| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Department of Anesthesiology, University of California Davis, Davis, California 95616
 |
ABSTRACT |
|---|
 TOP
 ABSTRACT
 INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
The relative contribution of the pulmonary and bronchial circulatory systems to heat and water exchange in normal lungs was evaluated in 20 isolated, in situ perfused dog lungs and in four patients undergoing elective cardiopulmonary bypass. In isolated dog lungs, if the pulmonary artery was perfused at a nominal flow rate (0.5 l/min), bronchial artery perfusion (up to 70 ml/min) did not significantly affect the expired gas temperature. When the lungs were not perfused through either system, 8 min of ventilation with cool, dry gas decreased the temperature of the expired gas by 6.2 ± 1.4°C. Selective perfusion of bronchial arteries at 68 ± 10 mmHg resulted in a mean flow rate of 28 ± 16 ml/min and increased the average temperature of the expired gas by 0.6°C. An increase in the rate of bronchial arterial perfusion to 55 ± 14 ml/min increased the average temperature of the expired gas by 1.3°C. The time constant for equilibration of tritiated water between the perfusate and the lung parenchyma was 130 ± 33 min for pulmonary arterial perfusion and 35 ± 13 min for combined bronchial and pulmonary perfusion, which indicated that filtration of water from high-pressure bronchial vessels facilitated water exchange in the lung interstitium. The rate of tracer equilibration was similar between the perfusate and gas in both variants of perfusion, but the ratios of tracer gas to perfusate were different (0.42 ± 0.06 for pulmonary, 0.98 ± 0.07 for combined), which indicates that bronchial vessels contribute mainly to the hydration of the bronchial mucosa. In humans, the bronchial blood flow was capable of maintaining heat supply after the initiation of cardiopulmonary bypass. Before bypass, when both pulmonary and bronchial blood flow were present, the mean time constant of the temperature decay after a switch to ventilation with cool, dry gas was 35 ± 12 s. The average temperature difference between the blood and expired gas was 2.4 ± 0.50°C. After 5 min of dry gas ventilation, the temperature difference between the expired gas and initial blood temperature decreased an average of 3.8 ± 0.06°C (P < 0.05). The time constant of temperature decay increased to 56 ± 14 s (P < 0.05). We conclude that bronchial perfusion has a less important role in the temperature balance of the respiratory tract compared with pulmonary arterial perfusion because heat flux is "flow limited" but is important in providing water for hydration of the mucosal surface and interstitial compartments of peribronchial tissues.
lung; heat exchange; bronchial arteries; pulmonary circulation; water transport; bronchial mucosa
| |
INTRODUCTION |
|---|
|
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
HEAT AND WATER EXCHANGE within the respiratory tract determines the temperature of the bronchial mucosa and the osmolarity and viscosity of the mucosal fluids. Inadequate heat exchange during hyperventilation may decrease mucosal temperature and lead to bronchoconstriction (8, 14). Increases in the osmolarity of the mucosal fluids may contribute to the failure of respiratory defense mechanisms in patients with cystic fibrosis or inflammation (9, 23). The heat and water that are transferred to condition the ambient air come from the walls of the bronchial tree and are replenished by the blood flow to the bronchial tissues (18, 24, 32). Previously, it was believed that the conditioning of inspired air occurred primarily in the upper airways and that the bronchial blood supply adequately provided the heat and water for this process. However, controlled studies have shown that conditioning of the inspired air actually occurs along nearly the entire length of the bronchial tree, up to the 10th or 12th generation, and unconditioned air may penetrate deep into the peripheral airways (16, 19, 20). Solway et al. (30) have shown a prominent role of the pulmonary circulatory system as a heat source to the lung. Although the bronchial blood flow is directed largely to the primary sites of heat exchange, the observed cooling of the pulmonary arterial blood, the esophagus, and the development of bronchospasm in hyperventilated patients suggests that the reserves of this system are limited (8, 9, 30). The role of the bronchial circulatory system as a source of extravascular fluid in acute lung injury has been evaluated previously by us (3, 29) and others (1, 7, 35). Other studies have demonstrated a substantial contribution of the bronchial circulation to transvascular fluid exchange and the development of both pulmonary edema and bronchial wall edema (22). The rate of water distribution from the two vascular systems into the lung interstitium, the rate of water transfer into the mucosal tissues, and its subsequent rate of evaporation into the exhaled gas have not been previously studied.
