Ramón Rama

Erythropoietin acute reaction and haematological adaptations to short, intermittent hypobaric hypoxia.

Abstract This study aimed to determine whether brief hypoxic stimuli in a hypobaric chamber are able to elicit erythropoietin (EPO) secretion, and to effectively stimulate erythropoiesis in the short term. In two different experiments, a set of haematological, biochemical, haemorheological, aerobic performance, and medical tests were performed in two groups of healthy subjects. In the first experiment, the mean plasma concentration of EPO ([EPO]) increased from 8.7 to 13.5 mU · ml−1 (55.2%; P < 0.01) after 90 min of acute exposure at 540 hPa, and continued to rise until a peak was attained 3 h after the termination of hypoxia. In the second experiment, in which subjects were exposed to a simulated altitude of up to 5500 m (504 hPa) for 90 min, three times a week for 3 weeks, all haematological indicators of red cell mass increased significantly, reaching the highest mean values at the end of the programme or during the subsequent 2 weeks, including packed cell volume (from 42.5 to 45.1%; P < 0.01), red blood cell count (from 4.55 × 106 to 4.86 × 106 · l−1; P < 0.01), reticulocytes (from 0.5 to 1.4%; P < 0.01), and haemoglobin concentration (from 14.3 to 16.2 g · dl−1; P < 0.01), without an increase in blood viscosity. Arterial blood oxygen saturation during hypoxia was improved (from 60% to 78%; P < 0.05). Our most relevant finding is the ability to effectively stimulate erythropoiesis through brief intermittent hypoxic stimuli (90 min), in a short period of time (3 weeks), leading to a lower arterial blood desaturation in hypoxia. The proposed mechanism for these haematological and functional adaptations is the repeated triggering effect of EPO production caused by the intermittent hypoxic stimuli.

Intermittent hypobaric hypoxia stimulates erythropoiesis and improves aerobic capacity

PURPOSE The purpose of the study was to examine the effect of a very short intermittent exposure to moderate hypoxia in a hypobaric chamber on aerobic performance capacity at sea level and the erythropoietic response. The effects of hypobaric hypoxia alone and combined with low-intensity exercise were also compared. METHODS Seventeen members of three high-altitude expeditions were exposed to intermittent hypoxia in a hypobaric chamber over 9 d at simulated altitude, which was progressively increased from 4000 to 5500 m in sessions ranging from 3 to 5 h x d(-1). One group (N = 7; HE group) combined passive exposure to hypoxia with low-intensity exercise on a cycle ergometer. Another group (N = 10; H group) was only exposed to passive hypoxia. Before and after the exposure to hypoxia, medical status, performance capacity, and complete hematological and hemorheological profile of subjects were evaluated. RESULTS No significant differences were observed between the two groups (HE vs H) in any of the parameters studied, indicating that hypoxia alone was responsible for the changes. After the acclimation period, a significant increase in exercise time (mean difference: +3.9%; P < 0.01), and maximal pulmonary ventilation (+5.5%; P < 0.05) was observed during the maximal incremental test at sea level. Individual lactate-velocity curves significantly shifted to the right (P < 0.05), thus revealing an improvement of aerobic endurance. A significant increase was found in PCV (42.1-45.1%; P < 0.0001), RBC count (5.16 to 5.79 x 10(6) x mm(-3); P < 0.0001), reticulocytes (0.5 to 1.1%; P < 0.0001) and hemoglobin (Hb) concentration (14.2 to 16.7 g x dL(-1); P < 0.002). CONCLUSIONS It was concluded that short-term hypobaric hypoxia can activate the erythropoietic response and improve the aerobic performance capacity in healthy subjects.

Nitric Oxide–Related Brain Damage in Acute Ischemic Stroke

BACKGROUND AND PURPOSE The neurotoxic and neuroprotective role of nitric oxide (NO) in experimental cerebral ischemia has generated considerable debate. The aim of this study was to analyze the relationship between NO metabolite (NO-m) concentrations in cerebrospinal fluid (CSF) and clinical and neuroimaging parameters of brain injury in patients with acute ischemic stroke. METHODS We studied 102 patients and 24 control subjects who were included in a larger previous study conducted to analyze risk factors of progressing stroke. NO generation was calculated by quantifying nitrates and nitrites with a colorimetric assay in CSF samples obtained within the first 24 hours from symptoms onset. Early neurological deterioration was defined as a fall of 1 or more points in Canadian Stroke Scale score between admission and 48 hours after inclusion. Infarct volume was measured on days 4 to 7 by cranial CT. RESULTS Median NO-m concentrations [quartiles] were 2.1 [1.0, 4.5] micromol/mL in patients and 1.0 [1.0, 1.0] micromol/mL in control subjects (P<0.0001). In 45 patients with subsequent early neurological deterioration, NO-m levels in CSF were significantly higher than in those with stable stroke (4.0 [1.7, 7.8] versus in 1. 6 [1.0, 2.5] micromol/mL, P<0.0001). There was a moderate correlation between NO-m and infarct volume (coefficient 0.39, P<0. 001). NO-m concentrations >5.0 micromol/mL were significantly associated with early neurological worsening (OR 5.7, 95% CI 1.2 to 27.4; P=0.030) independent of other important factors related to progressing stroke, such as CSF glutamate levels. CONCLUSIONS Our clinical findings suggest an important role of NO generation in acute ischemic stroke. Increased NO-m in CSF are associated with a greater brain injury and early neurological deterioration.

