Methaemoglobin in Man Living at High Altitude D. GOURDIN, H. VERGNES AND N . GUTIEREZ Iigstitiito Boliviano dc Biologiu de A l f u r a , La Pax, Bolivia, a d Ceritrc d ’ H i m y p o l o g i e dii C.N.R.S.X.H. U. dc, Pirryarr, Toiiloirsc, Fraiice (Received 17 Jaiiiiary 1974; u c c e p t c d f h pirblicatiori
10 M a y
1974)
SUMMARY. Metliaemoglobin has bccii found in the red cells of subjects living permanently at high altitudes (above 3500 in). Tlic Icvel of nietliaeinoglobiii appcared to be iiivcrsely relatcd to tlic red cclt count and was iiiucIi increased in anaemic subjects. The mctliacnioglobinacniia disappeared wlicii thc subjects descended to low altitude. Tlie ~iicchanisiiiof this nietliacii~oglobinaciiiia is not clear. Its presence appears to be relatcd to the liypoxia of altitude, for toxic factors, eiizymopenia and tlic prcsciicc of liacnioglobin M were elirninatcd. Tlic regulation of the oxygen dissociation curve in this condition is discussed. During recent years it has bccomc apparent that one of tlie functions of red ccll mctabolisni is to provide reducing potciitial in ordcr to protect tlie cell against oxidation. In thc cvciit of soine hereditary red-cell anoinaly, as for example NADH-linked metliaemoglobin rcductase deficiency, this reducing potcntial is not adequatcly utilized and mctliac~iioglobin accumulates in tlie ccll. In the present report a study has been made of huiiiaii subjects liviiig at high altitude in the Bolivian and Peruvian Andes. Under tlic coiiditions of low oxygen tciision which obtain thcrc, and despite apparently normal inctabolisiii of tlie red cells, it is shown that mcthacnioglobin lcvels are abnormally high. METHODS
Haemglobin was dctcriiiiiied by the method of Drabkin & Austin (1935). Methaenloglobin was measured using tlic proccdurc of Evelyn & Malloy (1938). Mctliaciiioglobin rcductioii was followcd by the method of Brcwcr ct a1 (1960, 1962). NADH-liizked nzethucnioglobiri redi4ctase activity was assayed according to Hegesh e f a1 (1968). Elcctrophoresis of this enz);inc was carried out as described by Harris ct a1 (1968). RESULTS Tlie first group studicd comprised 208 Quechua adults of both sexes living in tlie Aiidiiic vallcys (altitude c 3 500 in) south of Huancayo in central Peru. This group is representative of two prc-Inca districts, namely Asto aiid Chunku. The results of the haemoglobin and nietliacmoglobiii determinations are shown in Fig I and Table I. It inay be seen that within thc Corrcspoiidciicc: Dr D. Gourdin, Ccntrc d’Htmotypologic du C.N.R.S.-C.H.U. dc Purpan, Aveiiuc dc Gratide Brctagiic, 3 I 300 TOU~OL~SC, Francc.
243
Subjects and residence
Quechua, Peru (3500 rn) No. of subjects Av. Hi (%) SE
Polycythaemic subjects (Hb>21 g/dl blood)
t test
Normal subjects (Hb 14-21 g/dl blood)
t test
185
I
22
5.31
P
10 M a y
1974)
SUMMARY. Metliaemoglobin has bccii found in the red cells of subjects living permanently at high altitudes (above 3500 in). Tlic Icvel of nietliaeinoglobiii appcared to be iiivcrsely relatcd to tlic red cclt count and was iiiucIi increased in anaemic subjects. The mctliacnioglobinacniia disappeared wlicii thc subjects descended to low altitude. Tlie ~iicchanisiiiof this nietliacii~oglobinaciiiia is not clear. Its presence appears to be relatcd to the liypoxia of altitude, for toxic factors, eiizymopenia and tlic prcsciicc of liacnioglobin M were elirninatcd. Tlic regulation of the oxygen dissociation curve in this condition is discussed. During recent years it has bccomc apparent that one of tlie functions of red ccll mctabolisni is to provide reducing potciitial in ordcr to protect tlie cell against oxidation. In thc cvciit of soine hereditary red-cell anoinaly, as for example NADH-linked metliaemoglobin rcductase deficiency, this reducing potcntial is not adequatcly utilized and mctliac~iioglobin accumulates in tlie ccll. In the present report a study has been made of huiiiaii subjects liviiig at high altitude in the Bolivian and Peruvian Andes. Under tlic coiiditions of low oxygen tciision which obtain thcrc, and despite apparently normal inctabolisiii of tlie red cells, it is shown that mcthacnioglobin lcvels are abnormally high. METHODS
Haemglobin was dctcriiiiiied by the method of Drabkin & Austin (1935). Methaenloglobin was measured using tlic proccdurc of Evelyn & Malloy (1938). Mctliaciiioglobin rcductioii was followcd by the method of Brcwcr ct a1 (1960, 1962). NADH-liizked nzethucnioglobiri redi4ctase activity was assayed according to Hegesh e f a1 (1968). Elcctrophoresis of this enz);inc was carried out as described by Harris ct a1 (1968). RESULTS Tlie first group studicd comprised 208 Quechua adults of both sexes living in tlie Aiidiiic vallcys (altitude c 3 500 in) south of Huancayo in central Peru. This group is representative of two prc-Inca districts, namely Asto aiid Chunku. The results of the haemoglobin and nietliacmoglobiii determinations are shown in Fig I and Table I. It inay be seen that within thc Corrcspoiidciicc: Dr D. Gourdin, Ccntrc d’Htmotypologic du C.N.R.S.-C.H.U. dc Purpan, Aveiiuc dc Gratide Brctagiic, 3 I 300 TOU~OL~SC, Francc.
243
Subjects and residence
Quechua, Peru (3500 rn) No. of subjects Av. Hi (%) SE
Polycythaemic subjects (Hb>21 g/dl blood)
t test
Normal subjects (Hb 14-21 g/dl blood)
t test
185
I
22
5.31
P
