Intermittent Hypoxia 2: Cardiovascular and Metabolism

Summary

The purpose of this study is to compare cardiovascular physiological adaptation to intermittent hypoxia (IH) of nonobese healthy subjects. The exposure will be two periods of two weeks (IH versus exposure "placebo hypoxia"). The investigators will use pharmacological tools, peripheral vasodilator (amlodipine) or specific blocker of angiotensin receptor (valsartan) versus the taking of a placebo. The allocation of the tool and the exhibition will be randomized (HI / placebo, valsartan / amlodipine). The outcome measures evaluated concern the cardiovascular system, systemic inflammation and tissular and glucose metabolism. The investigators assume an increase in arterial resistance during the intermittent hypoxia compared to the control group, these being dependent on sympathetic tone. The investigators hypothesize that the metabolic alterations that will be observed after experimental simulation (IH and fragmentation of sleep for 15 consecutive nights) will be less severe in the valsartan group than in the amlodipine group in comparison with the placebo group. A serum bank and a gene bank will be performed for the requirements of subsequent studies if necessary.

Timeline

Start

2013-08-07

Primary completion

2014-07-17

Completion

2017-03-16

Publications

• Background Steiner S, Schueller PO, Schulze V, Strauer BE. Occurrence of coronary collateral vessels in patients with sleep apnea and total coronary occlusion. Chest. 2010 Mar;137(3):516-20. doi: 10.1378/chest.09-1136. Epub 2009 Oct 26.
• Background Lavie L. Obstructive sleep apnoea syndrome--an oxidative stress disorder. Sleep Med Rev. 2003 Feb;7(1):35-51. doi: 10.1053/smrv.2002.0261.
• Background Shamsuzzaman AS, Gersh BJ, Somers VK. Obstructive sleep apnea: implications for cardiac and vascular disease. JAMA. 2003 Oct 8;290(14):1906-14. doi: 10.1001/jama.290.14.1906.
• Background Carlson JT, Hedner J, Elam M, Ejnell H, Sellgren J, Wallin BG. Augmented resting sympathetic activity in awake patients with obstructive sleep apnea. Chest. 1993 Jun;103(6):1763-8. doi: 10.1378/chest.103.6.1763.
• Background Somers VK, Dyken ME, Clary MP, Abboud FM. Sympathetic neural mechanisms in obstructive sleep apnea. J Clin Invest. 1995 Oct;96(4):1897-904. doi: 10.1172/JCI118235.
• Background Hedner J, Darpo B, Ejnell H, Carlson J, Caidahl K. Reduction in sympathetic activity after long-term CPAP treatment in sleep apnoea: cardiovascular implications. Eur Respir J. 1995 Feb;8(2):222-9. doi: 10.1183/09031936.95.08020222.
• Background Fletcher EC, Lesske J, Culman J, Miller CC, Unger T. Sympathetic denervation blocks blood pressure elevation in episodic hypoxia. Hypertension. 1992 Nov;20(5):612-9. doi: 10.1161/01.hyp.20.5.612.
• Background Tamisier R, Pepin JL, Remy J, Baguet JP, Taylor JA, Weiss JW, Levy P. 14 nights of intermittent hypoxia elevate daytime blood pressure and sympathetic activity in healthy humans. Eur Respir J. 2011 Jan;37(1):119-28. doi: 10.1183/09031936.00204209. Epub 2010 Jun 4.
• Background Narkiewicz K, van de Borne PJ, Montano N, Dyken ME, Phillips BG, Somers VK. Contribution of tonic chemoreflex activation to sympathetic activity and blood pressure in patients with obstructive sleep apnea. Circulation. 1998 Mar 17;97(10):943-5. doi: 10.1161/01.cir.97.10.943.
