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Cardiogenic oscillations: A potential mechanism enhancing oxygenation during apneic respiration
Medical Hypotheses
8: 393-400,
CARDIOGENIC OSCILLATIONS: DURING APNEIC RESPIRATION
1982
A POTENTIAL MECHANISM
ENHANCING
OXYGENATION
Arthur S. Slutsky and Robert Brown. Veterans Administration Medical Center, 1400 VFW Parkway, West Roxbury, Massachusetts 02132.
ABSTRACT Adequate oxygen uptake by the lungs for prolonged apneic periods is possible even in the absence of respiratory movements provided The mechanism by which that 100% O2 is applied at the airway opening. adequate gas mixing takes place during this apneic respiration is not entirely clear. We propose that a major mechanism producing O2 uptake during apnea is the enhanced gas mixing secondary to airflow generated by the beating heart.
Supported in part by the Veterans Administration Heart, Lung and Blood Institute Grant 8HL26566.
393
and the National
INTRODUCTION It has been known since the studies of Volhard (l), early this century, that oxygen uptake by the lungs can take place in the absence of any respiratory movements in curarized rabbits supplied with 100% 02 at atmospheric pressure at the airway opening. However CO2 elimination was extremely ineffective using this technique and Volhard's animals died within one to two hours due to CO retention with its attendant acid-base disturbances. Although this techiique of apneic respiration has also been studied in dogs (2,3) and humans (4,5), the mechanism by which arterial oxygenation is maintained at relatively normal levels is still unclear. Draper and Whitehead (2) popularized this technique in the late 1940's and coined the expression "diffusion respiration" to describe it. They suggested that the mechanism responsible for this phenomenon was the "hemoglobin-oxygen pump" which actively removes 0 from the alveoli (3). They postulated that there was no such pump for C and thus CO accumulated as soon as ventilatory movements ceased. Ho $ mdahl (6) ex $ensively studied the mechanisms and physiological consequences of this technique and suggested that since the volume of 0 taken up by the blood is greater than the volume of CO eliminated by 8he blood, a subatmospheric pressure is established ?n the alveoli which causes external air (or oxygen) to be drawn into the lungs by bulk transport (convection). He felt that a better term to describe this phenomenon was "apneic diffusion oxygenation" (ADO). In contrast Comroe and Dripps (7) suggested that vigorous cardiac contractions, diaphragmatic flutter and ciliary action caused enough movement of air to provide adequate oxygenation, but they did not provide any theoretical basis or experimental results to show that these mechanisms might indeed play a major role in oxygenating the arterial blood. In fact, it has been known since the late nineteenth century (8) that cardiac contractions do generate pressure pulsations and airflow in the tracheobronchial tree. West and Hugh Jones (9) quantitated the airflow produced in lobar and segmental bronchi of humans by such pulsations and proposed that the airflow occurring with each cardiac cycle might play a significant role in promoting gas exchange by mixing gas between the anatomic dead space and the alveolar space. In the remainder of this paper we will show that the airflow generated by the beating heart could play a key role in the maintenance of oxygenation during apneic respiration. This hypothesis is based on a theoretical model of the gas mixing that would occur within the lung due solely to the action of cardiogenic oscillations. THEORETICAL
ANALYSIS
The analysis has been presented in detail previously (10) and is based on a theoretical model developed to explain the effective CO elimination observed with high frequency, low tidal volume ventila z. ion The key concept is (11). Thus, only a brief summary will be given here. that synchronous with each heart beat the heart generates oscillatory airflow within the tracheobronchial tree. This airflow acts to enhance gas mixing within the lung by a number of different mechanisms, as described below.
394
Airway Opening
Alveoli
ZONE A.
FLOWS
6.
MIXING
Dmol Lamina[ Wel I-Mixed I Dispersion I
Figure 1: Schematic representation of cross-sectional area of the lung and the corresponding flows (velocities) and mixing mechanisms operative in each zone. In zone I, major mixing mechanism is molecular diffusion; in zone II, laminar dispersion and in zone III, turbulence and well-mixed flow due to the high velocities.
