PEEP/ FIO2 ARDSNet Scale Grouping of a Single Ventilator for Two Patients: Modeling Tidal Volume Response.

Background: The COVID-19 pandemic is creating ventilator shortages in many countries that is sparking a conversation about placing multiple patients on a single ventilator. However, on March 26, 2020, six leading medical organizations released a joint statement warning clinicians that attempting this technique could lead to poor outcomes and high mortality. Nevertheless, hospitals around the United States and abroad are considering this technique out of desperation (eg, New York), but there is little data to guide their approach.

Embedding of Precision-Cut Lung Slices in Engineered Hydrogel Biomaterials Supports Extended Culture.

Maintaining the three-dimensional architecture and cellular complexity of lung tissue can enable elucidation of the cellular and molecular pathways underlying chronic pulmonary diseases. Precision-cut lung slices (PCLS) are one human-lung model with the potential to support critical mechanistic studies and early drug discovery. However, many studies report short culture times of 7-10 days.

Tissue-informed engineering strategies for modeling human pulmonary diseases.

Chronic pulmonary diseases, including idiopathic pulmonary fibrosis (IPF), pulmonary hypertension (PH), and chronic obstructive pulmonary disease (COPD), account for staggering morbidity and mortality worldwide but have limited clinical management options available. Although great progress has been made to elucidate the cellular and molecular pathways underlying these diseases, there remains a significant disparity between basic research endeavors and clinical outcomes. This discrepancy is due in part to the failure of many current disease models to recapitulate the dynamic changes that occur during pathogenesis in vivo.

Validation of a pressure diameter method for determining modulus and strain of collagen engagement for long branches of bovine pulmonary arteries.

Recent studies have shown that capacitance measurements of large arteries provide better prognosis and diagnosis than tests of resistance alone in pulmonary hypertension (Mahapatra et al., 2006, "Relationship of Pulmonary Arterial Capacitance and Mortality in Idiopathic Pulmonary Arterial Hypertension," J. Am.

Impact of residual stretch and remodeling on collagen engagement in healthy and pulmonary hypertensive calf pulmonary arteries at physiological pressures.

Understanding the mechanical behavior of proximal pulmonary arteries (PAs) is crucial to evaluating pulmonary vascular function and right ventricular afterload. Early and current efforts focus on these arteries' histological changes, in vivo pressure-diameter behavior and mechanical properties under in vitro mechanical testing. However, the in vivo stretch and stress states remain poorly characterized.

Linked opening angle and histological and mechanical aspects of the proximal pulmonary arteries of healthy and pulmonary hypertensive rats and calves.

Understanding how arterial remodeling changes the mechanical behavior of pulmonary arteries (PAs) is important to the evaluation of pulmonary vascular function. Early and current efforts have focused on the arteries' histological changes, their mechanical properties under in vitro mechanical testing, and their zero-stress and no-load states. However, the linkage between the histology and mechanical behavior is still not well understood.

Pulmonary vascular stiffness: measurement, modeling, and implications in normal and hypertensive pulmonary circulations.

This article introduces the concept of pulmonary vascular stiffness, discusses its increasingly recognized importance as a diagnostic marker in the evaluation of pulmonary vascular disease, and describes methods to measure and model it clinically, experimentally, and computationally. It begins with a description of systems-level methods to evaluate pulmonary vascular compliance and recent clinical efforts in applying such techniques to better predict patient outcomes in pulmonary arterial hypertension. It then progresses from the systems-level to the local level, discusses proposed methods by which upstream pulmonary vessels increase in stiffness, introduces concepts around vascular mechanics, and concludes by describing recent work incorporating advanced numerical methods to more thoroughly evaluate changes in local mechanical properties of pulmonary arteries.

A microstructurally driven model for pulmonary artery tissue.

A new constitutive model for elastic, proximal pulmonary artery tissue is presented here, called the total crimped fiber model. This model is based on the material and microstructural properties of the two main, passive, load-bearing components of the artery wall, elastin, and collagen. Elastin matrix proteins are modeled with an orthotropic neo-Hookean material.

Constitutive Modeling of Anisotropic Finite-Deformation Hyperelastic Behaviors of Soft Materials Reinforced by Tortuous Fibers.

Many biological materials are composites composed of a soft matrix reinforced with stiffer fibers. These stiffer fibers may have a tortuous shape and wind through the soft matrix. At small material deformation, these fibers deform in a bending mode and contribute little to the material stiffness; at large material deformation, these fibers deform in a stretching mode and induce a stiffening effect in the material behavior.

In vivo measurement of proximal pulmonary artery elastic modulus in the neonatal calf model of pulmonary hypertension: development and ex vivo validation.

Developing clinical work suggests that vascular stiffening plays a role in the progression of pulmonary hypertension (PH), while recent studies in animal models of hypoxic PH have found significant proximal vascular stiffening in the diseased population. Here, we develop and validate a minimally invasive, clinically realizable method to estimate the local elastic modulus of the proximal pulmonary arteries from pressure-diameter (PD) data. PD measurements were made in the main pulmonary arteries of 16 calves; lumen diameter was assessed using color M-mode tissue Doppler imaging ultrasound, while pressure was measured via catheter.

Changes in the structure-function relationship of elastin and its impact on the proximal pulmonary arterial mechanics of hypertensive calves.

Extracellular matrix remodeling has been proposed as one mechanism by which proximal pulmonary arteries stiffen during pulmonary arterial hypertension (PAH). Although some attention has been paid to the role of collagen and metallomatrix proteins in affecting vascular stiffness, much less work has been performed on changes in elastin structure-function relationships in PAH. Such work is warranted, given the importance of elastin as the structural protein primarily responsible for the passive elastic behavior of these conduit arteries.