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Biomedical subjects

R E Forster

Publications and source records attributed to R E Forster.

At least 91 records · Page 5Linked to original sources

Hydroxyl ion movements across the human erythrocyte membrane. Measurement of rapid pH changes in red cell suspensions.

A stopped flow rapid reaction apparatus capable of following changes of +/-0.02 pH unit in 0.1 ml of solution in less than 0.005 sec has been developed, utilizing a commercially available pH-sensitive glass electrode. Using this instrument, extracellular pH at 37 degrees C was followed from less than 0.025 sec to 300 sec after mixing equal volumes of the following CO(2)-free solutions: (A) normal human red cells, washed three times and resuspended in 150 mM NaCl at pH 7.2 with a hematocrit of 18%; and, (B) 150 mM NaCl adjusted with HCl or NaOH to pH 2.1 to pH 10.3. A minimum of 2 ml of mixture had to flow through the electrode chamber to ensure complete washout. The mixing process produced a step change in the pH of the extracellular fluid, after which exchanges across the red cell membrane and buffering by intracellular hemoglobin caused it to return toward pH 7.2 with an approximately exponential time course. Under the assumption that pH changes after mixing represent exchanges of hydroxyl for chloride ions across the cell membrane, hydroxyl ion permeabilities (P(OH) (-) in cm/sec) were calculated and found to vary from 2 x 10(-4) at pH 9 to 4 x 10(-1) at pH 4 according to the empirical relationship P(OH) (-) = 170 exp (-1.51 pH). The form of the dependence of P(OH) (-) on extracellular pH does not appear compatible with a simple fixed charge theory of membrane permselectivity.

Bicarbonates↗

Pulsatile uptake of CO in the human lung.

The instantaneous uptake of CO in the lungs was measured with a water-filled body plethysmograph in normal man. First, control measurements of plethysmograph pressure were made while the subject held his breath for 7 sec after breathing gas mixtures prepared to bring his alveolar P(O2) and P(CO2) close to mixed venous levels. Then, CO uptake measurements were made while he held his breath after inhaling the same gas mixtures with added CO (2.0%). The change in lung volume on CO minus the change in lung volume during the control measurement was a measure of the CO uptake in the lungs. Cardiopneumatic changes in lung gas volume were subtracted electrically. All of five subjects showed pulsatile CO uptake. The mean CO uptake was 103 ml/min. A peak uptake of 2.0 (range 1.6-2.3) times the mean uptake occurred 0.3-0.4 sec after the R wave of the EKG and a minimum uptake of 0.4 (range 0.2-0.5) times the mean uptake occurred during the tenth of a second before the R wave of the EKG. These results suggest that pulmonary capillary blood volume is pulsatile during the cardiac cycle.

Adult↗

Physiology.

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Education, Medical↗

The rate of the root shift in eel red cells and eel haemoglobin solutions.

1. We have measured the rate of the exchange of O(2) between eel red blood cells and their suspending fluid in a modified Hartridge-Roughton continuous-flow rapid-reaction velocity apparatus using an oxygen electrode to follow the progress of the reaction.2. The half-times for the uncomplicated oxygenation and deoxygenation reactions in red cells at 24 degrees C were approximately 0.025-0.08 sec.3. The rate of the Root shift in cell suspensions varied widely, depending on the initial condition of the CO(2)-bicarbonate buffer system in the suspending fluid, with the rate of oxygenation or deoxygenation of the intracellular haemoglobin as an upper limit.(a) The most rapid Root shift was produced by a change in extracellular P(CO2) with minimal contributions from CO(2) hydration-dehydration reactions in the suspending fluid or from ion exchanges across the membrane, and had a half-time as short as 0.040 sec.(b) The slowest Root shift was produced by an increase in the extracellular lactic acid concentration in the absence of any form of CO(2) or in the presence of acetazolamide. This process is presumed limited by the rate of H(+) or OH(-) transfer across the membrane and had a half-time in excess of 10 sec.(c) The Root off-shift produced by an increase in P(CO2) plus a decrease in extracellular pH showed no significant trend as temperature was lowered from 30 degrees to 11 degrees C.(d) The Root on-shift produced by a decrease in P(CO2) and increase in extracellular pH had a half-time of 3 sec at 30 degrees C, 9 sec at 24 degrees C and 20 sec at 11 degrees C. These changes appeared limited by the uncatalysed rate of extracellular CO(2) hydration.4. Root off- and on-shifts in cell haemolysates at 24 degrees C, produced predominantly by changing pH but with unavoidable subsequent readjustments of the CO(2)-bicarbonate buffer systems, had an initial rapid phase with half-times as low as 0.01 sec. However, the curves were not monotonic, although they became so in the presence of carbonic anhydrase, indicating partial rate limitation by CO(2) reactions.

Acetazolamide↗

Rate limiting processes in the Bohr shift in human red cells.

1. The rates of the Bohr shift of human red cells and some of its constituent reactions have been studied with a modified Hartridge-Roughton rapid reaction apparatus using an oxygen electrode to measure the progress of the reaction.2. The rate of the Bohr shift was compatible with the hypothesis that the transfer of H(+) across the membrane by means of CO(2) exchange and reaction with buffers is generally the rate-limiting step.(a) When the Bohr off-reaction was produced by a marked increase in P(CO2) around the cells, the half-time at 37 degrees C was 0.12 sec. In this case CO(2) was available initially to diffuse into the cells, the process being predominantly limited by the rate of intracellular CO(2) hydration.(b) When the Bohr off-shift was produced by an increase of [H(+)] outside the cell, P(CO2) being low and equal within and outside the cells, the half time became 0.31 sec. In this case, even at the start, the H(2)CO(3) formed by the almost instantaneous neutralization reaction of H(+) and HCO(3) (-) had to dehydrate to form CO(2) and this in turn had to diffuse into and react within the red cell before the [HbO(2)] could change. When a carbonic anhydrase inhibitor was added to slow the CO(2) reaction inside the cell, the half-time rose to 10 sec.(c) The Bohr off-shift in a haemolysed cell suspension produced by an increase in P(CO2) appeared to be limited by the rate at which the CO(2) could hydrate to form H(+).3. The Bohr off-shift has an average Q(10) of 2.5 between 42.5 and 28 degrees C with an activation energy of 8000 cal.4. The pronounced importance of the CO(2)-bicarbonate system for rapid intracellular pH changes is discussed in connexion with some physiological situations.

Acetazolamide↗