Conceptually, the lung is dividided into three zones as shown schema tically in Figure 1. In zone I, the alveolar region, the cross-sectional area of the lung is very large; thus for any given tracheal flow rate, the velocities in this region are virtually zero and molecular diffusion is the dominant mixing mechanism. In zone II, velocities are relatively low and laminar flow regimes are thought to exist. In this region, we use the analytic theory developed by Chatwin (12) to determine the enhancement of gas mixing due to the oscillatory flows generated by the heart. In the upper airways, zone III, velocities are relatively high and the theory developed previously (11,13) for turbulent and well-mixed flow is used to quantify the enhanced gas mixing. In both zones II and III, the augmentation of the mixing process due to cardiac action is greater for larger flows. In addition, the junction between various zones is not fixed but depends very much on the flow rate. For example, in the lower limit when airflow is zero (no cardiac oscillations), the entire lung can be thought of as just zone I, since molecular diffusion is the only mixing mechanism operative. 395
\iosc (m/s /see
1
Figure 2: Flux of O2 and CO2 versus oscillatory flow rate (Vosc = heart rate x volume displaced by each stroke). Room air denotes 0 flux with 21% 02 at the airway opening and CO2 denotes CO2 flux with 5.&X CO2 in the alveoli.
This formulation has been applied to the lung using the concept of resistance (R) to diffusion (13-15). The concept is similar to the well known flow resistance which is equal to the driving pressure divided by the resultant flow. In the case of diffusional resistance, the driving pressure (AP) is the difference in partial pressures of the gas between the two regions (in this case - the alveolar minus the airway opening pressure) and the flow is the flux (J) of the gas under study. Thus, one can write J = BP/R. For any given diffusional resistance, if the difference in partial pressure of one gas is double that of a second gas, then the flux of the first gas will be double that of the second. The diffusional resistance of the lung as a whole is a function of the magnitude of the flow and the molecular diffusivity of the gas. The formulae by which R is calculated have been given in greater detail in an earlier publication (10). To quantify the effect on gas exchange we have calculated the CO2 elimination from the lung and the O2 delivery to the alveolar region based
396
on this theory. Since the degree of gas mixing is related to the airflow generated by the heart,_we have plotted these predicted CO and 02 fluxes at various flow rates (Vosc = heart rate x gas volume disp 1 aced by each stroke). In calculating the predictions, we have assumed that the flow generated by each heart beat is.equally distributed to all branches of the tracheobronchial tree, so that Vosc represents the flow in any generation. Results based on this analysis as applied to the anatomy of the human lung as described by Weibel (16) is presented in Figure 2. For this graph, we have assumed that the partial pressure at the airway opening for O2 is either 713 (100% 0 ) or 150 mm Hg (air). For CO2 we have assumed the partial pressure to be 4 6 mm Hg in the alveoli. Since the transition between zone II and zone III is not known with certainty, we have assumed the transition occurs when the Reynolds number (Re = ud/v, where u = velocity, d = diameter, and v = kinematic viscoscity) is equal to 15. This value is midway between values that have been previously suggested in the literature (11, 13). Note that at zero Vosc (Figure 2) corresponding to the situation where there are no cardiogenic oscillations, the fluxes of gases are very small: 0.73 and 0.11 mls/minute 02 for the cases with 100% O2 and 21% 02 respectively at the airway opening. The CO2 elimination would be even smaller, (0.04 mls/minute). However, as Vosc increases, the 0 and CO fluxes increase in a relatively linear fashion. The values o $ Vosc ii humans are not known but to a first approximation are about equal to the value of the cardiac output (17). If we assume a cardiac output of 6 l/min (Vosc = 100 mls/s) the 02 fluxes would be about 100 and 15 mlsfminute for 100% 02 and 21% O2 respectively, and the CO2 flux would be about 6 mls/minute. DISCUSSION
AND CONCLUSIONS
We have shown that based on theoretical considerations cardiogenic oscillations could produce 0 fluxes of about 50% of the average 0 metabolic consumption observed ir? humans if the gas at the airway open&g is 100% 02. However, CO clearance from the lung is predicted to be substantially less than the 8 02 metabolic production. The major explanation for this dichotomy is that according to the theoretical model, the flux of gas is directly proportional to difference in partial pressure between the airway opening and the alveoli. Thus, the difference in partial pressure for CO2 is about 5-7% that of the O2 difference (for 100% 02). This fact could also explain why this mechanism is relatively inefficient for 0 transport when the gas at the airway opening is room air rather than 180% O2 (Figure 2). These predictions are in accord with data in the literature which show that apneic respiration is not very effective in removing CO and also that adequate oxygenation cannot be maintained if It is important to point out the gas at zhe airway opening is room air. that the theoretical model is based on a number of assumptions which have been discussed in detail previously (11) and thus, these results should not be interpreted as providing exact values of 0 and CO fluxes. Rather the results of the model show that cardiogenic os?illatio& are potentially an important 02 delivery mechanism. A major unknown is the value of vosc, since the 0 flux is critially dependent on Vosc, as can be seen from Figure 2. Thus: if Vosc was in fact 50 ml or 150 mls, the corresponding O2 flux on 100% O2 would be 55 and 150 mls/min respectively.
