Greater uterine artery blood flow during pregnancy in multigenerational (Andean) than shorter-term (European) high-altitude residents

Multigenerational (Andean) compared with shorter-term (European) high-altitude residents exhibit less hypoxia-associated reductions in birth weight. Because differences in arterial O(2) content are not responsible, we asked whether greater pregnancy-associated increases in uterine artery (UA) blood flow and O(2) delivery were involved. Serial studies were conducted in 42 Andean and 26 European residents of La Paz, Bolivia (3600 m) at weeks 20, 30, 36 of pregnancy and 4 mo postpartum using Doppler ultrasound. There were no differences postpartum but Andean vs. European women had greater UA diameter (0.65 +/- 0.01 vs. 0.56 +/- 0.01 cm), cross-sectional area (33.1 +/- 0.97 vs. 24.7 +/- 1.18 mm(2)), and blood flow at week 36 (743 +/- 87 vs. 474 +/- 36 ml/min) (all P < 0.05) and thus 1.6-fold greater uteroplacental O(2) delivery near term (126.82 +/- 18.47 vs. 80.33 +/- 8.69 ml O(2).ml blood(-1).min(-1), P < 0.05). Andeans had greater common iliac (CI) flow and lower external iliac relative to CI flow (0.52 +/- 0.11 vs. 0.95 +/- 0.14, P < 0.05) than Europeans at week 36. After adjusting for gestational age, maternal height, and parity, Andean babies weighed 209 g more than the Europeans. Greater UA cross-sectional area at week 30 related positively to birth weight in Andeans (r = +0.39) but negatively in Europeans (r = -0.37) (both P < 0.01). We concluded that a greater pregnancy-associated increase in UA diameter raised UA blood flow and uteroplacental O(2) delivery in the Andeans and contributed to their ability to maintain normal fetal growth under conditions of high-altitude hypoxia. These data implicate the involvement of genetic factors in protecting multigenerational populations from hypoxia-associated reductions in fetal growth, but future studies are required for confirmation and identification of the specific genes involved.     

Effect of altitude on the lung function of high altitude residents of European ancestry

The forced vital capacity (FVC), forced expiratory volume in one second (FEV), and ratio of FEV to FVC (%FEV) of 161 male and 158 female youths of European ancestry who were born at high altitudes and who were residing in La Paz, Bolivia (average altitude of 3,600 m) were examined and compared with those for lowland Europeans and highland Aymara Amerindians. FVC and FEV were significantly larger (p less than .001) in the La Paz Europeans than in two lowland control samples of European ancestry, with the relative differences between samples varying from small (1.5-4.1%) to moderate (7.7-11.9%). It could not be determined whether the enhanced lung volumes of the La Paz European children were acquired through an accelerated development of lung volumes relative to stature during adolescence, as is the case for Amerindian highlanders. After controlling for body and chest size, FVC and FEV were significantly smaller in the La Paz Europeans than in highland Aymara (p less than .001), suggesting that the lung volumes of the Aymara are influenced by factors other than simply growth and development at high altitude. Finally, as found in Amerindians, chest size is an important determinant of intra-individual variation in lung function among highland Europeans.     

Sleep of Andean high altitude natives.

The structure of sleep in lowland visitors to altitudes greater than 4000 m is grossly disturbed. There are no data on sleep in long-term residents of high altitudes. This paper describes an electroencephalographic study of sleep in high altitude dwellers who were born in and are permanent residents of Cerro de Pasco in the Peruvian Andes, situated at 4330 m. Eight healthy male volunteers aged between 18 and 69 years were studied. Sleep was measured on three consecutive nights for each subject. Electroencephalographs, submental electromyographs and electro-oculograms were recorded. Only data from the third night were used in the analysis. The sleep patterns of these subjects resembled the normal sleep patterns described by others in lowlanders at sea level. There were significant amounts of slow wave sleep in the younger subjects and rapid eye movement sleep seemed unimpaired.     

