Improvement of metabolic syndrome markers through altitude specific hiking vacations.

To study the influence of a 3-week hiking vacation at moderate (1700 m) and low altitude (LA) (200 m) on key-markers of the metabolic syndrome, 71 male volunteers (age 36-66 yr old) with the metabolic syndrome [according to the National Cholesterol Education Program's Adult Treatment Panel III (NCEP-ATP III) - or World Health Organization (WHO) - definition] participated in the study and were randomly assigned into a moderate altitude (MA) group (1700 m, no. 36) and a low altitude (LA) group (200 m, no. 35). The 3-week vacation program included 12 moderate- intensity guided hiking tours [4 times/week, 55-65% heart rate maximum (HRmax)] with a total exercise time of 29 h plus moderate recreational activities. Both study groups had a comparable and balanced nutrition with no specific dietary restrictions. Anthropometric, metabolic and cardiovascular parameters were measured 10-14 days before vacation, several times during the 3-week vacation, 7-10 days and 6-8 weeks after return. All participants tolerated the vacation without any adverse effects. Body weight, body fat, waist-circumference, fasting glucose, total cholesterol, LDL-cholesterol (LDL-C), plasma fibrinogen, resting systolic and diastolic blood pressure were significantly decreased over time in both study groups. In the LA group, fasting insulin and homeostasis model assessment (HOMA)-index were significantly decreased one week after return. Relative cycle ergometry performance was significantly increased after return compared to baseline. In both study groups, waist-to-hip ratio (WHR), 2-h oral glucose tolerance test (OGTT), HDL-cholesterol (HDL-C), and triglycerides remained unchanged. The 3-week vacation intervention at moderate and LA had a positive influence on all key-markers of the metabolic syndrome. No clinically relevant differences could be detected between the study groups. A hiking vacation at moderate and LA can be recommended for people with stable, controlled metabolic and cardiovascular risk factors.

Exercise performance of hemodialysis patients during short-term and prolonged exposure to altitude.

The work capacity of patients on maintenance hemodialysis is impaired even at normal inspiratory oxygen pressure. A further restriction can be expected when these patients are exposed to hypoxia at altitude, since most of the usual compensatory mechanisms required to adjust to this environment are impaired or even missing. We tested the tolerance of hemodialysis patients to hypoxia and measured work capacity, hematological, and cardiovascular parameters at rest and during incremental bicycle ergometry during 3-hour exposure to altitudes of 2,000 m and 3,000 m, and during 2 weeks of exposure to an altitude of 2,000 m and compared these data with prealtitude values or with data evaluated in a control group, respectively. In control tests the patients reached work loads at exercise termination of about 66% of age and sex-matched healthy controls, the reduction correlated well with the degree of anemia. During short-term altitude exposure to 2,000 m peak work performance remained unchanged in comparison to prealtitude tests, whereas at 3,000 m it was reduced by about 12%. During the 2-week stay at 2,000 m peak work loads increased significantly by 17% accompanied by an increase in peak oxygen uptake (+15%), blood lactate, heart rates (+10 min-1), and systolic blood pressure (+20 mmHg), whereas the diastolic pressure was comparable to prealtitude values. In another group of hemodialysis patients studied at low altitude under similar experimental conditions none of these parameters was changed. Our data show that during acute exposure to altitudes up to 2,000 m maximal work of hemodialysis patients is not reduced, but is restricted at altitudes higher than that.(ABSTRACT TRUNCATED AT 250 WORDS)

Red cell oxygen transport in man in relation to gender and age.

P50 values, the O2-partial pressure at 50% O2-saturation of hemoglobin, 2,3-DPG, hematological parameters and the plasma concentrations of sexual hormones were determined in 135 subjects of both sexes aged from 10 to 60 years. P50 was significantly higher in sexually mature women than in men, but did not differ between sexes before puberty and after menopause. In females P50 increased with sexual maturation by about 2 mmHg (0.27 kPa). RBC, Hb and Hct remained unchanged. In males Hb-O2-affinity, RBC, Hb and Hct increased with aging. In sexually mature females 2,3-DPG was significantly higher (2 mumol/gHb) than in males, although before puberty and postmaturity no difference was found. In males, 2,3-DPG increased slightly with maturation although P50 decreased. P50 values (pH = 7.4) correlated positively with red cell 2,3-DPG only when data from all groups were pooled (r = 0.330, P less than or equal to 0.0001). Hb was negatively correlated with P50 (r = 0.221, P less than or equal to 0.01). The data suggest a sex hormone and maturation induced influence in the development of the red cell O2-transport system. Estrogens seem to favour a decrease in Hb-O2-affinity rather than an elevation in O2-transport capacity, whereas androgens do the reverse.