397
We are not proposing that cardiac action is the only mechanism producing adequate arterial oxygenation during apneic respiration but rather we propose it acts in addition to the other postulated mechanisms. Holmdahl (6) on the other hand, proposed that cardio-respiratory movements were not necessary for apneic diffusion oxygenation based on an experiment in which he widely opened the chest in a dog and still found 02 uptake. However, this surgical maneuver does not abolish cardiogenic oscillations in dogs (8) and thus it was not an adequate test of the hypothesis. In addition, due to the development of atelectasis in the dog studied by Holmdahl, the period of the experiment was only two to three minutes, too short a period of time to determine if arterial oxygenation would have deteriorated under these conditions. Others have proposed that the bulk transport of gas to the alveoli due to the fact that the respiratory quotient is less than one, is the dominant mechanism (18). There are a number of predictions from each theory which are refutable. With the theory based on cardiogenic oscillations effective gas exchange depends on the airflow generated by the beating heart to be effective. Thus, an intervention that would limit cardiogenic oscillations should reduce the effectiveness of apneic respiration substantially. If, however, bulk transport of gas due to the difference in 02 consumption and CO2 production is important, then interventions which produce a respiratory quotient of 1.0 should abolish the adequate oxygenation observed during apneic respiration. The cardiac action theory would predict that there would be relatively little change in oxygenation by this latter intervention. If mixing due to cardiogenic oscillations is important during apneic respiration there may be clinical implications as well. For example, dis connecting patients from mechanical ventilators has been suggested as a method of testing for brain death since adequate arterial oxygenation occurs even if the patient does not make respiratory efforts (19). However, this test might be dangerous in situations in which the gas mixing due to cardiac action is markedly reduced such as diffuse peripheral bronchoconstriction (11) or cardiac tamponade (20).
398
REFERENCES 1.
Volhard F. Uber Kurstliche Atmung durch ventilation der trachea und eine einfache Vorrichtung zur rhytmischen Kiinstlichen Atmung. Munchen med Wehnsch 55: 209, 1908.
2.
Draper WB, Whitehead RW. Diffusion respiration in the dog anesAnaesthesiology 5: 262, 1944. thetized by pentothal sodium.
3.
Draper WB, Whitehead RW. The phenomenon Anesthesia and Analgesia 28: 307, 1949.
of diffusion
4.
Enghoff H, Holmdahl M Hison, Risholm L. man. Nature 168: 830, 1951.
Diffusion
5.
Frumin MJ, Epstein RM, Cohen G. Apneic oxygenation Anaesthesiology 20(6): 789, 1959.
6.
Pulmonary uptake of oxygen, acid-base metabolism, Holmdahl M Hison. and circulation during prolonged apnoea. Acta Chirurgica Scandinavita 212: 7, 1956.
7.
Comroe JH Jr, Dripps RD Jr. of Physiology 7: 653, 1945.
8.
Haycroft JB, Edie R. The cardiopneumatic Physiology (London) 12: 426, 1891.
9.
West JB, Hugh-Jones, P. Pulsatile gas flow in bronchi caused by the Journal of Applied Physiology 16: 697, 1961. heart beat.
10.
