systhiperСистемные гипертензииSystemic Hypertension2075-082X2542-2189LLC «ИнтерМедсервис»systhiper-486Research ArticleКАРДИОПУЛЬМОНОЛОГИЯМаркеры активации системы гемостаза у больных с синдромом обструктивного апноэ сна, возможности краткосрочной СИПАП-терапииCoagulation markers in patients with obstructive sleep apnea syndrome and effects of continuous positive airway pressureБугаевТ. Д.BugaevT. D.noemail@neicon.ruЕлфимоваЕ. М.ElfimovaE. M.noemail@neicon.ruАгееваН. В.AgeevaN. V.noemail@neicon.ruДобровольскийА. Б.DobrovolskiyA. B.noemail@neicon.ruЛитвинА. Ю.LitvinA. Yu.alelitvin@yandex.ruИнститут клинической кардиологии им. А.Л.Мясникова ФГБУ Российский кардиологический научно-производственный комплекс Минздрава РоссииРоссияA.L.Myasnikov Institute of Clinical Cardiology, Russian Cardiological Scientific-Industrial Complex of the Ministry of Health of the Russian FederationRussian Federation2016231220221344146Copyright © Бугаев Т.Д., Елфимова Е.М., Агеева Н.В., Добровольский А.Б., Литвин А.Ю., 20222022Бугаев Т.Д., Елфимова Е.М., Агеева Н.В., Добровольский А.Б., Литвин А.Ю.Bugaev T.D., Elfimova E.M., Ageeva N.V., Dobrovolskiy A.B., Litvin A.Y.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.syst-hypertension.ru/jour/article/view/486

Цель исследования: изучить маркеры активации системы гемостаза, в частности D-димера, ингибитора активатора плазминогена-1 (ИАП-1), комплексов: плазмин-α2-антиплазмин (ПАП), тканевой активатор плазминогена/ИАП-1 (ТАП-ИАП-1); фактора Виллебранда и параметров вязкости цельной крови у пациентов с артериальной гипертонией (АГ) в сочетании с синдромом обструктивного апноэ сна (СОАС) разной степени тяжести, а также возможного влияния краткосрочной терапии постоянным положительным давлением в верхних дыхательных путях (СИПАП) в отношении данных показателей. Материалы и методы. Включены 74 мужчины со средним возрастом 48 [40; 55] лет с АГ длительностью 8 [5; 10] лет, не принимающих антиагрегантную, антикоагулянтную терапию и не страдающих сахарным диабетом. Всем было проведено ночное кардиореспираторное исследование. По степени нарушения дыхания во время сна больные были разделены на 2 группы: 1-я группа - 34 пациента с АГ без СОАС и с СОАС легкой степени тяжести - индекс апноэ/гипопноэ - ИАГ 4,8 (2,6; 7,8); 2-я группа - 40 больных АГ и с СОАС тяжелой степени - ИАГ 50,2 (37,8; 75,2). Пациентам с тяжелой степенью СОАС проводилась эффективная СИПАП-терапия в течение 3-4 дней с определением анализов крови исходно и после терапии. Результаты. У больных с тяжелой степенью СОАС были выявлены более высокие уровни вязкости цельной крови, маркеров активации системы гемостаза (ПАП, ТАП-ИАП-1), фибриногена и гематокрита. Значения комплекса ТАП-ИАП-1 и гематокрита превышали нормальные значения. На фоне СИПАП-терапии в течение 3-4 ночей в группе с тяжелым СОАС установлено достоверное снижение параметров вязкости цельной крови с достижением нормальных уровней гематокрита, тогда как маркеры активации системы гемостаза остались без достоверных изменений. Заключение. Уровни маркеров активации системы гемостаза и параметры вязкости цельной крови повышены у лиц с СОАС тяжелой степени тяжести (АГ и ожирением). Краткосрочная (3-4 ночи) СИПАП-терапия благотворно влияет на все параметры вязкости цельной крови, снижая уровень гематокрита до нормальных параметров.

