EPO Modulation in a 14-Days Undersea Scuba Dive

Abstract

Erythropoiesis is affected during deep saturation dives. The mechanism should be related to a downregulation of serum Erythropoietin (s-EPO) concentration or to a toxic effect of the hyperbaric hyperoxia. We evaluated s-EPO and other haematological parameters in 6 scuba divers before, during and after a 14-days guinness saturation dive (8–10 m). Athletes were breathing air at 1.8–2 ATA, under the control of a team of physicians. Serum parameters were measured before diving (T0) and: 7 days (T1), 14 days (T2) after the beginning of the dive and 2 h (T3) and 24 h (T4) after resurfacing. Hgb, and many other haematological parameters did not change whereas Ht, s-EPO, the ratio between s-EPO predicted and that observed and reticulocytes (absolute, percent) declined progressively from T0 to T3. At T4 a significant rise in s-EPO was observed. Hgb did not vary but erythropoiesis seemed to be affected as s-EPO and reticulocyte counts showed. All these changes were statistically significant. The experiment, conducted in realistic conditions of dive length, oxygen concentration and pressure, allows us to formulate some hypotheses about the role of prolonged hyperbarism on erythropoiesis. The s-EPO rise, 24 h after resurfacing, is clearly documented and related to the “Normobaric Oxygen Paradox”. This evidence suggests interesting hypotheses for new clinical applications such as modulation of s-EPO production and Hgb content triggered by appropriate O₂ administration in pre-surgical patients or in some anemic disease.

Key words

erythropoietin (EPO) - hyperbarism - hyperoxia - reactive oxygen species (ROS) - normobaric oxygen paradox (NOP) - diving - scuba dive - free radicals