Slutsky AS. Gas mixing by cardiogenic oscillations: A quantitative, theoretical analysis. Journal of Applied Physiology:Respiratory Environmental and Exercise Physiology (in press).
11.
Slutsky AS, Drazen JM, Ingram RH Jr, Kamm RD, Shapiro AH, Fredberg JJ, Loring SH, Lehr J. Effective pulmonary ventilation with small volume oscillations at high frequency. Science 209: 609, 1980.
12.
Chatwin PC. On the longitudinal dispersion of passive contaminant in oscillatory flow in tubes. Journal of Fluid Mechanics 71(3): 513, 1975.
13.
Fredberg JJ. Augmented diffusion in the airways can support pulmonary gas exchange. Journal of Applied Physiology: Respiratory, Environmental and Exercise Physiology 49: 232, 1980.
14.
Sikand RS, Magnussen H, Scheid P, Piiper J. Convective and diffusive gas mixing in human lungs: experiments and model analysis. Journal of Applied Physiology 49(3): 362, 1976.
15.
Piiper J. Series ventilation, diffusion in airways, and stratified inhomogeneity. Federation Proceedings 38(l): 17, 1979.
16.
Weibel, 1963.
17.
Cara M. Influence de la circulation sue le taux alveolaire carbonique. C.R. Sot. Biol. 150, 1956.
ER.
Morphometry
Applied
physiology.
399
respiration
in
in man.
Annals of Review
movements.
of the Human Lung.
respiration.
Springer,
Journal
of
Berlin, du gaz
18.
Bartlett RG Jr, Bruback HF, Specht H. Demonstration of aventilatory mass flow during ventilation and apnea in man. Journal of Applied Physiology 14(l): 97, 1959.
19.
Milhaud A, Riboulot M, Gayet H. Disconnecting tests and oxygen uptake in the diagnosis of total brain death. Annals of the New York Academy of Science 315: 241, 1978.
20.
Fukuchi Y, Cosio M, Kelly S, Engel LA. Influence of pericardial fluid on cardiogenic gas mixing in the lung. Journal of Applied Physiology: Respiratory, Environmental and Exercise Physiology 42: 5, 1977.
400
8: 393-400,
CARDIOGENIC OSCILLATIONS: DURING APNEIC RESPIRATION
1982
A POTENTIAL MECHANISM
ENHANCING
OXYGENATION
Arthur S. Slutsky and Robert Brown. Veterans Administration Medical Center, 1400 VFW Parkway, West Roxbury, Massachusetts 02132.
ABSTRACT Adequate oxygen uptake by the lungs for prolonged apneic periods is possible even in the absence of respiratory movements provided The mechanism by which that 100% O2 is applied at the airway opening. adequate gas mixing takes place during this apneic respiration is not entirely clear. We propose that a major mechanism producing O2 uptake during apnea is the enhanced gas mixing secondary to airflow generated by the beating heart.
Supported in part by the Veterans Administration Heart, Lung and Blood Institute Grant 8HL26566.