Electrocardiographic observations in high altitude residents of Nepal and Bolivia

Parameters computed from electrocardiographic recordings (mean frontal QRS axis, â QRS, positive (R-S) difference in lead V₁, incidence of atypical conduction pattern in V₁) were compared: (1) in two populations residing at the same altitude (3 800 m) but in different geographical sites: Aymaras in Bolivia and Tibetans in Nepal, (2) in three groups of Bolivians dwellers, ethnically similar and fully acclimatized, at three altitudes (4 780 m, 3 800 m, 400 m). This work involved 661 subjects. Results: (a) The mean â QRS value in highlanders is shifted to the right when compared to that of lowlanders: the right axis deviation increases with altitude, (b) The mean â QRS value is identical in Bolivian and Tibetan groups living at the same altitude, (c) The axis deviates to the left with aging in all the environmental conditions. This migration is accompanied by a lower incidence of positive (R-S) difference in adults compared to younger subjects, (d) The mean â QRS value of the females is always situated to the left of that males for all age groups. This difference receives a possible confirmation by the lower incidence of atypical complexes in V₁ in females, (e) The present values of â QRS as well as others found in the litterature and those of mean pulmonary arterial pressure reported by different authors have been plotted, both as a function of elevation: The two relationships can be described by two linear functions with a point of intersection. Such points suggest an altitude threshold above which a further decrease in barometric pressure results in marked cardiovascular responses. They are both located in the vicinity of 2 500 m.This work was supported by the Department of Cooperation Technique (Ministère des Affaires Etrangères) and the Centre National de la Recherche Scientifique (RCP. 253).     

Urinary catecholamine excretion in temporary residents of high altitude

Urinary catecholamine excretion was estimated in 50 lowlanders temporarily staying at altitudes above 3,000 m. They were divided in subgroups according to the length of their continuous stay. For comparison, 25 highlanders who were born and brought up at high altitude and 50 lowlanders who had never been to altitudes of more than 1,000 m were also studied. High catecholamine excretion was noted in temporary residents staying at high altitude for up to 30 days as compared to that in lowlanders (P greater than 0.01). The excretion rate gradually returned to basal values thereafter. Catecholamines were essentially similar in lowlanders and highlanders. The significance of these findings is discussed regarding the possible pathogenetic role of the sympathoadrenal system in the development of ill effects in respone to high-altitude exposure.     

Role of the altitude level on cerebral autoregulation in residents at high altitude.

Cerebral autoregulation is impaired in Himalayan high-altitude residents who live above 4,200 m. This study was undertaken to determine the altitude at which this impairment of autoregulation occurs. A second aim of the study was to test the hypothesis that administration of oxygen can reverse this impairment in autoregulation at high altitudes. In four groups of 10 Himalayan high-altitude dwellers residing at 1,330, 2,650, 3,440, and 4,243 m, arterial oxygen saturation (Sa(O(2))), blood pressure, and middle cerebral artery blood velocity were monitored during infusion of phenylephrine to determine static cerebral autoregulation. On the basis of these measurements, the cerebral autoregulation index (AI) was calculated. Normally, AI is between zero and 1. AI of 0 implies absent autoregulation, and AI of 1 implies intact autoregulation. At 1,330 m (Sa(O(2)) = 97%), 2,650 m (Sa(O(2)) = 96%), and 3,440 m (Sa(O(2)) = 93%), AI values (mean +/- SD) were, respectively, 0.63 +/- 0.27, 0.57 +/- 0.22, and 0.57 +/- 0.15. At 4,243 m (Sa(O(2)) = 88%), AI was 0.22 +/- 0.18 (P < 0.0005, compared with AI at the lower altitudes) and increased to 0.49 +/- 0.23 (P = 0.008, paired t-test) when oxygen was administered (Sa(O(2)) = 98%). In conclusion, high-altitude residents living at 4,243 m have almost total loss of cerebral autoregulation, which improved during oxygen administration. Those people living at 3,440 m and lower have still functioning cerebral autoregulation. This study showed that the altitude region between 3,440 and 4,243 m, marked by Sa(O(2)) in the high-altitude dwellers of 93% and 88%, is a transitional zone, above which cerebral autoregulation becomes critically impaired.     

