Human Versus Porcine Localized Strain Mechanics

ABSTRACT

Rationale COVID-19 has inspired numerous studies on ventilated induced lung injury (VILI). To investigate the strains stimulating lung damage, animal lungs are often used as surrogate models for scarce human specimens. Such studies are restricted to bulk pressure and volume investigations instead of examining regional, real-time, and evolutionary pulmonary behavior offered by digital image correlation (DIC) techniques. Here we subject porcine lungs and a human lung case study to shared global loads and compare local strain distributions as yielded by DIC to assess the applicability of animal models to represent human pulmonary mechanics. Methods: One anonymized human cadaveric lung (854g) and four comparable sized Yorkshire Farm pig lungs (784-1218g) were tested ex vivo within 36hrs postmortem (no IACUC or IRB approval required). Specimens were ventilated at 15 breaths per minute to 675, 900 and 1350ml (6, 8, and 12mL/kg) using a recently established custom-designed electromechanical breathing apparatus interfaced with high resolution and high speed DIC cameras. Lungs were preloaded to 5cmH20 and preconditioned three times for reproducibility. The resulting local deformations associated with global ventilation loads were analyzed throughout the inflation cycle. Results: Similar peak inflation pressures were observed between human and porcine specimens (21-35 and 21±2 - 26±2cmH20 respectively) for the shared applied volumes. Despite comparable global mechanics, the topological strain distributions of human lungs were relatively reduced when the applied global volume was doubled from 675 to 1350ml, the local averaged strain across the specimen surface increased from 19 to 28%, while porcine strains showed a greater increase from 21±4 to 42±4%. Also from 675 to 1350ml, the human lung surface strains were prominently homogenous with a range of 43 to 58%, compared to the observed heterogeneous porcine strain contours, quantified with a range of 92±15 to 124±24%. The maximum strain values of the human lung were also smaller than porcine specimens (58 versus 106±17%). Conclusion: Collateral ventilation and respective monopodial versus bipodial bronchial networks may explain the discrepancies noted between porcine and human lung strains. While a single human lung specimen is statistically inconclusive, pairing new DIC applications with conventional global metrics offers the ability to characterize the localized strain distribution of the breathing lung and evaluate the anisotropic and heterogenous deformation profiles correlated with VILI, previously uncharacterized to date. These results have implications for understanding the role of amplified strains in translational animal to human lung studies.