• References

• 1 Balestra C, Germonprè P, Poortmans JR, Marroni A. Serum erythropoietin levels in healthy humans after a short period of normobaric and hyperbaric oxygen breathing: the normobaric oxygen paradox. J Appl Physiol 2006; 100: 512-518
• 2 Balestra C, Germonpré P. Increasing EPO using the normobaric oxygen paradox: a ‘not so simple’ task. Acta Physiol (Oxf) 2011; 203: 287-288
• 3 Balestra C, Germonpré P. Hypoxia, a multifaceted phenomenon: the example of the “Normobaric Oxygen Paradox”. Eur J Appl Physiol Mar 2012; 31 [Epub ahead of print]
• 4 Beguin Y, Clemoins GK, Pootrakul P, Fillet G. Quantitative assessment of erythropoietin and functional classification of anemia based on measurements of serum transferrin receptor and erythropoietin. Blood 1993; 81: 1067-1076
• 5 Benedetti S, Lamorgese A, Piersantelli M, Pagliaroni S, Benvenuti F, Canestrari F. Oxidative stress and antioxidant status in patients undergoing prolonged exposure to hyperbaric oxygen. Clin Biochem 2004; 37: 312-317
• 6 Burk R. Oxygen breathing may be a cheaper and safer alternative to exogenous erythropoietin. Med Hypotheses 2007; 69: 1200-1204
• 7 Christoulas K, Karamouzis M, Mandroukas K. “Living high-training low” vs. “living high-training high”: erythropoietic responses and performance of adolescent cross-country skiers. J Sports Med Phys Fitness 2011; 51: 74-81
• 8 Ciccarella Y, Balestra C, Valsamis J, Van der Linden P. Increase in endogenous erythropoietin synthesis through the normobaric oxygen paradox in cardiac surgery patients. Br J Anaesth 2011; 106: 752-753
• 9 Clement MV, Ponton A, Pervaiz S. Apoptosis induced by hydrogen peroxide is mediated by decreased superoxide anion concentration and reduction of intracellular milieu. FEBS Lett 1998; 440: 13-18
• 10 De Bels D, Corazza F, Germonpre P, Balestra C. The normobaric oxygen paradox: a novel way to administer oxygen as an adjuvant treatment for cancer?. Med Hypotheses 2011; 76: 467-470
• 11 De Bels D, Corazza F, Balestra C. Oxygen sensing, homeostasis, and disease. N Engl J Med Nov 10 2011; 365: 1845 author reply 1846
• 12 Debevec T, Keramidas ME, Norman B, Gustafsson T, Eiken O, Mekjavic IB. Acute short-term hyperoxia followed by mild hypoxia does not increase EPO production: resolving the “normobaric oxygen paradox”. Eur J Appl Physiol 2012; 112: 1059-1065
• 13 Embury SH, Garcia JF, Mohandas N, Pennathur-Das R, Clark MR. Effects of oxygen inhalation on endogenous erythropoietin kinetics, erythropoiesis, and properties of blood cells in sickle-cell anemia. N Engl J Med 1984; 311: 291-295
• 14 Ganguly BJ, Tonomura N, Benson RM, Osborne BA, Grenowits EV. Hyperbaric oxygen enhances apoptosis in hematopoietic cells. Apoptosis 2002; 7: 499-510
• 15 Gilman SC, Hunter WL, Mooney LW. Changes in serum ferritin and other factors associated with iron metabolism during chronic hyperbaric exposure. Aviat Space Environ Med 1979; 50: 223-226
• 16 Gilman SC, Biersner RJ, Piantadosi C. Serum ferritin increases during deep saturation dives. Aviat Space Environ Med 1982; 53: 1014-1016
• 17 Haddad JJ. Oxygen-sensing mechanisms and the regulation of redox-responsive transcription factors in development and pathophysiology. Respir Res 2002; 3: 26
• 18 Harriss DJ, Atkinson G. Update – ethical standards in sport and exercise science research. Int J Sports Med 2011; 32: 819-821
• 19 Hofso D, Ulvik RJ, Segadal K, Hope A. Changes in erythropoietin and hemoglobin concentrations in response to saturation diving. Eur J Appl Physiol 2005; 95: 191-196
• 20 Ikeda K, Kajiwara K, Tanabe E, Tokumaru S, Kishida E, Masuzawa Y. Involvement of hydrogen peroxide and hydroxyl radical in chemically induced apoptosis of HL-60 cells. Biochem Pharmacol 1999; 57: 1361-1365
• 21 Jaskunas SR, Stork EJ, Richardson B. Effects of a hyperoxic environment on erythropoietin production. Aerospace Med 1973; 44: 1112-1116
• 22 Jelkmann W. Molecular biology of erythropoietin. Int Med 2004; 43: 649-659
• 23 Kaplan SM, Piliero SJ, Gordon AS, Meagher R. Mechanisms underlying the suppression of erythropoiesis by hyperoxia. Am J Med Sci 1977; 273: 71-77
• 24 Keramidas ME, Kounalakis SN, Debevec T, Norman B, Gustafsson T, Eiken O, Mekjavic IB. Acute normobaric hyperoxia transiently attenuates plasma erythropoietin concentration in healthy males: evidence against the ‘normobaric oxygen paradox’ theory. Acta Physiol (Oxf) 2011; 202: 91-98
• 25 Koury MJ, Bondurant MC. The molecular mechanism of erythropoietin action. Eur J Biochem 1992; 210: 649-663
• 26 Martinez-Bello VE, Sanchis-Gomar F, Nascimento AL, Pallardo FV, Ibanez-Sania S, Olaso-Gonzalez G, Calbet JA, Gomez-Cabrera MC, Vina J. Living at high altitude in combination with sea-level sprint training increases hematological parameters but does not improve performance in rats. Eur J Appl Physiol 2011; 111: 1147-1156
• 27 Nakabayashi K, Mizukami H, Hashimoto A, Oiwa H. Change in red cell production rate during a 330 msw saturation dive simulation. Undersea Biomed Res 1991; 18 (suppl) 32
• 28 Puiu A, Giubileo G, Addolorato G, Revelli L, Gasbarrini G, Bellantone R, D’Amore A, Lombardi CP, Carrozza C. Stress monitoring in a Guinness 10-days scuba dive. Laser Physics 2007; 17: 448-452
• 29 Revelli L, Addolorato G, D’Amore A, Carrozza C, Giubileo G, Puiu A, Lombardi CP, Bellantone R, Gasbarrini G. Progetto Abissi 2005 Dive Medical Group. Neuroendocrine and psychological assessment in a Guinness 10 days scuba dive. Int J Sports Med 2007; 28: 1-5
• 30 Revelli L, D’Alatri L, Scorpecci A, D’Amore A, De Corso E, Lombardi CP, Fetoni AR. ENT Function in a 14-Days Guinness scuba dive. Int J Sports Med 2012; 33: 31-35
• 31 Smith SM, Davis-Street JE, Fesperman Jv, Smith MD, Rice BL, Zwart SR. Nutritional status changes in humans during a 14-day saturation dive: the NEEMO V project. J Nutr 2004; 134: 1765-1771
• 32 Thorsen E, Haave H, Hofso D, Ulvik J. Exposure to hyperoxia in diving and hyperbaric medicine-effects on blood cell counts and serum ferritin. Undersea Hyperb Med 2001; 28: 19-23
• 33 Tsangaris H, Pneumatikos J, Sdranis J, Frangides C, Nakos G. The effect of hyperoxemia on erythropoietin secretion in anaemic patients. Monaldi Arch Chest Dis 1999; 54: 120-125
• 34 Witenberg B, Kalir HH, Raviv Z, Kletter Y, Kravtsov V, Fabian I. Inhibition by ascorbic acid of apoptosis induced by oxidative stress in HL-60 myeloid leukemia cells. Biochem Pharmacol 1999; 57: 823-832
• 35 Zembron-Lacny A, Slowinska-Lisowska M, Szygula Z, Witkowski Z, Szyszka K. Modulatory effect of N-acetylcysteine on pro-antioxidant status and haematological response in healthy men. J Physiol Biochem 2010; 66: 15-21
• 36 Zwart SR, Kala C, Smith SM. Body iron stores and oxidative damage in humans increased during and after a 10- to 12-day undersea dive. J Nutr 2009; 139: 90-95