393
and the National
INTRODUCTION It has been known since the studies of Volhard (l), early this century, that oxygen uptake by the lungs can take place in the absence of any respiratory movements in curarized rabbits supplied with 100% 02 at atmospheric pressure at the airway opening. However CO2 elimination was extremely ineffective using this technique and Volhard's animals died within one to two hours due to CO retention with its attendant acid-base disturbances. Although this techiique of apneic respiration has also been studied in dogs (2,3) and humans (4,5), the mechanism by which arterial oxygenation is maintained at relatively normal levels is still unclear. Draper and Whitehead (2) popularized this technique in the late 1940's and coined the expression "diffusion respiration" to describe it. They suggested that the mechanism responsible for this phenomenon was the "hemoglobin-oxygen pump" which actively removes 0 from the alveoli (3). They postulated that there was no such pump for C and thus CO accumulated as soon as ventilatory movements ceased. Ho $ mdahl (6) ex $ensively studied the mechanisms and physiological consequences of this technique and suggested that since the volume of 0 taken up by the blood is greater than the volume of CO eliminated by 8he blood, a subatmospheric pressure is established ?n the alveoli which causes external air (or oxygen) to be drawn into the lungs by bulk transport (convection). He felt that a better term to describe this phenomenon was "apneic diffusion oxygenation" (ADO). In contrast Comroe and Dripps (7) suggested that vigorous cardiac contractions, diaphragmatic flutter and ciliary action caused enough movement of air to provide adequate oxygenation, but they did not provide any theoretical basis or experimental results to show that these mechanisms might indeed play a major role in oxygenating the arterial blood. In fact, it has been known since the late nineteenth century (8) that cardiac contractions do generate pressure pulsations and airflow in the tracheobronchial tree. West and Hugh Jones (9) quantitated the airflow produced in lobar and segmental bronchi of humans by such pulsations and proposed that the airflow occurring with each cardiac cycle might play a significant role in promoting gas exchange by mixing gas between the anatomic dead space and the alveolar space. In the remainder of this paper we will show that the airflow generated by the beating heart could play a key role in the maintenance of oxygenation during apneic respiration. This hypothesis is based on a theoretical model of the gas mixing that would occur within the lung due solely to the action of cardiogenic oscillations. THEORETICAL
ANALYSIS
The analysis has been presented in detail previously (10) and is based on a theoretical model developed to explain the effective CO elimination observed with high frequency, low tidal volume ventila z. ion The key concept is (11). Thus, only a brief summary will be given here. that synchronous with each heart beat the heart generates oscillatory airflow within the tracheobronchial tree. This airflow acts to enhance gas mixing within the lung by a number of different mechanisms, as described below.
394
Airway Opening
Alveoli
ZONE A.
FLOWS
6.
MIXING
Dmol Lamina[ Wel I-Mixed I Dispersion I
Figure 1: Schematic representation of cross-sectional area of the lung and the corresponding flows (velocities) and mixing mechanisms operative in each zone. In zone I, major mixing mechanism is molecular diffusion; in zone II, laminar dispersion and in zone III, turbulence and well-mixed flow due to the high velocities.
Conceptually, the lung is dividided into three zones as shown schema tically in Figure 1. In zone I, the alveolar region, the cross-sectional area of the lung is very large; thus for any given tracheal flow rate, the velocities in this region are virtually zero and molecular diffusion is the dominant mixing mechanism. In zone II, velocities are relatively low and laminar flow regimes are thought to exist. In this region, we use the analytic theory developed by Chatwin (12) to determine the enhancement of gas mixing due to the oscillatory flows generated by the heart. In the upper airways, zone III, velocities are relatively high and the theory developed previously (11,13) for turbulent and well-mixed flow is used to quantify the enhanced gas mixing. In both zones II and III, the augmentation of the mixing process due to cardiac action is greater for larger flows. In addition, the junction between various zones is not fixed but depends very much on the flow rate. For example, in the lower limit when airflow is zero (no cardiac oscillations), the entire lung can be thought of as just zone I, since molecular diffusion is the only mixing mechanism operative. 395
\iosc (m/s /see
1
Figure 2: Flux of O2 and CO2 versus oscillatory flow rate (Vosc = heart rate x volume displaced by each stroke). Room air denotes 0 flux with 21% 02 at the airway opening and CO2 denotes CO2 flux with 5.&X CO2 in the alveoli.
