Excised Rabbit Lungs Research Articles

Developing Hyperpolarized Butane Gas for Ventilation Lung Imaging.

NMR hyperpolarization dramatically improves the detection sensitivity of magnetic resonance through the increase in nuclear spin polarization. Because of the sensitivity increase by several orders of magnitude, additional applications have been unlocked, including imaging of gases in physiologically relevant conditions. Hyperpolarized 129Xe gas recently received FDA approval as the first inhalable gaseous MRI contrast agent for clinical functional lung imaging of a wide range of pulmonary diseases. However, production and utilization of hyperpolarized 129Xe gas faces a number of translational challenges including the high cost and complexity of contrast agent production and imaging using proton-only (i.e., conventional) clinical MRI scanners, which are typically not suited to scan 129Xe nuclei. As a solution to circumvent the translational challenges of hyperpolarized 129Xe, we have recently demonstrated the feasibility of a simple and cheap process for production of proton-hyperpolarized propane gas contrast agent using ultralow-cost disposable production equipment and demonstrated the feasibility of lung ventilation imaging using hyperpolarized propane gas in excised pig lungs. However, previous pilot studies have concluded that the hyperpolarized state of propane gas decays very fast with an exponential decay T 1 constant of ∼0.8 s at 1 bar (physiologically relevant pressure); moreover, the previously reported production rates were too slow for potential clinical utilization. Here, we investigate the feasibility of high-capacity production of hyperpolarized butane gas via heterogeneous parahydrogen-induced polarization using Rh nanoparticle-based catalyst utilizing butene gas as a precursor for parahydrogen pairwise addition. We demonstrate a remarkable result: the lifetime of the hyperpolarized state can be nearly doubled compared to that of propane (T 1 of ∼1.6 s and long-lived spin-state T S of ∼3.8 s at clinically relevant 1 bar pressure). Moreover, we demonstrate a production speed of up to 0.7 standard liters of hyperpolarized gas per second. These two synergistic developments pave the way to biomedical utilization of proton-hyperpolarized gas media for ventilation imaging. Indeed, here we demonstrate the feasibility of phantom imaging of hyperpolarized butane gas in Tedlar bags and also the feasibility of subsecond 2D ventilation gas imaging in excised rabbit lungs with 1.6 × 1.6 mm2 in-plane resolution using a clinical MRI scanner. The demonstrated results have the potential to revolutionize functional pulmonary imaging with a simple and inexpensive on-demand production of proton-hyperpolarized gas contrast media, followed by visualization on virtually any MRI scanner, including emerging bedside low-field MRI scanner technology.

Toward Lung Ventilation Imaging Using Hyperpolarized Diethyl Ether Gas Contrast Agent.

Hyperpolarized 129Xe gas was FDA-approved as an inhalable contrast agent for magnetic resonance imaging of a wide range of pulmonary diseases in December 2022. Despite the remarkable success in clinical research settings, the widespread clinical translation of HP 129Xe gas faces two critical challenges: the high cost of the relatively low-throughput hyperpolarization equipment and the lack of 129Xe imaging capability on clinical MRI scanners, which have narrow-bandwidth electronics designed only for proton (1H) imaging. To solve this translational grand challenge of gaseous hyperpolarized MRI contrast agents, here we demonstrate the utility of batch-mode production of proton-hyperpolarized diethyl ether gas via heterogeneous pairwise addition of parahydrogen to ethyl vinyl ether. An approximately 0.1-liter bolus of hyperpolarized diethyl ether gas was produced in 1 second and injected in excised rabbit lungs. Lung ventilation imaging was performed using sub-second 2D MRI with up to 2×2 mm2 in-plane resolution using a clinical 0.35 T MRI scanner without any modifications. This feasibility demonstration paves the way for the use of inhalable diethyl ether as a gaseous contrast agent for pulmonary MRI applications using any clinical MRI scanner.

Magnetomotive optical coherence elastography for microrheology of biological tissues.

