Kinetics of CO2 excretion and intravascular pH  disequilibria during carbonic anhydrase inhibition

Cardenas, Victor, Jr., Thomas A. Heming, and Akhil Bidani.Kinetics of CO2 excretion and intravascular pH disequilibria during carbonic anhydrase inhibition. J. Appl. Physiol. 84(2): 683–694, 1998.—Inhibition of carbonic anhydrase (CA) activity (activity in red blood cells and activity available on capillary endothelium) results in decrements in CO2 excretion (V˙co 2) and plasma-erythrocyte CO2-[Formula: see text]-H+disequilibrium as blood travels around the circulation. To investigate the kinetics of changes in blood [Formula: see text]and pH during progressive CA inhibition, we used our previously detailed mathematical model of capillary gas exchange to analyze experimental data of V˙co 2and blood-gas/pH parameters obtained from anesthetized, paralyzed, and mechanically ventilated dogs after treatment with acetazolamide (Actz, 0–100 mg/kg iv). Arterial and mixed venous blood samples were collected via indwelling femoral and pulmonary arterial catheters, respectively. Cardiac output was measured by thermodilution. End-tidal[Formula: see text], as a measure of alveolar[Formula: see text], was obtained from continuous records of airway [Formula: see text] above the carina. Experimental results were analyzed with the aid of a mathematical model of lung and tissue-gas exchange. Progressive CA inhibition was associated with stepwise increments in the equilibrated mixed venous-alveolar [Formula: see text] gradient (9, 19, and 26 Torr at 5, 20, and 100 mg/kg Actz, respectively). The maximum decrements in V˙co 2were 10, 24, and 26% with 5, 20, and 100 mg/kg Actz, respectively, without full recovery ofV˙co 2 at 1 h postinfusion. Equilibrated arterial [Formula: see text]overestimated alveolar [Formula: see text], and tissue [Formula: see text] was underestimated by the measured equilibrated mixed venous blood[Formula: see text]. Mathematical model computations predicted hysteresis loops of the instantaneous CO2-[Formula: see text]-H+relationship and in vivo blood[Formula: see text]-pH relationship due to the finite reaction times for CO2-[Formula: see text]-H+reactions. The shape of the hysteresis loops was affected by the extent of Actz inhibition of CA in red blood cells and plasma.

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Effect of carbonic anhydrase inhibition on mixed venous CO2 tension in anesthetized dogs

Journal of Applied Physiology ◽

10.1152/jappl.1960.15.3.390 ◽

1960 ◽

Vol 15 (3) ◽

pp. 390-392 ◽

Cited By ~ 18

Author(s):

Stephen M. Cain ◽

Arthur B. Otis

Keyword(s):

Carbonic Anhydrase ◽

Venous Blood ◽

Carbonic Anhydrase Inhibitor ◽

Mixed Venous Blood ◽

Bicarbonate Concentration ◽

Significant Difference ◽

Carbonic Anhydrase Inhibition ◽

Anesthetized Dogs ◽

The Difference ◽

Mixed Venous

The ventilation of one lung in dogs was isolated and that lung continually rebreathed into a small rubber bag. The Pco2 of a sample of the gas in the rebreathing bag was compared with the Pco2 calculated from pH and bicarbonate concentration determined in a sample of mixed venous blood drawn simultaneously. Before the injection of a carbonic anhydrase inhibitor, acetazolamide, the difference between the two values for Pco2 was not significant. After acetazolamide, a highly significant difference (P < 0.001) was found. Apparently, when carbonic anhydrase was inhibited, the dissolved CO2 of mixed venous blood did not attain equilibrium with bicarbonate by the time the blood entered the lung. Submitted on December 18, 1959

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Oxygen respiratory gas analysis by sine-wave measurement: a theoretical model

Journal of Applied Physiology ◽

10.1152/jappl.1996.81.2.985 ◽

1996 ◽

Vol 81 (2) ◽

pp. 985-997 ◽

Cited By ~ 14

Author(s):

C. E. Hahn

Keyword(s):

