Lung Perfusion Solution Viscosity Tuning for Ex Vivo Edema Control
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Solution Overview
Problem
Existing lung perfusion solutions do not adequately address the issue of optimal viscosity to maintain normal vascular function and prevent edema formation during ex vivo preservation, particularly in small vessels.
Innovation Solution
A lung perfusion solution with a viscosity adjusted to resemble that of blood in small vessels by incorporating a high molecular weight macromolecule, such as FICOLL PM400, to a base solution, maintaining a relative viscosity of 2.0-3.0, which minimizes edema and optimizes vascular function.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If a standard perfusion solution with normal viscosity is used, then the solution is easy to administer and maintains basic physiological parameters, but it fails to optimize vascular function and prevent edema in small vessels
Solution Approach 1:
The patent modifies the viscosity parameter of the perfusion solution by adding high molecular weight macromolecules ( Ficoll PM400 or dextran T40) to achieve a relative viscosity of 2.0-3.0, matching blood viscosity in small vessels. This parameter change optimizes vascular function and prevents edema formation in the microcirculation.
Solution Approach 2:
The perfusion solution is formulated as a composite containing multiple components: a base solution (DMEM or physiological salt solution), colloidal osmotic agents (albumin or globulin), and high molecular weight macromolecules (Ficoll PM400 or dextran T40). This composite structure allows the solution to simultaneously maintain colloidal osmotic pressure and optimize viscosity for small vessel perfusion.
2Reliability
If the viscosity of the perfusion solution is increased to match blood viscosity in small vessels, then vascular function is optimized and edema is prevented, but the solution becomes more complex to prepare and administer
Solution Approach 1:
The patent specifically targets the viscosity parameter by adding high molecular weight macromolecules to achieve a relative viscosity of 2.0-3.0. This parameter optimization prevents edema formation in small vessels by matching the rheological properties of native blood flow in the microcirculation.
Solution Approach 2:
The solution combines multiple functional components: base solution for physiological compatibility, colloidal agents for osmotic pressure maintenance, and high molecular weight macromolecules for viscosity optimization. This composite approach allows simultaneous achievement of multiple physiological requirements.
3Reliability
If high molecular weight macromolecules are added to adjust viscosity, then small vessel function is improved, but the colloidal osmotic pressure may be affected
Solution Approach 1:
The patent differentiates the functional roles of different macromolecular components: albumin or globulin provides colloidal osmotic pressure to prevent fluid leakage, while Ficoll PM400 or dextran T40 specifically adjusts viscosity for optimal small vessel perfusion. Each component targets a specific physiological requirement independently.
Solution Approach 2:
The perfusion solution is designed as a multi-component composite where albumin or globulin (3-6% w/v) maintains colloidal osmotic pressure, and high molecular weight macromolecules (2-5% w/v) optimize viscosity. This composite structure allows independent optimization of both osmotic pressure and viscosity parameters.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The solution effectively reduces pulmonary edema and maintains optimal vascular function by adjusting viscosity, as evidenced by lower peak airway pressures and improved vascular resistance characteristics.
Implementation Method 1
the solution comprises an amount of a second, high molecular weight, macromolecule sufficient to adjust the relative viscosity of the solution to 2.0-3.0
Implementation Method 2
a large molecular weight molecule or molecules such as albumin, globulins or other substitutes, is added to provide colloid osmotic pressure (oncotic pressure) to retain water within the intravascular compartment and thus prevent the formation of oedema
Data Source
AI summary
A lung perfusion solution comprises a base solution comprising a physiological mixture of electrolytes and buffers, 3.5-5.5% (w/v) a first macromolecule having a molecular weight of 40-100 KDa, and an amount of a second, high molecular weight, macromolecule sufficient to adjust the relative viscosity of the solution to 2.0-3.0.