Ventilated Rabbit Lungs Research Articles

Recovery of Treatment Doses of Surfactants from the Lungs and Vascular Compartments of Mechanically Ventilated Premature Rabbits

Premature rabbits delivered by cesarean section at 28 d of gestation were each given intratracheally 75 mg/kg of radiolabeled preparation of either natural rabbit surfactant, natural calf surfactant, or surfactant-TA. Each newborn rabbit was ventilated for up to 6 h in a ventilator-plethysmograph with individual adjustments of peak inspiratory pressures to attain tidal vol of 12-15 mL/kg body wt. Dynamic compliances were about 0.7-0.9 mL/cm H2O. kg after treatment with the three surfactants and did not deteriorate during the 6-h study. Rabbits were randomly studied at 0.5, 1.5, 3, 4.5, and 6 h of age for the recovery of the labeled surfactant phosphatidylcholine in the total lungs (alveolar wash plus postlavage lung tissue). The labeled phosphatidylcholine was cleared from the total lungs of rabbits treated with natural rabbit or calf surfactants at comparable rates of about 25%/6 h. In contrast, the clearance rate of surfactant-TA phosphatidylcholine from the total lungs was not significantly different from 0. Lipids from rabbit surfactant that had been administered intratracheally were only minimally present in the blood and liver. In other similarly treated rabbits, the lipids from radiolabeled rabbit surfactant and liposomes of dipalmitoylphosphatidylcholine that had been injected intravenously were recovered in blood and liver in substantial quantities. These studies documented significant losses of rabbit and calf surfactant phosphatidylcholine but not surfactant-TA phosphatidylcholine from the lungs of preterm ventilated rabbits. The losses were not explained by surfactant losses to the vascular compartment.

Vascular to alveolar leak of iron dextran (120 kD) in the immature ventilated rabbit lung.

Rabbit fetuses were delivered by hysterotomy on day 27 or 28 of gestation. Immediately after birth, the animals were tracheotomized and received by intravenous injection 0.2 mu Ci radiolabeled albumin and 11 mg iron dextran in 0.2 ml saline. The newborn rabbits then were ventilated artificially with a tidal vol of 12 ml/kg for 5-20 min. One group of nonventilated animals served as controls. At the end of the experiment, one lung was lavaged via the airways and the other was fixed for histologic examination. The recovery of labeled albumin and iron dextran in the lavage fluid was quantified. Iron dextran complexes were easily identified in the lung sections by staining with Prussian blue. Iron dextran accumulated in the airspaces of animals delivered on day 27 (about 4% of the injected dose during 10-20 min of ventilation). The albumin leakage was slightly higher than that of the dextran, a result consistent with different mol wt of the markers. The vol density of leaking alveoli in histologic sections increased with time, from 0 at birth to a mean value of 0.36 after 20 min of ventilation. The leakage starts as a focal event, gradually involving more and more terminal airspaces. In the histologic sections, there was no indication of a significant leakage at the bronchiolar level, although the epithelium of terminal and preterminal airways was clearly injured in all ventilated animals.

Corticosteroids and surfactant change lung function and protein leaks in the lungs of ventilated premature rabbits.

Fetal rabbits were treated with corticosteroids by maternal administration for 48 h before delivery at 27 d gestational age. The treated and control rabbits were placed on ventilator-plethysmographs so that ventilation could be adjusted by regulation of tidal volumes to 10-13 ml/kg body wt. [125I]albumin was mixed with fetal lung fluid at birth, alternate rabbits from each litter were treated with Surfactant-TA, and [131I]albumin was injected intravascularly. The movement of the labeled albumins into and out of the alveolar wash and lung tissue was measured after 30 min of ventilation. Corticosteroid treatment (total dose, 0.2 mg/kg betamethasone) significantly decreased the protein leak across the endothelium (P less than 0.001) but increased the protein leak across the epithelium (P less than 0.001). Surfactant treatment decreased both the endothelial and epithelial leaks, and the combination of surfactant and corticosteroid treatments decreased endothelial leaks to 29% of control values and increased compliance more than either treatment alone. The 48-h corticosteroid treatment did not increase alveolar surfactant pool sizes. Corticosteroids significantly changed lung protein leaks independently of surfactant, and improved the response of the preterm lung to surfactant treatments.

Influence of tocopherol, its chromane compound, phytyl chains and superoxide dismu8tase on increased vascular resistance and permeability due to arachidonate metabolism in isolated rabbit lung

In the model of isolated, ventilated rabbit lungs, perfused with isoionic and isooncotic fluid, the addition of arachindonic acid to the perfusion fluid or the liberation of arachidonic acid by the Ca-ionophore A 23187 results in an increase in pulmonary vascular resistance and permeability. The former can be ascribed to cyclooxygenase products, the later to lipoxygenase products of arachidonic acid. The effects of α-tocopherol, its chromane compound, α-tocopherolquinone, phytol, 2-methyl-1,4-napthoquinone, 2-methyl-3-phytyl-1, 4-naphthoquinone and of superoxide dismutase (SOD) on the increase in pulmonary vascular resistance and permeability was investigated. A membrane effect of the phytyl side chain and an antioxidative effect of the chromane compound can be distinguished: phytol increases the arachidonate-induced rise of pulmunary vascular resistance and permeability, whereas the chromane compound decreases both to a large degree. Methyl-phytyl-naphthoquinone and methyl-naphthoquinone gave equivalent results. SOD decreases the enhanced vascular resistance and the vascular leakage. The possibility of antioxidative therapy in acute pulmonary lesions with vascular leakage and increased vascular resistance is discussed.