We hypothesized that the pulmonary heat and water exchange with respired gas is "flow limited" in the walls of bronchial tree by the hemodynamics of bronchial circulation. The goal of this study was to determine the relative contributions of the two systems of lung circulation, pulmonary and bronchial, to the processes of heat and water exchange with inspired air. The first aim was to determine the relative contribution of both circulatory systems to heat exchange during normal ventilation using isolated, perfused canine lungs. However, in dogs, the bronchial tree is the primary heat-exchange system. Thus the relative role of the bronchial circulation in heat exchange may be different from that in humans. Therefore, we also performed comparative studies in human lungs during elective cardiopulmonary bypass. The second aim was to determine the rate of equilibration of tritiated water (THO) between the circulation and the respired air and the rate of humidification of the inspired air during selective perfusion of the two vascular systems, by using isolated canine lungs.
| |
METHODS |
|---|
|
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
Specific Protocols
1) To investigate the relative contributions of pulmonary and bronchial perfusion to lung heat exchange, we performed selective perfusion of the lung circulatory systems in isolated, perfused lungs from beagles (9-11 kg). In seven preparations, we perfused only the pulmonary arteries, and the pulmonary blood flow was varied between 0.1 and 2 l/min. In these experiments, the bronchial arteries and vein were ligated so that bronchial blood flow was zero. In five additional preparations, both the pulmonary artery and the thoracic aorta were perfused simultaneously, or only the bronchial arteries were perfused, as described in detail previously (11). To provide two different rates of bronchial perfusion, the perfusion pressure was set at either 50-60 or 90-100 mmHg. Perfusion lasted for 15-20 min because perfusate was not recovered and was partially lost to the body via anastomoses in the mediastinum. Total flow through the isolated portion of aorta varied from 25-40 (at low pressure) to 80-120 (at high pressure) ml/min. Concurrent recordings of tracheal airway temperature changes were compared.2) To investigate the contribution of pulmonary and bronchial vessels to water exchange with the respired gas, the same modes of perfusion were used. Isolated lung preparations from eight mongrel dogs (12-16 kg) were used for these studies. In four preparations, only the pulmonary artery was perfused with no bronchial blood flow. In the remaining four preparations, the pulmonary and bronchial arteries were perfused simultaneously. Perfusion of the bronchial arteries utilized a second roller pump, connected to the same perfusate reservoir.
3) To investigate role of the two arterial systems in heat exchange in humans, we measured the temperature changes in the expired gas in the tracheas of intubated patents (n = 4) undergoing cardiopulmonary bypass. Measurements were done before bypass (both pulmonary and bronchial blood flow present) and immediately after the onset of bypass (only bronchial blood flow).
General Methodologies, Animal Studies
Isolated, perfused lungs.
After institutional Animal Care and Use Committee approval, in situ
isolated, perfused, ventilated lungs were prepared as previously
described (11, 27) and as illustrated in Fig.
1. Dogs were anesthetized with a bolus of
pentobarbital sodium (30 mg/kg) followed by a maintenance
infusion titrated to hemodynamic and reflex responses. A cuffed
endotracheal tube (7.5-8.0 mm ID) was placed, heparin (1,000 U/kg)
was administered, and the dogs were then exsanguinated via a carotid
arterial catheter. A median sternotomy was performed, and the pulmonary
artery and left atrium were cannulated with large-bore plastic
catheters. Ligatures were placed around the superior and inferior venae
cavae, and brachiocephalic and left subclavian arteries, as well as the
descending thoracic aorta. In addition, the intercostal arteries and
veins from the third through the ninth intercostal spaces were isolated
and ligated bilaterally.
|
1. The
inspiratory-to-expiratory ratio was 1:1, and the peak inspiratory pressure was 21 ± 3 cmH2O with positive
end-expiratory pressure of 6-8 cmH2O. The inspired gas
was delivered either directly from the respirator (cool, dry) or
through a humidifier (model SCT 3000, Marquest Medical Products,
Englewood, CO) (heated, humidified) by using a three-way stopcock. The
expired gas returned first to a plastic mixing chamber (volume 0.75 liter) and then to the ventilator. Sampling tubes for the measurements
of humidity were attached to both the cross connector (inspiratory and
expiratory gas) and the mixing chamber (expiratory gas). Gas
temperature was measured by a thermocouple fixed in the middle of the
tracheostomy tube, 1 cm from the distal tip. Ventilatory parameters
[pressure, flow rates, tidal volumes, frequency, and minute
ventilation (ATPS)] were measured by using a Korr RSS 100 pneumotachometer system (Korr Medical Technologies, Salt Lake City,
UT). The portions of the ventilation circuit adjacent to the animal
were placed inside a plastic bag that was continuously filled with warm
air (42°C) (Bair Huggar model 500/OR, Augustine Medical, Eden
Prairie, MN), and the entire preparation was covered with water-filled heating blankets maintained at 38°C.
In five animals, in addition to perfusion via the pulmonary artery,
selective perfusion of the bronchial arteries through the isolated
portion of the thoracic aorta (11) was performed. A
catheter (1 cm OD, 10 cm length) was placed in the descending thoracic
aorta, and a second catheter (4 mm OD) was inserted into the
hemiazygous vein to allow drainage of the perfusate from the bronchial
veins. The aortic catheter was connected via a heat exchanger to a
2.5-l reservoir containing a mixture of normal saline and dextran 70 (1:1). The perfusate was pressurized (80-120 mmHg) and preheated
to 38°C before infusion to ensure a constant temperature throughout
the 10- to 15-min infusion period.
