# In Vivo Lung Perfusion for the Surgical Treatment of Acute Respiratory Distress Syndrome

> **NIH NIH R01** · UNIVERSITY OF VIRGINIA · 2021 · $580,182

## Abstract

Summary
Acute respiratory distress syndrome (ARDS) imposes high mortality and long-term effects on patient quality-of-
life. Circulatory shock secondary to sepsis is the leading cause of ARDS. Extracorporeal membrane
oxygenation (ECMO) and protective ventilation strategies are the current standards of care; yet provide
support only for innate mechanisms of healing. While these supportive therapies are helpful, they offer little
improvement in overall mortality for severe ARDS. Currently, no methods exist for targeted treatment for the
rapid rehabilitation of lungs affected by ARDS. To address this, our laboratory has designed a novel in vivo
lung perfusion (IVLP) technique for the perfusion of lungs in vivo with Steen solution in a preclinical porcine
model of ARDS, which allows for targeted lung rehabilitation. This technique involves cannulation of the
pulmonary artery (inflow) and pulmonary veins (outflow) of the injured lung to enable closed-circuit perfusion
and direct treatment. This technique combines the benefits of ECMO and ex vivo lung perfusion (EVLP, used
to assess marginal donor lungs for transplant) to provide a platform upon which injured lungs can be treated in
vivo with targeted therapies in an isolated fashion without the potential risks of systemic treatment. Clinically,
IVLP would be performed in a percutaneous fashion that could function as an adjuvant to ECMO therapy to
shorten duration of support resulting in reduced morbidity and mortality. IVLP represents a novel method of
therapy to reduce the severity of ARDS secondary to trauma or septic shock.
 Our prior experience with both EVLP and ILVP strongly suggest that injured lungs can be successfully
rehabilitated utilizing IVLP targeted therapy. This proposal will test the hypothesis that IVLP with Steen solution
will rehabilitate lungs with LPS-induced ARDS in a preclinical porcine model with subsequent development of
percutaneous techniques for this therapy. Specific Aim 1 will optimize the rehabilitative capacity of IVLP using
a porcine model of LPS-induced lung injury. This will be accomplished through experiments that will optimize
timing, confirm durability, and improve perfusion strategies. Specific Aim 2 will use in vitro models using
pulmonary microvascular endothelial cells and alveolar epithelial cells to define mechanisms for the protective
effects of Steen solution on the alveolar-capillary barrier during IVLP. Specific Aim 3 will demonstrate the
feasibility of percutaneous IVLP for the treatment of severe ARDS, which will be necessary for clinical
translation. Our recent studies with IVLP demonstrate the feasibility and efficacy of IVLP for the treatment of
ARDS, representing a major paradigm shift in the management of ARDS. If successful, our proposed studies
will define EVLP as a novel, viable platform for targeted therapy of ARDS and will lead a path for translation
into human studies.

## Key facts

- **NIH application ID:** 10148801
- **Project number:** 5R01HL142110-04
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Irving L. Kron
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $580,182
- **Award type:** 5
- **Project period:** 2018-04-15 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10148801

## Citation

> US National Institutes of Health, RePORTER application 10148801, In Vivo Lung Perfusion for the Surgical Treatment of Acute Respiratory Distress Syndrome (5R01HL142110-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10148801. Licensed CC0.

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