The aim of our study is to determine association between obstructive sleep apnea (OSA) syndrome and levels of blood coagulation markers and evaluate possible effects of continuous positive airway pressure (CPAP) therapy. Materials and methods. We included 74 middle-aged (mean age 48 [40; 55] years) male patients with arterial hypertension (AH) of average duration 8 [5; 10] years without antiplatelet, anticoagulant therapy and diabetes mellitus. All patients underwent sleep breathing study. According to the severity of OSA, patients were divided into 2 groups: 40 patients with severe OSA - apnea/hypopnea index - AHI 50.2 (37.8; 75.2) and control group with 34 patients with mild or no OSA - AHI 4.8 (2.6; 7.8). In all patients were analyzed markers of hemostasis system and parameters of whole blood viscosity; 34 patients with severe OSA underwent 3-4 nights of effective CPAP therapy (with achievement AHI<5) with evaluation of the above analysis at baseline and in the end of therapy. Results. We found a significant increase of fibrinogen, plasminogen activator inhibitor-1 (PAI-1), plasmin-a2-antiplasmin complex (PAP), tissue plasminogen activator/plasminogen activator inhibitor-1 complex (tPA-PAI-1), whole blood viscosity at low shear rates and erythrocytes aggregation index in the group with severe OSA compared with controls. After short-term (3-4 nights) CPAP therapy significantly decreased all parameters of whole blood viscosity with achieved normal levels of hematocrit, but markers of hemostasis system showed no significant difference. Conclusion: the coagulation status of blood is elevated in severe OSA patients (with AH and obessity). Short-term CPAP therapy can improve parameters of whole blood viscosity with achieved normal values of hematocrit. These results suggest that even few nights of CPAP therapy may reduce cardiovascular risk in OSA, in part through improving of whole blood viscosity.

нарушение дыхания во снесиндром обструктивного апноэ снакоагулогиягемостазфибринолизисвязкость кровиСИПАП-терапияdisorders of breathing during sleepobstructive sleep apneacoagulation markersblood viscosityCPAP therapyReferencesGastaut H, Tassarini C, Duron B et al. Polygraphiques des manifestations episodique (hypnique et respiratoire) du syndrome de Pickwick. Rev Neurol 1965; 112: 56-79.Gastaut H, Tassarini C, Duron B et al. Polygraphiques des manifestations episodique (hypnique et respiratoire) du syndrome de Pickwick. Rev Neurol 1965; 112: 56-79.Mc Gregor M.I, Block A.J, Ball W.S. Serious complications and sudden death in the Pickwickian syndrome. Johns Hopkins Med J 1970; 126-127: 279-95.Mc Gregor M.I, Block A.J, Ball W.S. Serious complications and sudden death in the Pickwickian syndrome. Johns Hopkins Med J 1970; 126-127: 279-95.Guilleminault C, Eldridge F, Dement W. Insomnia with sleep apnea: a new syndrome. Science 1973; 181: 856-8.Guilleminault C, Eldridge F, Dement W. Insomnia with sleep apnea: a new syndrome. Science 1973; 181: 856-8.Sullivan C.E, Issa F.G, Berthon-Jones M et al. Reversal of obstructive sleep apnoea by continuous positive airway pressure applied through the nares. Lancet 1981; 1 (8225): 862-5.Sullivan C.E, Issa F.G, Berthon-Jones M et al. Reversal of obstructive sleep apnoea by continuous positive airway pressure applied through the nares. Lancet 1981; 1 (8225): 862-5.Parati G, Lombardi C, Hedner J et al. Recommendations for the management of patients with obstructive sleep apnoea and hypertension Gianfranco. Eur Respir J 2013; 41: 523-38.Parati G, Lombardi C, Hedner J et al. Recommendations for the management of patients with obstructive sleep apnoea and hypertension Gianfranco. Eur Respir J 2013; 41: 523-38.Shahar E, Whitney C, Redline S et al. Sleep - disordered breathing and cardiovascular disease: cross - sectional