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Critical Care Research Laboratory, Department of Anesthesia, and Departments of Respiratory Therapy, Research Computing and Biostatistics, and Surgery, Children's Hospital and Harvard Medical School, Boston, Massachusetts 02115
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ABSTRACT |
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Top
Abstract
Introduction
Methods
Results
Discussion
References
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Regional pulmonary blood flow was investigated with radiolabeled microspheres in four supine lambs during the transition from conventional mechanical ventilation (CMV) to partial liquid ventilation (PLV) and with incremental dosing of perfluorocarbon liquid to a cumulative dose of 30 ml/kg. Four lambs supported with CMV served as controls. Formalin-fixed, air-dried lungs were sectioned according to a grid; activity was quantitated with a multichannel scintillation counter, corrected for weight, and normalized to mean flow. During CMV, flow in apical and hilar regions favored dependent lung (P < 0.001), with no gradient across transverse planes from apex to diaphragm. During PLV the gradient within transverse planes found during CMV reversed, most notably in the hilar region, favoring nondependent lung (P = 0.03). Also during PLV, flow was profoundly reduced near the diaphragm (P < 0.001), and across transverse planes from apex to diaphragm a dose-augmented flow gradient developed favoring apical lung (P < 0.01). We conclude that regional flow patterns during PLV partially reverse those noted during CMV and vary dramatically within the lung from apex to diaphragm.
pulmonary circulation; pulmonary vascular resistance; liquid ventilation; partial liquid ventilation; perfluorochemical; perflubron; mechanical ventilation
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INTRODUCTION |
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Top
Abstract
Introduction
Methods
Results
Discussion
References
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PERFLUOROCARBON (PFC) liquids were first demonstrated to be suitable as an alternate respiratory medium by Clark and Gollan in 1966 (4) and are characterized by the unique combination of high solubility for O2 and CO2, low surface tension, high spreading coefficient, and high density. Full-tidal or total liquid ventilation (TLV), which utilizes PFC tidal volumes delivered to the PFC-filled lung, has been shown to enhance gas exchange and improve pulmonary mechanics in animal models of preterm surfactant-deficient lungs (34) and mature, acutely injured lungs (19). Improved gas exchange during TLV in preterm human neonates has also been reported (14). During the technical development of TLV, it was discovered that animals with fluorocarbon-filled lungs could be supported with a conventional ventilator (10), thus effecting tidal gas ventilation of the fluorocarbon-filled lung. This technique has become known as partial liquid ventilation (PLV) and has been shown to improve gas exchange and mechanics in animal models of prematurity (24) and lung injury (36) and in preliminary human trials (11, 20, 25).
The physiology underlying improved gas exchange and lung mechanics during TLV and its salutary effects on pulmonary mechanics in the surfactant-deficient and the injured lung have been extensively studied. Because of the combination of properties mentioned above, replacement of the air-alveolar interface with a PFC-alveolar interface leads to a reduction in interfacial tension and an increase in compliance and supports the reestablishment or "normalization" of functional residual capacity in states of reduced lung compliance (23, 33, 42). In models of acute lung injury and surfactant deficiency due to prematurity, investigators have documented a reduction in shunt fraction (33) and additionally attributed improved gas exchange to improved ventilation-perfusion matching (24, 33, 42). Quantification of ventilation-perfusion relationships has not been applied during TLV; however, analysis of pulmonary blood flow distribution during TLV in an isolated lung preparation (26) and in preterm meconium-stained lambs (33) demonstrated attenuation of the regional blood flow gradient favoring dependent surface of the gas-filled lung, with a shift in flow from dependent to nondependent lung. This pattern has been attributed to the formation of an alveolar pressure gradient that, because of the dense nature of PFC liquids (specific gravity = 1.76), exceeds the hydrostatic pressure gradient in the pulmonary vascular tree (26).
