Analysis of postcapillary pH changes in blood in vivo after gas exchange

1978 ◽  
Vol 44 (5) ◽  
pp. 770-781 ◽  
Author(s):  
A. Bidani ◽  
E. D. Crandall ◽  
R. E. Forster
Keyword(s):  
Gas Exchange ◽  
Time Course ◽  
Quantitative Description ◽  
Carbonic Anhydrase Activity ◽  
Transport Processes ◽  
Red Cell Membrane ◽  
Ph Changes ◽  
Pulmonary Capillaries ◽  
Dehydration Reactions

A quantitative description of the reaction and transport processes that take place in blood during and after gas exchange in capillaries is developed and used to interpret recently reported experimental results. Included in the computation are 1) CO2-H2CO3 hydration-dehydration reactions in plasma and erythrocytes, 2) CO2 reactions with hemoglobin, 3) O2 binding to hemoglobin, 4) buffering of H+ intra- and extracellularly, 5) HCO3- Cl- exchange across the red cell membrane, 6) diffusion of gases between alveolar gas and blood, and 7) transcellular movement of water. Ion and water fluxes are described assuming passive diffusion down their electrochemical potential gradients. Recent data on the magnitude of the Bohr and Haldane shifts and on carbamate formation in the presence of 2,3-diphosphoglycerate are used. The analysis is used to examine the direction, magnitude, and time course of plasma pH changes in blood leaving the pulmonary capillaries and is shown to preduct results that agree very closely with recently reported experimental measurements in vivo. The time computed for plasma pH equilibration after gas exchange when carbonic anhydrase activity is absent from plasma is so great that blood may never be in complete electrochemical equilibrium as it travels around the circulation in normal man.

Time course of exchanges between red cells and extracellular fluid during CO2 uptake

1975 ◽  
Vol 38 (4) ◽  
pp. 710-718 ◽  
Author(s):  
R. E. Forster ◽  
E. D. Crandall
Keyword(s):  
Carbonic Anhydrase ◽  
Time Course ◽  
Extracellular Fluid ◽  
Extracellular Ph ◽  
Co2 Uptake ◽  
Sudden Increase ◽  
Red Cell ◽  
Ph Change ◽  
Red Cell Membrane

A stopped-flow rapid-reaction apparatus was used to follow the time course of extracellular pH in a human red cell suspension following a sudden increase in PCO2. The extracellular pH change was slow (t1/2 similar to 3.5 s) considering the presence of carbonic anhydrase in the cells. When carbonic anhydrase was added to the extracellular fluid, the half-time was reduced to less than 20 ms. The explanation for these phenomena is that the equilibration of H+ across the red cell membrane is rate-limited by the uncatalyzed reaction CO2 plus H2O formed from H2CO3 outside the cells. A theoretical model was developed which successfully reproduced the experimental results. When the model was used to simulate CO2 exchange in vivo, it was determined that blood PCO2 and pH require long times (greater than 50 s) to approach equilibrium between cells and plasma after leaving an exchange capillary. We conclude that cell-plasma equilibrium may never be reached in vivo, and that in vitro measurements of these quantities may not represent their true values at the site of sampling.

scholarly journals Early pH Changes in Musculoskeletal Tissues upon Injury—Aerobic Catabolic Pathway Activity Linked to Inter-Individual Differences in Local pH

2020 ◽  
Vol 21 (7) ◽  
pp. 2513 ◽  
Author(s):  
Julia C. Berkmann ◽  
Aaron X. Herrera Martin ◽  
Agnes Ellinghaus ◽  
Claudia Schlundt ◽  
Hanna Schell ◽  
...  
Keyword(s):  
Individual Differences ◽  
Animal Models ◽  
Time Course ◽  
Tricarboxylic Acid Cycle ◽  
Controlled Drug Release ◽  
Post Injury ◽  
Ph Changes ◽  
Ph Values ◽  
Local Ph

Local pH is stated to acidify after bone fracture. However, the time course and degree of acidification remain unknown. Whether the acidification pattern within a fracture hematoma is applicable to adjacent muscle hematoma or is exclusive to this regenerative tissue has not been studied to date. Thus, in this study, we aimed to unravel the extent and pattern of acidification in vivo during the early phase post musculoskeletal injury. Local pH changes after fracture and muscle trauma were measured simultaneously in two pre-clinical animal models (sheep/rats) immediately after and up to 48 h post injury. The rat fracture hematoma was further analyzed histologically and metabolomically. In vivo pH measurements in bone and muscle hematoma revealed a local acidification in both animal models, yielding mean pH values in rats of 6.69 and 6.89, with pronounced intra- and inter-individual differences. The metabolomic analysis of the hematomas indicated a link between reduction in tricarboxylic acid cycle activity and pH, thus, metabolic activity within the injured tissues could be causative for the different pH values. The significant acidification within the early musculoskeletal hematoma could enable the employment of the pH for novel, sought-after treatments that allow for spatially and temporally controlled drug release.

