Unaltered pulmonary capillary surface area in the presence of changing arterial resistance

Lyle E. Fisher Jr.1, Attila Cziraki2, Curt M. Steinhart1, and John D. Catravas2

1 Section of Pediatric Critical Care Medicine, Department of Pediatrics, and 2 Vascular Biology Center, Medical College of Georgia, Augusta, Georgia 30912

    ABSTRACT
Top
Abstract
Introduction
Methods
Results
Discussion
References

We hypothesized that capillary recruitment may not be solely dependent on extracapillary factors. To test this hypothesis, rabbits were anesthetized and placed on total cardiac bypass at a constant, physiological pulmonary blood flow. Vascular occlusion techniques were combined with measurement of the transpulmonary metabolism of an angiotensin-converting enzyme substrate, allowing the concomitant assessment of changes in segmental resistances and dynamically perfused capillary surface area. Intra-arterial serotonin infusion increased upstream pulmonary vascular resistances without affecting dynamically perfused capillary surface area. Intra-arterial isoproterenol infusion diminished serotonin-induced increased upstream resistances, also without affecting capillary surface area. These findings support the hypothesis that pulmonary capillary recruitment may not be solely dependent on extracapillary factors.

isoproterenol; serotonin; capillary recruitment; pulmonary circulation; pulmonary hypertension; rabbit

    INTRODUCTION
Top
Abstract
Introduction
Methods
Results
Discussion
References

PULMONARY CAPILLARY RECRUITMENT has been thought to be modulated by pressures in the extracapillary vessels and alveoli. West et al. (32) demonstrated that distribution of blood flow within the lung could be related to the relationship among alveolar, arterial, and venous pressures. Wagner and Latham (30) showed a strong correlation between pulmonary arterial pressure and capillary recruitment during hypoxia. These and other similar studies suggested that segmental capillary blood flow may depend solely on external forces, leading to the conclusion that capillaries open or close passively. This understanding was further supported by histological evidence (8) where only extracapillary vessels were shown to contain smooth muscle and autonomic innervation. Moreover, an early study (14) demonstrated that the sympathetic nervous system contributed to the pulmonary pressor response to hypoxia, suggesting that only extracapillary vessels possessed the apparatus needed to change vessel tone and resistance and that capillary segments served as "passive conduits" for blood flow.

More recently, there has been mounting evidence supporting a component of pulmonary capillary recruitment intrinsic to the capillary bed. Warrell et al. (31) examined rapidly frozen lung sections and found that patterns of capillary filling were not correlating purely with arteriolar distribution. They concluded that there was heterogeneous recruitment of capillary segments fed by the same arteriole. An electrical-mapping model by West et al. (33) lent further support to the concept of intrinsic recruitment. Very similar patterns were demonstrated by Okada et al. (18) using capillary video mapping of blood flow within individual alveolar walls. They found reproducible patterns of recruitment, concluding that individual capillary segments possessed properties affecting their recruitment.

To date, the nature of intrinsic factors affecting capillary recruitment remains unclear. These intrinsic factors could be characterized as either fixed or variable. Fixed factors would be those related to the spatial arrangement of each capillary segment within its surrounding tissue. Variable factors could be either external to the endothelial cell or inherent to the endothelial cell itself. There is evidence to support both types of variable factors. Kapanci et al. (13) demonstrated the presence of pulmonary interstitial cells with contractile elements. These contractile elements were noted to have anchoring points on both alveolar elements and capillary basement membranes. These anchoring points might allow transmission of the cell's contractile force to adjacent capillaries, allowing the Kapanci cell to be an effector of capillary recruitment.