• Background Carlson JT, Hedner JA, Sellgren J, Elam M, Wallin BG. Depressed baroreflex sensitivity in patients with obstructive sleep apnea. Am J Respir Crit Care Med. 1996 Nov;154(5):1490-6. doi: 10.1164/ajrccm.154.5.8912770.
• Background Punjabi NM, Beamer BA. Alterations in Glucose Disposal in Sleep-disordered Breathing. Am J Respir Crit Care Med. 2009 Feb 1;179(3):235-40. doi: 10.1164/rccm.200809-1392OC. Epub 2008 Nov 14.
• Background Spiegel K, Tasali E, Leproult R, Van Cauter E. Effects of poor and short sleep on glucose metabolism and obesity risk. Nat Rev Endocrinol. 2009 May;5(5):253-61. doi: 10.1038/nrendo.2009.23.
• Background Larsen JJ, Hansen JM, Olsen NV, Galbo H, Dela F. The effect of altitude hypoxia on glucose homeostasis in men. J Physiol. 1997 Oct 1;504 ( Pt 1)(Pt 1):241-9. doi: 10.1111/j.1469-7793.1997.241bf.x.
• Background Braun B, Rock PB, Zamudio S, Wolfel GE, Mazzeo RS, Muza SR, Fulco CS, Moore LG, Butterfield GE. Women at altitude: short-term exposure to hypoxia and/or alpha(1)-adrenergic blockade reduces insulin sensitivity. J Appl Physiol (1985). 2001 Aug;91(2):623-31. doi: 10.1152/jappl.2001.91.2.623.
• Background Spiegel K, Knutson K, Leproult R, Tasali E, Van Cauter E. Sleep loss: a novel risk factor for insulin resistance and Type 2 diabetes. J Appl Physiol (1985). 2005 Nov;99(5):2008-19. doi: 10.1152/japplphysiol.00660.2005.
• Background Spiegel K, Leproult R, Colecchia EF, L'Hermite-Baleriaux M, Nie Z, Copinschi G, Van Cauter E. Adaptation of the 24-h growth hormone profile to a state of sleep debt. Am J Physiol Regul Integr Comp Physiol. 2000 Sep;279(3):R874-83. doi: 10.1152/ajpregu.2000.279.3.R874.
• Background Spiegel K, Leproult R, L'hermite-Baleriaux M, Copinschi G, Penev PD, Van Cauter E. Leptin levels are dependent on sleep duration: relationships with sympathovagal balance, carbohydrate regulation, cortisol, and thyrotropin. J Clin Endocrinol Metab. 2004 Nov;89(11):5762-71. doi: 10.1210/jc.2004-1003.
• Background Spiegel K, Leproult R, Van Cauter E. Impact of sleep debt on metabolic and endocrine function. Lancet. 1999 Oct 23;354(9188):1435-9. doi: 10.1016/S0140-6736(99)01376-8.
• Background Tamisier R, Gilmartin GS, Launois SH, Pepin JL, Nespoulet H, Thomas R, Levy P, Weiss JW. A new model of chronic intermittent hypoxia in humans: effect on ventilation, sleep, and blood pressure. J Appl Physiol (1985). 2009 Jul;107(1):17-24. doi: 10.1152/japplphysiol.91165.2008. Epub 2009 Feb 19.
• Background Gilmartin GS, Lynch M, Tamisier R, Weiss JW. Chronic intermittent hypoxia in humans during 28 nights results in blood pressure elevation and increased muscle sympathetic nerve activity. Am J Physiol Heart Circ Physiol. 2010 Sep;299(3):H925-31. doi: 10.1152/ajpheart.00253.2009. Epub 2010 Jun 25.
• Background Bilo G, Caldara G, Styczkiewicz K, Revera M, Lombardi C, Giglio A, Zambon A, Corrao G, Faini A, Valentini M, Mancia G, Parati G. Effects of selective and nonselective beta-blockade on 24-h ambulatory blood pressure under hypobaric hypoxia at altitude. J Hypertens. 2011 Feb;29(2):380-7. doi: 10.1097/HJH.0b013e3283409014.
• Background Gilmartin GS, Tamisier R, Curley M, Weiss JW. Ventilatory, hemodynamic, sympathetic nervous system, and vascular reactivity changes after recurrent nocturnal sustained hypoxia in humans. Am J Physiol Heart Circ Physiol. 2008 Aug;295(2):H778-85. doi: 10.1152/ajpheart.00653.2007. Epub 2008 Jun 6.
