NormoNormo-- vs. vs. hypobarichypobarichypoxiahypoxia. . IsIs lipidlipid

peroxidationperoxidation involvedinvolved ??

ClausClaus BehnBehn

HAPPOM, ALFAHAPPOM, ALFALima 260607Lima 260607

0 25 50 75 10070

80

90

100

r = 0,15p = 0,78

SDNN (ms) hipoxia normobárica

SatO

2 re

poso

(%)

hipo

xia

norm

obár

ica

a) b)

0 25 50 75 10070

80

90

100

r = 0,77p < 0,05

SDNN (ms) hipoxia hipobárica

Sat O

2 re

poso

(%)

hipo

xia

hipo

bári

ca

BasualtoBasualto, 2007, 2007

lowerlower!! PaCOPaCO22 (P = 0.005) (P = 0.005) andand

higherhigher!! pHpH (P = 0.02) (P = 0.02)

Savourey et al., (2007) Eur J Appl Physiol 100 : 193-205

HypobaricHypobaric hypoxiahypoxia as as comparedcompared toto normobaricnormobaric hypoxiahypoxia

NH

CollahuasiCollahuasi

15

20

25

30

35

40

45

50**

**

**

*pCO

2 (m

mH

g)

pre HA post HA pre SL post SL

PrePre-- andand postexercisepostexercise capillarycapillary bloodbloodPCOPCO22 atat highhigh altitudealtitude (HA) (HA) andand sea sea levellevel(SL)(SL) n =16, p< 0,05*; 0,01**; 0,001*** Jiménez et al, n =16, p< 0,05*; 0,01**; 0,001*** Jiménez et al,

20002000

16

18

20

22

24

26

28

preHA post HA pre SL post SL

*

*****

Extr

acel

lula

r HC

O3- (m

mol

/L)

PrePre-- andand postexercisepostexercise extracellularextracellular [HCO[HCO33] ] atat highhigh altitudealtitude (HA) (HA) andand sea sea levellevel (SL)(SL)

n =16, p< 0,05*; 0,01**; 0,001*** Jiménez et al, 2000n =16, p< 0,05*; 0,01**; 0,001*** Jiménez et al, 2000

7,35

7,40

7,45

7,50

7,55

**

***B

lood

pH

pre HA post HA pre SL post SL

PrePre-- andand postexercisepostexercise capillarycapillary bloodblood pHpH atat highhigh altitudealtitude (HA) (HA) andand sea sea levellevel (SL)(SL)

n =16, p< 0,05*; 0,01**; 0,001*** Jiménez et al., 2000n =16, p< 0,05*; 0,01**; 0,001*** Jiménez et al., 2000

.

-18 -16 -14 -12 -10

50

52

54

56

58

60

62

64

66

68

Cajigal et al., 2002

r = 0.75p < 0.005

Capi

llary

PO 2 (

mm

Hg)

Base excess (mmol/l)

Santiago I (670 m)Santiago I (670 m) Santiago IISantiago II

CalamaCalama I(2500 m)I(2500 m) CalamaCalama IIII

ConchiConchi (3000 m)(3000 m)

Volcán San Pedro (6125 m)Volcán San Pedro (6125 m)

CampCamp. Base (5000 m). Base (5000 m)

B

E

D

C

A

B

A: MascarillaB: Válvula UnidireccionalC: Calefactor EléctricoD: VialE: Cubeta con hielo

LIPID PEROXIDATION FORMING MDALIPID PEROXIDATION FORMING MDA

Santiago I Calama I Conchi Calama II Santiago II0,00

0,02

0,04

0,06

0,08

0,10

0,12

0,14

0,16

0,18

**m

oles

/Litr

o)(

MD

Aμ

AranedaAraneda et al., 2005et al., 2005

-0,04 0,00 0,04 0,08 0,12 0,16

0

2

4

6

8

10

(Conchi-SantiagoI)

(Cam

p. B

ase)

AM

S S

core

Δ MDA

AranedaAraneda et al., 2005et al., 2005

HypocapniaHypocapnia

BarometricBarometric pressurepressure + + VentilationVentilation

OO22deliverydelivery

OO22demanddemand

HypobaricHypobaric hypoxiahypoxia

CaruanaCaruana--Montaldo, B. et al. (2000) Chest 117:205Montaldo, B. et al. (2000) Chest 117:205--225225

ROSROS

LPLP

NFNFκκBB

InflammationInflammation

HypoxiaHypoxia HypocapniaHypocapniaATPATP

HypocapniaHypocapnia ((PaCO2PaCO2 = 11= 11--15 15 mmHgmmHg) ) resultsresults intointo increasedincreased-- propro--apoptoticapoptotic proteinprotein BaxBax expressionexpression, , -- DNA DNA fragmentationfragmentation, , andand-- membranemembrane lipidlipid peroxidationperoxidation in in mitochondriamitochondria ofof cerebral cortical cerebral cortical neuronsneurons ofof newbornnewborn pigletspiglets, , andand may may resultresult in in apoptoticapoptotic cellcell deathdeath. .

Lasso Lasso PirotPirot et al., 2007,et al., 2007, NeonatologyNeonatology 91: 2091: 20--2727

HypocapniaHypocapnia

OO22deliverydelivery

OO22demanddemand

ATPATP

BarometricBarometric pressurepressure + + VentilationVentilation

Pluim et al. (1999) Heart 81: 612-617

0 25 50 75 10070

80

90

100

r = 0,15p = 0,78

SDNN (ms) hipoxia normobárica

SatO

2 re

poso

(%)

hipo

xia

norm

obár

ica

a) b)

0 25 50 75 10070

80

90

100

r = 0,77p < 0,05

SDNN (ms) hipoxia hipobárica

Sat O

2 re

poso

(%)

hipo

xia

hipo

bári

ca

BasualtoBasualto, 2007, 2007

!! AtAt similar similar decreasedecrease in in oxygenoxygen supplysupply, , hypobarichypobaric hypoxiahypoxia (HH) (HH) leadsleads toto a more a more pronouncedpronounced hypocapniahypocapnia thanthan normobaricnormobarichypoxiahypoxia (NH)(NH)

!! HypocapniaHypocapnia may may increaseincrease ATP ATP demanddemand, , andand, , thusthus, , intensifyintensify hypoxiahypoxia, by , by promotingpromoting oxidativeoxidative stressstress-- mediatedmediatedlipidlipid peroxidationperoxidation

!! AtAt similar similar decreasedecrease in in oxygenoxygen supplysupply, , hypoxiahypoxia andand correspondingcorresponding lacklack ofofenergyenergy, , willwill be more be more severesevere atat HH HH thanthanatat NH NH

!! DecreasedDecreased energyenergy availabilityavailability, , atat HH as HH as comparedcompared toto NH, can NH, can expressexpress as as changeschangesin in heartheart raterate variabilityvariability correlationscorrelations