Temperature and humidity measurements. Data from the thermocouples were conditioned by use of a custom-built multichannel amplifier and were captured by a computerized data acquisition system (model SCXI-1200, National Instruments, Austin, TX). Data were then logged to disk by using a laptop computer (model T1860CS, Toshiba American Information Services, Irvine, CA) running LabView software (Version 3.1.1, National Instruments) with custom routines for real-time displays. The humidity measurements utilized a specially constructed, rapid-response humidity probe as previously described (12). Briefly, nitrocellulose tubing (0.15-mm diameter) that allowed unrestricted transfer and evaporation of water from its surface was placed in the center of the Plexiglas body of the sensor (0.5 mm ID). A thermocouple (0.001 in.) was positioned inside the tubing, and the thermocouple wire served as a support for the tubing. Both sides of the tubing were then connected to water reservoirs of ~1 ml such that a free flow of water was allowed through the tubing. Continuous gas flow through the body of the sensor of 100 ml/min was maintained by using a calibrated pump. The linear velocity of the gas through the sensor was 3.25 m/s. The temperature of the gas entering the sensor was measured by a thermocouple located in front of the wet tubing. The body of the sensor was maintained at 40°C by a custom-built, temperature-controlled heater. The response time of the sensor was <100 ms. Humidity was calculated from the values of peak temperature recorded by the dry and wet thermocouples of a humidity probe in the mixing chamber (12). The sensor was calibrated for both dynamic response (100 ms) and steady-state values of humidity at 40°C by using a humidity generator and calibration system (models C-1 and D-2, respectively, General Eastern Instruments, Woburn, MA) in an environmental chamber (model 3528, Lab-Line Instruments, Melrose Park, IL). Calibration of the sensor was performed after each experiment. At a steady state, the overall thermal conductance was calculated as the ratio of total heat loss to the difference between the blood temperature and the temperature of the expired gas (15, 28). Total heat loss was calculated as the sum of dry gas enthalpy, the water vapor enthalpy, and the heat of water evaporation (24).
Distribution of THO. THO (10 µCi) was introduced into the perfusate reservoir and rapidly mixed. The changes in the specific activity of THO as a function of time were measured in both the expired gas (condensate) and the perfusate. Sample collection began after 3 min of perfusion to allow complete mixing of the THO with the perfusate. To measure the water content and THO activity of the expired gas, a three-way valve was used that directed the expired gas into a coiled copper tubing (6 mm ID), which was submerged in a canister of dry ice. The water vapor from the exhaled gas that passed into the tubing was collected as a condensate on the inner surface. The collecting tubing was exchanged every 15 min, and the condensate was collected and weighed. To measure the water content and specific activity of the perfusate, samples (5 ml) were evaporated in a glass tube, and the water vapor was condensed and then collected. The specific activity of THO was measured by using PRO-POP scintillation cocktail (Sigma Chemical, St. Louis, MO) and a Packard TR 2100 beta-counter.
Methodologies, Human Studies
After approval of the institutional Human Subjects Research Committee, written, informed consent was obtained from four patients (three men and one woman), age 66-78, average weight 74 kg, American Society of Anesthesiologists class II to IV, who were scheduled for elective cardiac surgery using cardiopulmonary bypass. After induction of general anesthesia, arterial pressure and flow-directed pulmonary arterial catheters were placed. A sternotomy was performed, and arterial and venous return cannulas were placed in preparation for cardiopulmonary bypass. The endotracheal tube was suctioned for mucus, and a sterile thermocouple probe was positioned 2-3 cm above the distal end. The temperature of the inspired and expired gas was recorded at the tip of endotracheal tube throughout the study period. A three-way stopcock was placed in the respiratory circuit proximal to a humidifier (model SCT 3000, Marquest Medical Products). The second port of this stopcock was attached to a T-connector that was placed just proximal to the endotracheal tube. Patients were ventilated by use of a servo ventilator (model 900C, Seimens-Elema, Solna, Sweden). As previously described (26), patients were ventilated with warm (36-40°C), humidified air until an equilibrium between the inspired and expired gas temperatures was achieved. The inspired gas was then switched to cool (room temperature), dry gas for 5-6 min. Concurrent measurements of the cardiac output by thermodilution were performed by the anesthesiologist using a cardiac output computer (model COM-2, Baxter-Edwards Critical Care Division, Irvine, CA). Concurrent estimates of the overall lung thermal conductance were calculated by using the time constant of temperature decay of the expired gas as described previously (25, 26). Initial measurements of cardiac output and overall thermal conductance were performed after sternotomy and cannulation for bypass. Immediately after the initiation of complete cardiopulmonary bypass (bypass flow rates 5-6 l/min), the lungs were ventilated for 5-6 min with dry gas without changing the tidal volume or respiratory rate. The temperature changes in the pulmonary artery were recorded and compared with prebypass values.Statistical Analysis
