Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Targeted treatment of acute lung injury using isolated lung perfusion

Award Number: R01HL168041
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 12/20/2023
PERIOD OF PERFORMANCE END DATE: 11/30/2027

Group Awards By:

View Award Description

Targeted treatment of acute lung injury using isolated lung perfusion - Summary Acute lung injury in the form of acute respiratory distress syndrome (ARDS) or ischemia-reperfusion injury (IRI) after lung transplant remains a major clinical issue associated with high morbidity and mortality. Currently, no methods exist for targeted treatment and rapid rehabilitation of lungs affected by ARDS. The majority of treatment strategies remain supportive in nature and are associated with continued poor outcomes. We have demonstrated breakthrough methods for treatment or prevention of acute lung injury via normothermic perfusion of isolated lungs in the form of ex vivo lung perfusion (EVLP) for marginal donor lungs or in vivo lung perfusion (IVLP) for ARDS. IVLP combines the benefits of extracorporeal membrane oxygenation and EVLP 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. We have demonstrated the rehabilitative capacity of isolated lung perfusion with Steen solution whereby sepsis-induced ARDS as well as IRI of transplanted donation after circulatory death (DCD) lungs are attenuated. We have also demonstrated that Steen solution directly preserves pulmonary endothelial barrier function and that inhibition of Panx1 or TRPV4 channels attenuates lung IRI via endothelial barrier protection. Thus, this project will test the overall hypothesis that rehabilitation of injured lungs by isolated, normothermic perfusion with Steen solution can be augmented by Panx1- or TRPV4-targeted therapy aimed at preserving endothelial barrier function to attenuate vascular inflammation and improve lung function. We will test our hypothesis using porcine and murine models of IVLP and EVLP of lungs injured by ARDS or IRI in three specific aims. Aim 1 will determine if isolated perfusion with Steen solution will rehabilitate injured lungs and if inhibition of Panx1 or TRPV4 during perfusion will augment rehabilitation and endothelial barrier function. Aim 1A will use a porcine, LPS-induced ARDS model to determine if IVLP provides durable lung rehabilitation up to 24 hours after IVLP. Aim 1B will determine if IVLP rehabilitates lungs injured in a porcine model of gastric aspiration-induced ARDS. Aim 1C will determine if EVLP rehabilitates murine lungs injured by ARDS caused by SARS-CoV-2 infection. Aim 2 will use a porcine lung transplant model to determine if rehabilitation of DCD lungs by EVLP can be augmented by treatment with Panx1 or TRPV4 inhibitor for successful transplant. Aim 3 will use in vitro models of LPS-induced injury to determine protective mechanisms of Steen solution involving direct anti-inflammatory effects on alveolar-capillary barrier or leukocytes. Our recent studies demonstrate the potential of IVLP for the treatment of severe ARDS, representing a major paradigm shift in the management of ARDS. If successful, our proposed studies will define IVLP as a novel platform for targeted therapy of severe ARDS and will facilitate clinical translation.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $765,632 )
2026	2026	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 EMMET ST N	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Lung Diseases Research	000	3	2/12/2026	NON-COMPETING CONTINUATION	$765,632
														Subtotal = $765,632

Issue Date FY: 2025 ( Subtotal = $806,617 )
2025	2025	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 EMMET ST N	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Lung Diseases Research	001	2	1/10/2025	NON-COMPETING CONTINUATION	$0
2025	2025	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 EMMET ST N	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Lung Diseases Research	002	2	8/14/2025	NON-COMPETING CONTINUATION	$80,662
2025	2025	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 EMMET ST N	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Lung Diseases Research	000	2	11/12/2024	NON-COMPETING CONTINUATION	$725,955
														Subtotal = $806,617

Issue Date FY: 2024 ( Subtotal = $800,467 )
2024	2024	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 EMMET ST N	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Lung Diseases Research	002	1	8/8/2024	NEW	$0
2024	2024	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 EMMET ST N	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Lung Diseases Research	000	1	12/14/2023	NEW	$720,420
2024	2024	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 EMMET ST N	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Lung Diseases Research	001	1	7/17/2024	NEW	$80,047
														Subtotal = $800,467

Grand Total All Awards = $2,372,716

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Targeted treatment of acute lung injury using isolated lung perfusion

Award Number: R01HL168041

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 12/20/2023

PERIOD OF PERFORMANCE END DATE: 11/30/2027

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer