ABSTRACT
Quantitative characterization of lung structures by morphometrical or stereological analysis of histological sections is a powerful means of elucidating pulmonary structure-function relations. The overwhelming majority of studies, however, fix lungs for histology at pressures outside the physiological/pathophysiological respiratory volume range. Thus, valuable information is being lost. In this perspective article, we argue that investigators performing pulmonary histological studies should consider whether the aims of their studies would benefit from fixation at functional transpulmonary pressures, particularly those of end-inspiration and end-expiration. We survey the pressures at which lungs are typically fixed in preclinical structure-function studies, provide examples of conditions that would benefit from histological evaluation at functional lung volumes, summarize available fixation methods, discuss alternative imaging modalities, and discuss challenges to implementing the suggested approach and means of addressing those challenges. We aim to persuade investigators that modifying or complementing the traditional histological approach by fixing lungs at minimal and maximal functional volumes could enable new understanding of pulmonary structure-function relations.
Subject(s)
Lung , Lung/physiology , Animals , Humans , Tissue Fixation/methodsABSTRACT
Within the pulmonary acini ventilation and blood perfusion are brought together on a huge surface area separated by a very thin blood-gas barrier of tissue components to allow efficient gas exchange. During ventilation pulmonary acini are cyclically subjected to deformations which become manifest in changes of the dimensions of both alveolar and ductal airspaces as well as the interalveolar septa, composed of a dense capillary network and the delicate tissue layer forming the blood-gas barrier. These ventilation-related changes are referred to as micromechanics. In lung diseases, abnormalities in acinar micromechanics can be linked with injurious stresses and strains acting on the blood-gas barrier. The mechanisms by which interalveolar septa and the blood-gas barrier adapt to an increase in alveolar volume have been suggested to include unfolding, stretching, or changes in shape other than stretching and unfolding. Folding results in the formation of pleats in which alveolar epithelium is not exposed to air and parts of the blood-gas barrier are folded on each other. The opening of a collapsed alveolus (recruitment) can be considered as an extreme variant of septal wall unfolding. Alveolar recruitment can be detected with imaging techniques which achieve light microscopic resolution. Unfolding of pleats and stretching of the blood-gas barrier, however, require electron microscopic resolution to identify the basement membrane. While stretching results in an increase of the area of the basement membrane, unfolding of pleats and shape changes do not. Real time visualization of these processes, however, is currently not possible. In this review we provide an overview of septal wall micromechanics with focus on unfolding/folding as well as stretching. At the same time we provide a state-of-the-art design-based stereology methodology to quantify microarchitecture of alveoli and interalveolar septa based on different imaging techniques and design-based stereology.
ABSTRACT
Advancements in methods, technology, and our understanding of the pathobiology of lung injury have created the need to update the definition of experimental acute lung injury (ALI). We queried 50 participants with expertise in ALI and acute respiratory distress syndrome using a Delphi method composed of a series of electronic surveys and a virtual workshop. We propose that ALI presents as a "multidimensional entity" characterized by four "domains" that reflect the key pathophysiologic features and underlying biology of human acute respiratory distress syndrome. These domains are 1) histological evidence of tissue injury, 2) alteration of the alveolar-capillary barrier, 3) presence of an inflammatory response, and 4) physiologic dysfunction. For each domain, we present "relevant measurements," defined as those proposed by at least 30% of respondents. We propose that experimental ALI encompasses a continuum of models ranging from those focusing on gaining specific mechanistic insights to those primarily concerned with preclinical testing of novel therapeutics or interventions. We suggest that mechanistic studies may justifiably focus on a single domain of lung injury, but models must document alterations of at least three of the four domains to qualify as "experimental ALI." Finally, we propose that a time criterion defining "acute" in ALI remains relevant, but the actual time may vary based on the specific model and the aspect of injury being modeled. The continuum concept of ALI increases the flexibility and applicability of the definition to multiple models while increasing the likelihood of translating preclinical findings to critically ill patients.