Likewise, the physiology of gas exchange during PLV has been extensively investigated. Although PLV in the normal lung is known to impair the efficiency of gas exchange (10, 38) and has been shown to increase intrapulmonary shunt and ventilation-perfusion heterogeneity (27), PLV has been shown to improve the efficiency of gas exchange and lung mechanics of injured lungs in models of premature (24, 35) and injured lungs (6, 39) and in preliminary human trials (11, 20, 25). When PLV is initiated with a PFC volume equivalent to estimated functional residual capacity, lung recruitment is believed to be promoted by the reduction of interfacial tension and by bulk distension of alveoli with a noncompressible medium, thereby increasing the alveolar-capillary surface area participating in gas exchange and thus reducing shunt fraction in injured lungs (16, 37). It has also been suggested that the alveolar hydrostatic pressure column generated by intrapulmonary PFC during PLV shifts regional blood flow within the lung in a manner similar to that during TLV, potentially leading to the normalization of disorganized regional ventilation-perfusion relationships within the injured lung and improving the efficiency of gas exchange (24). Although the precise patterns of regional flow redistribution within the lung during PLV have not been studied, the regional distribution of intrapulmonary PFC has been shown to be nonuniform and to vary throughout the respiratory cycle (5) and, at least in this manner, to differ from TLV (18). If regional pulmonary flow patterns reflect the intrapulmonary distribution of PFC, at least on this basis, one would expect regional blood flow distribution during TLV and PLV to differ. Understanding the relationship between gas exchange efficiency during PLV and intrapulmonary PFC volume and distribution is critical to optimizing PLV with respect to ventilator strategies and PFC dose.
The objective of our study was to quantitate changes in the regional pattern of pulmonary blood flow during the transition from conventional mechanical ventilation (CMV) to PLV and to examine the effect of incremental dosing of PFC on the evolution of regional pulmonary blood flow patterns during PLV. We hypothesized that blood flow would be redistributed to nondependent lung, as has been demonstrated during TLV (26). We also sought to characterize flow redistribution in the vertical axis within and across serial transverse sections from the apex to the diaphragmatic surface of the lung; this has not been previously reported during PLV or TLV.
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METHODS |
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Top
Abstract
Introduction
Methods
Results
Discussion
References
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Animal Preparation
This protocol was approved by the Animal Care and Use Committee of Children's Hospital, and the animals were handled according to National Institutes of Health guidelines for the care and use of laboratory animals (30). Eight healthy lambs (mean weight 11.0 kg, range 8.3-13.4 kg) were studied. Anesthesia was induced with ketamine (10 mg/kg im); the lambs were orally intubated with a cuffed 6.0-mm-ID endotracheal tube (Mallinckrodt, Glenn Falls, NY) and secured levelly in the supine position. Paralysis was induced with pancuronium bromide (0.1 mg/kg iv) and maintained with a continuous infusion (0.1 mg · kg
1 · h1);
anesthesia was maintained with a continuous infusion of ketamine (2-4
mg · kg1 · h1). The animals were
mechanically ventilated with a Servo 900C ventilator (Siemens, Solna,
Sweden) in a volume-limited, time-cycled mode with the following
settings: 0.6 inspired O2
fraction, 10-12 ml/kg tidal volume, and 0.66 s inspiratory time,
with rate adjusted to maintain arterial
PCO2 at 40 ± 5 Torr. The right
and left internal jugular veins were cannulated with 6-Fr and 8.5-Fr percutaneous introducers, respectively. Two Swan-Ganz thermodilution catheters were guided into the pulmonary artery and maneuvered into the
wedge position (5-Fr) or into the main pulmonary artery trunk (7-Fr).
Monitoring also included continuous electrocardiography and display of
the arterial pressure waveform obtained from a catheter in the femoral
artery.