Optical coherence elastography (OCE) is an established paradigm for measuring biomechanical properties of tissues and cells noninvasively, in real time, and with high resolution. We present a different development of a spectral domain OCE technique that enables simultaneous measurements of multiple biomechanical parameters of biological tissues. Our approach extends the capabilities of magnetomotive OCE (MM-OCE), which utilizes iron oxide magnetic nanoparticles (MNPs) distributed and embedded in the specimens as transducers for inducing motion. Step-wise application of an external magnetic field results in displacements in the tissue specimens that are deduced from sensitive phase measurements made with the MM-OCE system. We analyzed freshly excised rabbit lung and muscle tissues. We observe that while they present some similarities, rabbit lung and muscle tissue displacements display characteristic differentiating features. Both tissue types undergo a fast initial displacement followed by a rapidly damped oscillation and the onset of creep. However, the damping is faster in muscle compared to lung tissue, while the creep is steeper in muscle. This approach has the potential to become a novel way of performing real-time measurements of biomechanical properties of tissues and to enable the development of different diagnostic and monitoring tools in biology and medicine.

Estimating the diameter of airways susceptible for collapse using crackle sound

Airways that collapse during deflation generate a crackle sound when they reopen during subsequent reinflation. Since each crackle is associated with the reopening of a collapsed airway, the likelihood of an airway to be a crackle source is identical to its vulnerability to collapse. To investigate this vulnerability of airways to collapse, crackles were recorded during the first inflation of six excised rabbit lungs from the collapsed state, and subsequent reinflations from 5, 2, 1, and 0 cmH(2)O end-expiratory pressure levels. We derived a relationship between the amplitude of a crackle sound at the trachea and the generation number (n) of the source airway where the crackle was generated. Using an asymmetrical tree model of the rabbit airways with elastic walls, airway vulnerability to collapse was also determined in terms of airway diameter D. During the reinflation from end-expiratory pressure = 0 cmH(2)O, the most vulnerable airways were estimated to be centered at n = 12 with a peak. Vulnerability in terms of D ranged between 0.1 and 1.3 mm, with a peak at 0.3 mm. During the inflation from the collapsed state, however, vulnerability was much less localized to a particular n or D, with maximum values of n = 8 and D = 0.75 mm. Numerical simulations using a tree model that incorporates airway opening and closing support these conclusions. Thus our results indicate that there are airways of a given range of diameters that can become unstable during deflation and vulnerable to collapse and subsequent injury.

Effect of surface tension on alveolar surface area.

At fixed lung volume (VL), alterations in surface tension change alveolar surface area (S) and lung recoil (PL). Wilson (26), using data from fixed lungs (1, 9), quantified the isovolume change in S with PL. We reexamined this question in fresh excised rabbit lungs, with two important differences. First, we measured fractional changes in S by using diffuse light scattering, avoiding the potential upset of the balance of tissue and surface forces during fixation. Second, we altered surface tension by ventilating the lungs with nebulized polydimethylsiloxane, with much less residual fluid compared with lavage. We found that S decreased at low and mid VL (treatment surface tension > control) by about half of Wilson's estimates and was nearly unaffected by treatment at high VL. This suggests that with increased surface tension there is 1) greater septal retraction in lungs fixed by vascular perfusion compared with unfixed lungs and 2) a greater increase in PL and less loss of S than would have been predicted.

Mechanical properties of lung parenchyma during bronchoconstriction.

Interdependence between airways and the lung parenchyma is thought to be a major mechanism preventing excessive airway narrowing during bronchoconstriction. Because the elastance of the lung increases during bronchoconstriction, the lung's tethering force could also increase, further attenuating bronchoconstriction. We hypothesized that the bulk (kappa) and shear moduli (mu) of the lung increase similarly during bronchoconstriction. To test this hypothesis, we excised rabbit lungs and measured the lung volume, pulmonary elastance, kappa, and mu at transpulmonary pressures of 4, 6, 8, 12, and 16 cmH2O using pressure-volume curves, slow oscillations of the lung, and an indentation test. Bronchoconstriction was induced by nebulizing carbachol by using small tidal-volume ventilation to prevent hyperinflation. The measurement of kappa and mu was repeated after carbachol treatment. After carbachol treatment, the increase in kappa was significantly greater than that in mu. The estimated value for mu was approximately 0.5 x transpulmonary pressure both before and after carbachol treatment. These data suggest that the tethering effect of the lung parenchyma, which serves to attenuate bronchoconstriction, is not significantly increased during carbachol administration unless there is hyperinflation.