Subject(s)
Acute Lung Injury/pathology , Inflammation/physiopathology , Research Report/trends , Acute Lung Injury/immunology , AnimalsABSTRACT
In the neonatal respiratory distress syndrome (NRDS) and acute respiratory distress syndrome (ARDS), mechanical ventilation supports gas exchange but can cause ventilation-induced lung injury (VILI) that contributes to high mortality. Further, surface tension, T, should be elevated and VILI is proportional to T. Surfactant therapy is effective in NRDS but not ARDS. Sulforhodamine B (SRB) is a potential alternative T-lowering therapeutic. In anesthetized male rats, we injure the lungs with 15 min of 42 mL/kg tidal volume, VT, and zero end-expiratory pressure ventilation. Then, over 4 h, we support the rats with protective ventilation-VT of 6 mL/kg with positive end-expiratory pressure. At the start of the support period, we administer intravenous non-T-altering fluorescein (targeting 27 µM in plasma) without or with therapeutic SRB (10 nM). Throughout the support period, we increase inspired oxygen fraction, as necessary, to maintain >90% arterial oxygen saturation. At the end of the support period, we euthanize the rat; sample systemic venous blood for injury marker ELISAs; excise the lungs; combine confocal microscopy and servo-nulling pressure measurement to determine T in situ in the lungs; image fluorescein in alveolar liquid to assess local permeability; and determine lavage protein content and wet-to-dry ratio (W/D) to assess global permeability. Lungs exhibit focal injury. Surface tension is elevated 72% throughout control lungs and in uninjured regions of SRB-treated lungs, but normal in injured regions of treated lungs. SRB administration improves oxygenation, reduces W/D, and reduces plasma injury markers. Intravenous SRB holds promise as a therapy for respiratory distress.NEW & NOTEWORTHY Sulforhodmaine B lowers T in alveolar edema liquid. Given the problematic intratracheal delivery of surfactant therapy for ARDS, intravenous SRB might constitute an alternative therapeutic. In a lung injury model, we find that intravenously administered SRB crosses the injured alveolar-capillary barrier thus reduces T specifically in injured lung regions; improves oxygenation; and reduces the degree of further lung injury. Intravenous SRB administration might help respiratory distress patients, including those with the novel coronavirus, avoid mechanical ventilation or, once ventilated, survive.
Subject(s)
COVID-19 , Respiratory Distress Syndrome , Animals , Humans , Lung , Male , Rats , Respiration, Artificial , Rhodamines , SARS-CoV-2 , Surface TensionABSTRACT
In the acute respiratory distress syndrome (ARDS), alveolar surface tension, T, may be elevated. Elevated T should increase ventilation-induced lung injury. Exogenous surfactant therapy, intended to lower T, has not reduced mortality. Sulforhodamine B (SRB) might, alternatively, be used to lower T. We test whether substances suspected of elevating T in ARDS raise T in the lungs and test the abilities of exogenous surfactant and SRB to reduce T. In isolated rat lungs, we micropuncture a surface alveolus and instill a solution of a purported T-raising substance: control saline, cell debris, secretory phospholipase A2 (sPLA2), acid, or mucins. We test each substance alone; with albumin, to model proteinaceous edema liquid; with albumin and exogenous surfactant; and with albumin and SRB. We determine T in situ in the lungs by combining servo-nulling pressure measurement with confocal microscopy and applying the Laplace relation. With control saline, albumin does not alter T, additional surfactant raises T, and additional SRB lowers T. The experimental substances, without or with albumin, raise T. Excepting under aspiration conditions, addition of surfactant or SRB lowers T. Exogenous surfactant activity is concentration and ventilation dependent. Sulforhodamine B, which could be delivered intravascularly, holds promise as an alternative therapeutic.NEW & NOTEWORTHY In the acute respiratory distress syndrome (ARDS), lowering surface tension, T, should reduce ventilation injury yet exogenous surfactant has not reduced mortality. We show with direct T determination in isolated lungs that substances suggested to elevate T in ARDS indeed raise T, and exogenous surfactant reduces T. Further, we extend our previous finding that sulforhodamine B (SRB) reduces T below normal in healthy lungs and show that SRB, too, reduces T under ARDS conditions.