Beneficial effects of exercising at moderate altitude on red cell oxygen transport and on exercise performance.

The effect of a ascent to moderate altitude (2,300 m) and altitude training on the O2-transport properties of Hb and their possible consequences on tissue oxygenation during exercise were studied on six control and six training subjects. A rapid increase in P-50 values (+2.4 mm Hg, 0.32 kPa) was measured within one day after ascent. At the end of the stay at altitude (13th day) P-50 values were higher in subjects performing training than in controls. At altitude a slow but constant increase in 2,3-DPG, pyruvate kinase activity and reticulocyte count was found, which was more pronounced in training subjects as compared to controls. Ascent to altitude resulted in a decreased maximal performance capacity (-9%), but both groups recovered during the stay. In training subjects maximal exercise performance was increased after descent. Exercise at altitude was performed at a lower heart rate (controls: -10/min; training: -18/min) and at a lower lactate concentration (-4 mmol/l). These data indicate a positive effect of adaptation to altitude on exercise performance. Training itself shifts the ODC to the right and adds this effect to the effects of passive altitude adaptation on the O2-binding properties of hemoglobin.

Training-dependent changes of red cell density and erythrocytic oxygen transport.

Prolonged endurance training causes a decreased O2 affinity of Hb, which is due to an increase in erythrocyte 2,3-diphosphoglycerate (2,3-DPG) concentration. Possible mechanisms were studied in 20 males with varying degrees of fitness. Training status was tested by ergometry. Red cell density and O2 transport parameters were determined before this test. The O2 tension at 50% O2 saturation of Hb (P50) was higher in the more fit subjects (+1.3 mmHg) and the 2,3-DPG concentration was higher (+2.3 mumol/g Hb) in this group. The mean density was significantly lower in fit subjects (1.1002 g/ml) as compared with less fit subjects (1.1056 g/ml), indicating a lower mean age. Density distribution curves show that in the fit subjects more young erythrocytes were in blood and that the very old erythrocytes were missing. After correction for the differences in the density distribution, no differences in the P50 value and 2,3-DPG concentration between less fit and fit subjects were found. Therefore, the decreased Hb-O2 affinity after training can be explained by the presence of more young erythrocytes in the blood of trained subjects. The magnitude of this effect correlates with the training status.

May high oxygen affinity of maternal hemoglobin cause fetal growth retardation?

Eleven pregnant women with normal fetal outcome (controls), seven women with small for dates babies and 15 non-pregnant women were studied. Hemoglobin (Hb), hematocrit (Hct) and the half saturation tension of oxygen, P50-value (as a measure for the oxygen affinity of Hb) were measured. Urine estriol excretion, HPL in plasma and antepartum cardiotocograms served as parameters of fetal well-being. The placental weight and the largest placental diameter were measured immediately after birth. The patients with small for dates babies showed significant lower P50-values (27.3 +/- 0.4 mm Hg) than those without growth retardation (28.5 +/- 0.3 mm Hg) and were in the range of the non-pregnant controls (27.4 +/- 0.2 mm Hg). Hb was 135.2 +/- 3.8 g/l in the patients with small for dates babies, 118.3 +/- 4.3 g/l in pregnant controls and 136.8 +/- 3.3 g/l in non-pregnant women. Hematocrit paralleled the Hb. The placental weights were significantly lower in women with small for dates babies, but no difference in placental diameters was found. These data, higher oxygen affinity of Hb, increased Hct and lower placental weight, indicate an unfavourable situation in regards to placental oxygen transfer with possible chronic hypoxia of the fetus.

Effects of whole body UV-irradiation on oxygen delivery from the erythrocyte.

In 16 healthy caucasian volunteers (mean age: 22.2 years) the influence of whole body UV-irradiation on the oxygen transport properties of erythrocytes was investigated. Four hours after irradiation with UV (using the minimal erythema dose, MED) no variation of haemoglobin concentration, hematocrit, mean corpuscular haemoglobin concentration, pH or standard bicarbonate could be found, whereas inorganic plasma phosphate (Pi), calcium, the intraerythrocytic 2,3-diphosphoglycerate (2,3-DPG), the activity of erythrocytic phosphofructokinase (PFK) and pyruvatekinase (PK) increased significantly. The half saturation tension of oxygen (P50-value) tended to increase. The increase of Pi causes--via a stimulation of the glycolytic pathway--an increase in 2,3-DPG concentration and thus results in a shift of the oxygen dissociation curve. It is therefore possible to enhance tissue oxygenation by whole body UV-irradiation.

