Normothermic Negative Pressure Ventilation Ex Situ Lung Perfusion: Evaluation of Lung Function and Metabolism
February 14th, 2022
2.5K views
This paper describes a porcine model of negative pressure ventilation ex situ lung perfusion, including procurement, attachment, and management on the custom-made platform. Focus is made on anesthetic and surgical techniques, as well as troubleshooting.
Overview
This paper describes a porcine model of negative pressure ventilation ex situ lung perfusion, focusing on anesthetic and surgical techniques. The study emphasizes the management of the custom-made platform and troubleshooting methods.
Key Study Components
Area of Science
- Respiratory physiology
- Lung transplantation
- Negative pressure ventilation
Background
- Negative pressure ventilation technology is unique in ESLP research.
- Previous studies indicate reduced lung injury with negative pressure compared to positive pressure ventilation.
- The device aims to extend the safe preservation time of donor lungs.
- It is designed to recondition marginal lungs for transplantation.
Purpose of Study
- To develop a reliable method for lung preservation.
- To evaluate the efficacy of negative pressure ventilation in lung perfusion.
- To provide a simple operational protocol for surgical teams.
Methods Used
- Creation of a custom ESLP device.
- Application of negative pressure ventilation techniques.
- Surgical removal of juvenile pig lungs.
- Management of the lung perfusion process.
Main Results
- The device demonstrated ease of operation.
- Negative pressure ventilation resulted in less lung injury.
- Successful management of lung procurement and attachment.
- Effective troubleshooting methods were established.
Conclusions
- The ESLP device is a promising tool for lung preservation.
- Negative pressure ventilation offers significant advantages over traditional methods.
- Further research is needed to optimize the protocol for clinical use.
Frequently Asked Questions
What is negative pressure ventilation?
Negative pressure ventilation is a technique that uses a vacuum to expand the lungs, reducing the risk of injury compared to positive pressure methods.
How does the ESLP device work?
The ESLP device utilizes patented technology to maintain lung function during ex situ perfusion, allowing for better preservation of donor lungs.
What are the main advantages of this study?
The study highlights reduced lung injury and a simplified surgical protocol for lung procurement and management.
What challenges were faced during the study?
The primary challenge was the surgical removal of juvenile pig lungs without causing injury.
What future research is suggested?
Further studies are needed to refine the protocol and assess its clinical applicability for lung transplantation.
Executive Industry Relevance
Normothermic negative pressure ventilation ex situ lung perfusion (NPV-ESLP) addresses donor lung scarcity by enabling preservation and reconditioning of marginal organs. This approach reduces ventilator-induced lung injury and inflammatory responses compared to positive pressure ventilation, improving graft viability. The technology supports extended preservation windows and metabolic assessment, enhancing decision-making in lung transplantation workflows.
Strategic Applications in Biopharma R&D
Early Discovery & Target Validation
- Scientific Value: Enables interrogation of pulmonary injury mechanisms under controlled ex vivo conditions.
- Operational Value: Provides a reproducible platform for evaluating ventilatory strategies and their impact on lung function.
Screening & Assay Development
- Scientific Value: Facilitates standardized assessment of lung edema, compliance, and gas exchange as quantitative endpoints.
- Operational Value: Supports perfusion circuit priming, de-airing, and real-time monitoring of metabolic parameters for assay readiness.
Translational & Preclinical Research
- Scientific Value: Uses juvenile porcine model to mimic human lung physiology for preclinical safety and efficacy evaluation.
- Operational Value: Details anesthetic management, surgical explantation, and device initialization for protocol translation.
Pipeline & Workflow Integration
NPV-ESLP integrates into the discovery continuum by providing a metabolically active system for lung evaluation prior to preclinical validation, supporting go/no-go decisions based on functional readouts.
- Discovery Biology: Enables dynamic organ management through adjustable ventilation and perfusion parameters to optimize lung function.
- Screening: Ensures assay standardization via controlled perfusate composition, temperature, and flow rates.
- Analytics: Generates time-series data on pulmonary artery pressure, dynamic compliance, and PaO2/FiO2 ratio for comparative analysis.
- Translational Research: Maintains physiological normothermia to preserve metabolic continuity from explant to assessment.
- Enterprise Reuse: Establishes a standardized ESLP platform adaptable across injury models and reconditioning strategies.
Operational & Enterprise Impact
- Scientific Value: Reduces mechanistic ambiguity in ventilator-induced lung injury by isolating negative pressure effects.
- Operational Value: Standardizes surgical and perfusion techniques to minimize variability in lung preparation.
- Strategic Value: Improves go/no-go confidence through objective metabolic and functional thresholds.
- Portfolio Impact: Enables risk-adjusted prioritization of marginal lungs for transplantation based on 12-hour perfusion trends.
Implementation Considerations
- Requires expertise in thoracic surgery, anesthesiology, and perfusion technology.
- Depends on custom ESLP device with integrated negative pressure ventilation and software controls.
- Necessitates cross-team standardization for lung handling, circuit priming, and parameter adjustment.
- Involves adaptation considerations when translating from juvenile porcine to human donor lungs.
- Limited by the technical challenge of preventing air leaks and ensuring optimal lung positioning during perfusion.
Biopharma FAQs
Why does negative pressure ventilation reduce lung injury in ESLP?
Negative pressure ventilation provides more homogeneous intrathoracic pressure distribution compared to positive pressure, reducing regional overdistension and ventilator-induced lung injury during ex situ perfusion.
How is cardiac output flow calculated and adjusted during NPV-ESLP?
The perfusion flow is calculated based on the pig's weight and initiated at 10% of cardiac output, then incrementally increased to 20% at 10 minutes and 30% at 20 minutes of perfusion to support metabolic demand.
What quantitative metrics are used to assess lung function during evaluation mode?
Lung function is evaluated using the PaO2/FiO2 ratio, mean pulmonary artery pressure, dynamic compliance, and pulmonary vascular resistance at 3, 5, 7, 9, and 11 hours during a 12-hour perfusion run.
Why is perfusate sampling performed at odd-hour intervals during preservation mode?
Perfusate samples are collected every odd hour to monitor metabolic trends and assess lung status, with blood gas analysis providing insight into the lungs' metabolic state during extended preservation.
What statistical analysis is required to interpret trends in lung function over time?
Analysis of mean pulmonary artery pressure, dynamic compliance, and pulmonary vascular resistance trends over 12 hours is necessary to evaluate the impact of the ESLP experimental protocol on lung function.
Chapters in this video
0:05
Introduction
0:57
Pneumonectomy
2:58
Placement of the Lungs onto the Ex‐Situ Lung Perfusion (ESLP) Apparatus
4:35
Initiation of Perfusion and Ventilation
7:44
Results: Analysis of Blood Gas and Functional Parameters During Evaluation Modes Over 12 Hours of ESLP and NPV‐ESLP
8:57
Conclusion