results of the Sleep Heart Health Study. Am J Respir Crit Care Med 200; 163 (1): 19-25.Shahar E, Whitney C, Redline S et al. Sleep - disordered breathing and cardiovascular disease: cross - sectional results of the Sleep Heart Health Study. Am J Respir Crit Care Med 200; 163 (1): 19-25.Young T, Finn L, Peppard P et al. Sleep disordered breathing and mortality: eighteen - year follow - up of the Wisconsin sleep cohort. Sleep 2008; 31 (8): 1071-8.Young T, Finn L, Peppard P et al. Sleep disordered breathing and mortality: eighteen - year follow - up of the Wisconsin sleep cohort. Sleep 2008; 31 (8): 1071-8.Lee J-E, Lee C.H, Lee S.J et al. Mortality of Patients with Obstructive Sleep Apnea in Korea. J Clin Sleep Med 2013; 9 (10): 997-1002.Lee J-E, Lee C.H, Lee S.J et al. Mortality of Patients with Obstructive Sleep Apnea in Korea. J Clin Sleep Med 2013; 9 (10): 997-1002.Lavie P, Hoffstein V. Sleep apnea syndrome: a possible contributing factor to resistant hypertension. Sleep 2001; 24 (6): 721-5.Lavie P, Hoffstein V. Sleep apnea syndrome: a possible contributing factor to resistant hypertension. Sleep 2001; 24 (6): 721-5.Grote L, Hedner J, Peter J. Sleep - related breathing disorder is an independent risk factor for uncontrolled hypertension. J Hypertens 2000; 18 (6): 679-85.Grote L, Hedner J, Peter J. Sleep - related breathing disorder is an independent risk factor for uncontrolled hypertension. J Hypertens 2000; 18 (6): 679-85.Khan A, Patel N.K, O’Hearn D.J et al. Resistant Hypertension and Obstructive Sleep Apnea. Int J Hypertens 2013; 2013: Article ID 193010.Khan A, Patel N.K, O’Hearn D.J et al. Resistant Hypertension and Obstructive Sleep Apnea. Int J Hypertens 2013; 2013: Article ID 193010.Frenţ S, Tudorache V, Ardelean C et al. Sleep apnea syndrome - cause of resistance to treatment of arterial hypertension. Pneumologia 2011; 60 (4): 202-7.Frenţ S, Tudorache V, Ardelean C et al. Sleep apnea syndrome - cause of resistance to treatment of arterial hypertension. Pneumologia 2011; 60 (4): 202-7.Logan A, Perlikowski S, Mente A et al. High prevalence of unrecognized sleep apnoea in drug - resistant hypertension. J Hypertens 2001; 19 (12): 2271-7.Logan A, Perlikowski S, Mente A et al. High prevalence of unrecognized sleep apnoea in drug - resistant hypertension. J Hypertens 2001; 19 (12): 2271-7.Szyguła-Jurkiewicz B, Hudzik B, Nowak J et al. Sleep apnea syndrome in patients with chronic heart failure. Wiad Lek 2004; 57 (3-4): 161-5.Szyguła-Jurkiewicz B, Hudzik B, Nowak J et al. Sleep apnea syndrome in patients with chronic heart failure. Wiad Lek 2004; 57 (3-4): 161-5.Naughton M.T, Bradley T.D. Sleep apnea in congestive heart failure. Clin Chest Med 1998; 19 (1): 99-113.Naughton M.T, Bradley T.D. Sleep apnea in congestive heart failure. Clin Chest Med 1998; 19 (1): 99-113.Mehra R, Benjamin E.J, Shahar E et al. Association of nocturnal arrhythmias with sleep - disordered breathing: The Sleep Heart Health Study. Am J Respir Crit Care Med 2006; 173 (8): 910-6.Mehra R, Benjamin E.J, Shahar E et al. Association of nocturnal arrhythmias with sleep - disordered breathing: The Sleep Heart Health Study. Am J Respir Crit Care Med 2006; 173 (8): 910-6.Gami A.S, Pressman G, Caples S.M et al. Association of atrial fibrillation and obstructive sleep apnea. Circulation 2004; 110 (4): 364-7.Gami A.S, Pressman G, Caples S.M et al. Association of atrial fibrillation and obstructive sleep apnea. Circulation 2004; 110 (4): 364-7.Monahan K, Brewster J, Wang L et al. Relation of the severity of obstructive sleep apnea in response to anti - arrhythmic drugs in patients with atrial fibrillation or atrial flutter. Am J Cardiol 2012; 110 (3): 369-72.Monahan K, Brewster J, Wang L et al. Relation of the severity of obstructive sleep apnea in response to anti - arrhythmic drugs in