1,721,107 research outputs found
Energy metabolism in hypoxia: reinterpreting some features of muscle physiology on molecular grounds
No full textAn holistic approach for interpreting classical data on the adaptation of the animal and, particularly, of the human body to hypoxic stress was promoted by the discovery of HIF-1, the "master regulator" of cell hypoxic signaling. Mitochondrial production of ROS stabilizes the O2- regulated HIF-1α subunit of the HIF-1 dimer promoting transaction functions in a large number of potential target genes, activating transcription of sequences into RNA and, eventually, protein production. The aim of the present preliminary study is to assess whether adaptive changes in oxygen sensing and metabolic signaling, particularly in the control of energy turnover known to occur in cultured cells exposed to hypoxia, are detectable also in the muscles of animals and man. For the present analysis, data obtained from the proteome of the rat gastrocnemius and of the vastus lateralis muscle of humans together with functional measurements were compared with homologous data from hypoxic cultured cells. In particular, the following variables were assessed: (1) the role of stress response proteins in the maintenance of ROS homeostasis, (2) the activity of the PDK1 gene on the shunting of pyruvate away from the TCA cycle in rodents and in humans, (3) the COX-4/COX-2 ratio in hypoxic rodents, (4) the overall efficiency of oxidative phosphorylation in humans during exercise in hypoxia, (5) some features of muscle mitochondrial autophagy in humans undergoing subchronic and chronic altitude exposure. Despite the limited number of observations and the differences in the experimental approach, some initial interesting results were obtained encouraging to pursue this innovative effort
Oxygen affinity of blood in altitude Sherpas
Full text linkOxygen equilibrium curves on blood within 6 h from sampling have been estimated from polarographic measurements of oxyhemoglobin concentration, in 13 male 14- to 50-yr old Sherpas residing at 3,850 m above sea level (Kumjung, Nepal). In samples with red blood cell counts = 4.7 +/- 0.8 (SD) x 10(6)/mm3, total hemoglobin concentration [Hb] = 17.0 +/- 1.9 g/dl, and hematocrit = 53.3 +/- 5.0, the mean oxygen half-saturation of hemoglobin (P50) (pH = 7.4 and PCO2 = 40 Torr) was 27.3 +/- 1.8 Torr. The P50 of altitude Sherpas was not significantly different from that of acclimatized lowlanders (28.2 +/- 1.3; n = 7), sea-level Caucasian residents (26.5 +/- 1.0; n = 17), and Sherpas at sea level (27.1; n = 3). The 2,3-diphosphoglyceric acid-to-hemoglobin concentration ratio ([2,3-DPG]/[Hb]) in altitude Sherpas was 1.22 +/- 0.03, the same as that of acclimatized Caucasians (1.22 +/- 0.10). The Bohr effect measured for the blood of one altitude Sherpas by the ratio deltalog P50/deltapH was -0.32 and -0.45 at PCO2 levels of 40 and 20 Torr, respectively. These values are not significantly different from those found in Caucasians at sea level where deltalog P50/deltalpH was -0.35 and -0.42, respectively. It is concluded that the P50 in native highlanders is not significantly different from that observed in sea-level dwellers. [2,3-DPG]/[Hb] at altitude, both in natives and in newcomers, is 20% higher than in sea-level residents
THE ROLE OF 2,3-DPG IN THE OXYGEN-TRANSPORT AT ALTITUDE
No full textA computer program is described, relating blood flow with venous PO2 for any given set of the following parameter: oxygen uptake, respiratory quotient, the 2,3-DPG/Hb molar concentration ratio (G), arterial PO2, PCO2 and pH. Two compartments (total body and one leg) and two conditions (rest and maximal exercise) are considered. Calculations are performed at five altitudes (0, 3850, 5400, 6300 and 8848 m), for which the above variables are known. The results indicate that an increased G value has a negative effect on the oxygen delivery to tissues at very high altitudes (> 5400 m), irrespectively of the work load, since larger blood flows ΔĊ on the summit of Mt. Everest is +4 to +7 1/min, and +1 to + 2.5 1/min, for whole body and one leg, respectively) are required for a given oxygen uptake. For submaximal work at altitudes ranging from sea level up to 5400 m, as well as for moderate work at 5400 m, high G values improve the oxygen delivery to tissues
Estimation of heart stroke volume from blood hemoglobin and heart rate at submaximal exercise
No full textEstimation by a rebreathing method of pulmonary O2 diffusing capacity in man
No full textThe pulmonary O 2 diffusing capacity (DO 2) can be estimated in man from the kinetics of PO 2 equilibration between lung gas and mixed venous blood during a rebreathing maneuver, when the following variables are known or can be simultaneously determined: mean rebreathing bag volume (VR), mean lung volume (VA), effective ventilation ([rate of change of V]eff), pulmonary capillary blood flow [rate of change of Q], and slope of the blood O 2 dissociation curve (βO 2). Two rebreathing maneuvers, both performed after breathing 11.5% O 2 in N 2 at steady state, are required. In the first maneuver, an appropriate volume of 8% CO 2 in N 2 is rebreathed for determination of mixed venous blood PO 2 (P(average V)O 2). V)O2. The second maneuver, in which a mixture containing 8% O 2, 7% CO 2, 20% N 2O and 10% He in N 2 is rebreathed, allows the determination of the remaining variables: the rate constant of PO 2 equilibration (KO 2) from the exponential approach of lung PO 2 to P(average V)O 2; Va and [rate of change of V]eff, from He dilution and mixing rate; [rate of change of Q], from the transfer rate of N 2O. The mean DO 2 value found in 19 experiments on 4 healthy young males at rest was 31 ml/min -1/Torr -1. The validity and the applicability of the method are critically discussed
Acid-base balance at exercise in normoxia and in chronic hypoxia: revisiting the 'lactate paradox'
No full textTransitions between rest and work, in either direction, and heavy exercise loads are characterized by changes of muscle pH depending on the buffer power and capacity of the tissues and on the metabolic processes involved. Among the latter, in chronological sequence: (1). aerobic glycolysis generates sizeable amounts of lactate and H(+) by way of the recently described, extremely fast (20-100 ms) "glycogen shunt" and of the excess of glycolytic pyruvate supply; (2). hydrolysis of phosphocreatine, tightly coupled with that of ATP in the Lohmann reaction, is known to consume protons, a process undergoing reversal during recovery; (3). anaerobic glycolysis sustaining ATP production in supramaximal exercise as well as in conditions of hypoxia and ischemia, is responsible for the accumulation of large amounts of lactic acid (up to 1 mol for the whole body). The handling of metabolic acids, i.e., acid-base regulation, occurs both in blood and in tissues, mainly in muscles which are the main producers and consumers of lactic acid. The role of both blood and muscle bicarbonate and non-bicarbonate buffers as well as that of lactate/H(+) cotransport mechanisms is analyzed in relation to acid-base homeostasis in the course of exercise. A section of the review deals with the analysis of the acid-base state of humans exposed to chronic hypoxia. Particular emphasis is put on anaerobic glycolysis. In this context, the so-called lactate paradox is revisited and interpreted on the basis of the most recent findings on exercise at altitude
ARTERIAL BLOOD ACID-BASE STATUS AND GAS CONTENT AT ALTITUDE - RESPIRATORY ALKALOSIS AS BUFFER OF BLOOD O-2 TRANSPORT
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