Subject(s)
Pulmonary Surfactants , Respiratory Distress Syndrome , Animals , Rats , Respiratory Distress Syndrome/chemically induced , Respiratory Distress Syndrome/drug therapy , Rhodamines , Surface Tension , Surface-Active AgentsABSTRACT
In the acute respiratory distress syndrome (ARDS), surface tension, T, is likely elevated. And mechanical ventilation of ARDS patients causes ventilation-induced lung injury (VILI), which is believed to be proportional to T. However, the mechanisms through which elevated T may contribute to VILI have been under-studied. This conceptual analysis considers experimental and theoretical evidence for static and dynamic mechanical mechanisms, at the alveolar scale, through which elevated T exacerbates VILI; potential causes of elevated T in ARDS; and T-dependent means of reducing VILI. In the last section, possible means of reducing T and improving the efficacy of recruitment maneuvers during mechanical ventilation of ARDS patients are discussed.
Subject(s)
Pulmonary Fibrosis/metabolism , Pulmonary Surfactant-Associated Proteins/metabolism , Ventilator-Induced Lung Injury/metabolism , Age Factors , Alveolar Epithelial Cells/physiology , Animals , Disease Models, Animal , Environmental Exposure/statistics & numerical data , Gastroesophageal Reflux/epidemiology , Humans , Pulmonary Fibrosis/epidemiology , Pulmonary Fibrosis/physiopathology , Pulmonary Surfactant-Associated Proteins/genetics , Risk Factors , Smoking/epidemiology , Ventilator-Induced Lung Injury/physiopathologyABSTRACT
Whether alveolar liquid surface tension, T, is elevated in the acute respiratory distress syndrome (ARDS) has not been demonstrated in situ in the lungs. Neither is it known how exogenous surfactant, which has failed to treat ARDS, affects in situ T. We aim to determine T in an acid-aspiration ARDS model before and after exogenous surfactant administration. In isolated rat lungs, we combine servo-nulling pressure measurement and confocal microscopy to determine alveolar liquid T according to the Laplace relation. Administering 0.01 N (pH 1.9) HCl solution by alveolar injection or tracheal instillation, to model gastric liquid aspiration, raises T. Subsequent surfactant administration fails to normalize T. Furthermore, in normal lungs, tracheal instillation of control saline or exogenous surfactant raises T. Lavaging the trachea with saline and injecting the lavage solution into the alveolus raises T, suggesting that tracheal instillation may wash T-raising airway contents to the alveolus. Adding 0.01 N HCl or 5 mM CaCl2-either of which aggregates mucins-to tracheal lavage solution reduces or eliminates the effect of lavage solution on alveolar T. Following tracheal saline instillation, liquid suctioned directly out of alveoli through a micropipette contains mucins. Additionally, alveolar injection of gastric mucin solution raises T. We conclude that 1) tracheal liquid instillation likely washes T-raising mucins to the alveolus and 2) even exogenous surfactant that could be delivered mucin-free to the alveolus might not normalize T in acid-aspiration ARDS. NEW & NOTEWORTHY We demonstrate in situ in isolated lungs that surface tension is elevated in an acid-aspiration acute respiratory distress syndrome (ARDS) model. Following tracheal liquid instillation, also in isolated lungs, we directly sample alveolar liquid. We find that liquid instillation into normal lungs washes mucins to the alveolus, thereby raising alveolar surface tension. Furthermore, even if exogenous surfactant could be delivered mucin-free to the alveolus, exogenous surfactant might fail to normalize alveolar surface tension in acid-aspiration ARDS.