Gas Exchange ◽

Dead Space ◽

Venous Blood ◽

Sine Wave ◽

Inert Gas ◽

Mixed Venous Blood ◽

Arterial Blood ◽

Partial Pressures ◽

The Mean ◽

Mixed Venous

A sinusoidal forcing function inert-gas-exchange model (C. E. W. Hahn, A. M. S. Black, S. A. Barton, and I. Scott. J. Appl. Physiol. 75: 1863–1876, 1993) is modified by replacing the inspired inert gas with oxygen, which then behaves mathematically in the gas phase as if it were an inert gas. A simple perturbation theory is developed that relates the ratios of the amplitudes of the inspired, end-expired, and mixed-expired oxygen sine-wave oscillations to the airways' dead space volume and lung alveolar volume. These relationships are independent of oxygen consumption, the gas-exchange ratio, and the mean fractional inspired (FIO2) and expired oxygen partial pressures. The model also predicts that blood flow shunt fraction (Qs/QT) is directly related to the oxygen sine-wave amplitude perturbations transmitted to end-expired air and arterial and mixed-venous blood through two simple equations. When the mean FIO2 is sufficiently high for arterial hemoglobin to be fully saturated, oxygen behaves mathematically in the blood like a low-solubility inert gas, and the amplitudes of the arterial and end-expired sine-wave perturbations are directly related to Qs/QT. This relationship is independent of the mean arterial and mixed-venous oxygen partial pressures and is also free from mixed-venous perturbation effects at high forcing frequencies. When arterial blood is not fully saturated, the theory predicts that QS/QT is directly related to the ratio of the amplitudes of the induced-saturation sinusoids in arterial and mixed-venous blood. The model therefore predicts that 1) on-line calculation of airway dead space and end-expired lung volume can be made by the addition of an oxygen sine-wave perturbation component to the mean FIO2; and (2) QS/QT can be measured from the resultant oxygen perturbation sine-wave amplitudes in the expired gas and in arterial and mixed-venous blood and is independent of the mean blood oxygen partial pressure and oxyhemoglobin saturation values. These calculations can be updated at the sine-wave forcing period, typically 2–4 min.

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Mechanism of pulmonary gas exchange and CO2 transport during breath holding

Journal of Applied Physiology ◽

10.1152/jappl.1959.14.5.706 ◽

1959 ◽

Vol 14 (5) ◽

pp. 706-710 ◽

Cited By ~ 20

Author(s):

John C. Mithoefer

Keyword(s):

Gas Exchange ◽

Lung Volume ◽

Venous Blood ◽

Volume Shrinkage ◽

Breath Holding ◽

Mixed Venous Blood ◽

Co2 Transport ◽

Arterial Blood ◽

Mixed Venous ◽

Haldane Effect

Experiments describe the changes in PaCOCO2 and lung volume shrinkage during breath holding with O2 in man and the PaCOCO2, pH and CO2 content of arterial and mixed venous blood during breath holding in the dog. An explanation is offered for the aberrations in CO2 transport and exchange which occur during apnea. A self-perpetuating cycle is established during breath holding which is initiated by the arrest of the ventilatory output of Co2. The arterial PaCOCo2 rises rapidly as a result of decreased clearance of Co2 from venous blood, the concentrating effect of lung volume shrinkage and the Haldane effect from oxygenation of hemoglobin. The venous PaCOCO2 rises more slowly because of the uptake of Co2 by the tissues and the Haldane effect from reduction of oxyhemoglobin. By this mechanism the Co2 output into the lungs progressively falls and eventually stops. The cycle then is reversed and Co2 moves from lungs to arterial blood. Submitted on March 2, 1959

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Modelling Inert Gas Exchange in Tissue and Mixed–Venous Blood Return to the Lungs

Journal of Theoretical Biology ◽

10.1006/jtbi.2001.2278 ◽

2001 ◽

Vol 209 (4) ◽

pp. 431-443 ◽

Cited By ~ 4

Author(s):

J.P. WHITELEY ◽

D.J. GAVAGHAN ◽

C.E.W. HAHN

Keyword(s):

Gas Exchange ◽

Venous Blood ◽

Inert Gas ◽

Mixed Venous Blood ◽

Mixed Venous

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Effects of cocaine on incremental treadmill exercise in horses