This formulation has been applied to the lung using the concept of resistance (R) to diffusion (13-15). The concept is similar to the well known flow resistance which is equal to the driving pressure divided by the resultant flow. In the case of diffusional resistance, the driving pressure (AP) is the difference in partial pressures of the gas between the two regions (in this case - the alveolar minus the airway opening pressure) and the flow is the flux (J) of the gas under study. Thus, one can write J = BP/R. For any given diffusional resistance, if the difference in partial pressure of one gas is double that of a second gas, then the flux of the first gas will be double that of the second. The diffusional resistance of the lung as a whole is a function of the magnitude of the flow and the molecular diffusivity of the gas. The formulae by which R is calculated have been given in greater detail in an earlier publication (10). To quantify the effect on gas exchange we have calculated the CO2 elimination from the lung and the O2 delivery to the alveolar region based
396
on this theory. Since the degree of gas mixing is related to the airflow generated by the heart,_we have plotted these predicted CO and 02 fluxes at various flow rates (Vosc = heart rate x gas volume disp 1 aced by each stroke). In calculating the predictions, we have assumed that the flow generated by each heart beat is.equally distributed to all branches of the tracheobronchial tree, so that Vosc represents the flow in any generation. Results based on this analysis as applied to the anatomy of the human lung as described by Weibel (16) is presented in Figure 2. For this graph, we have assumed that the partial pressure at the airway opening for O2 is either 713 (100% 0 ) or 150 mm Hg (air). For CO2 we have assumed the partial pressure to be 4 6 mm Hg in the alveoli. Since the transition between zone II and zone III is not known with certainty, we have assumed the transition occurs when the Reynolds number (Re = ud/v, where u = velocity, d = diameter, and v = kinematic viscoscity) is equal to 15. This value is midway between values that have been previously suggested in the literature (11, 13). Note that at zero Vosc (Figure 2) corresponding to the situation where there are no cardiogenic oscillations, the fluxes of gases are very small: 0.73 and 0.11 mls/minute 02 for the cases with 100% O2 and 21% 02 respectively at the airway opening. The CO2 elimination would be even smaller, (0.04 mls/minute). However, as Vosc increases, the 0 and CO fluxes increase in a relatively linear fashion. The values o $ Vosc ii humans are not known but to a first approximation are about equal to the value of the cardiac output (17). If we assume a cardiac output of 6 l/min (Vosc = 100 mls/s) the 02 fluxes would be about 100 and 15 mlsfminute for 100% 02 and 21% O2 respectively, and the CO2 flux would be about 6 mls/minute. DISCUSSION
AND CONCLUSIONS
We have shown that based on theoretical considerations cardiogenic oscillations could produce 0 fluxes of about 50% of the average 0 metabolic consumption observed ir? humans if the gas at the airway open&g is 100% 02. However, CO clearance from the lung is predicted to be substantially less than the 8 02 metabolic production. The major explanation for this dichotomy is that according to the theoretical model, the flux of gas is directly proportional to difference in partial pressure between the airway opening and the alveoli. Thus, the difference in partial pressure for CO2 is about 5-7% that of the O2 difference (for 100% 02). This fact could also explain why this mechanism is relatively inefficient for 0 transport when the gas at the airway opening is room air rather than 180% O2 (Figure 2). These predictions are in accord with data in the literature which show that apneic respiration is not very effective in removing CO and also that adequate oxygenation cannot be maintained if It is important to point out the gas at zhe airway opening is room air. that the theoretical model is based on a number of assumptions which have been discussed in detail previously (11) and thus, these results should not be interpreted as providing exact values of 0 and CO fluxes. Rather the results of the model show that cardiogenic os?illatio& are potentially an important 02 delivery mechanism. A major unknown is the value of vosc, since the 0 flux is critially dependent on Vosc, as can be seen from Figure 2. Thus: if Vosc was in fact 50 ml or 150 mls, the corresponding O2 flux on 100% O2 would be 55 and 150 mls/min respectively.
397
We are not proposing that cardiac action is the only mechanism producing adequate arterial oxygenation during apneic respiration but rather we propose it acts in addition to the other postulated mechanisms. Holmdahl (6) on the other hand, proposed that cardio-respiratory movements were not necessary for apneic diffusion oxygenation based on an experiment in which he widely opened the chest in a dog and still found 02 uptake. However, this surgical maneuver does not abolish cardiogenic oscillations in dogs (8) and thus it was not an adequate test of the hypothesis. In addition, due to the development of atelectasis in the dog studied by Holmdahl, the period of the experiment was only two to three minutes, too short a period of time to determine if arterial oxygenation would have deteriorated under these conditions. Others have proposed that the bulk transport of gas to the alveoli due to the fact that the respiratory quotient is less than one, is the dominant mechanism (18). There are a number of predictions from each theory which are refutable. With the theory based on cardiogenic oscillations effective gas exchange depends on the airflow generated by the beating heart to be effective. Thus, an intervention that would limit cardiogenic oscillations should reduce the effectiveness of apneic respiration substantially. If, however, bulk transport of gas due to the difference in 02 consumption and CO2 production is important, then interventions which produce a respiratory quotient of 1.0 should abolish the adequate oxygenation observed during apneic respiration. The cardiac action theory would predict that there would be relatively little change in oxygenation by this latter intervention. If mixing due to cardiogenic oscillations is important during apneic respiration there may be clinical implications as well. For example, dis connecting patients from mechanical ventilators has been suggested as a method of testing for brain death since adequate arterial oxygenation occurs even if the patient does not make respiratory efforts (19). However, this test might be dangerous in situations in which the gas mixing due to cardiac action is markedly reduced such as diffuse peripheral bronchoconstriction (11) or cardiac tamponade (20).