Slow postcapillary changes in blood pH in vivo: titration with acetazolamide

1978 ◽  
Vol 45 (4) ◽  
pp. 565-573 ◽  
Author(s):  
A. Bidani ◽  
E. D. Crandall
Keyword(s):  
Carbonic Anhydrase ◽  
Transport Processes ◽  
Arterial Blood ◽  
Blood Ph ◽  
Pulmonary Capillaries ◽  
Before And After ◽  
Time Courses ◽  
Electrode Chamber ◽  
Good Agreement

A stopped-flow pH electrode apparatus was used to investigate the mechanisms underlying slow changes in plasma pH (pHO) after blood leaves the pulmonary capillaries in carbonic anhydrase-inhibited animals. After acetazolamide was administered to an anesthetized dog or cat, arterial blood was withdrawn through the electrode apparatus into a syringe. Syringe movement was then suddenly stopped. Temperature and pHO of the blood in the electrode chamber were monitored both before and after blood withdrawal ceased. After stopping flow, pHO of the blood in the electrode chamber a) rose 0.02 after a dose of about 1 mg/kg acetazolamide; b) did not change after a dose of about 2 mg/kg acetazolamide; and c) fell 0.10 after a dose greater than about 5 mg/kg acetazolamide. With reasonable red cell and plasma carbonic anhydrase activities assumed for each dose level of acetazolamide, a computer model of the reaction and transport processes occurring in blood after gas exchange in the lung yielded predicted time courses of pHo that were in good agreement with the experimental results. The observed slow pHo changes are largely a result of disequilibrium of [H+] between red blood cells and plasma as blood leaves the pulmonary capillaries.

Analysis of abnormalities of capillary CO2 exchange in vivo

1991 ◽  
Vol 70 (4) ◽  
pp. 1686-1699 ◽  
Author(s):  
A. Bidani
Keyword(s):  
Cardiac Output ◽  
Gas Exchange ◽  
Venous Blood ◽  
Co2 Exchange ◽  
Transport Processes ◽  
Complete Inhibition ◽  
Mixed Venous Blood ◽  
Moderate Exercise ◽  
Significant Chemical

Capillary CO2 exchange in vivo is affected by several interdependent reactions and transport processes. A mathematical model that includes all the significant chemical and transport events that are presumed to occur during capillary gas exchange has been used to investigate the effect of inhibition of 1) erythrocyte HCO(3-)-Cl- exchange, 2) lung carbonic anhydrase (CA) activity with access to plasma, and 3) erythrocyte CA activity on overall pulmonary CO2 excretion (VCO2) during rest and moderate exercise. Any decrement in VCO2 due to inhibition of HCO(3-)-Cl- exchange and/or CA activity, should result in compensatory alterations in cardiac output and/or an increase in the mixed venous blood-to-alveolar PCO2 gradient [(delta PCO2)V-A] to restore steady-state VCO2. Our computations show that complete inhibition of erythrocyte anion exchange would require a compensatory increment in cardiac output of approximately 30-40% or an increase in (delta PCO2)V-A from 6 to 8.3 Torr at rest and from 12 to 15.6 Torr during moderate exercise, if lung CA activity is intact. In the absence of availability of lung CA activity to plasma, the necessary (delta PCO2)V-A is 10.5 Torr at rest and 19.5 Torr during moderate exercise. Complete inhibition of lung and erythrocyte CA activity is predicted to require (delta PCO2)V-A of 39.1 Torr at rest and 74.2 Torr during moderate exercise. These results suggest that HCO(3-)-Cl- exchange might not be vital to maintenance of CO2 transfer and perhaps has a more important role in minimizing the changes in plasma pH associated with microvascular gas exchange in vivo.

