For patients with BAV, increased aortic valve-mediated WSS is significantly associated with elastic fiber thinning, particularly with aortic valve stenosis and in earlier stages of aortopathy. Elastic fiber thinning correlates with impaired tissue biomechanics. These novel findings further implicate valve-mediated hemodynamics in the progression of BAV aortopathy.
Respiratory illnesses, such as bronchitis, emphysema, asthma, and COVID-19, substantially remodel lung tissue, deteriorate function, and culminate in a compromised breathing ability. Yet, the structural mechanics of the lung is significantly understudied. Classical pressure-volume air or saline inflation studies of the lung have attempted to characterize the organ’s elasticity and compliance, measuring deviatory responses in diseased states; however, these investigations are exclusively limited to the bulk composite or global response of the entire lung and disregard local expansion and stretch phenomena within the lung lobes, overlooking potentially valuable physiological insights, as particularly related to mechanical ventilation. Here, we present a method to collect the first non-contact, full-field deformation measures of ex vivo porcine and murine lungs and interface with a pressure-volume ventilation system to investigate lung behavior in real time. We share preliminary observations of heterogeneous and anisotropic strain distributions of the parenchymal surface, associative pressure-volume-strain loading dependencies during continuous loading, and consider the influence of inflation rate and maximum volume. This study serves as a crucial basis for future works to comprehensively characterize the regional response of the lung across various species, link local strains to global lung mechanics, examine the effect of breathing frequencies and volumes, investigate deformation gradients and evolutionary behaviors during breathing, and contrast healthy and pathological states. Measurements collected in this framework ultimately aim to inform predictive computational models and enable the effective development of ventilators and early diagnostic strategies.
Asthma, emphysema, COVID-19 and other lung-impacting diseases cause the remodeling of tissue structural properties and can lead to changes in conducting pulmonary volume, viscoelasticity, and air flow distribution. Whole organ experimental inflation tests are commonly used to understand the impact of these modifications on lung mechanics. Here we introduce a novel, automated, custom-designed device for measuring the volume and pressure response of lungs, surpassing the capabilities of traditional machines and built to range size-scales to accommodate both murine and porcine tests. The software-controlled system is capable of constructing standardized continuous volume-pressure curves, while accounting for air compressibility, yielding consistent and reproducible measures while eliminating the need for pulmonary degassing. This device uses volume-control to enable viscoelastic whole lung macromechanical insights from rate dependencies and pressure-time curves. Moreover, the conceptual design of this device facilitates studies relating the phenomenon of diaphragm breathing and artificial ventilation induced by pushing air inside the lungs. System capabilities are demonstrated and validated via a comparative study between ex vivo murine lungs and elastic balloons, using various testing protocols. Volumepressure curve comparisons with previous pressure-controlled systems yield good agreement, confirming accuracy. This work expands the capabilities of current lung experiments, improving scientific investigations of healthy and diseased pulmonary biomechanics. Ultimately, the methodologies demonstrated in the manufacturing of this system enable future studies centered on investigating viscoelasticity as a potential biomarker and improvements to patient ventilators based on direct assessment and comparisons of positive-and negative-pressure mechanics.
Background
Mechanical ventilation is often employed to facilitate breathing in patients suffering from respiratory illnesses and disabilities. Despite the benefits, there are risks associated with ventilator-induced lung injuries and death, driving investigations for alternative ventilation techniques to improve mechanical ventilation, such as multi-oscillatory and high-frequency ventilation; however, few studies have evaluated fundamental lung mechanical local deformations under variable loading.
Methods
Porcine whole lung samples were analyzed using a novel application of digital image correlation interfaced with an electromechanical ventilation system to associate the local behavior to the global volume and pressure loading in response to various inflation volumes and breathing rates. Strains, anisotropy, tissue compliance, and the evolutionary response of the inflating lung were analyzed.
Results
Experiments demonstrated a direct and near one-to-one linear relationship between applied lung volumes and resulting local mean strain, and a nonlinear relationship between lung pressures and strains. As the applied air delivery volume was doubled, the tissue surface mean strains approximately increased from 20 to 40%, and average maximum strains measured 70–110%. The tissue strain anisotropic ratio ranged from 0.81 to 0.86 and decreased with greater inflation volumes. Local tissue compliance during the inflation cycle, associating evolutionary strains in response to inflation pressures, was also quantified.
Conclusion
Ventilation frequencies were not found to influence the local stretch response. Strain measures significantly increased and the anisotropic ratio decreased between the smallest and greatest tidal volumes. Tissue compliance did not exhibit a unifying trend. The insights provided by the real-time continuous measures, and the kinetics to kinematics pulmonary linkage established by this study offers valuable characterizations for computational models and establishes a framework for future studies to compare healthy and diseased lung mechanics to further consider alternatives for effective ventilation strategies.
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