The endothelial cell itself may actively participate in capillary recruitment, in contradistinction to previous thinking that the capillary endothelial cell was a passive cell lining a passive conduit system. Endothelial cells are metabolically active. Ectoenzymes such as angiotensin-converting enzyme (ACE), 5'-nucleotidase, carboxypeptidase N, and aminopeptidase P are involved in regulating circulating hormones (25). Via catecholamine uptake (4), endothelial cells contribute to sympathetic regulation. Endothelium-derived relaxing factor (nitric oxide) is now known to be a modulator of blood pressure due to its effects on vascular smooth muscle tone (21). In addition to hormonal regulation, endothelial cells have been shown to interact with blood elements, including altered expression of white cell adhesion molecules in response to tumor necrosis factor-alpha (17). Along with these metabolic and cell-to-cell activities, endothelial cells may regulate their own recruitment by virtue of contractile properties. Elliott et al. (7) showed that changes in the structure of pulmonary capillaries were quickly reversible. Shasby et al. (26) suggested that the endothelial cytoskeleton played a role in endothelial permeability, whereas McDonald (16) found evidence for endothelial cell motility in tracheal venules. Therefore, there is evidence to support intrinsic capillary segmental recruitment and that such recruitment may be influenced by variable elements. These elements may be external to the endothelium (i.e., Kapanci cells) or may involve the metabolically active endothelium.

The present study begins to test the hypothesis that mechanisms of pulmonary capillary recruitment are not solely dependent on changes in the extracapillary vasculature; i.e., there is a component of intrinsic regulation. To that end, we examined whether changes in extracapillary vessel tone can occur without affecting capillary recruitment-derecruitment.

    METHODS
Top
Abstract
Introduction
Methods
Results
Discussion
References

Drug and animal preparation. The experimental protocol was reviewed and approved by the Institutional Committee on Animal Research and complied with the guidelines on the humane treatment of animals of the American Physiological Society. Male New Zealand White rabbits, mean weight 3.6 kg, were housed in individual cages and were allowed food and water ad libitum up to the time of the experiment. After being anesthetized with urethan-5,5-diallylbarbituric acid (Sigma Chemical, St. Louis, MO) administered in a marginal ear vein, each animal was placed supine, tracheostomized, and ventilated with a small-animal ventilator (Harvard Apparatus, Mills, MA). Airway pressure was continuously measured with a pressure transducer (Statham Instruments, Hato Riley, PR) connected to the expiratory limb of the ventilator circuit and recorded on a Gould 2400 (Gould Instruments, Columbus, OH) physiograph. After the left carotid artery was cannulated, 1 mg of pancuronium bromide (Organon, W. Orange, NJ) was administered. The catheter was then connected to a pressure transducer zeroed to midthorax to continuously monitor and record systemic arterial pressure. After a median sternotomy was performed, an anterior pericardiectomy and bilateral anterior pleurectomies were performed to expose the heart and great vessels. In preparation for cardiac bypass, silk sutures were loosely tied around the ascending aorta and the pulmonary artery. Before cardiac bypass, the animal was then given 1,000 U/kg of heparin (Elkin-Sinn, Cherry Hill, NJ) to provide anticoagulation and 5 mg/kg of indomethacin (Sigma Chemical) to inhibit the production and release of cyclooxygenase pressor products.

Cardiac bypass. The extracorporeal bypass system consisted of two parallel circuits to provide systemic and pulmonary blood flows. Each circuit contained a double-jacketed Plexiglas reservoir with Tygon tubing leading from the base of each reservoir through a roller pump (P/N 13400, Sarns, Ann Arbor, MI) and then to a vascular (pulmonary or aortic) cannula. The pulmonary circuit also incorporated a bubble filter and a flow probe (300A, Carolina Medical Electronics, King, NC). The pump was calibrated so that the systemic and pulmonary flows were equal. The bypass circuit was primed with a mixture of rabbit blood and Krebs-Henseleit solution.

After a purse-string suture was placed in each ventricular free wall, a catheter was placed in the right ventricle and advanced through the tricuspid annulus into the right atrium. The catheter was secured with the previously placed suture so that systemic venous drainage returned into the "pulmonary" reservoir. The left atrium was cannulated similarly to drain all pulmonary venous blood into the "systemic" reservoir. The ascending aorta was rapidly tied off, and the cannula was secured with the previously placed ligature. The pulmonary artery was cannulated immediately above the pulmonary valve, with care being taken to avoid introduction of air emboli. The mean time of interrupted circulation was 7.9 min.