Effects of red blood cell HCO3(-)/Cl- exchange kinetics on lung CO2 transfer: theory

1981 ◽  
Vol 50 (2) ◽  
pp. 265-271 ◽  
Author(s):  
E. D. Crandall ◽  
A. Bidani
Keyword(s):  
Carbonic Anhydrase ◽  
Carbonic Anhydrase Activity ◽  
Major Influence ◽  
Gas Transfer ◽  
Red Cell ◽  
Dehydration Reactions ◽  
Lung Capillaries ◽  
Co2 Elimination

A mathematical model has been used to study the influences of the kinetics of erythrocyte HCO3(-)/Cl-- exchange on CO2 elimination in the lung. In addition to the chloride shift, the model includes 1) CO2-H2CO3 hydration-dehydration reactions in plasma and erythrocytes; 2) CO2 reactions with hemoglobin; 3) O2 binding to hemoglobin; 4)buffering of H+ intra- and extracellularly; 5) red cell volume changes; and 6) diffusion of gases between alveoli and blood. Carbonic anhydrase activity was assumed to be available to plasma as it passes through the lung capillaries. The results show that a reduction of PHCO3(-) leads to a reduction in pulmonary CO2 elimination of up to 30%, whether or not carbonic anhydrase activity is available to plasma. Characteristic slow downstream pH and PCO2 changes predicted for each case may represent an explanation for the apparent discrepancy between in vivo and in vitro slow downstream pH changes reported previously. We conclude that red cell HCO3(-)/Cl- exchange partially limits CO2 elimination from blood in the lung and may have a major influence on capillary gas transfer when its speed is abnormally slow.

Analysis of the effects of hematocrit on pulmonary CO2 transfer

1982 ◽  
Vol 53 (2) ◽  
pp. 413-418 ◽  
Author(s):  
A. Bidani ◽  
E. D. Crandall
Keyword(s):  
Gas Exchange ◽  
Venous Blood ◽  
Total Surface Area ◽  
Pulmonary Vasculature ◽  
Mixed Venous Blood ◽  
Red Cell Membrane ◽  
Dehydration Reactions ◽  
High Buffer Capacity ◽  
Different Levels ◽  
Co2 Excretion

A mathematical model of the chemical and transport events in blood during and after gas exchange has been used to examine the rates of CO2 excretion (Vco2) and O2 uptake (Vo2) in the lung at different levels of hematocrit (Hct), assuming fixed mixed venous blood O2 and CO2 contents and alveolar gases and constant cardiac output. The results show that a reduction in Hct from 45 to 30% leads to approximately 25% reduction in Vco2 compared with approximately 30% reduction in Vo2. Reduction of Hct from 45 to 15% results in approximately 50% reduction in Vco2 and approximately 63% reduction in Vo2. An increase in Hct from 45 to 60% results in approximately 25% increase in Vco2, accompanied by approximately 30% increase in Vo2. These fractional changes in gas exchange are only slightly affected by the extent of catalysis of the plasma CO2-H2CO3 hydration-dehydration reactions in the pulmonary vasculature. The reduction in Vco2 with reductions in Hct are due to 1) decrease in the total quantity of Bohr protons released during diminution of Vo2, 2) decrease in the size of the high buffer capacity intraerythrocytic pool, and 3) decrease in the total surface area available for HCO-3/Cl- exchange across the red cell membrane. We conclude that hitherto unrecognized changes in Vco2 (in addition to the well-known changes in Vo2) may occur as a consequence of alterations in Hct.

Comparison of High Purity Factor IX Concentrates and a Prothrombin Complex Concentrate in a Canine Model of Thrombogenicity

1991 ◽  
Vol 66 (05) ◽  
pp. 609-613 ◽  
Author(s):  
I R MacGregor ◽  
J M Ferguson ◽  
L F McLaughlin ◽  
T Burnouf ◽  
C V Prowse
Keyword(s):  
High Purity ◽  
Time Course ◽  
Prothrombin Complex Concentrate ◽  
Degradation Products ◽  
Canine Model ◽  
Factor Ix ◽  
In Vitro Tests ◽  
Albumin Infusion

SummaryA non-stasis canine model of thrombogenicity has been used to evaluate batches of high purity factor IX concentrates from 4 manufacturers and a conventional prothrombin complex concentrate (PCC). Platelets, activated partial thromboplastin time (APTT), fibrinogen, fibrin(ogen) degradation products and fibrinopeptide A (FPA) were monitored before and after infusion of concentrate. Changes in FPA were found to be the most sensitive and reproducible indicator of thrombogenicity after infusion of batches of the PCC at doses of between 60 and 180 IU/kg, with a dose related delayed increase in FPA occurring. Total FPA generated after 100-120 IU/kg of 3 batches of PCC over the 3 h time course was 9-12 times that generated after albumin infusion. In contrast the amounts of FPA generated after 200 IU/kg of the 4 high purity factor IX products were in all cases similar to albumin infusion. It was noted that some batches of high purity concentrates had short NAPTTs indicating that current in vitro tests for potential thrombogenicity may be misleading in predicting the effects of these concentrates in vivo.