Increased pulmonary vascular resistance and permebility due to arachidonate metabolism in isolated rabbit lungs

Liberation and metabolism of arachidonic acid may be the common final pathway of different stimuli on the pulmunary vascular bed. In a model of isolated, ventilated rabbit lungs, perfused with krebs Henseleit albumin buffer in a recirculating system, changes of pulmonary vascular resistance and of vascular permeability are monitored continously. The addition of free arachidonic acid or of the Ca-ionophore A 23187 to the perfusion fluid consistently evokes a biphasic increases in vascular resistance as well as an initially reversible increase in vascular permeability, followed by pulmonary edema. Both phases of increased vascular resistance are completely suppressed by inhibition of the cyclooxygenase, decreased to a large degree by inhibitors of thromnoxane synthetase, and markedly augmented by short preincubation of arachidonic acid with ram seminal vescular microsomes and by sulfhydryl reagents. The increased pulmonary vascular permeability is augmented by inhibition of cyclooxygenase and reduced by simulteneous lipoxygenase inhibition. Antagonists of histamine, serotonin and sympathic or parasympathic activity do not have any influence. PG F 2α, TxB E 2 and PG I 2 alter the pulmonary vascular resistance, but do not increase vascular permeability. In inclusion, increased availability of free arachidonic acid evokes a rise in pulmonary vascular resistance, which can be ascribed to cyclooxygenase products, especially to thromboxane, and causes a rise in vascular permeability which can be ascribed to lipoxygenase products. The findings may be related to acute pulmonary lesions with increase in vascular resistance and with vascular leakage.

Vascular and extravascular compartments of the isolated perfused rabbit lung

The vascular, interstitial, and cellular compartments of 15 isolated, perfused and ventilated rabbit lungs determined by a steady-state indicator-dilution procedure. Five lungs were perfused with constant pulmonary artery flow and zero left atrial pressure for more than 1 h. Edema formation was continuous and pulmonary vascular volume (PVV) decreased initially at a time when pulmonary vascular resistance (PVR) was falling. Increases in PVR were not seen until edema formation had become severe. In 10 other lungs, increases in pulmonary artery or left atrial pressure resulted in elevation of PVV and accelerated edema formation. The initially abrupt increase in PVV was followed by a more gradual increase over a 10-min period. Return of fluid to the vasculature was never observed in these studies. Labeled albumin readily entered the extravascular space but a relatively constant fraction of the interstitium remained inaccessible to albumin. No changes were found in the cellular volume during edema formation.

Interrelations between pulmonary liquid volumes and lung compliance.

We have investigated the relative effects of lung edema and of increases in pulmonary blood volume (PBV) on lung compliance (CL), and also the effects of selective elevations of pulmonary arterial (Ppa) and left atrial (Pla) pressures on PBV and on CL, using an isolated, perfused, and ventilated rabbit lung preparation. Lung weight was continuously recorded. A step rise in Pla at constant flow caused a rapid rise in PBV accompanied by an immediate fall in CL. With maintained high vascular pressures interstitial edema accumulated with no further fall in CL. Not until 3 times the normal amount of extra-vascular fluid had accumulated did a further, secondary reduction in CL occur. When Ppa was elevated to the same level by 1) a rise in flow and 2) a rise in Pla, the latter type of experiment gave 3-5 times larger increases in PBV. Pla elevations with or without rise in Ppa (flow adjusted) gave almost the same rises in PBV. The fall in CL was related to rises in PBV regardless of how such rises were obtained. Our conclusion is that increases in PBV, but not accumulation of interstitial edema, reduced CL in this preparation.

Increase in capillary filtration rate resulting from reduction in the intravascular calcium ion-concentration.

AbstractNicolaysen, G. Increase in capillary filtration rate resulting from reduction in the intravascular calcium ion‐concentration. Acta physiol. scand. 1971. 81. 517–527.Marked reductions in intravascular concentrations of Ca++ and Mg++ has previously been shown to cause edema development. The effect of moderate reductions in the intra‐vascular concentration of Ca++ on the net rate of filtration from a vascular bed during increased capillary pressure has been analyzed. Isolated, ventilated rabbit lungs were perfused with plasma at 2° C. In each preparation repeated filtration tests were performed by standardized increases in the outflow pressure lasting for 6 or 10 min. The rate of weight increase for the preparation when 4 min of a test had elapsed was taken as the net rate of filtration. This net rate of filtration was shown to be increased when the [Ca++] was reduced to about 0.1 mM. This increase in filtration rate could be reversed by Ca++‐addition, but not by Mg++‐addition. Evidence is presented that this increase in filtration rate was due to changes in the “hydraulic conductivity” of the capillary wall.