After bypass was established, the rabbit was allowed to stabilize (mean time 32 min). Arterial blood gases were measured (Instrumentation Laboratory 1304, Lexington, MA), and minute ventilation was adjusted to keep the pH at ~7.40. Pulmonary arterial and left atrial pressures were continuously monitored and recorded from catheters placed within the appropriate cannulas connected to pressure transducers zeroed at the midthoracic level. Pulmonary blood flow was continuously measured with an electromagnetic flowmeter (Cliniflow II, Carolina Medical Electronics) and was initially adjusted to 100 ml · min-1 · kg body weight-1; this flow produced a stable pulmonary arterial pressure of ~20 mmHg [normal for rabbit (28)], with a left atrial pressure of 1-2 mmHg. Pulmonary blood flow was thereafter kept constant.

Fresh solutions of the vasoactive drugs were prepared in normal saline for each experiment. Serotonin [5-hydoxytryptamine creatinine sulfate complex (5-HT); Sigma Chemical] was prepared as a 1 mg/ml solution and stored and administered in light-shielded containers. Isoproterenol (Sigma Chemical) was prepared at 0.6 mg · kg-1 · ml-1.

Estimation of capillary surface area. Dynamically perfused capillary surface area was calculated from the single-pass transpulmonary metabolism of the specific ACE substrate [3H]benzoyl-phenylalanyl-alanyl-proline ([3H]BPAP; 20 Ci/mmol; Ventrex). For each determination, 2 µCi of [3H]BPAP were injected into the pulmonary artery, and left atrial outflow was collected in 19 0.6-s samples by a fraction collector (Gilson Escargot, Gilson Instruments, Lexington, MA). Measurements were obtained during end expiration. Blood samples were centrifuged at 3,000 revolutions/min for 10 min to separate the plasma. To determine the total 3H radioactivity in each sample, a 0.5-ml plasma aliquot was placed in a 7-ml plastic scintillation vial (Fisher Scientific, Atlanta, GA) to which 5 ml of Ecoscint A scintillation cocktail (National Diagnostics, Atlanta, GA) were added. To determine the radioactivity due to the metabolite of [3H]BPAP, [3H]benzoyl-phenylalanine, a 0.5-ml plasma aliquot from each sample was placed in a 7-ml plastic scintillation vial (Fisher) to which was added 2.5 ml of 0.12 N HCl and 3 ml of 4 g/l Omnifluor (Dupont, Boston, MA) in toluene (Baxter, Muskegon, MI). The samples were then capped and inverted 20 times for thorough mixing and stored in a dark cabinet for 48 h before being placed in a scintillation spectrometer (LS7000, Beckman Instruments, Irvine, CA).

Experimental procedures and protocol. The experimental protocol is shown in Fig. 1. After the stabilization period, baseline measurements were taken. All measurements were obtained at end expiration, with the lungs in zone III conditions. Pulmonary arterial occlusion, simultaneous arterial and venous occlusion, and venous occlusion maneuvers were performed (see Determination of segmental pressures). An aliquot of left atrial outflow blood was obtained for blood gas and hematocrit (Hct) determinations.


View larger version (7K):
[in this window]
[in a new window]
 
Fig. 1.   Experimental protocol. Serotonin [5-hydroxytryptamine (5-HT)] infusion began after baseline measurements and was then kept constant throughout the experiment. Isoproterenol infusion began after constricted (5-HT) measurements were made and was increased until mean pulmonary arterial pressure decreased ~50% toward pre-5-HT baseline (Iso1). After measurements were made again, infusion was increased until pulmonary arterial pressure was approximately at pre-5-HT level (Iso2).

After baseline measurements were made, pulmonary hypertension was induced by continuously infusing 5-HT into the pulmonary artery with a syringe pump (242A, Sarns). The infusion was increased until a maximal pressor response was established (mean infusion rate 91 µg · kg-1 · min-1). The rate of 5-HT infusion remained constant until the end of the experiment. Pulmonary blood flow was kept constant by adjusting the pump speed.

An isoproterenol infusion into the pulmonary artery was begun and gradually increased until the mean pulmonary arterial pressure decreased by ~50% toward the pre-5HT baseline (Iso1). All measurements were then repeated, after which the isoproterenol infusion was gradually increased again until the pulmonary arterial pressure was approximately at the pre-5HT baseline (Iso2). A final series of measurements was taken before the experiment was terminated.