All data are expressed as means ± SE. Data were compared by ANOVA, either unpaired or paired Student's t-test, and regression analysis. Statistical significance was accepted at P < 0.05.| |
RESULTS |
|---|
|
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
Selective Perfusion of the Circulatory Systems
During the dual perfusion of the pulmonary and bronchial arteries in isolated dog lungs, the flow in the pulmonary artery was maintained at 0.5 ± 0.05 l/min, the arterial pressure was 25 ± 3 mmHg, left atrial pressure was 0-4 mmHg, and the perfusate temperature was 37°C. A typical result demonstrating the effects of selective perfusion of the pulmonary or bronchial vessels is shown in Fig. 2. When the pulmonary artery was perfused at a nominal flow rate (0.5 l/min), bronchial artery perfusion (0-70 ml/min) did not significantly affect the temperature of the expired gas (Table 1). When the lungs were not perfused through either system, 8 min of ventilation with cool, dry gas decreased the temperature of the expired gas by 6.2 ± 1.4°C. Selective perfusion of bronchial arteries at 68 ± 10 mmHg resulted in a mean flow rate of 28 ± 16 ml/min and increased the average temperature of the expired gas by 0.6°C. An increase in the rate of bronchial arterial perfusion to 55 ± 14 ml/min at a mean pressure of 105 ± 22 mmHg further increased the average temperature of the expired gas by 1.3°C. When the lungs are not perfused, they are cooled by ventilation. Because water evaporation occurs at the mucosal surface, the temperature in ideal conditions should equilibrate to the temperature of the "wet bulb" thermometer, which will be ~6-8°C under these conditions. However, because the heat flux with evaporation from the lungs is rather small (~5-10 W), the lung mass is ~200-300 g, and there are additional structures in the mediastinum and chest wall through which heat exchange occurs, this process would take 70-90 min to reach equilibrium. Also, in the absence of blood flow, mucous surfaces will dry, evaporation will stop first in the large bronchi, then in the distal bronchi, and the rate of cooling will change. We observed these phenomena in our experiments in many instances and, according to our experience, drying of the airways becomes quite evident after 8-10 min of dry gas ventilation without perfusion. For this reason, we used a time interval of 8 min to assess the temperature changes. In addition, the overall estimated thermal conductivity of the lung as a function of pulmonary blood flow with or without the bronchial blood flow was calculated. Figure 3 shows the linear relationship between these two variables. Changes in bronchial perfusion were associated with small changes in the lung thermal conductivity, and in the presence of the pulmonary blood flow the influence of bronchial blood flow on the temperature of the expired gas was minimal
|
|
|
In the surgical patient studies, the mean cardiac output before
initiation of cardiopulmonary bypass was 5.43 ± 1.56 l/min. Minute ventilation was 6.17 ± 1.18 l/min with an average tidal volume of 0.64 ± 0.1 l (0.009 l/kg) and a rate of 8.3 ± 1.5 min1. Blood temperature was 36.8 ± 0.3°C, and the
mean time constant of the temperature decay after a switch to
ventilation with cool, dry gas was 35 ± 12 s. The average
temperature difference between the blood and expired gas was 2.4 ± 0.50°C. After the initiation of bypass (average bypass flow
5.45 ± 0.6 l/min), the blood flow to the lungs was limited to the
bronchial circulation. The temperature in the pulmonary artery changed
after the onset of bypass (decreased in 1 patient, increased in 3, maximal amplitude of change 0.7°C) and we corrected the instant
temperature of the expired gas to the instant changes in the
temperature of the blood in the pulmonary artery by subtracting or
adding the respective changes. Patients were first ventilated with
warm, humidified gas. After initiation of bypass, they were switched to
cool, dry gas ventilation for 5 min. The changes in the rate of
temperature decline before and after bypass are summarized in Fig.
4. During the 5 min of dry gas
ventilation, the temperature difference between the expired gas and
initial blood temperature decreased an average of 3.8 ± 0.06°C
(P < 0.05). The time constant of temperature decay
increased to 56 ± 14 s (P < 0.05).
|
Dynamics of Water Distribution in Normal Lungs
The rate of equilibration of THO between perfusate, lung tissue, and expired gas was evaluated in isolated, perfused dog lungs. All preparations were ventilated at a rate of 12 min1 and a
tidal volume of 20 ml/kg body wt. Perfusion via the pulmonary artery
was adjusted to produce a mean pulmonary arterial pressure of 23 ± 6 mmHg, left atrial pressure was 0-4 mmHg, and the perfusate flow was 0.65 ± 0.05 l/min. Temperature was maintained at 37°C. Perfusion of the aortic segment with bronchial arteries was at a rate
of 60 ml/min, resulting in an arterial pressure of 92 ± 9 mmHg.
Measurements of the total water content in the expired gas showed that
it was near saturation for 37°C (0.042 ± 0.03 g/l) during
perfusion of both the pulmonary system alone and the pulmonary and
bronchial systems combined, without any difference between the groups.
