Irving Kron, MD (left), Victor Laubach, PhD
Irving Kron, MD, and Vic Laubach, PhD, professors in the Department of Surgery, were awarded a 4-year, $3.1 million grant from the NIH to study groundbreaking, perfusion-based methods to treat severe acute respiratory distress syndrome (ARDS) or ischemia-reperfusion injury (IRI) after lung transplant. Both ARDS and IRI remain major clinical issues associated with high morbidity and mortality, and currently no methods exist for targeted treatment of injured lungs.
For the past 28 years, the Kron/Laubach laboratory has studied mechanisms of lung IRI and, more recently, innovative methods to prevent acute lung injury via perfusion of isolated lungs with Steen solution in the form of ex vivo lung perfusion (EVLP) for IRI or in vivo lung perfusion (IVLP) for ARDS. In particular, IVLP is a novel technique pioneered by this laboratory that provides 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.
The Kron/Laubach laboratory has recently defined an endothelial Panx1-P2Y2R-TRPV4 signaling axis whereby pharmacologic inhibition of Panx1 (ATP channels) or TRPV4 (calcium channels) mitigates lung IRI. Thus, their studies will test the hypothesis that rehabilitation of injured lungs via isolated perfusion with Steen solution can be augmented by Panx1- or TRPV4-targeted therapy. These therapies are aimed at rehabilitating injured lungs by preserving the delicate pulmonary vascular network to prevent inflammation, edema, and organ failure. Recent studies from this laboratory represent a paradigm shift in the management of ARDS, and, if successful, the newly-funded project will define IVLP as a novel platform for targeted therapy of severe ARDS and will facilitate clinical translation. As a long-term goal, the most severely injured lungs, regardless of etiology, will be treated directly using a percutaneous approach in order to prevent prolonged ventilation.
The newly-funded studies will build upon recent, exciting research findings on novel mechanisms of lung IRI, which the lab published in Science Signaling. These results were summarized in a UVA Health press release here and published in UVA Today.
Mark Roeser, MD, and Huy Ta, PhD, in the Department of Surgery are collaborators on this award.