Determination of segmental pressures. Segmental resistances were estimated by vascular occlusion techniques (10). During pulmonary arterial occlusion, the point of inflection in the pulmonary arterial occlusion pressure (Ppao) tracing corresponds to the arteriolar pressure. During simultaneous arterial and venous occlusions, the two pressures equilibrate at the double-occlusion pressure (Pdo), which closely approximates the capillary pressure. During venous occlusion, the inflection point in the venous occlusion pressure (Pvo) tracing is equivalent to the pulmonary venule pressure (10). With total pulmonary blood flow (QT) at the time of occlusion known, the segmental resistances were calculated as large-artery resistance (Rla) = (Ppa - Pao)/QT, small-artery resistance (Rsa) = (Ppao - Pdo)/QT, small-vein resistance (Rsv) = (Pdo - Pvo)/QT, large-vein resistance (Rlv) = (Pvo - Ppv)/QT, and total pulmonary resistance = (Ppa - Ppv)/QT, where Ppa is pulmonary arterial pressure and Ppv is pulmonary venous pressure.

Calculation of perfused capillary surface area. ACE is distributed homogeneously over the entire endothelial luminal surface (25); thus the amounts of ACE reflect the dynamically perfused capillary surface area (5). Under first-order reaction conditions, the integrated form of the Henri-Michaelis-Menten equation can be rearranged to Amax /Km = Qp · ln ([S0]/[S]), where Qp is the pulmonary plasma flow, [S0] and [S] are the initial and surviving substrate concentrations, respectively, Amax is the product of enzyme mass and kcat (turnover number; a constant), and Km is the Michaelis-Menten constant. Changes in perfused capillary surface area as reflected by changes in enzyme mass are thus indicated by changes in the quantity Amax /Km.

Statistical analysis. Statistical analysis of obtained parameters utilized one-way analysis of variance followed by the Newman-Keuls test. A P value < 0.05 was accepted as indicating a significant difference.

    RESULTS
Top
Abstract
Introduction
Methods
Results
Discussion
References

Baseline hemodynamic measurements on cardiac bypass were a mean systemic arterial pressure of 91.5 ± 3.8 mmHg, mean pulmonary arterial pressure of 20 ± 1.8 mmHg, and left atrial pressure of 1.9 ± 0.04 mmHg. Mean pulmonary arterial pressure increased significantly during the infusion of 5-HT (P < 0.01) and then significantly decreased during the graduated infusions of isoproterenol (Table 1). Small-artery pressures also rose significantly (from 12.8 ± 0.5 to 14.8 ± 1.3 mmHg; P < 0.05) with 5-HT, then fell to 12.0 ± 1.1 (P < 0.05) and 11.3 ± 1.2 mmHg (P < 0.01) during Iso1 and Iso2 infusions, respectively. Neither capillary, small-vein, nor large-vein pressures were significantly affected by the 5-HT or isoproterenol infusions. 5-HT did not affect mean systemic arterial pressure, but isoproterenol did result in a significant decrease in mean systemic pressure to 76.7 ± 5.4 mmHg at Iso2. Pulmonary blood flow remained stable at approx 106 ml · kg-1 · min-1.

                              
View this table:
[in this window]
[in a new window]
 
Table 1.   Effects of 5-HT and isoproterenol on hemodynamic parameters

The Hct decreased, but stable pH and arterial PO2 values (as shown in Table 1) suggested adequate lung function throughout the protocol.

Despite changes in large- and small-artery pressures, dynamically perfused capillary surface area (as reflected by Amax /Km) did not change in response to 5-HT, Iso1, or Iso2 (Table 1).

Figure 2 shows the time course of total pulmonary vascular resistance and capillary surface area (values expressed as multiples of baseline) during the 5-HT infusion alone (constricted) and with increasing infusions of isoproterenol (Iso1 and Iso2). Capillary surface area did not change significantly. In contrast, total pulmonary resistance first increased significantly and then dropped significantly at Iso1 and Iso2. Large-artery resistance more than doubled during the 5-HT infusion, then significantly decreased at both stages of the isoproterenol infusion (Fig. 3). Resistance in the small arteries was similarly affected (Fig. 3). There were no significant changes in downstream resistances throughout the experiment (Fig. 4).