Subject(s)
Pulmonary Alveoli/drug effects , Pulmonary Surfactants/therapeutic use , Respiratory Distress Syndrome/drug therapy , Animals , Hydrochloric Acid , In Vitro Techniques , Instillation, Drug , Male , Pulmonary Surfactants/pharmacology , Rats, Sprague-Dawley , Respiratory Distress Syndrome/chemically induced , Surface Tension/drug effectsABSTRACT
Edematous lungs contain regions with heterogeneous alveolar flooding. Liquid is trapped in flooded alveoli by a pressure barrier-higher liquid pressure at the border than in the center of flooded alveoli-that is proportional to surface tension, T Stress is concentrated between aerated and flooded alveoli, to a degree proportional to T Mechanical ventilation, by cyclically increasing T, injuriously exacerbates stress concentrations. Overcoming the pressure barrier to redistribute liquid more homogeneously between alveoli should reduce stress concentration prevalence and ventilation injury. In isolated rat lungs, we test whether accelerated deflation can overcome the pressure barrier and catapult liquid out of flooded alveoli. We generate a local edema model with normal T by microinfusing liquid into surface alveoli. We generate a global edema model with high T by establishing hydrostatic edema, which does not alter T, and then gently ventilating the edematous lungs, which increases T at 15 cmH2O transpulmonary pressure by 52%. Thus ventilation of globally edematous lungs increases T, which should increase stress concentrations and, with positive feedback, cause escalating ventilation injury. In the local model, when the pressure barrier is moderate, accelerated deflation causes liquid to escape from flooded alveoli and redistribute more equitably. Flooding heterogeneity tends to decrease. In the global model, accelerated deflation causes liquid escape, but-because of elevated T-the liquid jumps to nearby, aerated alveoli. Flooding heterogeneity is unaltered. In pulmonary edema with normal T, early ventilation with accelerated deflation might reduce the positive feedback mechanism through which ventilation injury increases over time.NEW & NOTEWORTHY We introduce, in the isolated rat lung, a new model of pulmonary edema with elevated surface tension. We first generate hydrostatic edema and then ventilate gently to increase surface tension. We investigate the mechanical mechanisms through which 1) ventilation injures edematous lungs and 2) ventilation with accelerated deflation might lessen ventilation injury.
Subject(s)
Pulmonary Alveoli/physiopathology , Pulmonary Edema/physiopathology , Animals , Disease Models, Animal , Male , Pressure , Pulmonary Alveoli/injuries , Pulmonary Ventilation/physiology , Rats , Rats, Sprague-Dawley , Respiration , Respiratory Mechanics/physiology , Surface TensionABSTRACT
In the acute respiratory distress syndrome, alveolar flooding by proteinaceous edema liquid impairs gas exchange. Mechanical ventilation is used as a supportive therapy. In regions of the edematous lung, alveolar flooding is heterogeneous, and stress is concentrated in aerated alveoli. Ventilation exacerbates stress concentrations and injuriously overexpands aerated alveoli. Injury degree is proportional to surface tension, T. Lowering T directly lessens injury. Furthermore, as heterogeneous flooding causes the stress concentrations, promoting equitable liquid distribution between alveoli should, indirectly, lessen injury. We present a new theoretical analysis suggesting that liquid is trapped in discrete alveoli by a pressure barrier that is proportional to T. Experimentally, we identify two rhodamine dyes, sulforhodamine B and rhodamine WT, as surface active in albumin solution and investigate whether the dyes lessen ventilation injury. In the isolated rat lung, we micropuncture a surface alveolus, instill albumin solution, and obtain an area with heterogeneous alveolar flooding. We demonstrate that rhodamine dye addition lowers T, reduces ventilation-induced injury, and facilitates liquid escape from flooded alveoli. In vitro we show that rhodamine dye is directly surface active in albumin solution. We identify sulforhodamine B as a potential new therapeutic agent for the treatment of the acute respiratory distress syndrome.