Evaluation of 18-hour lung preservation with oxygenated blood for optimal oxygen delivery

Background. Previous studies have shown that availability of oxygen during lung preservation to maintain aerobic metabolism may be essential for the optimal viability of preserved lung tissue. The purpose of this study was to evaluate lung preservation with oxygenated blood for optimal oxygen delivery to the lung graft in a rabbit model. Methods. Eighteen excised rabbit lungs were flushed and stored for 18 hours at 10°C with one of the following: Euro-Collins solution (EC; n = 6), oxygenated homologous blood (OB; n = 6), or low-potassium dextran solution (LPD; n = 6). Poststorage lung functions were evaluated with isolated, blood-perfused lung model for 10 minutes. Results. The mean oxygen tensions after reperfusion for the EC, OB, and LPD groups (47.0 ± 2.8, 76.9 ± 13.1, 96.2 ± 10.9 mm Hg at 10 minutes, respectively) were significantly different throughout the perfusion period (EC < OB < LPD, p < 0.05; EC < LPD, p < 0.01). Pulmonary artery pressure during the reperfusion period in the EC group (35.8 ± 4.4 mm Hg at 10 minutes) was higher than that in the OB and LPD groups (29.8 ± 4.3 and 22.4 ± 2.2 mm Hg, respectively) (EC > OB, EC > LPD, p < 0.05). However, the E-selectin level in the reperfused blood in the OB group (5.04 ± 0.24 ng/mL) was significantly elevated compared with that in other groups (EC, 3.56 ± 0.54; LPD, 2.92 ± 0.35 ng/mL, p < 0.05), which indicated enhanced neutrophil recruitment in the OB group. Comparisons of thrombomodulin and endothelin among the three groups did not reach statistical significance. Conclusions. We conclude that OB may enhance lung preservation as compared with EC solution, probably through its enriched oxygen delivery during storage and extracellular composition. However, the availability of oxygenated blood does not exceed that of LPD solution because of augmented neutrophil recruitment, which may activate neutrophil–endothelial interactions.

Effects of hypoxia, blood P CO 2 and flow on O 2 transport in excised rabbit lungs

In previous studies using isolated perfused rabbit lungs, an O 2 deficit measured by an alveolar gas-to-end capillary blood P O 2 difference ( a-aD O 2 ) was absent at blood flows ( Q ̇ ) consistent with severe exercise. Thus factors such as V ̇ a/ Q ̇ heterogeneity, shunt and diffusion limitation that contribute to an O 2 deficit in vivo were absent. Here we attempted to increase diffusion limitation to O 2 transport by reducing the equilibration coefficient D/( β Q ̇ ), the ratio of the diffusing capacity (D) to the product of Q ̇ and the capacitance coefficient ( β, the slope of the blood O 2 content-P O 2 curve). First, we used hypoxic (10% O 2) ventilation in conjunction with a low P v ̄ O 2 (≈25 mmHg) because β is largest in this region of the O 2 dissociation curve. Second, we increased β by decreasing blood P CO 2 which shifts the O 2 dissociation curve to the left (Bohr effect). Third, we increased Q ̇ to three times control to reduce D/ Q ̇ . CO diffusing capacity was measured as a function of blood flow and blood P O 2 . A deficit in O 2 transport as measured by a significant a-aD O 2 was measured only under conditions of hypoxia and high blood flow. The measured O 2 deficit matched the predictions from the equilibration coefficients D/( β Q ̇ ) based on measurements of β, D and Q ̇ .

Effect of macroscopic deformation on lung microstructure.

