exercise at high altitude : adaptation of oxygen
TRANSCRIPT
EXERCISE AT HIGH ALTITUDE :ADAPTATION OF OXYGEN TRANSPORT
FROM AIR TO MITOCHONDRIA
Jean COUDERT
Laboratoire de Physiologie – Biologie du SportFaculté de Médecine – Université d’AuvergneCLERMONT-FERRAND, FRANCE
HA ↓ PB ↓ PIO2
PIO2 = PB x 0.2093
Exercise ↑ VO2•
↓ SaO2 ↓ CaO2↓ PaO2 (Hypobaric hypoxia)
! Adaptative responses of the respiratory system
The respiratory system
The oxygen cascade
From Rahn H., 1966
Tissues
Mitochondria
vSL
HA
aA
SL
HA(5500m)
IPO2 (mmHg)
From Pugh et al, 1964
Relationship between VEBTPS and VSTPD and VO2•••
S.L.4600 m5800 m6400 m7400 m
Cardiovascular adaptative responses
VO2 =• Qc ( CaO2 – CvO2)
•
Qc = Qs x HR •
Exercise ↑ VO2•
! In Non-Acclimatized Lowlanders (NALL)
! In Acclimatized LL (ALL) and Highlanders (HL)
" ↓ CaO2 ↑ Qc•
(↑HR)
" CaO2, Qc and HR•
to sea-level values
Cardiac responses during acute hypoxiaand after acclimatization
(4000m) (5800m)ACUTE HYPOXIA ACCLIMATIZED SUBJECT
VO2 (l.min-1)•
Qc (l.min-1)•
HR(b.min-1)
HR max(hyp+norm)
HR (norm max)
HR max(hyp+norm)
From Cerretelli P., PUF edition, 1988
Hematological responses
! Quantitative aspect :
" ↑ of the carrying capacity of the blood
! Qualitative aspect :
" alteration of the oxygen affinity of hemoglobin
# ↑ of the carrying capacity of the blood at HA
↓ PO2 ↑ erythropoietin ↑ erythropoiesis
! ↑ red cell mass
! ↑[Hb] and Hb mass
! ↑ Ht
↑ Oxygen content of arterial blood in an acclimatized subject at 5300 m and at sea level
From Ward M.P. et al, 1989
From Pugh, 1964
Delay between : ↑ erythropoietin and ↑ red cell mass
Days
From Richalet J.P. et al , Science et Sport, 1999
Red cell volume
EPO
From Milledge and Coates,1985
Hematological responses and ethnic differences
From Ward M.P. et al, 1989
↓ Oxygen affinity of haemoglobin at HA ( ↑P50 )
From Hurtado, 1964
Evolution of oxygen affinity of Hb, in LL in LA PAZ (3700m)
From Coudert J. et al, Bull. Soc. Ecophysio., 1977
0.36 ± 0.020.35 ± 0.020.28 ± 0.020.23 ± 0.02ATPmol/mol Hb
1.12 ± 0.081.08 ± 0.040.90 ± 0.050.73 ± 0.052-3DPGmol/mol Hb
29.0 ± 0.528.4 ± 1.028.5 ± 0.826.8 ± 0.9P50 mm Hg
17.9 ± 1.117.6 ± 0.818.1 ± 1.116.8 ± 0.9Hb g/dl
50.6 ± 2.948.6 ± 2.150.0 ± 2.646.7 ± 2.6Ht %
J12J5J2J0
↑Oxygen affinity of Hb (↓ P50 ) at very high altitude, specially on exercise
From Bencowitz et al, 1982
! enhances the loading of O2 in the lung
Concept of optimum haemoglobin concentration at HA and exercise
! Problem of viscosity, when [Hb] and [Ht] are too high
# ↓ cardiac output
# ↑ of arterial pressures (pulmonary and systemic)
# risk of thrombosis
From Winslow and Monge, 1987
optimal values [Hb]18g / dl ? Ht ?
Transport from tissues to mitochondria : classical concepts
Interaction between exercise and high altitude hypoxia
Transport from tissues to mitochondria : new concepts
↓ Cellular PO2 (2-4 mmHg)
during muscular exercise stimulating adaptative responses
# ↑ of PO2 gradient between red cells and mitochondria
# Interaction with myoglobin (P50 ≈ 5 mmHg)
# Stimulation of vascular endothelial Growth Factor (VEGF)
(induction by accumulation of HIF-1α in muscle cells)
HIF-1 α + β
Hémoprotéine oxygène Sensor O2
Hémoprotéine oxygène SensorO2 O2
Phosphorylation des protéines
Factor X
VOIES DE REPONSES A L’HYPOXIE, INDUITES PAR HIF-1
Métabolismeanaérobie
Induction des gènes desenzymes de la glycolyse
Induction du géne dela tyrosine hydroxylase
Induction dugène EPO
Induction dugène vEGF
Angiogénèse Vasodilatation Erythropoïèse Respirationaugmentée
Induction des gènesI-NOS et HO-1
From Coudert J., Urgence pratique, 66, 2004
Comparison of the oxygen dissociation curves for normal human (curve A)and myoglobin (curve B). The P50 values are approximately 27 and 5 mmHg(3.6 and 0.7 Ka) respectively.
Myoglobin
Normal human blood
% Saturation
Oxygen pressure (mmHg)
A
B
50
275
Cellular hypoxia and ↑ of reactive O2 species (ROS)
" Hypoxia induced by exercise ?
" Stimulation of angiogenesis ?Independently of the HIF pathway
# Possibilities actively investigated at present time