Subject(s)
Albumins/metabolism , Lung Injury/drug therapy , Pulmonary Alveoli/drug effects , Pulmonary Edema/drug therapy , Rhodamines/pharmacology , Surface Tension/drug effects , Animals , Lung Injury/metabolism , Male , Pulmonary Alveoli/metabolism , Pulmonary Edema/metabolism , Pulmonary Gas Exchange , Rats , Rats, Sprague-Dawley , Respiration/drug effects , Respiration, Artificial/methods , Respiratory Distress Syndrome/drug therapy , Respiratory Distress Syndrome/metabolismABSTRACT
With proteinaceous-liquid flooding of discrete alveoli, a model of the edema pattern in the acute respiratory distress syndrome, lung inflation over expands aerated alveoli adjacent to flooded alveoli. Theoretical considerations suggest that the overexpansion may be proportional to surface tension, T. Yet recent evidence indicates proteinaceous edema liquid may not elevate T. Thus whether the overexpansion is injurious is not known. Here, working in the isolated, perfused rat lung, we quantify fluorescence movement from the vasculature to the alveolar liquid phase as a measure of overdistension injury to the alveolar-capillary barrier. We label the perfusate with fluorescence; micropuncture a surface alveolus and instill a controlled volume of nonfluorescent liquid to obtain a micropunctured-but-aerated region (control group) or a region with discrete alveolar flooding; image the region at a constant transpulmonary pressure of 5 cmH2O; apply five ventilation cycles with a positive end-expiratory pressure of 0-20 cmH2O and tidal volume of 6 or 12 ml/kg; return the lung to a constant transpulmonary pressure of 5 cmH2O; and image for an additional 10 min. In aerated areas, ventilation is not injurious. With discrete alveolar flooding, all ventilation protocols cause sustained injury. Greater positive end-expiratory pressure or tidal volume increases injury. Furthermore, we determine T and find injury increases with T. Inclusion of either plasma proteins or Survanta in the flooding liquid does not alter T or injury. Inclusion of 2.7-10% albumin and 1% Survanta together, however, lowers T and injury. Contrary to expectation, albumin inclusion in our model facilitates exogenous surfactant activity.
Subject(s)
Lung Injury/etiology , Lung/physiopathology , Pulmonary Alveoli/injuries , Respiration, Artificial/adverse effects , Respiratory Distress Syndrome/etiology , Animals , Disease Models, Animal , Lung Injury/physiopathology , Male , Positive-Pressure Respiration/adverse effects , Pulmonary Alveoli/physiopathology , Rats , Rats, Sprague-Dawley , Respiratory Distress Syndrome/physiopathology , Respiratory Mechanics , Surface TensionABSTRACT
Alveolar septa, which have often been modeled as linear elements, may distend due to inflation-induced reduction in slack or increase in tissue stretch. The distended septum supports tissue elastic and interfacial forces. An effective Young's modulus, describing the inflation-induced relative displacement of septal end points, has not been determined in situ for lack of a means of determining the forces supported by septa in situ. Here we determine such forces indirectly according to Mead, Takishima, and Leith's classic lung mechanics analysis (J Appl Physiol 28: 596-608, 1970), which demonstrates that septal connections transmit the transpulmonary pressure, PTP, from the pleural surface to interior regions. We combine experimental septal strain determination and computational stress determination, according to Mead et al., to calculate effective Young's modulus. In the isolated, perfused rat lung, we label the perfusate with fluorescence to visualize the alveolar septa. At eight PTP values around a ventilation loop between 4 and 25 cmH2O, and upon total deflation, we image the same region by confocal microscopy. Within an analysis region, we measure septal lengths. Normalizing by unstressed lengths at total deflation, we calculate septal strains for all PTP > 0 cmH2O. For the static imaging conditions, we computationally model application of PTP to the boundary of the analysis region and solve for septal stresses by least squares fit of an overdetermined system. From group septal strain and stress values, we find effective septal Young's modulus to range from 1.2 × 10(5) dyn/cm(2) at low P(TP) to 1.4 × 10(6) dyn/cm(2) at high P(TP).