Using an anisotropic theory of diffuse light scattering in lungs, we measured the fractional changes in geometric mean linear intercepts in orthogonal directions when freshly excised rabbit lungs were subjected to isovolume uniaxial strains. Results from the optical technique were compared with morphometric estimates of fractional changes in mean linear intercepts from the same strained and unstrained (control) lobes, with the conclusion that diffuse light scattering is adequate to estimate changes in mean free paths in different directions. We compared optical estimates of fractional changes in mean linear intercepts with the macroscopic strain field measured by displacements of pleural markers; this relationship did not significantly differ from the line of identity. We conclude that the microscopic strain field is closely matched to the macroscopic strain field during uniaxial distortion. This suggests that surface reorientation may not play a large role in the origin of the low shear modulus of the lung, but this cannot be definitively stated without comparison of these experimental results to specific model predictions of the changes in mean linear intercepts in shear deformation.

Effect of blood flow on capillary transit time and oxygenation in excised rabbit lung

We used an isolated perfused lung preparation of the rabbit to study the effect of increasing blood flow on pulmonary capillary transit time by two methods. In one method, capillary transit time was measured from fluorescent dye dilution curves from arterioles and venules of the subpleural microcirculation. Values of transit time were similar to those for the whole lung determined by dividing capillary blood volume by blood flow. Capillary transit times averaged 0.50–0.62 sec at a control blood flow of 80 ml min −1 kg −1 and decreased to 0.14–0.18 sec as blood flow increased to 6 times control. To determine whether the reduced transit time would limit O 2 transport, we studied the effect of blood flow on oxygenation. Two isolated rabbit lungs were perfused in series. Blood from one lung deoxygenated by ventilation with a N 2CO 2 mixture was oxygenated by the test lung ventilated with air. Ventilation was matched to blood flow. P O 2 and P CO 2 were measured in blood flowing into and out of the test lung. At all flows, no significant alveolar gas-to-end-capillary blood P O 2 gradient (A-aDO 2) was measured. The isolated perfused rabbit lung showed no transit time limitation to oxygenation for blood flows that are consistent with heavy exercise in vivo.

Dynamic behavior of lung parenchyma in shear.

Dynamic shear properties of excised rabbit lungs were studied by measuring creep deformation after application of a step indentation force to the pleural surfaces by a rigid cylindrical punch. The punch diameter was 9.5 mm, and punch forces were 2,4, and 6 g. Measurements were made at lung volumes of 40, 60, and 90% of the total lung capacity before and after lavage with 3-dimethyl siloxane, which provided a constant surface tension of 16 dyn/cm at the alveolar surfaces. A power-law model was fitted to creep data and then transformed into the frequency (f) domain by using Laplace transforms. The optimum model parameters were used to calculate shear elastance (E mu), shear resistance (R mu), and shear hysteresivity (2 pi fR mu/E mu) between 0.01 and 2.0 Hz. It was found that E mu slightly increased and R mu decreased nearly hyperbolically with increasing f, both decreased with increasing indentation force, and both increased with increasing mean lung volume. Shear hysteresivity decreased sharply from 0.01 to 0.25 Hz and then assumed a nearly steady value that was an order of magnitude lower than the value reported previously for uniformly oscillated lungs. Changes in E mu and R mu after lavage were correlated with changes in transpulmonary pressure and not with changes in surface film properties. These results suggest that in the breathing range of frequencies 1) the energy loss of lung parenchyma is a much smaller fraction of the stored elastic energy in shear than in uniformly oscillated lungs and 2) transpulmonary pressure, not dynamic properties of surface film, is the primary determinant of lung dynamic properties in shear.

Effect of surface forces on oscillatory behavior of lungs.

