Microvascular ion transport through endothelial glycocalyx layer: new mechanism and improved Starling principle

Xi Zhuo Jiang, Yiannis Ventikos,* and Kai H. Luo* 

Department of Mechanical Engineering, University College London, London, United Kingdom 

Submitted 11 December 2018; accepted in final form 19 April 2019 

Am J Physiol Heart Circ Physiol 317: H104–H113, 2019.
First published April 26, 2019; doi:10.1152/ajpheart.00794.2018. 

Well, I’ve bought a download of this amazing piece of work and read it as well as I can. My highest achievement in mathematics was at Ordinary Level 3. I have learned that theoretical and computational scientists have access to NAMD, a “parallel molecular dynamics code designed for high-performance simulation of large bimolecular systems.” My Latin classification of biological experiments is now extended from in vivo or in vitro to a third mode, in silico.

In their experiments the ICL researchers built an in silico wedge of the vascular permeability barrier 72 nanometers high, in a hexagonal prism shape with a surface area of 820 square nanometers and comprising 5.8 million atoms.

I’ll leap to their key finding, their Improvement to the evolving Starling principle. They found that as they increased the flow rate of solvent and sodium ions through the glycocalyx layer there was a deformation of the glycocalyx molecules which changed the effective osmotic pressure difference opposing filtration across the permeability barrier.  Translating into clinicalese, they conclude that “the slightly elevated blood flow velocity after moderate exercise training will result in a reduction in the osmotic part of Eq. 4, leading to a decrease in transvascular fluid permeability, which alleviates edema.”  We therefore have another justification for keeping our patients active and ambulant if we want to minimise oedema. I would caution clinicians against presuming that inotropes or even volume loading might achieve the desired increase in tissue blood flow velocity. This can lead to redistribution of cardiac output, sending ever higher proportions of blood to the sinusoidal tissues where this in silico model does not apply.

It’s “one small step” for sure, but inspiring to see and admire the work done in University laboratories to underpin and to guide our clinical practices. Thanks, team!

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