View larger version (12K):
[in this window]
[in a new window]
 
Fig. 2.   Changes in total pulmonary resistance and capillary surface area [as reflected by change in enzyme mass (Amax/Km), where Amax is product of enzyme mass and kcat (turnover number; a constant) and Km is Michaelis-Menten constant]. Results are means ± SE of multiples of pre-5-HT baseline. Significantly different (P < 0.05) from: * baseline; + constricted condition.


View larger version (15K):
[in this window]
[in a new window]
 
Fig. 3.   Changes in pulmonary large-artery and small-artery upstream resistances. Results are means ± SE. Significantly different (P < 0.01) from: * baseline; + 5-HT measurements.


View larger version (15K):
[in this window]
[in a new window]
 
Fig. 4.   Changes in pulmonary large-vein and small-vein downstream resistances. Results are means ± SE.

    DISCUSSION
Top
Abstract
Introduction
Methods
Results
Discussion
References

Pressure measurements in the pulmonary artery and left atrium allow assessment of total pulmonary vascular tone and control but do not assess the contributions of the various populations of vessels within the pulmonary vasculature. Bhattacharya et al. (3) measured pressures in 10-µm-diameter vessels with micropipette techniques. Such measurements are technically difficult and restricted to vessels near the pleural surface. Mathematical models equating the vascular tree to an electrical circuit have resulted in techniques that examine small vascular pressures using combinations of large-vessel occlusions. Inflection points in the resultant pressure waveforms are then equated with various segmental pressures (10). Other techniques have been used to assess vascular responsiveness. Intrapulmonary fluid volumes have been measured with techniques such as dye dilution (6) and blood pool scintigraphy (27) to look at volume distributions within the lung, whereas the low-viscosity bolus technique (9) shows the distribution of resistances across the vascular bed without indicating the anatomic location of those resistances.

Although these techniques, singly or in combination, have allowed investigation into the extracapillary vessels, examining the function of the capillary bed has been more difficult. Investigators have analyzed the anatomic morphology of the capillary-alveolar unit. Lung tissue has been quick-frozen (26) or direct observations of the pleural surface have been performed using video mapping (18). Such techniques are useful but difficult to apply to the entire lung. Capillary function has been assessed indirectly by measuring filtration coefficients (2). Investigations into the perfused capillary surface area using gases such as ether (20) depend on ventilation-perfusion matching, thus missing segments of the capillary bed that may be active but associated with nonventilated alveoli. Techniques based on a metabolically active endothelium are therefore attractive, in that they will assess potential changes in the total capillary bed independent of the status of alveolar ventilation. Examples of such methods include 5-HT uptake (23), blue dextran binding (24), and measurement of endothelial ectoenzyme function (28). Assessment of pulmonary capillary surface area via ACE activity has been shown to correlate well with measurements based on carbon monoxide diffusing capacity and postmortem structural assessments (19).

The "passive conduit" concept holds that the pulmonary capillary bed is simply a network of tubes where recruitment of individual segments depends mostly on extracapillary changes in blood pressure and volume. The model has been supported by histological findings that show that the arteries and, to a lesser extent, the veins are the only portions of the pulmonary vasculature that are endowed with smooth muscle; the same segments possess innervation as well (8).

Precapillary factors, primarily the pressure in the small arterioles just upstream from the capillary network, are believed to exert a major influence on capillary recruitment (30). Certainly, precapillary mechanisms have an effect on capillary blood volume. Changes in cardiac output as well as in arterial and arteriolar tone will affect the amount of blood per unit time that the capillary bed must accommodate (11, 29), with the altered blood volume potentially resulting in changes in segmental filling and recruitment.

Postcapillary effects on the capillary bed have also been studied; when venous pressure increases temporarily, alveolar vessel volume increases (6) and pulmonary vascular resistance decreases (1).