The effect of alveolar surface tension on lung dynamic behavior was investigated by measuring total lung and tissue impedances in excised rabbit lungs at breathing frequencies of 0.2-0.8 Hz and tidal volumes of 10, 20, and 30 ml before and after lavage with 3-dimethyl siloxane, which provided a constant surface tension of 16 dyn/cm. The lungs were oscillated around the mean deflation pressures of 5 (control) and 8 cmH2O (lavaged), i.e., lung volume of 60% of total lung capacity. The total lung impedance was calculated from measurements of pressure and airflow at the trachea, and tissue impedance was measured by the alveolar capsule technique. The airway contribution was obtained as the difference between total lung and tissue impedances. In the lavaged lungs, dynamic elastance (Edyn) decreased and tissue resistance (Rti) increased relative to the control values over the entire frequency range. Airway resistance increased at the higher flow rates only. The decrease in Edyn could be attributed to the absence of surface film elastance in the lavaged lungs. The increase in airway resistance could be attributed to accentuated flow dependence due to changes in airway geometry and residual lavage liquid. However, the most intriguing result was the increase in Rti in the lavaged lungs. It could be attributed to altered mechanics at the alveolar duct level after lavage. It is concluded that dissipative properties of lung tissue are major determinants of Rti, whereas elastic properties of both tissue and surface film are important determinants of Edyn.

The effects of pulsatile flow on the pressure-flow relationships in zone 3 excised rabbit lungs

The effects of pulsatile flow on the pressure-flow relationships in zone 3 excised rabbit lungs

Disturbance of alveolar lining layer: effects on alveolar microstructure

To further study the influence of altered surface tensions on alveolar micromechanics, we analyzed the structure-function relationships in excised rabbit lungs filled with or rinsed by a fluorocarbon (approximately 15 mN/m) or by hexadecane (approximately 25 mN/m). The lungs were fixed and dehydrated by vascular perfusion, and the tissue samples were analyzed by light, transmission, and scanning electron microscopy. We made three observations. 1) Pressure-volume (P-V) loops hexadecane-filled lungs are shifted to the left and coincide with those of saline-filled lungs, indicating near-zero interfacial tension. In accordance, the alveolar microstructure and surface area of hexadecane-filled lungs resemble those of saline-filled lungs. 2) The P-V loops of fluorocarbon-filled lungs are not shifted to the left but coincide with those of fluorocarbon-rinsed lungs. Under both conditions, the alveolar microstructure is qualitatively identical and the alveolar surface areas are markedly reduced compared with normal air-filled lungs. These findings show that fluorocarbon-filled or fluorocarbon-rinsed lungs are subjected to similar interfacial tensions at the alveolar level. 3) Hexadecane-rinsed lungs show a pear-shaped P-V curve and a complex surface texture of peripheral air spaces. These results, together with in vitro observations, suggest a metamorphic interplay between lung surfactant and hexadecane in lining the surface and determining the surface tension. Evidently, the effects of foreign liquids introduced into the lung on the structure-function relationship cannot accurately be predicted from their in vitro surface tensions. This fact should be considered in the development of artificial surfactants.

Pulsatile and nonpulsatile pressure-flow relationships in zone 3 excised rabbit lungs

We compared the effects of pulsatile vs. nonpulsatile flow (Q) on pulmonary arterial pressure (Ppa)-Q relationships in zone 3 over wide ranges of pulse rate, stroke volume (SV), and Q. Excised left lungs of rabbits (n = 15) were perfused with tris(hydroxymethyl)aminomethane-buffered Tyrode solution containing 4% dextran, 1% albumin, and 10 mg/l of indomethacin and were ventilated with room air. Pulsatile Q was generated by a diaphragm pump delivering SV of 0.5, 1, or 2 ml (representing approximately 0.3, 0.6, and 1.2 times, respectively, the normal resting SV for rabbit left lung) and adjusting the pump frequency. Nonpulsatile Q was generated by raising an arterial reservoir to the required height. Mean pulmonary arterial (Ppa) and left atrial pressures were measured at end exhalation (positive end-expiratory pressure = 2.5 cmH2O) near the tips of the perfusion cannulas and were referenced to the lung base. Left atrial pressure was held constant at 7 cmH2O.Q was alternated between pulsatile and nonpulsatile, increasing Q stepwise from 100 to 600 ml/min (Q from approximately 0.3 to 2 times the normal resting Q for rabbit left lung), after which Q was reduced stepwise back to initial values. For the smallest SV there were no differences between Ppa-Q curves under pulsatile and nonpulsatile conditions. At the largest SV, Ppa was greater during pulsatile than nonpulsatile Q at Q > 100 ml/min. The slopes of the Ppa-Q curves were greater during pulsatile Q at the two larger SV values. These results can be explained by increasing Q turbulence and less ideal velocity profiles at higher peak Q resulting from the effects of rapidly changing inertial forces.