patients with atrial fibrillation or atrial flutter. Am J Cardiol 2012; 110 (3): 369-72.Jennum P, Soul A. Epidemiology of snoring and obstructive sleep apnoea in the Dannish population age 30-60. J Sleep Res 1992; 1: 240-4.Jennum P, Soul A. Epidemiology of snoring and obstructive sleep apnoea in the Dannish population age 30-60. J Sleep Res 1992; 1: 240-4.Young T, Zaccaro D, Leder R et al. Prevalence and correlates of sleep disordered breathing in the Wisconsin sleep cohort study. Am Rev Respir Dis 1991; 143: A380.Young T, Zaccaro D, Leder R et al. Prevalence and correlates of sleep disordered breathing in the Wisconsin sleep cohort study. Am Rev Respir Dis 1991; 143: A380.Stradling J.R, Crosby J.H. Predictors and prevalence of obstructive sleep apnoea and snoring in 1001 middle aged men. Thorax 1991; 46 (2): 85-90.Stradling J.R, Crosby J.H. Predictors and prevalence of obstructive sleep apnoea and snoring in 1001 middle aged men. Thorax 1991; 46 (2): 85-90.Marin J.M, Gascon J.M, Carrizo S et al. Prevalence of sleep apnoea syndrome in the Spanish adult population. Int J Epidemiol 1997; 26 (2): 381-6.Marin J.M, Gascon J.M, Carrizo S et al. Prevalence of sleep apnoea syndrome in the Spanish adult population. Int J Epidemiol 1997; 26 (2): 381-6.Quintana-Gallego E, Carmona-Bernal C, Capote F et al. Gender differences in obstructive sleep apnea syndrome: a clinical study of 1166 patients. Respir Med 2004; 98: 984-9.Quintana-Gallego E, Carmona-Bernal C, Capote F et al. Gender differences in obstructive sleep apnea syndrome: a clinical study of 1166 patients. Respir Med 2004; 98: 984-9.Wild S, Roglic G, Green A et al. Global prevalence of diabetes estimates for the year 2000 and projections for 2030. Diabetes Care 2004; 27 (5): 1053.Wild S, Roglic G, Green A et al. Global prevalence of diabetes estimates for the year 2000 and projections for 2030. Diabetes Care 2004; 27 (5): 1053.Zhang W, Chen X, Ma L et al. Epidemiology of bronchial asthma and asthma control assessment in Henan Province. China Translation Respir Med 2014; 2: 5.Zhang W, Chen X, Ma L et al. Epidemiology of bronchial asthma and asthma control assessment in Henan Province. China Translation Respir Med 2014; 2: 5.Lindberg E, Elmasry A, Gislason T. Evolution of sleep apnea syndrome in sleepy snorers: a population - based prospective study. Am J Respir Crit Care Med 1999; 159 (6): 2024-7.Lindberg E, Elmasry A, Gislason T. Evolution of sleep apnea syndrome in sleepy snorers: a population - based prospective study. Am J Respir Crit Care Med 1999; 159 (6): 2024-7.Davies R.J, Stradling J.R. The epidemiology of sleep apnoea. Thorax 1996; 51 (Suppl. 2): S65-S70.Davies R.J, Stradling J.R. The epidemiology of sleep apnoea. Thorax 1996; 51 (Suppl. 2): S65-S70.Пальман А.Д. Синдром обструктивного апноэ во сне в клинике внутренних болезней. Под ред. А.И.Синопальникова. М., 2007; с. 13-5.Пальман А.Д. Синдром обструктивного апноэ во сне в клинике внутренних болезней. Под ред. А.И.Синопальникова. М., 2007; с. 13-5.Аксенова А.В., Елфимова Е.М., Галицин П.В. и др. Значение компьютерной пульсоксиметрии в практике врача - кардиолога // Системные гипертензии. 2014; 11 (4): 26-30.Аксенова А.В., Елфимова Е.М., Галицин П.В. и др. Значение компьютерной пульсоксиметрии в практике врача - кардиолога // Системные гипертензии. 2014; 11 (4): 26-30.Шахматов И.И. и др. Состояние системы гемостаза при различных видах гипоксического воздействия. Бюллетень СО РАМН. 2010; 30 (2): 131-8.Шахматов И.