Journal of Applied Physiology ◽

10.1152/jappl.1993.75.6.2727 ◽

1993 ◽

Vol 75 (6) ◽

pp. 2727-2733 ◽

Cited By ~ 10

Author(s):

K. H. McKeever ◽

K. W. Hinchcliff ◽

D. F. Gerken ◽

R. A. Sams

Keyword(s):

Right Ventricular ◽

Blood Lactate ◽

Venous Blood ◽

Lactate Concentration ◽

Blood Lactate Concentration ◽

Ventricular Pressure ◽

Mixed Venous Blood ◽

Work Intensity ◽

Venous Blood Lactate ◽

Mixed Venous

Four mature horses were used to test the effects of two doses (50 and 200 mg) of intravenously administered cocaine on hemodynamics and selected indexes of performance [maximal heart rate (HRmax), treadmill velocity at HRmax, treadmill velocity needed to produce a blood lactate concentration of 4 mmol/l, maximal mixed venous blood lactate concentration, maximal treadmill work intensity, and test duration] measured during an incremental treadmill test. Both doses of cocaine increased HRmax approximately 7% (P < 0.05). Mean arterial pressure was 30 mmHg greater (P < 0.05) during the 4- to 7-m/s steps of the exercise test in the 200-mg trial. Neither dose of cocaine had an effect on the responses to exertion of right atrial pressure, right ventricular pressure, or maximal change in right ventricular pressure over time. Maximal mixed venous blood lactate concentration increased 41% (P < 0.05) with the 50-mg dose and 75% (P < 0.05) with the 200-mg dose during exercise. Administration of cocaine resulted in decreases (P < 0.05) in the treadmill velocity needed to produce a blood lactate concentration of 4 mmol/l from 6.9 +/- 0.5 and 6.8 +/- 0.9 m/s during the control trials to 4.4 +/- 0.1 m/s during the 200-mg cocaine trial. Cocaine did not alter maximal treadmill work intensity (P > 0.05); however, time to exhaustion increased by approximately 92 s (15%; P < 0.05) during the 200-mg trial.(ABSTRACT TRUNCATED AT 250 WORDS)

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Pulmonary diffusion in the dog lung

Journal of Applied Physiology ◽

10.1152/jappl.1962.17.6.885 ◽

1962 ◽

Vol 17 (6) ◽

pp. 885-892 ◽

Cited By ~ 7

Author(s):

Albert H. Niden ◽

Charles Mittman ◽

Benjamin Burrows

Keyword(s):

Carbon Monoxide ◽

Pulmonary Artery ◽

Experimental Animal ◽

Venous Blood ◽

Whole Body ◽

Mixed Venous Blood ◽

Pulmonary Diffusion ◽

Perfused Lung ◽

Pulmonary Arterial ◽

Mixed Venous

Methods have been presented for assessing pulmonary diffusion by the “equilibration technique” in the experimental intact dog and perfused lung while controlling ventilation with a whole body respirator. No significant change in diffusion of carbon monoxide was noted between open and closed chest anesthetized animals, with duration of anesthesia in the intact dog, or with duration of perfusion of the isolated dog's lung. There was no demonstrable difference in diffusion when arterialized blood was used as the perfusate in place of mixed venous blood in the lung perfusions suggesting that within the range studied the Po2, Pco2, and pH of pulmonary artery blood does not directly affect the diffusion of carbon monoxide. Retrograde perfusions of dogs' lungs did not significantly alter diffusion, suggesting that pulmonary venous resistance was not significantly lower than pulmonary arterial resistance in the perfused dog lung at the flows and pressures studied. The equilibration technique for measuring pulmonary diffusion and assessing the uniformity of diffusion was well suited to the study of pulmonary diffusing characteristics in the experimental animal. Submitted on January 8, 1962

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An electrical analyzer for carbon dioxide in respiratory gases

Journal of Applied Physiology ◽

10.1152/jappl.1962.17.1.126 ◽

1962 ◽

Vol 17 (1) ◽

pp. 126-130

Author(s):

Leon Bernstein ◽

Chiyoshi Yoshimoto

Keyword(s):