Purification and characterization of a soybean hull allergen responsible for the Barcelona asthma outbreaks. II. Purification and sequencing of the Gly m 2 allergen

Background A low MW allergen from soybean hull, Gly m 1, with two isoallergens, Gly m 1 A and Gly m 1 B, was associated with the asthma outbreaks that occurred in Cartagena, Spain. Using sera of asthmatic epidemic patients (AEP) from Barcelona, three main soybean hull allergens, two of them with MWs atid pIs identical to those reported for Gly m 1 A and Gly m 1 B, were identified.

Acclimatization Near Home? Early Respiratory Changes After Short-Term Intermittent Exposure to Simulated Altitude

OBJECTIVE With the ultimate goal of finding a straightforward protocol for acclimatization at simulated altitude, we evaluated the early effects of repeated short-term exposure to hypobaric hypoxia on the respiratory response to exercise in hypoxia. METHODS Nine subjects were exposed to a simulated altitude of 5000 m for 2 hours a day for 14 days. Arterial oxygen saturation (SaO2), expired volume per minute (VE), respiratory rate, tidal volume (VT), and heart rate were measured during rest and during exercise (cycloergometer, at 30% of maximum oxygen consumption at sea level), both in normoxia and at 5000 m of simulated altitude on the first and 15th days. On the same days, blood samples were obtained for hematological tests. RESULTS During exercise in hypoxia, SaO2 rose from 65 to 71% (P = .02), and VE rose from 55.5 to 67.6 L.min-1 (P = .02) due to an increase in VT from 2 to 2.6 L (P = .003). No significant differences were found in any of the variables studied at rest either in normoxia or in hypoxia or in exercise in normoxia after the exposure program. In the second week, changes in packed cell volume and blood hemoglobin concentration were nonsignificant. CONCLUSIONS After short-term intermittent exposure to hypobaric hypoxia, subjects increased their ventilatory response and SaO2 during exercise at simulated altitude. These changes may be interpreted as acclimatization to altitude. The monitoring of ventilatory response and SaO2 during moderate exercise in hypobaric hypoxia may be used to detect the first stages of acclimatization to altitude.

Iron intake increases infarct volume after permanent middle cerebral artery occlusion in rats

Experimental and clinical data suggest an important role of iron in cerebral ischaemia. We measured infarct volume and analysed the oxidative stress, and also the excitatory and inflammatory responses to brain injury in a rat stroke model after an increased oral iron intake. Permanent middle cerebral artery occlusion (MCAO) was performed in ten male Wistar rats fed with a diet containing 2.5% carbonyl iron for 9 weeks, and in ten control animals. Glutamate, interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) were determined in blood samples before and at 2, 4, 6, 8, 24 and 48 h after MCAO, and thiobarbituric acid reaction substances (TBARS) were analysed at 48 h. Infarct volume was measured at 48 h by image analysis on brain slices stained with 1% TTC. Tissue iron was measured by atomic absorption spectrophotometry. Infarct volume was 66% greater in the iron fed rats than in the control group (178+/-49 mm(3) versus 107+/-53 mm(3), P<0.01). Significant higher levels of glutamate, IL-6 and TNF-alpha were observed in the group with iron intake (peak values were obtained at 6, 8 and 4 h, respectively). Iron-fed animals also showed significantly higher levels of TBARS than those receiving a normal diet (6.52+/-0.59 vs. 5.62+/-0.86 micro mol/l, P=0.033) Liver iron stores (3500+/-199 vs. 352+/-28 micro g Fe/g, P<0.0001), but not brain iron stores (131 vs. 139 micro g Fe/g, P=0.617), were significantly higher in the iron fed rats group. These results suggest that iron intake is associated with larger infarct volumes after MCAO in the rat. This effect seems to be associated with higher oxidative stress, excitotoxicity and inflammatory responses.

Severe hypoxia decreases oxygen uptake relative to intensity during submaximal graded exercise

SummaryThe effect of severe acute hypoxia (fractional concentration of inspired oxygen equalled 0.104) was studied in nine male subjects performing an incremental exercise test. For power outputs over 125 W, all the subjects in a state of hypoxia showed a decrease in oxygen consumption (

Identification of the Soybean Hull Allergens Responsible for the Barcelona Asthma Outbreaks

\dot V