Abnormalities of blood coagulation at high altitude

Immediately on arrival of man at 3,600 m altitude there was a tendency towards hypercoagulation with increase in the platelet count, factor X, factor XII, thrombotest activity and thrombin clotting time with compensatory increase in fibrinolysis and reduction in factor VIII. During continuous stay there was a regression of the hypercoagulation state with reduction in platelet count, platelet factor 3, clot retraction, factor X, factor XII, thrombotest activity and persistence of increased fibrinolytic activity. The main difference in the hypercoagulation state in high-altitude pulmonary oedema and the corresponding highaltitude controls was the absence of a compensatory increase in fibrinolysis and increase in factor VIII. The main difference in the hypercoagulation state in highaltitude pulmonary hypertension and the corresponding high-altitude controls was an increase in platelet adhesiveness, platelet factor 3, factor V and factor VIII. The outstanding difference between high-altitude pulmonary oedema and highaltitude pulmonary hypertension was in the fibrinolytic activity and thrombin clotting time which were reduced in pulmonary oedema but were increased in pulmonary hypertension.

---

Zusammenfassung Unmittelbar nach der Ankunft von Männern in 3.600 m Höhe zeigte sich eine Hyperkoagulation mit Anstieg der Plättchenzahl, Faktor X und Faktor XII, Thrombotest-Aktivität und Thrombin-Gerinnungszeit mit kompensatorischem Anstieg der Fibrinolyse und Verminderung von Faktor VIII. Bei längerem Aufenthalt ging der Hyperkoagulationszustand zurück mit verminderter Plättchenzahl, Plättchenfaktor 3, Thrombusretraktion, Faktor X, Faktor XII, Thrombotest-Aktivität und Verbleiben oder Anstieg der fibrinolytischen Aktivität. Der Hauptunterschied in der Hyperkoagulationsphase von Personen mit Lungenoedem und Gesunden in der Höhe war das Fehlen eines kompensatorischen Anstieges der Fibrinolyse und Faktor VIII. Der Hauptunterschied in der Hyperkoagulationsphase von Personen mit pulmonalem Hochdruck und Gesunden in der Höhe war ein Anstieg der Klebrigkeit der Plättchen, Plättchenfaktor 3, Faktor V und Faktor VIII. Die fibrinolytische Aktivität und die Thrombin-Gerinnungszeit waren bei Lungenoedem vermindert und bei pulmonalem Hochdruck erhöht.

---

Resume A l'arrivée à 3.600 m d'altitude, on constate chez des sujets d'expérience une hypercoagulation accompagnée d'une hausse du nombre de plaquettes, du facteur X et du facteur XII, de l'activité du thrombotest et du temps de réaction de la thrombine. En compensation, on note une hausse de la fibrinolyse et une baisse du facteur VIII. Un séjour prolongé en altitude a pour conséquence une normalisation des réactions sanguines. Dans la phase d'hypercoagulation, la principale différence observée entre les personnes souffrant d'oedème pulmonaire et les personnes en bonne santé a été que, chez les premières, on n'a pas constaté de hausse compensatoire de la fibrinolyse ni de baisse du facteur VIII. Dans cette même phase, les personnes souffrant d'hypertension pulmonaires se distinguent des gens en bonne santé par le fait que les plaquettes collent entre elles et par une augmentation du facteur de plaques 3, du facteur V et du facteur VIII. L'activité fibrinolytique et le temps de coagulation de la thrombine sont diminués par l'oedème et augmentés par l'hypertension pulmonaire.