[Oxygen affinity of haemoglobin 3 hours after passive increase in altitude from 400 to 1800 metres (author's transl)]. / Die Sauerstoffaffinität des Hämoglobins 3 Stunden nach passivem Höhenwechsel von 400 auf 1800 m.

An investigation was undertaken in 9 male subjects of the effect of short exposure to moderate altitude on the oxygen affinity of haemoglobin and other parameters. Initial measurements were performed at 425 m and repeated 3 hours after ascent by cable car to an altitude of 1800 m (Untersberg, Salzburg), no muscular activity being allowed (first period). The same protocol was repeated 3 days subsequently except that after ascent the individuals were exercised on an ergometer bicycle (second part). Altitude exposure without exercise leads to a small, but significant increase in the pH corrected P50 value (= half-saturation tension), whereas the non-corrected P50 value showed no significant change. In the second part of the study the corrected and non-corrected P50 values both increased significantly. The whole body pH and the intraerythrocytic pH rose, whereas PCO2 decreased significantly. The intraerythrocytic 2,3-DPG concentration showed a significant increase (1.2 mumol/gHb) after 3 hours of altitude exposure with and without muscular exercise. The prealtitude DPG concentration and the P50 values in the second period were higher than the first control values. The red blood count and sodium and chloride concentration showed no changes. Potassium rose in both experimental periods, whereas inorganic plasma phosphates decreased. These findings show that 3 hours after cable-car ascent to a medium altitude a DPG increase occurs which is able to counteract the Bohr effect. This means that the expected impairment of tissue oxygenation, caused by the alkalosis-induced shift of the dissociation curve to the left, is prevented. These findings also indicate that a repeated "passive" ascent to moderate altitude can lead to an increased oxygen delivery to the tissue.

Diminution of the temperature effects on the oxygen affinity of hemoglobin after prolonged hypothermia.

The influence of temperature on the oxygen affinity of hemoglobin, expressed as half saturation tension P50, was investigated in male Sprague Dawley rats, which had been exposed to a cold environment for about 12 h. P50-values were determined by equilibrating blood samples to a known PO2 at different temperatures. The well known increase in oxygen affinity at low temperatures was observed, but after a longer hypothermic period this effect was diminished. This reduction of the temperature effect is manifested in a change of the ratio delta log P50/delta T from 0.022 in control experiments to 0.0115 in hypothermia. In cold adapted rats such an effect means a better oxygen supply to tissue at low body temperatures than in control animals. These changes in oxygen delivery after cold acclimatisation may partially be interpreted as the result of the decreased intraerythrocytic pH and elevated concentration of ATP found in the present study.

Influence of exposure to moderate altitude on the plasma concentraton of cortisol, aldosterone, renin, testosterone, and gonadotropins.

The influence of 11 days at moderate altitude (2,000 m) combined with exercise on plasma concentration of testosterone, FSH (follicle-stimulating hormone), LH (luteinizing hormone), cortisol, aldosterone, and renin activity was studied in ten healthy subjects. Within 48 h of arrival at moderate altitude a significant increase in testosterone was found whereas FSH had decreased significantly and LH showed a tendency to decrease. Cortisol increased significantly at the beginning and reached a maximum at the end of altitude exposure. The plasma aldosterone level rose continuously and on the last day of altitude was significantly elevated. Plasma renin activity showed a tendency to decrease. On return to low land all measured parameters returned to base line values within 2 days. The findings of increases in plasma levels of aldosterone and testosterone (and serum T3 and T4, as reported by others) are in contrast to the previously found decrease of urinary excretion of all these hormones. This appears to be a distinct dissociation of serum levels of adrenal (and thyroid) hormones from their urinary excretion. The observed increase in plasma aldosterone is probably mediated through ACTH and the rise in plasma potassium, since plasma renin activity showed an opposite trend. The rise in plasma testosterone is probably of adrenal origin since plasma gonadotropins declined simultaneously. The increase of plasma levels of glucocorticoids, mineralocorticoids, and androgens after an ascent from 600 m to 2,000 m above sea level is compatible with an ACTH-mediated stimulation of the entire adrenal cortex and/or a diminished elimination of adrenal steroids: The concomitant fall of FSH, LH, and plasma renin would then be a consequence of a direct negative feedback inhibition of these hormones.

Oxygen affinity of hemoglobin in postmenopausal women.

In a group of 12 postmenopausal women the P50-value (i.e. half saturation tension of oxygen) and other parameters of the red blood count were determined and compared with values of a male group of the same age. A small but significant difference could be found between the hematocrit values but no other values differed. In particular, the sex difference in oxygen affinity reported earlier does not exist in men and women on this age group.