Experimental Design
After intubation, a 3-h stabilization period preceded the 4-h study. At the end of the 3-h stabilization, lambs underwent continued CMV or conversion to PLV. PLV was initiated with the tracheal instillation of PFC liquid (10 ml/kg, perfluorooctyl bromide, perflubron, LiquiVent, Alliance Pharmaceutical, San Diego, CA). The initial 10 ml/kg of PFC was administered over 10-15 min via an endotracheal tube side-port adapter without adjustment of ventilatory parameters. Two additional 10 ml/kg doses of PFC were administered with the same technique at hourly intervals, to a cumulative dose of 30 ml/kg. Regional pulmonary blood flow determination via microsphere injection, pulmonary mechanics, and hemodynamic data were collected as described below. Data were collected at baseline immediately before conversion to PLV, 1 h after each PFC aliquot, and again 2 h after the last PFC dose.Data Collection
At all data collection points the following hemodynamic data were measured directly: heart rate, femoral arterial pressure, pulmonary arterial pressure (PAP), pulmonary capillary wedge pressure (PCWP), and cardiac output (CO). PCWP was measured during balloon occlusion of a pulmonary artery branch via a Swan-Ganz catheter and recorded during its nadir at end expiration. CO was calculated with a CO computer (model COM-2, Baxter, Irvine, CA) after serial injections of 5 ml of iced saline (0°C) into the right atrium via Swan-Ganz catheter. At each data point, iced saline injection was repeated until three CO computations grouped within 10% were obtained. The group mean was recorded. Pulmonary vascular resistance (PVR) was calculated as follows
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(1) |
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(2) |
Regional Blood Flow Determination
The distribution of regional pulmonary blood flow was estimated by measuring pulmonary capillary trapping of 15.5 ± 0.1 µm radiolabeled carbonized plastic microspheres (DuPont NEN, Nuclear Products Division, Boston, MA) (2). To permit data collection at five time points during the protocol as listed above, five different sets of microspheres labeled with the following isotopes were used in the experiment: 141Ce, 113Sn, 85Sr, 95Nb, and 46Sc.A 1-ml injectate was used, with an estimated dose of 2.5 × 106 microspheres (10 µCi). The microspheres were suspended in a 10% dextran solution with 0.01% Tween 80 added to prevent aggregation. Immediately before injection, the microspheres were placed in an ultrasonic bath for 30 min and agitated with a vortex mixer for 3 min to ensure maximal dispersion of microspheres. The microspheres were then injected over 20-30 s into the right atrium. A blood sample was simultaneously drawn from the femoral artery to assess nonentrapment of the microspheres, and a reference blood sample was obtained from the pulmonary artery as described below.
Microspheres were injected in concert with hemodynamic, gas exchange, and pulmonary mechanics data collection at the following time points: at baseline immediately before conversion to PLV, at hourly intervals immediately before each PFC aliquot, and again 2 h after the last PFC dose (Fig. 1).
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The animals were killed after the last microsphere injection. The intrathoracic position of the ventral surface of the lungs relative to a horizontal plane was noted; the lungs were excised en bloc and separated from the heart, and blood was passively drained from the pulmonary vasculature. Intratracheal saline was used to rinse residual PFC until the lungs were clear by fluoroscopy. To ensure anatomic integrity, the lungs were placed in a 10% buffered Formalin bath and fixed with intratracheal Formalin for 24 h at a constant transpulmonary pressure of 20 cmH2O. With the lung in anatomic position in the supine lamb, nondependent (ventral) surface of the lung is parallel to the horizontal plane and dependent (dorsal) surface of the lung forms an angle of ~15-20° anteriorly with respect to the horizontal. After fixation the intrathoracic position of the lung relative to a horizontal plane was reproduced and the lung was sectioned according to a grid, allowing reconstruction in the transverse (dependent-nondependent) plane and along a coronal (apical-diaphragmatic) plane. Each lung was divided evenly into nine serial transverse sections from apex to diaphragm, with slices made perpendicular to the longitudinal axis of the lung. Even-numbered lung sections were used for analysis. Each lung section was then divided into five sequential, evenly proportioned segments by coronal slices through its vertical axis from dependent (dorsal) to nondependent (ventral) lung (Fig. 2). Wet weight of tissue segments ranged from 400 to 700 mg. All conducting airways >3 mm in diameter were dissected free of the samples. Tissue segments were then air dried for 24 h and weighed before estimation of regional microsphere trapping with a gamma counter.