Subject(s)
Computational Biology , Elastic Modulus/physiology , Pulmonary Alveoli/physiology , Animals , In Vitro Techniques , Male , Microscopy, Confocal , Pulmonary Alveoli/ultrastructure , RatsABSTRACT
In the acute respiratory distress syndrome, plasma proteins in alveolar edema liquid are thought to inactivate lung surfactant and raise surface tension, T. However, plasma protein-surfactant interaction has been assessed only in vitro, during unphysiologically large surface area compression (%ΔA). Here, we investigate whether plasma proteins raise T in situ in the isolated rat lung under physiologic conditions. We flood alveoli with liquid that omits/includes plasma proteins. We ventilate the lung between transpulmonary pressures of 5 and 15 cmH2O to apply a near-maximal physiologic %ΔA, comparable to that of severe mechanical ventilation, or between 1 and 30 cmH2O, to apply a supraphysiologic %ΔA. We pause ventilation for 20 min and determine T at the meniscus that is present at the flooded alveolar mouth. We determine alveolar air pressure at the trachea, alveolar liquid phase pressure by servo-nulling pressure measurement, and meniscus radius by confocal microscopy, and we calculate T according to the Laplace relation. Over 60 ventilation cycles, application of maximal physiologic %ΔA to alveoli flooded with 4.6% albumin solution does not alter T; supraphysiologic %ΔA raise T, transiently, by 51 ± 4%. In separate experiments, we find that addition of exogenous surfactant to the alveolar liquid can, with two cycles of maximal physiologic %ΔA, reduce T by 29 ± 11% despite the presence of albumin. We interpret that supraphysiologic %ΔA likely collapses the interfacial surfactant monolayer, allowing albumin to raise T. With maximal physiologic %ΔA, the monolayer likely remains intact such that albumin, blocked from the interface, cannot interfere with native or exogenous surfactant activity.
Subject(s)
Albumins/pharmacology , Pulmonary Alveoli/physiopathology , Surface Tension/drug effects , Animals , Bronchoalveolar Lavage Fluid , In Vitro Techniques , Male , Pulmonary Surfactants/pharmacology , Rats , Rats, Sprague-Dawley , Respiratory Mechanics/physiologyABSTRACT
A thoracic artificial lung (TAL) provides respiratory support for lung disease. How well a TAL improves blood oxygenation for a specific pathology depends on how the TAL is attached to the pulmonary circulation: in series with the natural lungs (NLs), in parallel, or in a hybrid series/parallel combination. A computational model, including hemodynamic and O(2) and CO(2) exchange components, predicts TAL effects on blood flow rates and gas transport in pulmonary disease states modeled by elevated pulmonary vascular resistance (PVR) or reduced oxygen diffusivity in the NLs. In most cases, parallel and series TAL attachment provide comparable, maximal oxygenation. Series, with passage of total cardiac output (CO) through the NLs, is preferred for its filtration of emboli. Hybrid TAL attachment is more complicated, requiring a third graft, yet oxygenates less well than parallel and series. With extreme elevations of PVR, as in primary pulmonary hypertension, parallel TAL attachment provides an oxygenating shunt around the high resistance of the NLs, thus unloading the right ventricle, normalizing CO, and maximizing oxygenation.
Subject(s)
Artificial Organs , Lung , Oxygen/blood , Cardiac Output , Humans , Models, Biological , Vascular ResistanceABSTRACT
Lung mechanics are an important determinant of physiological and pathophysiological lung function. Recent light microscopy studies of the intact lung have furthered the understanding of lung mechanics but used methodologies that may have introduced artifacts. To address this concern, we employed a short working distance water immersion objective to capture confocal images of a fluorescently labeled alveolar field on the costal surface of the isolated, perfused rat lung. Surface tension held a saline drop between the objective tip and the lung surface, such that the lung surface was unconstrained. For comparison, we also imaged with O-ring and coverslip; with O-ring, coverslip, and vacuum pressure; and without perfusion. Under each condition, we ventilated the lung and imaged the same region at the endpoints of ventilation. We found use of a coverslip caused a minimal enlargement of the alveolar field; additional use of vacuum pressure caused no further dimensional change; and absence of perfusion did not affect alveolar field dimension. Inflation-induced expansion was unaltered by methodology. In response to inflation, percent expansion was the same as recorded by all four alternative methods.