Experimental hydrostatic pulmonary edema in rabbit lungs. Morphology.

To study the accumulation and distribution of edema fluid and the associated changes in alveolar microarchitecture, edema was induced in excised rabbit lungs perfused with 6% albumin solution. The lungs, including the edema fluid, were then fixed by vascular perfusion with glutaraldehyde, osmium tetroxide, and uranyl acetate. Tissue samples were analyzed by light microscopy and transmission and scanning electron microscopy. We found (1) fixation was successful in that the albumin in the edema fluid formed coherent webs indicating the location and arrangement of the extravascular fluid accumulations; (2) regardless of the filtration pressure (about 29 mm Hg in one set of experiments and about 14 mm Hg in the other), an apical to basal gradient of fluid accumulation was found. This gradient was absent in lungs held in the inverse position, suggesting that the regional distribution of pulmonary edema is not simply gravity dependent. At the same lung height, there was a remarkable inhomogeneity of interstitial and alveolar edema. (3) Both the inhomogeneous distribution of fluid and the resulting changes in surface tension affected the entire alveolar architecture. (4) Within interstitial and alveolar spaces, there were striking inequalities in the density of the proteinaceous fluid pools that suggest local differences in the sieving properties of the barriers, that is, in the reflection coefficients for albumin. In conclusion, our findings suggest that the formation of pulmonary edema cannot be explained solely by uniform membrane models for fluid exchange.

Experimental Hydrostatic Pulmonary Edema in Rabbit Lungs: Barrier Lesions

In excised rabbit lungs perfused with a 6% albumin solution, hydrostatic pulmonary edema was induced by moderate (about 14 mm Hg) and high increases (about 29 mm Hg) of capillary transmural pressure. Thereafter, lung tissue and proteinaceous edema fluid were fixed by vascular perfusion and analyzed by electron microscopy for possible lesions of the blood-gas barrier. The following observations appear noteworthy: (1) There were distinct and numerous lesions of the epithelial cell layer. In high-pressure edema, frank disruptions on the thin and thick sides of the blood-gas barrier were prominent. In moderate pressure edema epithelial blebs were more conspicuous. (2) In contrast, endothelial lesions were rare in both high- and moderate-pressure experiments. (3) Epithelial Type I cells revealed an enormous plasticity as illustrated by the formation of large epithelial blebs. (4) Although the entire microvasculature was subjected to high pressures, barrier lesions were exclusively seen in regions with alveolar edema. These findings suggest that barrier leaks play a role in both hydrostatic and permeability lung edema and that the differences between both types of edema rather reflects the type and extent of injury to the alveolar epithelial barrier and the associated inflammatory reaction.

Changes in alveolar oxygen and carbon dioxide concentration and oxygen consumption during lung preservation The maintenance of aerobic metabolism during lung preservation

The lung is the only organ to which oxygen may be supplied after its blood supply is stopped. Before this study, we were not certain whether lung cells were able to maintain aerobic metabolism with the oxygen in the alveoli during preservation. Excised rabbit lungs were used to measure changes in the concentration of oxygen and carbon dioxide in the airway and changes in glucose, glucose-6-phosphate, lactate, adenosine triphosphate, and phosphocreatine levels in the lung tissue during preservation under different conditions. Twenty-seven lungs were flushed with low-potassium dextran electrolyte solution, inflated with room air, and preserved at 1 degree C (n = 8), 10 degrees C (n = 8), or 22 degrees (n = 11) for 4, 12, or 24 hours. Eight additional lungs were inflated with 100% nitrogen and preserved at 10 degrees C for 4 (n = 4) or 24 (n = 4) hours. Oxygen levels decreased and carbon dioxide levels increased in the airway of the lungs that were inflated with room air at rates dependent on the preservation temperature. The increase of carbon dioxide in the lungs that were inflated with 100% nitrogen was very small. When the oxygen was not available in the alveoli, lactate accumulated, and adenosine triphosphate and phosphocreatine decreased in the lung tissue. We concluded that lung cells are able to maintain aerobic metabolism with the oxygen in the alveoli during preservation and that the maintenance of aerobic metabolism may be essential to maintain the optimum viability of preserved lung tissue.