The dynamics of THO equilibration are summarized in Table
2 for pulmonary perfusion and in Table
3 for pulmonary and bronchial arterial
perfusion. For the pulmonary arterial perfusion alone, the time
constant of equilibration (blood-tissue) was 130 ± 33 min. For
bronchial and pulmonary perfusion combined, it was 35 ± 23 min
(P < 0.05). The perfusate volume was 790 ± 65 ml
for pulmonary perfusion alone and 830 ± 75 ml for pulmonary and
bronchial perfusion combined. Postmortem total lung mass (with blood in the small vessels) was 235 ± 23 g for the group of pulmonary
perfusion alone and 260 ± 35 g for the group of pulmonary
and bronchial perfusion combined. In the group with dual perfusion of
bronchial and pulmonary vessels, THO appeared in expired gas at the
same rate (time constant 34 ± 11 min) as during perfusion of
pulmonary arteries alone (time constant 31 ± 13 min). The ratio
of instant values of THO activity in exhaled gas to perfusate was
significantly higher during pulmonary and bronchial perfusion
(0.98 ± 0.07, P < 0.05) than during pulmonary
perfusion alone (0.42 ± 0.06, P < 0.05). In the
case of combined pulmonary and bronchial perfusion, equilibration
between the perfusate and the exhaled gas occurred within 1 h.
|
|
| |
DISCUSSION |
|---|
|
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
If the inspired gas temperature and humidity change, expired gas
temperature will shift to a new equilibrium due to the cooling of
bronchial tree. Changes in the time constant of temperature decay after
a switch from ventilation with heated, humidified gas to cool, dry gas
can be related to changes in the pulmonary blood supply (25,
26). However, the lung has two separate circulatory systems,
pulmonary arterial and bronchial arterial. These two systems generally
supply different structures and have different functions, but they also
have numerous anastomoses (34). The studies reported here
demonstrate that, in the presence of normal pulmonary arterial blood
flow, perfusion of the bronchial arteries does not significantly affect
expired gas temperature measured at the level of the trachea (Fig. 2).
This is consistent with the previous findings of Solway et al.
(30), who performed similar measurements in the more
distal airways of anesthetized dogs after selective occlusions of the
pulmonary or bronchial circulation. In this study, hyperventilation
using 18-28 l/min dry, room temperature or 
10°C gas was used
to provide the heat challenge to the lungs. The temperature
measurements were done deep in the bronchial tree, at the level of the
segmental or subsegmental bronchi (4-5 mm diameter in dogs) with
the proximal airways excluded. For our studies, we used normal
ventilation with dry gas at room temperature and measured the expired
gas temperature at the level of the trachea, because it depends on the
temperature of the bronchial mucosa (16) and includes the
contributions of both the segmental and lobar bronchi in the
heat-exchange evaluations. Furthermore, because the breathing pattern
affects both the site and mechanism of heat exchange in the bronchial
tree (16, 19, 20), the ventilatory parameters were kept constant.
Heat is transferred from the blood in the arteries, capillaries, and veins of the lungs to the bronchial mucosa by lateral conduction through the tissues (28, 30, 32). Despite the optimal location of the bronchial circulation for heat exchange, it is such a small fraction of the total pulmonary circulation in normal lungs that it can be effective in heating the airway only during a low thermal burden. These experimental protocols allowed us to demonstrate that in the absence of pulmonary arterial blood flow the bronchial arterial blood flow did provide a measurable heat flux to the lungs, which was proportional to the flow rate (Table 1). However, it was not sufficient to keep the bronchial tree adequately warm, even at low rates of ventilation. Other conditions may increase the relative contribution of the bronchial arterial system to heat-exchange processes. The bronchial circulation may undergo profound changes during certain pathological conditions and may increase from its normal physiological level. With a constant cardiac output, changes in expired gas temperature after repeated exposure to dry and cold gas were interpreted as changes in mucosal blood flow (13). Pathological conditions under which the bronchial microvasculature can respond by increasing flow rate are numerous and include chemical, hormonal, immunologic, and thermal stimuli (1, 2, 35). In addition, blood flow in the bronchial microvasculature is locally regulated and also responds to changes in ventilation (2, 17, 21). For example, the hyperventilation of exercise leads to an increase in bronchial vascular perfusion in humans (17, 21). In the study of Baile et al. (2), hyperventilation with dry gas up to 12-15 l/min was used, which is severalfold different from the conditions of this study; hyperventilation with dry warm gas increased bronchial blood flow by 2-3 times, and with dry cold gas by 1.5-2 times. The severity of hyperventilation or heat loss determines the magnitude of the increased bronchial vascular flow. However, the increase in ventilation, which leads to augmentation of bronchial blood flow, also increases the heat flux from the bronchial tree. It is unlikely that the increase in bronchial blood flow would be more substantial than the increase in heat loss, otherwise one would not observe deep cooling of the bronchial tree during hyperventilation in the isolated lung preparation, which lacks systemic refluxes, including possible change in mucosal blood flow due to hyperventilation or cooling. To address the possible effects of increased bronchial blood flow, we used two different bronchial arterial perfusion pressures during conditions of normal ventilation. This increased bronchial blood flow did not produce significant changes in the indexes of heat exchange. Because bronchial blood flow has, at least, severalfold less potency in its ability to affect the indexes of heat exchange, even if it increases during hyperventilation, it is likely that the effects will be balanced by the increased heat loss produced by hyperventilation. We cannot rule out the possibility that if the bronchial blood supply is increased severalfold by a reactive hyperemia of the bronchial mucosa in the nonisolated, intact whole body, its relative contribution may become substantial. This is a limitation of the current approach using isolated, perfused lung preparations.
