Optimum viscosity of a perfusion solution reduces oedema formation in the isolated mouse lung.

Title: Optimum viscosity of a perfusion solution reduces oedema formation in the isolated mouse lung.
Author(s): D Walsh (1) J Boylan (2) P McLoughlin (3)
Institution: (1) Conway Institute, School of Medicine, University College Dublin, Dublin. (2) Department of Anaesthesia and Intensive Care, St. Vincent's University Hospital, Dublin, Ireland.
Poster: Click to view poster
Category: Lung Cancer/CF/ILD/Surgery
Abstract: Introduction: Intravenous fluid therapy is a cornerstone in the resuscitation of acute hypotensive states. However, resuscitation strategies can cause marked haemodilution, reducing plasma protein concentration, plasma oncotic pressure, and blood viscosity, with subsequent interstitial and pulmonary oedema formation (1). We have recently reported that perfusing isolated murine lungs with a solution with a relative viscosity (RV) of 2.5, adjusted with a biocompatible macromolecule, reduced the rate of oedema formation when compared to a solution with a viscosity lower than blood (RV1.5) (2). We now report work identifying the optimum viscosity of perfusing solutions and demonstrate that the beneficial effect of optimum viscosity solutions is independent of the macromolecules used to increase RV.

Methods: Mouse lungs were isolated and perfused ex vivo until oedema developed or 180 minutes had elapsed. Perfusion solution with low viscosity (RV 1.5) was compared to higher viscosity solutions (RV 2.0, 2.25, 2.5). RV1.5 comprised Dulbecco’s Modified Eagle Medium with Ficoll PM (40g/l) added. Higher viscosities solutions were prepared by adding one of the following high molecular weight polymers: Ficoll PM400, or Dextrans of different molecular weights (>300kDa) at concentrations sufficient to achieve the target RV. Oedema formation was assessed using Wet:Dry weight ratios(W:D).

Results: Using Ficoll 400kDa, lungs perfused with solution RV2.5 had significantly lower (P<0.05) W:D than RV2.0. Perfusate with RV2.25 was similar to RV2.5. When perfusates with RV2.5 were prepared using two different high molecular Dextran solutions (>300kDa), W:D was also significantly lower (P<0.05) compared to RV1.5.

Discussion: Perfusion solutions exhibiting an optimum viscosity (RV2.5) reduced interstitial oedema formation in isolated lungs. This effect is independent of the exact concentrations or chemical structures of the biocompatible macromolecules used to alter viscosity. Further work exploring the potential impact of reduced blood viscosity caused by haemodilution during standard resuscitation protocols is needed.

1. British Journal of Anaesthesia/ Royal College of Anaesthesia - WKR0-2019-0074 Project Grant.
2. St Vincent’s Anaesthesia Foundation.

1. Maiden MJ, Finnis ME, Peake S, McRae S, Delaney A, Bailey M, et al. Haemoglobin concentration and volume of intravenous fluids in septic shock in the ARISE trial. Critical Care. 2018;22:118.
2. Rowan SC, Rochfort KD, Piouceau L, Cummins PM, O’Rourke M, McLoughlin P. Pulmonary endothelial permeability and tissue fluid balance depend on the viscosity of the perfusion solution. American Journal of Physiology-Lung Cellular and Molecular Physiology. 2018;315:L476-L84.