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Regional lung activity was quantitated with a computer-controlled gamma
counter and a multichannel pulse-height analyzer (1282 CompuGamma CS,
Pharmacia-Wallac, Turku, Finland). Inasmuch as the tissue samples
contained five radiolabels with overlapping spectra, counts were
corrected for spillover from adjacent energy peaks. Individual lung
tissue counts were converted to flows after measurement of a surrogate
organ flow with the reference sample technique (17). To calculate a
reference flow
(
ref) to a
surrogate organ during microsphere injection, a timed reference blood
sample was obtained with an infusion-withdrawal variable-speed pump
from the main pulmonary artery trunk. The sample was drawn into a
preweighed syringe over 2 min, beginning 45 s before microsphere
injection. The full syringe was then reweighed, and the volume of blood
withdrawn over 2 min was calculated and converted to a
ref for substitution in
Eq. 4 as follows
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(3) |
i) with
the standard ref formula
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(4) |
Statistical Analysis
Statistical comparisons were performed on hemodynamic, gas exchange, and pulmonary mechanics data with a paired, two-tailed t-test.Regional flow measurements were standardized relative to sample weight and individual lamb's mean baseline regional flow. Each animal generated 20 samples of pulmonary tissue; weight-normalized flow to each piece at baseline from Eq. 1 was averaged to generate a mean regional baseline flow. This flow was used as an index for flow measurements at baseline and at all other data collection points, generating a weight-normalized relative regional flow measure.
Simple linear (least-squares) regression was used to establish the relationship between regional blood flow at baseline and sample location along the vertical axis within each transverse plane. To increase the power of this analysis, regional CMV and PLV measurements at baseline were pooled. The slopes of the linear relationship were compared with zero by the two-tailed t-test. The Pearson correlation coefficient (r) was used to measure the strength of the linear association, and the coefficient of determination (r2) was used to indicate the proportion of variation in flow that was accounted for by the regression model.
Linear regression was also used to assess change over time in the
regional blood flow patterns along the vertical axis within each
transverse plane. A four-way repeated-measures multivariate analysis of
variance was used to assess differences in the distribution of
pulmonary blood flow with respect to mode of ventilation
(between-animals factor) as well as transverse section location along
the longitudinal axis from the apex to the diaphragmatic surface of the
lung, location along the vertical axis from nondependent to dependent
lung within each transverse section, and PFC dose (within-animals
factors) (29). Comparisons between CMV and PLV lambs at baseline were based on Hotelling's multivariate F
test. Linear contrasts were used to determine whether the regional
blood flow pattern across transverse sections changed after PFC
administration and was dose dependent. In our regional flow
comparisons, two-tailed values of P 
0.05 with Scheffé's technique for multiple comparisons were
considered significant throughout (32). Data analysis was conducted
using PROC GLM (SAS statistical package, version 6.11, SAS Institute,
Cary, NC).
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RESULTS |
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Top
Abstract
Introduction
Methods
Results
Discussion
References
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Four lambs completed the protocol in each group; values are means ± SE.
Gas Exchange
In CMV lambs all gas exchange parameters were stable throughout the experiment. In PLV lambs, however, arterial PO2 fell from 227 ± 16 to 139 ± 17 Torr after the first 10 ml/kg of PFC and progressively to 88 ± 7 Torr with further filling to 30 ml/kg. This decrement reached statistical significance after the first dose of PFC and remained so for the remainder of the study. Over the last hour of the study period, when no further PFC was given, oxygenation was unchanged (Table 1).
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Inasmuch as the respiratory rate was manipulated to maintain arterial PCO2 between 40 and 45 Torr, arterial PCO2 cannot be considered a dependent variable. The mean respiratory rate was increased after the second 10 ml/kg fill from 23 ± 1 to 24 ± 1 and was stable for the duration of the study period (Table 2). The changes in respiratory rate during the course of the protocol were not statistically significant.