И. и др. Состояние системы гемостаза при различных видах гипоксического воздействия. Бюллетень СО РАМН. 2010; 30 (2): 131-8.Peng Y.H, Liao W.C, Chung W.S et al. Association between obstructive sleep apnea and deep vein thrombosis/pulmonary embolism: a population - based retrospective cohort study. Thromb Res 2014; 34: 340-5.Peng Y.H, Liao W.C, Chung W.S et al. Association between obstructive sleep apnea and deep vein thrombosis/pulmonary embolism: a population - based retrospective cohort study. Thromb Res 2014; 34: 340-5.Nobili L, Schiavi G, Bozano E et al. Morning increase of whole blood viscosity in obstructive sleep apnea syndrome. Clin Hemorheol Microcirc 2000; 22 (1): 21-7.Nobili L, Schiavi G, Bozano E et al. Morning increase of whole blood viscosity in obstructive sleep apnea syndrome. Clin Hemorheol Microcirc 2000; 22 (1): 21-7.Steiner S, Jax T, Evers S et al. Altered blood rheology in obstructive sleep apnea as a mediator of cardiovascular risk. Cardiology 2005; 104 (2): 92-6.Steiner S, Jax T, Evers S et al. Altered blood rheology in obstructive sleep apnea as a mediator of cardiovascular risk. Cardiology 2005; 104 (2): 92-6.Dikmenoğlu N, Ciftçi B, Ileri E et al. Erythrocyte deformability, plasma viscosity and oxidative status in patients with severe obstructive sleep apnea syndrome. Sleep Med 2006; 7 (3): 255-61.Dikmenoğlu N, Ciftçi B, Ileri E et al. Erythrocyte deformability, plasma viscosity and oxidative status in patients with severe obstructive sleep apnea syndrome. Sleep Med 2006; 7 (3): 255-61.Robinson G.V, Pepperell J.C, Segal H.C et al. Circulating cardiovascular risk factors in obstructive sleep apnoea: data from randomised controlled trials. Thorax 2004; 59 (9): 777-82.Robinson G.V, Pepperell J.C, Segal H.C et al. Circulating cardiovascular risk factors in obstructive sleep apnoea: data from randomised controlled trials. Thorax 2004; 59 (9): 777-82.Wessendorf T.E, Thilmann A.F, Wang Y.M et al. Fibrinogen levels and obstructive sleep apnea in ischemic stroke. Am J Respir Crit Care Med 2000; 162 (6): 2039-42.Wessendorf T.E, Thilmann A.F, Wang Y.M et al. Fibrinogen levels and obstructive sleep apnea in ischemic stroke. Am J Respir Crit Care Med 2000; 162 (6): 2039-42.Hayashi M, Fujimoto K, Urushibata K et al. Respirology. Hypoxia - sensitive molecules may modulate the development of atherosclerosis in sleep apnoea syndrome. Respirology 2006; 11 (1): 24-31.Hayashi M, Fujimoto K, Urushibata K et al. Respirology. Hypoxia - sensitive molecules may modulate the development of atherosclerosis in sleep apnoea syndrome. Respirology 2006; 11 (1): 24-31.Shimizu M, Kamio K, Haida M et al. Platelet activation in patients with obstructive sleep apnea syndrome and effects of nasal - continuous positive airway pressure. Tokai J Exp Clin Med 2002; 27 (4): 107-12.Shimizu M, Kamio K, Haida M et al. Platelet activation in patients with obstructive sleep apnea syndrome and effects of nasal - continuous positive airway pressure. Tokai J Exp Clin Med 2002; 27 (4): 107-12.Geiser T, Buck F, Meyer B et al. In vivo platelet activation is increased during sleep in patients with obstructive sleep apnea syndrome. Respiration 2002; 69 (3): 229-34.Geiser T, Buck F, Meyer B et al. In vivo platelet activation is increased during sleep in patients with obstructive sleep apnea syndrome. Respiration 2002; 69 (3): 229-34.El Solh A.A, Akinnusi M.E, Berim I.G et al. Hemostatic implications of endothelial cell apoptosis in obstructive sleep apnea. Sleep Breath 2008; 12 (4): 331-7.El Solh A.A, Akinnusi M.E, Berim I.G et al. Hemostatic implications of endothelial cell apoptosis in obstructive sleep apnea. Sleep Breath 2008; 12 (4): 331-7.Shitrit D, Peled N et al. An association between oxygen desaturation and D-dimer in patients with obstructive sleep apnea syndrome. Thromb Haemost 2005; 94 (3): 544-7.Shitrit D, Peled N et al. An association between oxygen desaturation and D-dimer in patients with obstructive sleep apnea syndrome. Thromb Haemost 2005; 94 (3): 544-7.Ishikawa J, Hoshide S, Eguchi K et al. Increased low - grade inflammation and plasminogen - activator inhibitor-1 level in nondippers