Human studies provide strong support to the findings in perfused dog lungs. Immediately after the initiation of cardiopulmonary bypass, pulmonary arterial blood flow ceases as all the venous blood is diverted to the bypass circuit, but the arterial return from the circuit via the aortic arch provides continued perfusion of the bronchial arteries. We did not measure bronchial blood flow in humans, but it should be substantial (4), and anastomotic bronchopulmonary flow may even be higher than the prebypass level because pulmonary arterial perfusion was stopped. This provides a condition that is comparable to the isolated perfused dog lung preparation. A switch to ventilation with cool, dry gas will cause the bronchial mucosal temperature (and thus the expired gas temperature) to decrease. During selective perfusion of the bronchial arteries, there was a substantially lower rate of heat exchange compared with perfusion of both the pulmonary and bronchial systems. With only bronchial arterial blood flow, the mean time constant of temperature decay decreased significantly from 35 to 56 s, and peak expired gas temperature decreased by an average of 1.4°C. These values were obtained only after 5 min of ventilation, and it is likely that longer periods of ventilation would further increase this difference. In combination, these observations provide additional experimental evidence in support of previous observations made in humans and animals, suggesting that the bronchial circulation alone is not adequate to completely condition inspired gas during even during moderate ventilation loads (8, 19, 20).
To further investigate the physiological roles of the two systems of lung circulation, the rates of distribution of water into the parenchymal tissues and expired gas were evaluated by using THO. Previous transient extraction studies have used THO to measure interstitial fluid volume changes after the development of pulmonary edema (5, 6). These transient distribution techniques showed a very rapid rate of water exchange (5) and are based on the assumption that the distribution of water is flow limited. In the experiments reported here, we measured overall water exchange in the lower respiratory system and observed a slower rate of water distribution (half-time 133 min), which is at least two orders of magnitude lower than previously observed (5). The rate of water distribution during the perfusion of the pulmonary circulation alone was fourfold lower than during combined perfusion of the pulmonary and bronchial circulations. This discrepancy suggests that, during isolated perfusion of the pulmonary arterial system, substantial volumes of the interstitial tissues are either poorly perfused or not perfused at all. This is consistent with previous findings suggesting the substantial role of the bronchial circulation in lung fluid balance (11). Pare et al. (22) demonstrated that systemic venous hypertension and fluid overload increased the lung water content and consequently increased pulmonary resistance. Using canine lungs isolated in situ and perfused via the pulmonary and the bronchial arteries, with lymphatic cannulas placed to analyze flow, we demonstrated that the filtration of fluid from the bronchial vessels was the main source for the lymph formation (29) and the source of proteins in the peribronchial interstitium (4). The bronchial circulation has been shown to substantially contribute to edema formation occurring after smoke inhalation (1, 7).
Elements of the pulmonary interstitium may be considered as one functional unit that serves as a reservoir for distribution of fluids and is drained either by the lymphatic system or by other routes. The pulmonary interstitium may be subdivided into parenchymal connective tissue, situated inside the alveolar walls; the peripheral connective tissue; and the axial connective tissue, which comes from the hilum and in which the pulmonary arteries and airways are embedded (14). It is likely that selective pulmonary arterial perfusion allows the exchange of water between the capillary volume and the first constituent of the pulmonary interstitium, whereas the other two components serve as a slow-exchanging nonperfused reservoir, consistent with what was observed in our THO distribution studies. In the case of the selective bronchial arterial perfusion, all of the interstitial volumes are supplied with water, and it is likely that the exchange of THO in the peripheral and axial connective tissue occurs even faster than in the parenchymal tissue.
The degree of mucosal hydration of the bronchial tree is affected by the rate of water evaporation and regulated by the ion composition and osmolarity of the mucosal secretions, the geometry of the airways, the activity of the cilia, and the hydrostatic pressure of the mucosal blood vessels (36). Our results indicate that water content of the expired gas was unchanged regardless of which circulatory system was perfused. It is likely that, in the absence of bronchial arterial perfusion, flow through vascular anastomoses into the bronchial mucosa is minimal. Central connective tissue spaces are therefore poorly perfused, and the overall rate of THO exchange is low. In the presence of a large, unperfused space that serves as a sink, the water in the expired gas will be diluted by water without THO from the peribronchial spaces, which diminishes the ratio of relative distribution to 0.42. When the bronchial arteries are perfused, the interstitium and mucosa are filled with THO, which distributes rapidly, and the distribution ratio is close to unity.