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Lung Mechanics
All lambs were ventilated in a volume-limited, time-cycled mode. PIP and Cdyn were similar between CMV and PLV lambs at baseline (Table 2). In the CMV group, lung mechanics were stable over the course of the experiment. In PLV lambs, lung mechanics were unaffected by successive dosing of PFC.Hemodynamics
There were no significant changes in hemodynamic parameters in either treatment group during the study period. Although PVR index trended downward in both groups over the course of the experiment, these changes were not statistically significant (Table 3).
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Pulmonary Blood Flow
Regional blood flow was examined along an axis from nondependent to dependent lung in five sequential segments within four transverse planes from apical to diaphragmatic lung. Each lamb's regional flow measurements were indexed relative to sample weight and the individual lamb's mean baseline regional flow; all flows are therefore expressed without units. The mean individual regional flow at baseline was 27.8 ± 12.2 and 29.6 ± 10.7 ml · min1 · g1
for CMV and PLV lambs, respectively.
Regional flows at baseline. After the 3-h stabilization period, before experimental manipulation, baseline regional blood flow data were pooled from CMV and PLV lambs. We found marked variation in flow patterns within the vertical axis from nondependent to dependent lung in sequential transverse sections taken along the longitudinal axis from apex to diaphragm. Patterns favoring flow to dependent lung were found in the apical and hilar (H1) sections (P < 0.001), and we found no flow gradient relative to gravity in the hilar (H2) or the diaphragmatic section (Fig. 3). When flow is compared from apex to diaphragm across transverse planes, a slight gradient favoring diaphragmatic lung was noted in each group (Fig. 4). However, the proportion of variation in flow that was accounted for by this relationship was slight (r2 = 0.09 and 0.01 for CMV and PLV, respectively); thus at baseline we found no strong apical-diaphragmatic gradient. There were no statistical differences in regional flow patterns between unpooled CMV and PLV data at baseline.
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Regional flow evolution during CMV. In the four lambs remaining on CMV, we found the dependent-favored regional flow pattern in the vertical plane and the relatively uniform flow pattern from apex to diaphragm, noted at baseline, to be stable over the 4-h study period (Figs. 4 and 5).
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Regional flow evolution during PLV. In the four lambs undergoing conversion to PLV, we found significant redistribution in the pattern of regional pulmonary blood flow after the first dose of PFC (Fig. 6). The nature and magnitude of pattern evolution during PLV were not uniform within the lung, varying within the transverse planes from apex to diaphragm. In the diaphragmatic section we found global reduction of flow after the first 10 ml/kg of PFC (P < 0.001), without development of a gradient in the vertical axis from nondependent to dependent lung. The reduction in flow to diaphragmatic lung did not progress with subsequent doses of PFC. In the transverse sections from the hilar region (H1 and H2), we found redistribution of flow in the vertical axis, with reversal of the gradient at baseline and establishment of a pattern favoring flow to nondependent (ventral) lung. In comparison with the patterns we found at baseline, this shift was significant in the H2 section at 1 h after 10 ml/kg of PFC (P = 0.025), in the H1 section at 2 h after a cumulative 20 ml/kg of PFC (P = 0.034), and again in the H2 section at 3 h after a cumulative 30 ml/kg of PFC (P = 0.035). In the apical section we found no significant change in the regional flow pattern but noted a dose-dependent trend in augmentation of the magnitude of flow. Across transverse planes we found redistribution of flow on initiation of PLV, establishing a pattern favoring flow to apical lung from a relatively uniform distribution at baseline (Fig. 4). This change was significant after the first instillation of 10 ml/kg of PFC at 1 h (P = 0.001) and was noted to increase in magnitude on subsequent dosing at 2 h after a cumulative dose of 20 ml/kg (P < 0.001) and at 3 h after a cumulative dose of 30 ml/kg (P < 0.001).