Carbon Dioxide ◽

Thermal Conductivity ◽

Medical Students ◽

Venous Blood ◽

Mixed Venous Blood ◽

The Subject ◽

Respiratory Gases ◽

Rebreathing Method ◽

Mixed Venous

The analyzer described was de signed for measuring the concentration of carbon dioxide in the bag of gas from which the subject rebreathes in the “rebreathing method” for estimating the tension of carbon dioxide in mixed venous blood. Its merits are that it is cheap, robust, simple to construct and to service, easy to operate, and accurate when used by untrained operators. (Medical students, unacquainted with the instrument, and working with written instructions only, obtained at their first attempt results accurate to within ±0.36% [sd] of carbon dioxide.) The instrument is suitable for use by nurse or physician at the bedside, and also for classes in experimental physiology. Some discussion is presented of the theoretical principles underlying the design of analyzers employing thermal conductivity cells. Submitted on July 13, 1961

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Respiratory measurements of cardiac output: from elegant idea to useful test

Journal of Applied Physiology ◽

10.1152/japplphysiol.01074.2001 ◽

2004 ◽

Vol 96 (2) ◽

pp. 428-437 ◽

Cited By ~ 41

Author(s):

Gabriel Laszlo

Keyword(s):

Cardiac Output ◽

Human Subjects ◽

Venous Blood ◽

The Body ◽

Mixed Venous Blood ◽

Indirect Determination ◽

Arterial Blood ◽

Pulmonary Capillary ◽

Pulmonary Arterial ◽

Mixed Venous

The measurement of cardiac output was first proposed by Fick, who published his equation in 1870. Fick's calculation called for the measurement of the contents of oxygen or CO2 in pulmonary arterial and systemic arterial blood. These values could not be determined directly in human subjects until the acceptance of cardiac catheterization as a clinical procedure in 1940. In the meanwhile, several attempts were made to perfect respiratory methods for the indirect determination of blood-gas contents by respiratory techniques that yielded estimates of the mixed venous and pulmonary capillary gas pressures. The immediate uptake of nonresident gases can be used in a similar way to calculate cardiac output, with the added advantage that they are absent from the mixed venous blood. The fact that these procedures are safe and relatively nonintrusive makes them attractive to physiologists, pharmacologists, and sports scientists as well as to clinicians concerned with the physiopathology of the heart and lung. This paper outlines the development of these techniques, with a discussion of some of the ways in which they stimulated research into the transport of gases in the body through the alveolar membrane.

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Analysis of PCO2 differences during rebreathing due to slow pH equilibration in blood

Journal of Applied Physiology ◽

10.1152/jappl.1978.45.5.666 ◽

1978 ◽

Vol 45 (5) ◽

pp. 666-673 ◽

Cited By ~ 7

Author(s):

A. Bidani ◽

E. D. Crandall

Keyword(s):

Quantitative Analysis ◽

Gas Exchange ◽

Red Blood Cells ◽

Blood Cells ◽

Transport Processes ◽

O2 Uptake ◽

Lung Capillaries ◽

Mixed Venous ◽

Co2 Elimination

A quantitative analysis of the reaction and transport processes that occur in blood during and after gas exchange has been used to investigate mechanisms that might account for positive alveolar-mixed venous (A-V) and alveolar-arterial (Aa) PCO2 differences during rebreathing. The analysis was used to determine PCO2 changes that take place in blood as it travels from veins to arteries under conditions in which no CO2 is exchanged in the lung. The predicted A-V and Aa PCO2 differences are all positive and lie within the range of reported measured values. The differences are due to disequilibrium of [H+] between plasma and red blood cells, and to disequilibrium of the reactions CO2 in equilibrium HCO3- + H+ in plasma, as blood leaves the tissue and/or lung capillaries. The differences are increased with exercise and with continued O2 uptake in the lung, the latter due to the Haldane shift. We conclude that the two disequilibria and the Haldane shift contribute to the reported PCO2 differences in rebreathing animals but may not fully account for them. These mechanisms cannot explain any PCO2 differences that might exist during net CO2 elimination from blood in the lung.

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