Commentary: Making lungs great again—introducing new modifications to the Toronto ex vivo lung perfusion protocol

Kesseli, Samuel J.; Davis, Robert P.; Hartwig, Matthew G.

doi:10.1016/j.jtcvs.2020.08.016

Cited by 3 publications

(3 citation statements)

References 27 publications

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“…Utilizing these advances 41 , we will adapt the crystal ribcage to maintain lung viability for multi-day studies of disease dynamics. Specifically, given that the crystal ribcage enables real-time imaging of lung injury and at the single alveolus level, our platform can be used to design strategies for improving human donor lung preservation over time and push the duration of lung viability ex vivo , with impacts on lung transplantation research 42 .…”

Section: Discussionmentioning

confidence: 99%

Crystal ribcage: a platform for probing real-time lung function at cellular resolution in health and disease

Banerji

Grifno

Shi

et al. 2022

Preprint

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Real-time, cellular resolution imaging is essential for probing the highly dynamic functions of the lung at the interface of physics, biology, and immunology. CT and MRI modalities have low spatial resolution, and histological approaches provide only snapshots of fixed lungs with little temporal information. Existing intravital imaging approaches cannot include and manipulate the physical and spatiotemporal changes involved in respiratory function. Here, we describe the development of a platform, termed "LungEx", to visualize and mechanistically probe the dynamics of a functioning lung at optical resolutions. LungEx is equipped with a novel transparent ribcage, termed "crystal" ribcage, that provides physiological conditions for a functioning lung and allows high-resolution and real-time optical imaging of nearly the entire lung surface. This imaging capability is obtained while LungEx preserves the complex 3-D architecture, cellular diversity, and integrative function of the ex vivo ventilated and perfused lung at near in vivo conditions. Utilizing LungEx in health and key lung diseases such as metastasis, pneumonia, and fibrosis, we probed a wide range of lung dynamic functions and remodeling at multiple spatial scales including alveolar deformation and elasticity, circulation-respiration coupling at the capillary level, cellular deformation, immune cell motility, and vascular transport. By modulating the biophysical environment of LungEx, we discovered that intravascular and interstitial, but not intra-alveolar neutrophils are highly and reversibly responsive to vascular pressure. Thus, by allowing high spatiotemporal imaging coupled with controlled biophysical interventions, LungEx, provides a powerful platform to mechanistically probe dynamic and multiscale lung functions in health and disease.

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Section: Discussionmentioning

confidence: 99%

Crystal ribcage: a platform for probing real-time lung function at cellular resolution in health and disease

Banerji

Grifno

Shi

et al. 2022

Preprint

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“…74 Perfusate enrichment with vitamins and amino acids has been previously shown to improve the performance of allografts. 83,84 These studies highlight the possibility of targeting some in vivo homeostatic systems, which regulate pulmonary metabolism, nutrition, and fluidelectrolyte balance in achieving stable EVLP beyond 24 h. 85 The Lund protocol is the first EVLP protocol that aims to assess questionable donor lungs for a short period of time at full perfusion flow. The Toronto protocol is the most widely accepted protocol that endorses protective ventilation/perfusion strategies using closed left atrium strategy.…”

Section: Perfusate Replacement and Additivesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Technical Advances Targeting Multiday Preservation of Isolated Ex Vivo Lung Perfusion

Iskender

2024

Transplantation

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Indications for ex vivo lung perfusion (EVLP) have evolved from assessment of questionable donor lungs to treatment of some pathologies and the logistics. Yet up to 3 quarters of donor lungs remain discarded across the globe. Multiday preservation of discarded human lungs on EVLP platforms would improve donor lung utilization rates via application of sophisticated treatment modalities, which could eventually result in zero waitlist mortality. The purpose of this article is to summarize advances made on the technical aspects of the protocols in achieving a stable multiday preservation of isolated EVLP. Based on the evidence derived from large animal and/or human studies, the following advances have been considered important in achieving this goal: ability to reposition donor lungs during EVLP; perfusate adsorption/filtration modalities; perfusate enrichment with plasma and/or donor whole blood, nutrients, vitamins, and amino acids; low-flow, pulsatile, and subnormothermic perfusion; positive outflow pressure; injury specific personalized ventilation strategies; and negative pressure ventilation. Combination of some of these advances in an automatized EVLP device capable of managing perfusate biochemistry and ventilation would likely speed up the processes of achieving multiday preservation of isolated EVLP.

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Subnormothermic ex vivo lung perfusion attenuates graft inflammation in a rat transplant model

Gloria

Yerxa

Kesseli

et al. 2022

The Journal of Thoracic and Cardiovascular Surgery

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Commentary: Making lungs great again—introducing new modifications to the Toronto ex vivo lung perfusion protocol

Cited by 3 publications

References 27 publications

Crystal ribcage: a platform for probing real-time lung function at cellular resolution in health and disease

Crystal ribcage: a platform for probing real-time lung function at cellular resolution in health and disease

Technical Advances Targeting Multiday Preservation of Isolated Ex Vivo Lung Perfusion

Subnormothermic ex vivo lung perfusion attenuates graft inflammation in a rat transplant model

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