Despite these findings, both morphological and pressure-volume studies (15, 31) have suggested that there are changes within the capillary beds that occur independently of changes in the extracapillary beds. It remains unclear whether such effects are due to fixed mechanical properties of the lung (i.e., the structural composition of the lungs) (33) or whether they are due to variable qualities within the capillary bed, e.g., endothelial or interstitial contractile elements.

The concept of variable factors of intrinsic capillary control is supported by the presence of cells with contractile elements [Kapanci cells (13)], which are closely associated with the capillaries. In addition to contractile elements external to the endothelial cell, there is evidence that endothelial cells themselves possess active internal contractile elements (26). Pursuit of the intrinsic variable properties may eventually lead to manipulation of pulmonary capillary vasomodulation and allow therapeutic contributions to clinical conditions such as pulmonary hypertension, pneumonia, pulmonary edema, and adult respiratory distress syndrome.

If pulmonary capillary bed surface area (hence capillary recruitment) is not solely dependent on extracapillary vessel tone, capillary responsiveness to vasomodulators could function independently of extracapillary effects of those modulators. To evaluate this, we combined techniques to study segmental resistances and perfused capillary surface area. Experiments were performed at constant flow because blood volume changes could affect capillary recruitment. We demonstrated that after upstream constriction with a continuous infusion of 5-HT, isoproterenol effectively lowered upstream resistances. These findings were anticipated because others (12) have demonstrated this previously in the canine pulmonary macrovasculature, an area with known beta -receptors. However, we found that the capillary surface area remained unchanged. This occurred despite the fact that pressures in the vessels upstream from the capillary bed were elevated and then brought back to baseline. This supports the hypothesis that the capillary bed may have modulatory properties that are independent of changes in the upstream vascular tone.

As shown in Table 1, mean arterial pressure (MAP), Hct, and arterial PCO2 decreased significantly during the experiment. The decrease in MAP is not surprising because isoproterenol is known to cause systemic vasodilation, but the MAP did not fall abnormally low. The fall in Hct is not unexpected because ~13 ml of blood are withdrawn for each measurement of transpulmonary metabolism. Although the resultant decrease in viscosity could possibly potentiate the decreases in upstream resistances observed with isoproterenol, Hct value differences at the initial vs. final measurements were of a magnitude unlikely to significantly affect viscosity. The observed drop in arterial PCO2 without a significant change in pH is indicative of a compensated metabolic acidosis, which may be due to a combination of the decreases in MAP and Hct. Because there was no acidemia, ACE function would have remained stable throughout each protocol (22). Even if such changes resulted in upstream pressure drops, there still was no change in the estimated perfused capillary surface area.

In this rabbit constant pulsatile flow cardiac-bypass model, we demonstrated that large- and small-artery resistances in the pulmonary circulation could be altered without any significant change in the perfused capillary surface area. In contrast to earlier thought, there was no decrease in capillary recruitment despite a decrease in the small-artery pressure. This supports the hypothesis that recruitment of the pulmonary capillary circulation is not solely dependent on changes in extracapillary tone.

    ACKNOWLEDGEMENTS

We acknowledge the diligent expertise of Jim Parkerson and Dr. Wendell Hoffman.

    FOOTNOTES

Address for reprint requests: L. E. Fisher, Jr., 1120 15th St., BIW-6033, Medical College of Georgia, Augusta, GA 30912-3758.

Received 25 March 1996; accepted in final form 29 October 1997.

    REFERENCES
Top
Abstract
Introduction
Methods
Results
Discussion
References

1.   Barman, S., and A. Taylor. Effects of pulmonary venous pressure elevation on vascular resistance and compliance. Am. J. Physiol. 258 (Heart Circ. Physiol. 27): H1164-H1170, 1990[Abstract/Free Full Text].

2.   Barnard, J., S. A. Barman, W. K. Adkins, G. L. Longenecker, and A. E. Taylor. Sustained effects of endothelin-1 on rabbit, dog, and rat pulmonary circulations. Am. J. Physiol. 261 (Heart Circ. Physiol. 30): H479-H486, 1991[Abstract/Free Full Text].

3.   Bhattacharya, J., S. Nanjo, and N. C. Staub. Micropuncture measurement of lung microvascular pressure during 5-HT infusion. J. Appl. Physiol. 52: 634-637, 1982[Abstract/Free Full Text].