Subject(s)
Pulmonary Alveoli/physiology , Respiratory Mechanics/physiology , Animals , Blood Pressure/physiology , Fluorescence , Male , Microscopy, Confocal/methods , Perfusion/adverse effects , Pulmonary Alveoli/physiopathology , Pulmonary Artery/physiology , Pulmonary Artery/physiopathology , Rats , Rats, Sprague-Dawley , Surface Tension , Ventilation/methodsABSTRACT
The decrease of lung compliance in pulmonary edema underlies ventilator-induced lung injury. However, the cause of the decrease in compliance is unknown. We tested the hypothesis that in pulmonary edema, the mechanical effects of liquid-filled alveoli increase tissue stress in adjacent air-filled alveoli. By micropuncture of isolated, perfused rat lungs, we established a single-alveolus model of pulmonary edema that we imaged using confocal microscopy. In this model, we viewed a liquid-filled alveolus together with its air-filled neighbor at different transpulmonary pressures, both before and after liquid-filling. Instilling liquid in an alveolus caused alveolar shrinkage. As a result, the interalveolar septum was stretched, causing the neighboring air-filled alveolus to bulge. Thus, the air-filled alveolus was overexpanded by virtue of its adjacency to a liquid-filled alveolus. Confocal microscopy at different depths of the liquid-filled alveolus revealed a meniscus. Lung inflation to near-total lung capacity (TLC) demonstrated decreased compliance of the air-filled but not liquid-filled alveolus. However, at near TLC, the air-filled alveolus was larger than it was in the pre-edematous control tissue. In pulmonary edema, liquid-filled alveoli induce mechanical stress on air-filled alveoli, reducing the compliance of air-filled alveoli, and hence overall lung compliance. Because of increased mechanical stress, air-filled alveoli may be susceptible to overdistension injury during mechanical ventilation of the edematous lung.
Subject(s)
Pulmonary Alveoli/physiopathology , Pulmonary Edema/physiopathology , Air Pressure , Animals , Functional Residual Capacity , Lung Compliance , Male , Microscopy, Confocal , Models, Biological , Perfusion , Pulmonary Alveoli/injuries , Pulmonary Alveoli/pathology , Pulmonary Edema/pathology , Pulmonary Edema/therapy , Rats , Rats, Sprague-Dawley , Serum Albumin/administration & dosage , Stress, Mechanical , Surface Tension , Total Lung Capacity , Ventilator-Induced Lung Injury/etiology , Ventilator-Induced Lung Injury/physiopathologySubject(s)
Diagnostic Imaging/standards , Lung Diseases/diagnosis , Lung , Pulmonary Alveoli , Animals , Europe , Guideline Adherence , Guidelines as Topic , Histological Techniques/standards , Humans , Lung/anatomy & histology , Lung/pathology , Lung/physiopathology , Lung Diseases/pathology , Lung Diseases/physiopathology , Microscopy, Confocal/standards , Observer Variation , Predictive Value of Tests , Pulmonary Alveoli/anatomy & histology , Pulmonary Alveoli/pathology , Pulmonary Alveoli/physiopathology , Reproducibility of Results , Respiratory Function Tests/standards , Societies, Medical , Species Specificity , United StatesABSTRACT
Pulmonic valve incompetence has been observed during implantation of total artificial lungs (TAL) and may contribute to right ventricular dysfunction in certain attachment modes. The roles of pulmonary system resistance and inertia on valve function were examined retrospectively using data from attachments of a prototype TAL in six pigs. The TAL was attached in parallel and in series with the natural lungs and a hybrid of parallel and series. These conditions lead to varying conditions of resistance and inertia in each animal. The periods of ejection (TE), regurgitation (TR), and sealed valve (TSV), and the regurgitant fraction (Fr) were determined at each condition. The relationships between these variables and the effective pulmonary system resistance (R) and the calculated inertial pressure drop during flow deceleration (DeltaPI) were determined. A large R created pulmonic valve incompetence and increased regurgitation, as evidenced by a decreased TSV. A highly negative DeltaPI decreased regurgitation by increasing TE. When R <5 mm Hg/(L/min), Fr remained at baseline levels, regardless of other conditions. When R >5 mm Hg/(L/min), the relationship between Fr, R, and DeltaPI was found to be Fr = 0.014R + 0.011DeltaPI + 0.15 (R = 0.82). Thus, pulmonary system resistance should be maintained <5 mm Hg/(L/min) to avoid pulmonic valve incompetence. High device inertance reduced regurgitation but also lead to increased pulmonary system impedances and ventricular work. The design and implementation of a TAL, thus, should focus on having a small effective pulmonary system resistance.