398
REFERENCES 1.
Volhard F. Uber Kurstliche Atmung durch ventilation der trachea und eine einfache Vorrichtung zur rhytmischen Kiinstlichen Atmung. Munchen med Wehnsch 55: 209, 1908.
2.
Draper WB, Whitehead RW. Diffusion respiration in the dog anesAnaesthesiology 5: 262, 1944. thetized by pentothal sodium.
3.
Draper WB, Whitehead RW. The phenomenon Anesthesia and Analgesia 28: 307, 1949.
of diffusion
4.
Enghoff H, Holmdahl M Hison, Risholm L. man. Nature 168: 830, 1951.
Diffusion
5.
Frumin MJ, Epstein RM, Cohen G. Apneic oxygenation Anaesthesiology 20(6): 789, 1959.
6.
Pulmonary uptake of oxygen, acid-base metabolism, Holmdahl M Hison. and circulation during prolonged apnoea. Acta Chirurgica Scandinavita 212: 7, 1956.
7.
Comroe JH Jr, Dripps RD Jr. of Physiology 7: 653, 1945.
8.
Haycroft JB, Edie R. The cardiopneumatic Physiology (London) 12: 426, 1891.
9.
West JB, Hugh-Jones, P. Pulsatile gas flow in bronchi caused by the Journal of Applied Physiology 16: 697, 1961. heart beat.
10.
Slutsky AS. Gas mixing by cardiogenic oscillations: A quantitative, theoretical analysis. Journal of Applied Physiology:Respiratory Environmental and Exercise Physiology (in press).
11.
Slutsky AS, Drazen JM, Ingram RH Jr, Kamm RD, Shapiro AH, Fredberg JJ, Loring SH, Lehr J. Effective pulmonary ventilation with small volume oscillations at high frequency. Science 209: 609, 1980.
12.
Chatwin PC. On the longitudinal dispersion of passive contaminant in oscillatory flow in tubes. Journal of Fluid Mechanics 71(3): 513, 1975.
13.
Fredberg JJ. Augmented diffusion in the airways can support pulmonary gas exchange. Journal of Applied Physiology: Respiratory, Environmental and Exercise Physiology 49: 232, 1980.
14.
Sikand RS, Magnussen H, Scheid P, Piiper J. Convective and diffusive gas mixing in human lungs: experiments and model analysis. Journal of Applied Physiology 49(3): 362, 1976.
15.
Piiper J. Series ventilation, diffusion in airways, and stratified inhomogeneity. Federation Proceedings 38(l): 17, 1979.
16.
Weibel, 1963.
17.
Cara M. Influence de la circulation sue le taux alveolaire carbonique. C.R. Sot. Biol. 150, 1956.
ER.
Morphometry
Applied
physiology.
399
respiration
in
in man.
Annals of Review
movements.
of the Human Lung.
respiration.
Springer,
Journal
of
Berlin, du gaz
18.
Bartlett RG Jr, Bruback HF, Specht H. Demonstration of aventilatory mass flow during ventilation and apnea in man. Journal of Applied Physiology 14(l): 97, 1959.
19.
Milhaud A, Riboulot M, Gayet H. Disconnecting tests and oxygen uptake in the diagnosis of total brain death. Annals of the New York Academy of Science 315: 241, 1978.
20.
Fukuchi Y, Cosio M, Kelly S, Engel LA. Influence of pericardial fluid on cardiogenic gas mixing in the lung. Journal of Applied Physiology: Respiratory, Environmental and Exercise Physiology 42: 5, 1977.
400