The exchange of both substances and heat between tissues can, in general, be presented by the concepts of diffusion-limited and flow-limited processes, depending on the permeability of the barriers (6). Heat has the highest conductivity (or coefficient of thermal diffusion) compared with the diffusion coefficient of all other substances; thus its exchange is certainly flow limited. The majority of osmotically driven water transport in the lung microvascular endothelial cells occurs by a transcellular route through the water channels (33), which can limit the osmotic diffusion coefficient (10). Water exchange in alveolar capillaries occurs predominantly by diffusion and may be permeability limited. The situation is different for the bronchial circulation, in which filtration is likely to occur in physiological conditions because the hydrostatic pressure is as high as in the systemic vessels. The bronchial blood flow provides enough water for hydration of mucosa and saturation of the respired gas, although its volume flow is not sufficient to adequately warm the bronchial tree during ventilation with dry gas. The blood flow in the pulmonary artery is orders of magnitude higher and serves as a sufficient heat source for this process.
In summary, in the presence of pulmonary circulation, bronchial arterial blood flow contributes minimally to heat exchange, although it is important in water transport to the bronchial mucosa.
| |
ACKNOWLEDGEMENTS |
|---|
This study was supported in part by a Hewlett-Packard External Research Project grant.
| |
FOOTNOTES |
|---|
Address for reprint requests and other correspondence: N. W. Fleming, Dept. of Anesthesiology, UC Davis School of Medicine, TB-170, One Shields Ave., Davis, CA 95616 (E-mail: nwfleming{at}ucdavis.edu).
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Received 27 February 2001; accepted in final form 26 June 2001.
| |
REFERENCES |
|---|
|
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
1.
Abdi, S,
Herndon DH,
Traber LD,
Ashley KD,
Stothert JC,
Maguire J, Jr,
Butler R,
and
Traber DL.
Lung edema formation following inhalation injury: role of bronchial blood flow.
J Appl Physiol
71:
727-734,
1991
2.
Baile, EM,
Dahlby RW,
Wiggs BR,
Parsons GB,
and
Pare PD.
Effect of cold and warm dry air hyperventilation on canine airway blood flow.
J Appl Physiol
62:
526-532,
1987
3.
Belyakov, NA,
and
Serikov VB.
Changes in bronchial blood flow and its role in the lung fluid accumulation in experimental toxic pulmonary edema and ganglionic blockade.
Patol Fiziol Eksp Ter
4:
48-53,
1986.
4.
Butler, J
(Editor).
The Bronchial Circulation. New York: Dekker, 1992.
5.
Chinard, FP,
and
Cua WO.
Endothelial extraction of tracer water varies with extravascular water in dog lungs.
Am J Physiol Heart Circ Physiol
252:
H340-H348,
1987
6.
Effros, RM.
Small solutes and water.
In: Lung Water and Solute Exchange, edited by Staub NC.. New York: Dekker, 1978, p. 183-222. (Lung Biol Health Dis 7)
7.
Efimova, O,
Volokhov AB,
Iliaifar S,
and
Hales CA.
Ligation of the bronchial artery in sheep attenuates early pulmonary changes following exposure to smoke.
J Appl Physiol
88:
888-893,
2000
8.
Eschenbacher, WL,
and
Sheppard D.
Respiratory heat loss is not the sole stimulus for bronchoconstriction induced by isocapnic hyperpnea with dry air.
Am Rev Respir Dis
131:
894-901,
1985[ISI][Medline].
9.
Ferrus, L,
Guenard H,
Vardon G,
and
Varene P.
Respiratory water loss.
Respir Physiol
39:
367-381,
1980[ISI][Medline].
10.
Folkesson, HG,
Matthay MA,
Frigeri A,
and
Verkman AS.
Transepithelial water permeability in microperfused distal airways.
J Clin Invest
97:
664-671,
1996[ISI][Medline].
11.
Fukue, M,
Serikov VB,
and
Jerome EH.
Bronchial vascular reabsorption of low protein interstitial edema liquid in perfused sheep lung.
J Appl Physiol
81:
810-815,
1996
12.
Ganapati, M,
Serikov VB,
and
Greenstein M.
A fast miniature sensor for real-time monitoring of humidity in human breathing circuits.
In: Proc Int Symp Humid Moisture, Natl Physical Lab 3rd London, 1998, p. 343-344.
13.
Gilbert, IA,
and
McFadden ER, Jr.
Airway cooling and rewarming: the second reaction sequence in exercise-induced asthma.
J Clin Invest
90:
699-704,
1991.
14.
Gump, FE.
Lung fluid and solute compartments.
In: Lung Water and Solute Exchange, edited by Staub NC.. New York: Dekker, 1978, p. 75-92. (Lung Biol Health Dis 7)
15.
Hanna, LM,
and
Scherer WP.
A theoretical model of localized heat and water vapor transport in the human respiratory tract.
J Biomech Eng
108:
12-18,
1986[ISI][Medline].
16.