Extra-alveolar veins are contiguous with, and leak fluid into, periarterial cuffs in rabbit lungs

We previously observed physiological evidence that arterial and venous extra-alveolar vessels shared a common interstitial space. The purpose of the present investigation was to determine the site of this continuity to improve our understanding of interstitial fluid movement in the lung. Orange G and Evans blue dyes were added to the arterial and venous reservoirs, respectively, of excised rabbit lungs as they were placed 20 cmH2O into zone 1 (pulmonary arterial and venous pressures = 5 cmH2O, alveolar pressure = 25 cmH2O). After 10 s or 4 h the lungs were fixed by immersion in liquid N2, freeze-dried, cut into 5-mm serial slices, and examined by light macroscopy. Serial sections of 0.25-0.5 mm were subsequently examined by scanning electron microscopy. In the animals subjected to the zone 1 stress for 4 h, arterial and venous extra-alveolar vessels were surrounded by cuffs of edema. The edema ratio (cuff area divided by vessel lumen area) was greater around arteries than veins and decreased with increasing vessel size. Periarterial cuffs usually contained orange dye and frequently contained both orange and blue dye. Lymphatics containing orange or blue dye were frequently seen in periarterial cuffs. Scanning electron microscopy demonstrated that extra-alveolar veins of approximately 100 microns diameter were anatomically contiguous with arterial extra-alveolar vessel cuffs. In rabbit lungs, both arterial and venous extra-alveolar vessels (and/or alveolar corner vessels) leak fluid into perivascular cuffs surrounding arterial extra-alveolar vessels, and lymphatics located in the periarterial cuff contain fluid that originates from both the arterial and venous extra-alveolar vessels.

Surfactant Replacement Improves Lung Recoil in Rabbit Lungs after Acid Aspiration

SUMMARY We tested the hypothesis that surfactant replacement would be beneficial In the acld­ aspiration model of acute lung Injury. HCI (0.1 N, 2 mllkg) was Injected Into the trachea of excised rabbit lungs (n = 8). Control lungs (n = 4) had no Intervention. All were perfused with lYrode's solution mixed 1:1 with autologous whole blood at 40 mllmin/kg for 30 min, and then degassed. A modified natural surfactant (Survanta@, Ross Laboratories) was then Injected Into the trachea of four lungs Injured with HCI (100 mg/kg at 25 mg/ml). lWo quasi-static pressure-volume curves were determined. The mean alveolar pressures at 50,60,70,80, and 90% of TLC were greater In the HCI group than In the control group (p < 0.05). However, no difference was observed between the control lungs and thosethat received HCI + Survanta. In 13 anesthetized, paralyzed, and venti­ lated rabbits, deflation pressure-volume curvas were determined from TLC to FRC (measured by helium dilution). Then, 0.1 N HCI (3 ml/kg) was Injected into the trachea and, in seven, Survanta was Instilled 5 min later. The mean alveolar pressures at 60, 70, 80, and 90% TLC were higher at 15 and 60 min In the HCI group compared with their pre-HCI time point (p < 0.05). In the HCI + Survanta group, no differences were seen at 15 min, and only slight Increased were seen at 60 min. No effect of surfactant replacement on arterial blood gases was observed. HCI aspiration Increased recoil In both excised and in "i"o lungs, and surfactant replacement with Survanta returned recoil to normal. AM REV RESPIR DIS 1990; 142:1279-1283