• Background Tamisier R, Anand A, Nieto LM, Cunnington D, Weiss JW. Arterial pressure and muscle sympathetic nerve activity are increased after two hours of sustained but not cyclic hypoxia in healthy humans. J Appl Physiol (1985). 2005 Jan;98(1):343-9. doi: 10.1152/japplphysiol.00495.2004. Epub 2004 Sep 24.
• Background Tamisier R, Hunt BE, Gilmartin GS, Curley M, Anand A, Weiss JW. Hemodynamics and muscle sympathetic nerve activity after 8 h of sustained hypoxia in healthy humans. Am J Physiol Heart Circ Physiol. 2007 Nov;293(5):H3027-35. doi: 10.1152/ajpheart.00277.2007. Epub 2007 Sep 14.
• Background Tamisier R, Nieto L, Anand A, Cunnington D, Weiss JW. Sustained muscle sympathetic activity after hypercapnic but not hypocapnic hypoxia in normal humans. Respir Physiol Neurobiol. 2004 Jul 20;141(2):145-55. doi: 10.1016/j.resp.2004.04.006.
• Background Garet M, Barthelemy JC, Degache F, Pichot V, Duverney D, Roche F. Modulations of human autonomic function induced by positive pressure-assisted breathing. Clin Physiol Funct Imaging. 2006 Jan;26(1):15-20. doi: 10.1111/j.1475-097X.2005.00645.x.
• Background Roche F, Barthelemy JC, Garet M, Duverney D, Pichot V, Sforza E. Continuous positive airway pressure treatment improves the QT rate dependence adaptation of obstructive sleep apnea patients. Pacing Clin Electrophysiol. 2005 Aug;28(8):819-25. doi: 10.1111/j.1540-8159.2005.00188.x.
• Background Roche F, Gaspoz JM, Court-Fortune I, Minini P, Pichot V, Duverney D, Costes F, Lacour JR, Barthelemy JC. Screening of obstructive sleep apnea syndrome by heart rate variability analysis. Circulation. 1999 Sep 28;100(13):1411-5. doi: 10.1161/01.cir.100.13.1411.
• Background Spiegel K, Tasali E, Penev P, Van Cauter E. Brief communication: Sleep curtailment in healthy young men is associated with decreased leptin levels, elevated ghrelin levels, and increased hunger and appetite. Ann Intern Med. 2004 Dec 7;141(11):846-50. doi: 10.7326/0003-4819-141-11-200412070-00008.
• Background Tasali E, Leproult R, Ehrmann DA, Van Cauter E. Slow-wave sleep and the risk of type 2 diabetes in humans. Proc Natl Acad Sci U S A. 2008 Jan 22;105(3):1044-9. doi: 10.1073/pnas.0706446105. Epub 2008 Jan 2.
• Background Hoppeler H, Vogt M. Hypoxia training for sea-level performance. Training high-living low. Adv Exp Med Biol. 2001;502:61-73. doi: 10.1007/978-1-4757-3401-0_6.
• Background Somers VK, White DP, Amin R, Abraham WT, Costa F, Culebras A, Daniels S, Floras JS, Hunt CE, Olson LJ, Pickering TG, Russell R, Woo M, Young T; American Heart Association Council for High Blood Pressure Research Professional Education Committee, Council on Clinical Cardiology; American Heart Association Stroke Council; American Heart Association Council on Cardiovascular Nursing; American College of Cardiology Foundation. Sleep apnea and cardiovascular disease: an American Heart Association/american College Of Cardiology Foundation Scientific Statement from the American Heart Association Council for High Blood Pressure Research Professional Education Committee, Council on Clinical Cardiology, Stroke Council, and Council On Cardiovascular Nursing. In collaboration with the National Heart, Lung, and Blood Institute National Center on Sleep Disorders Research (National Institutes of Health). Circulation. 2008 Sep 2;118(10):1080-111. doi: 10.1161/CIRCULATIONAHA.107.189375. Epub 2008 Aug 25. No abstract available.

Drugs

Indications