, 2006.
[15]
R. E. Kaplon, A. E. Walker, and D. R. Seals, “Plasma norepinephrine is an independent predictor of vascular endothelial function with aging in healthy women,” Journal of Applied Physiology, vol. 111, no. 5, pp. 1416–1421, 2011.
[16]
L. Lind, “Impact of ageing on the measurement of endothelium-dependent vasodilation,” Pharmacological Reports, vol. 58, supplement, pp. 41–46, 2006.
[17]
D. A. Cox, J. A. Vita, C. B. Treasure et al., “Atherosclerosis impairs flow-mediated dilation of coronary arteries in humans,” Circulation, vol. 80, no. 3, pp. 458–465, 1989.
[18]
M. E. Widlansky, N. Gokce, J. F. Keaney Jr., and J. A. Vita, “The clinical implications of endothelial dysfunction,” Journal of the American College of Cardiology, vol. 42, no. 7, pp. 1149–1160, 2003.
[19]
J. A. Vita and J. F. Keaney Jr., “Endothelial function: a barometer for cardiovascular risk?” Circulation, vol. 106, no. 6, pp. 640–642, 2002.
[20]
J. C. Schneider, I. Blazy, M. Déchaux, D. Rabier, N. P. Mason, and J. P. Richalet, “Response of nitric oxide pathway to L-arginine infusion at the altitude of 4,350？m,” European Respiratory Journal, vol. 18, no. 2, pp. 286–292, 2001.
[21]
J. C. López-Ramos, R. Martínez-Romero, F. Molina et al., “Evidence of a decrease in nitric oxide-storage molecules following acute hypoxia and/or hypobaria, by means of chemiluminescence analysis,” Nitric Oxide, vol. 13, no. 1, pp. 62–67, 2005.
[22]
M. E. Tschakovsky and K. E. Pyke, “Counterpoint: flow-mediated dilation does not reflect nitric oxide-mediated endothelial function,” Journal of Applied Physiology, vol. 99, no. 3, pp. 1235–1237, 2005.
