L. Palacios

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.

Minimally invasive silicon probe for electrical impedance measurements in small animals

It is commonly accepted that electrical impedance provides relevant information about the physiological condition of living tissues. Currently, impedance measurements are performed with relatively large electrodes not suitable for studies in small animals due to their poor spatial resolution and to the damage that they cause to the tissue. A minimally invasive needle shaped probe for electrical impedance measurements of living tissues is presented in this paper. This micro-probe consists of four square platinum electrodes (300 microm x 300 microm) on a silicon substrate (9 mm x 0.6 mm x 0.5 mm) and has been fabricated by using standard Si microelectronic techniques. The electrodes are not equally spaced in order to optimise the signal strength and the spatial resolution. Characterisation data obtained indicate that these probes provide high spatial resolution (measurement radius <4 mm) with a useful wide frequency band going from 100 Hz to 100 kHz. A series of in vivo experiments in rat kidneys subjected to ischemia was performed to demonstrate the feasibility of the probes and the measurement system. The impedance modulus and phase were measured at 1 kHz since this frequency is sufficiently low to permit the study of the extracellular medium. The extracellular pH and K+ were also simultaneously measured by using commercial miniaturised Ion Selective Electrodes. The induced ischemia period (45 min) resulted in significant changes of all measured parameters (Delta/Z/ approximately 65%; DeltapH approximately 0.8; DeltaK+ approximately 30 mM).

Hematological values of some great flying and aquatic-diving birds.

Abstract 1. 1. Hematological data were analysed in great flying birds, aquaticdiving birds and galliformes. 2. 2. p CO 2 , p O 2 , pH, hematocrit, hemoglobin, erythrocyte number, sedimentation rate, plasma proteins, glucose, total glucides, total proteins, urea, lactate, plasmatic Cl − , Na± and K + and the red cell indices were determined. 3. 3. Most of the parameters studied showed no clear differences. 4. 4. The values with significant differences were lactic acid, erythrocyte number, hematocrit and the amount of hemoglobin.

Bioimpedance dispersion width as a parameter to monitor living tissues

In the case of living tissues, the spectral width of the electrical bioimpedance dispersions (closely related with the alpha parameter in the Cole equation) evolves during the ischemic periods. This parameter is often ignored in favor of other bioimpedance parameters such as the central frequency or the resistivity at low frequencies. The object of this paper is to analyze the significance of this parameter through computer simulations (in the alpha and beta dispersion regions) and to demonstrate its practical importance through experimental studies performed in rat kidneys during cold preservation. The simulations indicate that the dispersion width could be determined by the morphology of the extra-cellular spaces. The experimental studies show that it is a unique parameter able to detect certain conditions such as a warm ischemia period prior to cold preservation or the effect of a drug (Swinholide A) able to disrupt the cytoskeleton. The main conclusion is that, thanks to the alpha parameter in the Cole equation, the bioimpedance is not only useful to monitor the intra/extra-cellular volume imbalances or the inter-cellular junctions resistance but also to detect tissue structural alterations.

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.

Comparative respiratory functions of blood in some passeriform birds

Abstract 1. 1. Classical hematological parameters, hemoglobin oxygen affinity and Bohr effect have been determined in 16 species of 9 families (Fringilidae, Sylvidae, Turdidae, Prunellidae, Ploceidae, Certhidae, Emberizidae. Paridae and Troglodytidae) of the order Passeriform. 2. 2. The average values of the hematological parameters show a tendency to be high due to the greater metabolic rate of the passeriform group. 3. 3. The P50 of the different species was between 43 and 53 torr, and the Bohr effect ranged from −0.403 to −0.532. 4. 4. A parallel may be made between altitude adaptation for hypoxia and high oxygen requirements for activity.

Low O2 and high CO2 in LLC-PK1 cells culture mimics renal ischemia-induced apoptosis.

Ischemia, absence or loss of blood flow in organs always presents as a dual phenomenon: tissue oxygen deficit and CO2 excess (hypercapnia). Commonly hypoxic cell culture models kept CO2 at normal nonischemic values. We report a study of apoptosis in an in vitro model of renal hypoxia that mimics in vivo tissue gas atmosphere composition determined during experimental ischemia in rat kidney (low O2 plus high CO2). Renal tubular LLC-PK1 cell were transiently exposed to hypoxia, to hypercapnia or to both conditions (simulated ischemia). Exposure to simulated ischemic atmosphere, but not to low O2 or high CO2 alone, induced cell apoptosis in vitro. This suggests that ischemia-induced apoptosis in vivo would be dependent on the natural, joint action of hypoxia and hypercapnia. This should be taken into account in cell culture studies that would like to mimic in vivo ischemic conditions.

Modification of glyceraldehyde-3-phosphate dehydrogenase in response to nitric oxide in intestinal preconditioning

BACKGROUND Previous studies have demonstrated that intestinal preconditioning is triggered by an initial increase in nitric oxide synthesis. This confers resistance to the organ in face of a subsequently sustained period of ischemia-reperfusion. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a key enzyme in the glycolytic cascade that could be modulated by nitric oxide. The purpose of the present study is to evaluate a possible inhibitory effect on intestinal GAPDH by the nitric oxide generated during preconditioning. This could lead to a reduction of lactate accumulation during subsequent ischemia. METHODS GAPDH activity was measured after intestinal preconditioning, and the effect of nitric oxide synthase inhibition was evaluated. RESULTS Preconditioning induced a significant, but transient, decrease in GAPDH activity. This effect appears to be correlated with a reduced amount of lactate accumulation during ischemia. Inhibition of nitric oxide synthesis reversed these changes. In addition, increased synthesis of nitric oxide was detected after preconditioning. CONCLUSIONS In summary, this study indicates that nitric oxide generated during ischemic preconditioning could act as a glycolytic modulator during subsequent ischemia, through its effect on GAPDH activity.

Multiparametric monitoring of ischemia-reperfusion in rat kidney: effect of ischemic preconditioning.

Background. Microelectrode technology is a promising tool for monitoring kidney ischemia and the changes induced by its therapeutic management. Ischemic preconditioning, that is, brief ischemic periods before sustained ischemia, has been shown to protect several organs, including the kidney, from ischemia-reperfusion injury. We tested whether the effect of preconditioning could be appraised by real-time measurement of parameters representative of tissue hypoxia. Methods. In a sample of pentobarbital-anesthetized and mechanically ventilated rats, we studied the effect of renal ischemic preconditioning (10-min ischemia and 10-min reflow interval) on subsequent ischemia-reperfusion (45 min and 60 min). Renal tissue electrical impedance, extracellular pH, and potassium concentration [K+] were measured continuously by implanted microelectrodes. Results. Ischemia induced an early, rapid rise in extracellular potassium and impedance module, followed by a phase of slower increase, whereas pH decreased rapidly, reaching a plateau. Preconditioning treatment did not cause significant changes in interstitial pH and [K+] but increased ischemic tissue impedance. During reperfusion, the three variables recovered progressively; however, after a decline, electrical impedance showed a clear postischemic increase. This rise was suppressed by preconditioning. Conclusions. Real-time measurement of any of the three parameters showed capability for early detection of ischemia. In contrast with findings in myocardial tissue, preconditioning in the kidney did not increase potassium cell loss during ischemia or improve ischemic acidosis or tissue impedance. Electrical impedance increased for a second time during reperfusion, indicating the presence of a postischemic cellular edema; concealing this episode was the most noticeable effect of the preconditioning treatment.

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 (