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DISCUSSION |
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Top
Abstract
Introduction
Methods
Results
Discussion
References
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This study was designed to utilize intrapulmonary microsphere trapping to quantify regional pulmonary blood flow pattern evolution in normal lungs during the transition from CMV to PLV and with progressive dosing during PLV. During the experiment we noted a moderate impairment in oxygenation and minimal effect on pulmonary mechanics similar to that previously reported during PLV in the normal animal (10, 38). The principal findings of this study are that, during CMV, regional pulmonary blood flow favored dependent over nondependent lung, and a relatively uniform flow pattern without gradient was observed across transverse planes from apex to diaphragm. In the CMV group this pattern was stable over the course of the experiment. In examining regional flow along the vertical axis within transverse sections on conversion to PLV, we found reduced flow to nondependent and dependent lung within the diaphragmatic section, flow redistribution favoring nondependent lung in hilar sections, and a trend to augmented flow without a change in gradient in the apical section. Across transverse planes a flow gradient developed favoring apical lung. Additional PFC did not magnify the redistribution noted along the vertical axis within transverse sections but increased the dose-dependent asymmetry in flow favoring apical lung. This pattern remained stable over a 2-h period after the last dose of PFC. These findings were not associated with a change in cardiac index, global changes in PVR, or Cdyn.
In interpreting our data, one possible source of bias should be noted. We chose to normalize our raw regional flow data to tissue segment weight and each animal's mean baseline regional flow. Normalizing to mean baseline regional flow eliminated bias in the data because of variations in individual subject's total pulmonary blood flow, so only regional intrapulmonary relative flow was examined. Normalizing to dry weight after the dissection of conducting airways eliminated bias due to variation in sample size and character. We did not flush blood from the lungs before tissue fixation. Therefore, weight indexing may falsely depress flows to segments with more blood mass per tissue volume. We believe that although this method did permit a bias in our measurements, it is attenuated by several factors. Blood was drained passively from the lungs, and after fixation all tissue segments were thoroughly air dried before they were weighed. Therefore, our lung tissue weights are in variance with their true blood-free weight only by the mass of dried red blood cells not drained passively before fixation. This bias in our data, if present, would serve to underestimate the true magnitude of the regional flow gradient.
Our understanding of regional pulmonary blood flow pattern evolution in disease and during therapeutic intervention had been principally based on the zonal perfusion model proposed by West et al. (41), which predicts regional flow on the basis of the balance of intravascular, alveolar, and interstitial pressures with their relationships modulated by lung volume (22) and in which a predominant determinant of regional blood flow is gravitational force. More recently, it has been appreciated that nongravitational factors play the major role in the spatial distribution of pulmonary blood flow (21, 28, 31). Newer theories account for the influence of regionally related differences in vascular architecture in the determination of vascular conductance (3, 15) and incorporate a fractal model of vascular anatomy and regional flows (12, 13).
To weigh our findings in light of these models, it is necessary to
consider the influence of an alveolar pressure gradient created by
partial replacement of alveolar gas with a fluid nearly twice as dense
as blood. D'Angelo et al. (7, 8) performed topographical mapping of
transpulmonary pressure gradients in gas-, saline-, and PFC-filled
lungs and described a vertical transpulmonary pressure gradient in the
gas-filled lung regressing from nondependent to dependent lung at
0.34 cmH2O/cm. These
investigators partitioned the contribution to this gradient into lung
tissue density and elastance, recoil forces, intrapulmonary blood
volume, abdominal pressure, and chest wall compliance (9). In the
saline-filled lung, this gradient was abolished; in the PFC-filled lung
the transpulmonary pressure gradient reversed with respect to that of
the gas-filled lung, progressing from nondependent lung to dependent
lung at a rate of 0.5 cmH2O/cm
(7). In these experiments one can see the effect on transpulmonary
pressure when the density of alveolar contents is changed, presumably
due to intra-alveolar hydrostatic pressure gradients that would vary
with fluid density, regionally with lung height, and overall with lung
volume. In the same experiment, increased lung volume attenuated the
slope of the gradient in the gas-filled lung, did not modify uniform transpulmonary pressure in the saline-filled lung, and increased the
slope of the pressure gradient in the PFC-filled lung. This effect has
been ascribed to a transdiaphragmatic abdominal hydrostatic pressure
gradient that is inversely proportional to lung volume (1).
