# Pre-Clinical Large and Small Animal Models of ARDS/VILI

> **NIH NIH P01** · UNIVERSITY OF ARIZONA · 2022 · $285,647

## Abstract

ABSTRACT:
The Pre-Clinical models of acute lung injury Core (Core C) is designed to provide PPG investigators with
rigorously defined and reproducible rat and porcine models of combined acute respiratory distress syndrome
(ARDS) and ventilation-induced lung injury (VILI). The unprecedented COVID-19 pandemic with high mortality
rates of COVID-19-induced ARDS has dramatically raised the demand for a deeper understanding of the critical
role of the EC cytoskeleton in the pathobiology of ARDS and VILI and deepened the unmet need for FDA-
approved ARDS pharmacotherapies. Core C will comprehensively generate, manage, and provide all animal-
related experiments, resources, and expertise to all four projects by accomplishing five specific aims. Specific
Aim #1 provides a complete range of expertise, training, equipment, and data analysis tools to extensively study
and characterize the role of the cytoskeleton in preclinical models of lung injury. Core C will employ the state-of-
the-art techniques to a) characterize the role of the cytoskeleton in regulating lung endothelial cell (EC) barrier
function, b) determine the effects of specific interventions to provide insight into the efficacy and mechanisms of
novel therapeutic strategies, and c) facilitate the translation of basic research to clinical interventions. Specific
Aim #2 is to house and maintain rats and pigs utilized in this PPG. Specific Aim #3 examines selective
pharmacological agonists, antagonists, or monoclonal antibodies for PPG-targeted effectors, cytoskeletal, and
focal adhesion proteins as potential therapeutic strategies and approaches for ARDS/VILI models. Specific Aim
#4 provides rigorously performed, protocol-driven performance of specific experimental strategies involving
preclinical models of ARDS/VILI. Specific Aim #5 is to perform highly detailed studies and provide high quality
genomic, biochemical phenotyping (BAL protein, BAL cell count/cellularity, lung tissue albumin levels,
assessment of lung capillary leakage by Evans Blue dye (EBD), quantitative lung histology, and
immunohistochemistry). Also, Core C provides physiologic measurements (static and dynamic compliance of
the respiratory system, oxygenation index), radiographic and ultrasound images to support these studies. The
magnitude of ARDS and recovery responses will be determined by generating the acute lung injury severity
score (ALISS). Core C will perform lung injury assessment, provide plasma, and tissue samples to individual
projects for specific assays (including immunohistochemistry and western blot analysis). Our work in Core C will
provide full preclinical support to all four projects and provide the tools they need to get a greater mechanistic
understanding of lung EC barrier regulation while driving therapeutic developments directed toward restoring the
integrity of the injured pulmonary circulation, thereby reducing ARDS mortality.

## Key facts

- **NIH application ID:** 10496458
- **Project number:** 2P01HL126609-06A1
- **Recipient organization:** UNIVERSITY OF ARIZONA
- **Principal Investigator:** Saad Sammani
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $285,647
- **Award type:** 2
- **Project period:** 2016-09-20 → 2023-01-05

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10496458

## Citation

> US National Institutes of Health, RePORTER application 10496458, Pre-Clinical Large and Small Animal Models of ARDS/VILI (2P01HL126609-06A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10496458. Licensed CC0.

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