with sleep apnea syndrome. J Hypertens 2008; 26 (6): 1181-7.Ishikawa J, Hoshide S, Eguchi K et al. Increased low - grade inflammation and plasminogen - activator inhibitor-1 level in nondippers with sleep apnea syndrome. J Hypertens 2008; 26 (6): 1181-7.Zamarrón C, Ricoy J, Riveiro A et al. Plasminogen activator inhibitor-1 in obstructive sleep apnea patients with and without hypertension. Lung 2008; 186 (3): 151-6.Zamarrón C, Ricoy J, Riveiro A et al. Plasminogen activator inhibitor-1 in obstructive sleep apnea patients with and without hypertension. Lung 2008; 186 (3): 151-6.Tazbirek M, Slowinska L, Skoczynski S et al. Short - term continuous positive airway pressure therapy reverses the pathological influence of obstructive sleep apnea on blood rheology parameters. Clin Hemorheol Microcirc 2009; 41 (4): 241-9.Tazbirek M, Slowinska L, Skoczynski S et al. Short - term continuous positive airway pressure therapy reverses the pathological influence of obstructive sleep apnea on blood rheology parameters. Clin Hemorheol Microcirc 2009; 41 (4): 241-9.Hui D.S, Ko F.W, Fok J.P et al. The effects of nasal continuous positive airway pressure on platelet activation in obstructive sleep apnea syndrome. Chest 2004; 125 (5): 1768-75.Hui D.S, Ko F.W, Fok J.P et al. The effects of nasal continuous positive airway pressure on platelet activation in obstructive sleep apnea syndrome. Chest 2004; 125 (5): 1768-75.Akinnusi M.E, Paasch L.L, Szarpa K.R et al. Impact of nasal continuous positive airway pressure therapy on markers of platelet activation in patients with obstructive sleep apnea. Respiration 2009; 77 (1): 25-31.Akinnusi M.E, Paasch L.L, Szarpa K.R et al. Impact of nasal continuous positive airway pressure therapy on markers of platelet activation in patients with obstructive sleep apnea. Respiration 2009; 77 (1): 25-31.Zhang X, Yin K, Wang H et al. Effect of continuous positive airway pressure treatment on elderly Chinese patients with obstructive sleep apnea in the prethrombotic state. Chin Med J (Engl) 2003; 116 (9): 1426-8.Zhang X, Yin K, Wang H et al. Effect of continuous positive airway pressure treatment on elderly Chinese patients with obstructive sleep apnea in the prethrombotic state. Chin Med J (Engl) 2003; 116 (9): 1426-8.von Känel R, Loredo J, Ancoli-Israel S et al. Association between sleep apnea severity and blood coagulability: Treatment effects of nasal continuous positive airway pressure. Sleep Breath 2006; 10 (3): 139-46.von Känel R, Loredo J, Ancoli-Israel S et al. Association between sleep apnea severity and blood coagulability: Treatment effects of nasal continuous positive airway pressure. Sleep Breath 2006; 10 (3): 139-46.Parati G, Lombardi C, Hedner J et al. Recommendations for the management of patients with obstructive sleep apnoea and hypertension. Eur Respir J 2013; 41: 523-38.Parati G, Lombardi C, Hedner J et al. Recommendations for the management of patients with obstructive sleep apnoea and hypertension. Eur Respir J 2013; 41: 523-38.Агеева Н.В. Состояние периферической гемодинамики, микроциркуляции и реологических свойств крови у больных семейной гиперхолестеринемией при медикаментозном и экстракорпоральном методах лечения. Автореф. дис. … канд. мед. наук. М., 1998.Агеева Н.В. Состояние периферической гемодинамики, микроциркуляции и реологических свойств крови у больных семейной гиперхолестеринемией при медикаментозном и экстракорпоральном методах лечения. Автореф. дис. … канд. мед. наук. М., 1998.Zubieta-Calleja G.R, Paulev P.E, Zubieta-Calleja L et al. Altitude adaptation through hematocrit changes. J Physiol Pharmacol 2007.Zubieta-Calleja G.R, Paulev P.E, Zubieta-Calleja L et al. Altitude adaptation through hematocrit changes. J Physiol Pharmacol 2007.

The authors declare that there are no conflicts of interest present.