In experiments on the saline-filled lung, West et al. (40) demonstrated regional perfusion in the vertical axis to be relatively uniform, with a focal area of higher flow in the midlung. This shift to uniform flow was attributed to a balancing of the intravascular hydrostatic pressure gradient with a corresponding alveolar pressure gradient (40), and perhaps also with the transdiaphragmatic hydrostatic pressure gradient described above. Higher flow in the midlung was not explained by the zonal perfusion model. Redistribution of blood flow has been examined in the PFC-filled lung by Lowe, Shaffer, and co-workers (26, 33), who described a lung volume-amplified shift in regional flow from dependent to nondependent regions. This study was performed in an isolated-perfused model during TLV, and regional flow was examined along the vertical axis without partition along the longitudinal axis. They did not detect complete flow pattern reversal, as one would expect given the zonal perfusion model and the pressure gradient data of D'Angelo and Agostoni (7) in PFC-filled lungs. In addition, Lowe and Shaffer (26) noted an overall increase in total PVR, also proportional to lung volume.
The gradients affecting regional PVR and thus regional flow are likely to be more complex in the lung only partially filled with PFC and should be related to the relative distribution of PFC within the lung and the mode of ventilation. The distribution of PFC within the lung during TLV has been shown to be uniform (18). During PLV, gas and PFC have been shown to partition, with PFC preferentially distributed to dependent lung regions and distributing more uniformly at high airway pressures (5).
It is apparent from our data that, during PLV, regional blood flow redistribution patterns in the vertical plane vary dramatically on the basis of transverse section location along an apical-diaphragmatic axis. We found flow shunted away from diaphragmatic lung irrespective of location in the vertical plane and away from dependent lung in the hilar region. As part of this pattern, flow was augmented in nondependent hilar lung and in apical lung in general. It is interesting that the focus of increased flow in the midlung (within the vertical plane) noted by West et al. in the saline-filled lung (40) is also evident in our data in the H1 section. Inasmuch as we did not find an increase in overall PVR, it seems likely that the changes in regional PVR responsible for the shift in flow away from dependent and diaphragmatic lung must have been accompanied by a reciprocal fall in PVR in nondependent and apical lung. This may be due to a diminution of recoil pressure in nondependent lung secondary to an alveolar-PFC film in nondependent lung. The combination of a reduced recoil pressure in nondependent gas-filled lung and an alveolar hydrostatic pressure column in dependent PFC-filled lung would produce an even steeper gradient in PVR than during TLV and may be responsible for the more profound redistribution in flow noted here than during TLV.
We also noted relatively uniform flow across transverse planes from apex to diaphragm during CMV. In the saline-filled lung, West et al. (40) noted near-uniform flow in the same plane. There are no data regarding regional blood flow along this axis in the PFC-filled lung. During PLV we noted the formation of a PFC dose-dependent asymmetry in flow across transverse planes favoring apical lung. This likely reflects asymmetric distribution of PFC within the lung along the same axis. It seems probable that because of the 15-20° in vivo slope of the dorsal surface of the lamb lung, during progressive PFC dosing in the supine position, PFC will fill the lung in the region of the diaphragm before distributing apically.
These blood flow redistribution data, if matched by reciprocal change in regional ventilation, are in accordance with the suggestion that PLV may enhance gas exchange in the injured lung by improving disorganized regional ventilation-perfusion matching. It will be important to correlate these data with measures of intrapulmonary PFC distribution.
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ACKNOWLEDGEMENTS |
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This work was supported in part by Alliance Pharmaceutical (San Diego, CA) and Hoechst Marion Roussel (Frankfurt, Germany).
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FOOTNOTES |
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Address for reprint requests: A. Doctor, Children's Hospital, MICU Office/FA-108, 300 Longwood Ave., Boston, MA 02115.
Received 18 October 1996; accepted in final form 15 December 1997.
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REFERENCES |
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Top
Abstract
Introduction
Methods
Results
Discussion
References
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