4.   Catravas, J. D., J. S. Lazo, and C. N. Gillis. Biochemical markers of bleomycin toxicity: clearance of [14C]-5-hydroxytryptamine and [3H]norepinephrine by rabbit lung in vivo. J. Pharmacol. Exp. Ther. 217: 524-529, 1981[Medline].

5.   Catravas, J. D., and R. E. White. Kinetics of pulmonary angiotensin-converting enzyme and 5'-nucleotidase in vivo. J. Appl. Physiol. 57: 1173-1181, 1984[Abstract/Free Full Text].

6.   Dawson, C. A., D. A. Rickaby, and J. H. Linehan. Location and mechanisms of pulmonary vascular volume changes. J. Appl. Physiol. 60: 402-409, 1986[Abstract/Free Full Text].

7.   Elliott, A. R., Z. Fu, K. Tsukimoto, R. Prediletto, O. Mathieu-Costello, and J. B. West. Short-term reversibility of ultrastructural changes in pulmonary capillaries caused by stress failure. J. Appl. Physiol. 73: 1150-1158, 1992[Abstract/Free Full Text].

8.   Fishman, A. P. Dynamics of the pulmonary circulation. In: Handbook of Physiology. Circulation. Washington, DC: Am. Physiol. Soc., 1963, sect. 2, vol. II, chapt. 48, p. 1673-1681.

9.   Grimm, D., J. Linehan, and C. Dawson. Longitudinal distribution of vascular resistance in the lung. J. Appl. Physiol. 43: 1093-1101, 1977[Abstract/Free Full Text].

10.   Hakim, T. S. Identification of constriction in large versus small vessels using the arterial-venous and double-occlusion techniques in isolated canine lungs. Respiration 54: 61-69, 1988[Medline].

11.   Hyman, A. Effects of large increases in pulmonary blood flow on pulmonary venous pressure. J. Appl. Physiol. 27: 179-185, 1969[Free Full Text].

12.   Hyman, A. L. The direct effects of vasoactive agents on pulmonary veins. Studies of responses to acetylcholine, serotonin, histamine and isoproterenol in intact dogs. J. Pharmacol. Exp. Ther. 168: 96-105, 1969[Medline].

13.   Kapanci, Y., A. Assimacopoulos, C. Irle, A. Zwahlen, and G. Gabbiani. Contractile interstitial cells in pulmonary alveolar septa: a possible regulator of ventilation/perfusion ratio? J. Cell Biol. 60: 375-392, 1974[Abstract/Free Full Text].

14.   Kazemi, H., P. E. Bruecke, and E. F. Parsons. Role of the autonomic nervous system in the hypoxic response of the pulmonary vascular bed. Respir. Physiol. 15: 245-254, 1972[Medline].

15.   Mayers, I., and D. Johnson. Vasodilators do not abolish pulmonary vascular closing pressure. Respir. Physiol. 81: 63-74, 1990[Medline].

16.   McDonald, D. Endothelial gaps and permeability of venules in tracheas exposed to inflammatory stimuli. Am. J. Physiol. 266 (Lung Cell. Mol. Physiol. 10): L61-L83, 1994[Abstract/Free Full Text].

17.   Mulligan, M. S., A. A. Vaporciyan, M. Miyasaka, T. Tamatani, and P. Ward. Tumor necrosis factor alpha  regulates in vivo intrapulmonary expression of ICAM-1. Am. J. Pathol. 142: 1739-1748, 1993[Abstract].

18.   Okada, O., R. G. Presson, Jr., K. R. Kirk, P. S. Godbey, R. L. Capen, and W. W. Wagner, Jr. Capillary perfusion in patterns in single alveolar walls. J. Appl. Physiol. 72: 1838-1844, 1992[Abstract/Free Full Text].

19.   Pitt, B. R., G. Lister, P. Davies, and L. Reid. Correlation of pulmonary ACE activity and capillary surface area during postnatal development. J. Appl. Physiol. 62: 2031-2041, 1987[Abstract/Free Full Text].