Time Course Change of the Heat-generating Capability of Dextran Magnetite Complex (DM) in vivo.

2001 ◽  
Vol 17 (2) ◽  
pp. 85-91 ◽  
Author(s):  
MICHIHIDE MITSUMORI ◽  
TORU SHIBATA ◽  
YASUSHI NAGATA ◽  
MASAHIRO HIRAOKA ◽  
MASAKATSU HASEGAWA ◽  
...  
Keyword(s):  
Time Course

Studies on the mechanism of acute inhibition of thyroglobulin hydrolysis by iodine

1985 ◽  
Vol 108 (4) ◽  
pp. 511-517 ◽  
Author(s):  
Nandalal Bagchi ◽  
Birdie Shivers ◽  
Thomas R. Brown
Keyword(s):  
Time Course ◽  
Period 2 ◽  
Iodotyrosine Deiodinase ◽  
Rate Of Hydrolysis ◽  
Underlying Mechanisms ◽  
Excess Iodide ◽  
Sites Of Action ◽  
Hydrolysis Of

Abstract. Iodine in excess is known to acutely inhibit thyroidal secretion. In the present study we have characterized the time course of the iodine effect in vitro and investigated the underlying mechanisms. Labelled thyroid glands were cultured in vitro in medium containing mononitrotyrosine, an inhibitor of iodotyrosine deiodinase. The rate of hydrolysis of labelled thyroglobulin was measured as the proportion of labelled iodotyrosines and iodothyronines recovered at the end of culture and was used as an index of thyroidal secretion. Thyrotrophin (TSH) administered in vivo acutely stimulated the rate of thyroglobulin hydrolysis. Addition of Nal to the culture medium acutely inhibited both basal and TSH-stimulated thyroglobulin hydrolysis. The effect of iodide was demonstrable after 2 h, maximal after 6 h and was not reversible upon removal of iodide. Iodide abolished the dibutyryl cAMP induced stimulation of thyroglobulin hydrolysis. Iodide required organic binding of iodine for its effect but new protein or RNA synthesis was not necessary. The inhibitory effects of iodide and lysosomotrophic agents such as NH4C1 and chloroquin on thyroglobulin hydrolysis were additive suggesting different sites of action. Iodide added in vitro altered the distribution of label in prelabelled thyroglobulin in a way that suggested increased coupling in the thyroglobulin molecule. These data indicate that 1) the iodide effect occurs progressively over a 6 h period, 2) continued presence of iodide is not necessary once the inhibition is established, 3) iodide exerts its action primarily at a post cAMP, prelysosomal site and 4) the effect requires organic binding of iodine, but not new RNA or protein synthesis. Our data are consistent with the hypothesis that excess iodide acutely inhibits thyroglobulin hydrolysis by increasing the resistance of thyroglobulin to proteolytic degradation through increased iodination and coupling.

Time Series Analysis of Transmesothelial Invasion by Endometrial Stromal and Epithelial Cells Using Three-dimensional Confocal Microscopy

2001 ◽  
Vol 7 (S2) ◽  
pp. 580-581
Author(s):  
CA Witz ◽  
S Cho ◽  
VE Centonze ◽  
IA Montoya-Rodriguez ◽  
RS Schenken
Keyword(s):  
Epithelial Cells ◽  
Stromal Cells ◽  
Time Course ◽  
Three Dimensional ◽  
Collagen Iv ◽  
Mesothelial Cells ◽  
Endometrial Stromal Cells ◽  
Human Collagen ◽  
Endometrial Epithelial Cells

Using human peritoneal explants, we have previously demonstrated that endometrial stromal cells (ESCs) and endometrial epithelial cells (EECs) attach to intact mesothelium. Attachment occurs within one hour and mesothelial invasion occurs within 18 hours (Figure 1). We have also demonstrated that, in vivo, the mesothelium overlies a continuous layer of collagen IV (Col IV).More recently we have used CLSM, to study the mechanism and time course of ESC and EEC attachment and invasion through mesothelial monolayers. in these studies, CellTracker® dyes were used to label cells. Mesothelial cells were labeled with chloromethylbenzoylaminotetramethylrhodamine (CellTracker Orange). Mesothelial cells were then plated on human collagen IV coated, laser etched coverslips. Mesothelial cells were cultured to subconfluence. ESCs and EECs, labeled with chloromethylfluorscein diacetate (CellTracker Green) were plated on the mesothelial monolayers. Cultures were examined at 1, 6, 12 and 24 hours with simultaneous differential interference contrast and CLSM.

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