Ingenito, EP,
Solway J,
McFadden ER,
Pichurko B,
Bowman HF,
Michaels D,
and
Drazen JM.
Indirect assessment of mucosal surface temperature in the airways: theory and tests.
J Appl Physiol
63:
2075-2083,
1987
17.
Kim, HM,
LeMerre C,
Demirozu CM,
Chediak AD,
and
Wanner A.
Effect of hyperventilation on airway mucosal blood flow in normal subjects.
Am J Crit Care
154:
1563-1566,
1996.
18.
Laksminarayan, S,
Kowalski TF,
Kirk W,
Graham MM,
and
Butler J.
The drainage routes of the bronchial blood flow in anesthetized dogs.
Respir Physiol
82:
65-73,
1990[ISI][Medline].
19.
McFadden, ER, Jr,
and
Pichurko BM.
Intra-airway thermal profiles during exercise and hyperventilation in normal man.
J Clin Invest
76:
1007-1010,
1985.
20.
McFadden, ER, Jr,
Pichurko BM,
Bowman HF,
Ingenito E,
Burns S,
Dowling N,
and
Solway J.
Thermal mapping of the airways in humans.
J Appl Physiol
58:
564-570,
1985
21.
Onorato, DJ,
Demirozu MC,
Breitenbucher A,
Atkins ND,
Chediak AD,
and
Wanner A.
Airway mucosal blood flow in humans response to adrenergic agonists.
Am J Respir Crit Care Med
149:
1132-1137,
1994[Abstract].
22.
Pare, PD,
Brooks LA,
and
Baile EM.
Effects of systemic venous hypertension on pulmonary function and lung water.
J Appl Physiol
51:
592-597,
1981
23.
Primiano, FP,
Saidel GM,
Montague FW,
Kruse KL,
Green CG,
and
Horowitz JG.
Water vapour and temperature dynamics in the upper airways of normal and CF subjects.
Eur Respir J
1:
407-414,
1988[Abstract].
24.
Ray, DW,
Ingenito EP,
Strek M,
Schumacker PT,
and
Solway J.
Longitudinal distribution of canine respiratory heat and water exchange.
J Appl Physiol
66:
2788-2798,
1989
25.
Serikov, VB,
and
Jerome EH.
Noninvasive measurements of cardiac output in sheep: a new improved method.
J Biomed Eng
19:
618-629,
1997.
26.
Serikov, VB,
Jerome EH,
Fleming NW,
Moore PG,
Stawitcke FA,
and
Staub NC.
Airway thermal volume in humans and its relation to body size.
J Appl Physiol
83:
668-676,
1997
27.
Serikov, VB,
Rumm MS,
Kambara K,
Bootomo MI,
Osmack AR,
and
Staub NC.
Application of respiratory heat exchange for the measurement of lung water.
J Appl Physiol
72:
943-955,
1992.
28.
Shitzer, A,
and
Eberhart RC
(Editors).
Heat Transfer in Medicine and Biology. New York: Plenum, 1985, p. 193-232.
29.
Simbirtsev, SA,
Belyakov NA,
and
Serikov VB.
Lung lymph flow under conditions of normal capillary permeability.
Sechenov Physiol J USSR
69:
925-932,
1983.
30.
Solway, J,
Leff AR,
Dreshaj I,
Munoz NM,
Ingenito EP,
Michaels D,
Ingram RH,
and
Drazen JM.
Circulatory heat sources for canine respiratory heat exchange.
J Clin Invest
78:
1015-1019,
1986.
32.
Tsai, CL,
Saidel GM,
McFadden ER, Jr,
and
Fouke JM.
Radial heat and water transport across the airway wall.
J Appl Physiol
69:
222-231,
1990
33.
Verkman, AS,
and
Mitra AK.
Structure and function of aquaporin water channels.
Am J Physiol Renal Physiol
278:
F13-F28,
2000
34.
Von Hayek, H.
The Human Lung. New York: Hafner, 1960.
35.
Wagner, EM,
Blosser S,
and
Mitzner W.
Bronchial vascular contribution to lung lymph flow.
J Appl Physiol
85:
2190-2195,
1998
36.
Yager, D,
Clouter T,
Heldman H,
Bastacky J,
Drazen JM,
and
Kamm RD.
Airway surface liquid thickness as a function of lung volume in small airways of guinea pig.
J Appl Physiol
77:
2333-2340,
1994
This article has been cited by other articles:
|
|
 |
|
  J.B. McCafferty and J.A. Innes Exhaled breath temperature in airways disease Eur. Respir. J., August 1, 2003; 22(2): 393 - 394. [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
) or bronchial blood flow (n = 5, squares). 
, Perfusion of bronchial vessels without
pulmonary perfusion; 
, perfusion of bronchial vessels
simultaneously with pulmonary perfusion. *P < 0.05 compared with initial blood flow by paired t-test,
+P < 0.05 for the difference between groups by
unpaired t-test.
). *P < 0.05 between groups by paired
t-test, n = 4.