20.   Quebbeman, E., and C. Dawson. Effect of lung inflation and hypoxia on pulmonary arterial blood volume. J. Appl. Physiol. 43: 8-13, 1977[Abstract/Free Full Text].

21.   Rees, D. D., R. M. J. Palmer, and S. Moncada. Role of endothelium-derived nitric oxide in the regulation of blood pressure. Proc. Natl. Acad. Sci. USA 86: 3375-3378, 1989[Abstract].

22.   Rickaby, D. A., R. D. Bongard, M. J. Tristani, J. H. Linehan, and C. A. Dawson. Effects of gas composition and pH on kinetics of lung angiotensin-converting enzyme. J. Appl. Physiol. 62: 1216-1221, 1987[Abstract/Free Full Text].

23.   Rickaby, D., C. Dawson, J. Linehan, and T. Bronikowski. Alveolar vessel behavior in the zone 2 lung inferred from indicator-dilution data. J. Appl. Physiol. 63: 778-784, 1987[Abstract/Free Full Text].

24.   Roerig, D., C. Dawson, S. Ahlf, R. Bongar, J. Linehan, and J. Kampine. Use of blue dextran for measuring changes in perfused vascular surface area in lungs. Am. J. Physiol. 262 (Heart Circ. Physiol. 31): H728-H733, 1992[Abstract/Free Full Text].

25.   Ryan, J. W., U. S. Ryan, D. R. Schultz, C. Whitaker, and A. Chung. Subcellular localization of pulmonary angiotensin-converting enzyme (kininase II). Biochem. J. 146: 497-499, 1975[Medline].

26.   Shasby, D. M., S. S. Shasby, J. M. Sullivan, and M. J. Peach. Role of endothelial cell cytoskeleton in control of endothelial permeability. Circ. Res. 51: 657-661, 1982[Abstract].

27.   Smiseth, O., N. Scott-Douglas, D. Manyari, I. Kingma, E. Smith, and J. Tyberg. Increased pulmonary vascular capacitance with beta-adrenergic receptor stimulation: an experimental study of the effect of isoproterenol on the pulmonary vascular volume-pressure relationship. Can. J. Physiol. Pharmacol. 66: 85-89, 1988[Medline].

28.   Toivonen, H. J., and J. D. Catravas. Effects of alveolar pressure on lung angiotensin-converting enzyme function in vivo. J. Appl. Physiol. 61: 1041-1050, 1986[Abstract/Free Full Text].

29.   Toivonen, H. J., and J. D. Catravas. Effects of blood flow on lung ACE kinetics: evidence for microvascular recruitment. J. Appl. Physiol. 71: 2244-2254, 1991[Abstract/Free Full Text].

30.   Wagner, W. W., and L. P. Latham. Pulmonary capillary recruitment during airway hypoxia in the dog. J. Appl. Physiol. 39: 900-905, 1975[Abstract/Free Full Text].

31.   Warrell, D. A., J. E. Evans, R. O. Clarke, G. P. Kingaby, and J. B. West. Pattern of filling in the pulmonary capillary bed. J. Appl. Physiol. 32: 346-356, 1972[Free Full Text].

32.   West, J. B., C. T. Dollery, and A. Naimark. Distribution of blood flow in isolated lung: relation to vascular and alveolar pressures. J. Appl. Physiol. 19: 713-724, 1964.

33.   West, J. B., A. M. Schneider, and M. M. Mitchell. Recruitment in networks of pulmonary capillaries. J. Appl. Physiol. 39: 976-984, 1975[Abstract/Free Full Text].


AJP Lung Cell Mol Physiol 274(2):L264-L269
1040-0605/98 $5.00 Copyright © 1998 the American Physiological Society




This Article
Abstract
Full Text (PDF)
Alert me when this article is cited
Alert me if a correction is posted
Citation Map
Services
Email this article to a friend
Similar articles in this journal
Similar articles in PubMed
Alert me to new issues of the journal
Download to citation manager
Google Scholar
Articles by Fisher, L. E.
Articles by Catravas, J. D.
Articles citing this Article
PubMed
PubMed Citation
Articles by Fisher, L. E., Jr.
Articles by Catravas, J. D.


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online