Hydrodynamics and Interfacial Surfactant Transport in Vascular Gas Embolism

Abstract

Vascular gas embolism - bubble entry into the blood circulation - is pervasive in medicine, including over 340,000 cardiac surgery patients in the US annually. The gas-liquid interface interacts directly with constituents in blood, including cells and proteins, and with the endothelial cells lining blood vessels to provoke a variety of undesired biological reactions. Surfactant therapy, a potential preventative approach, is based in fluid dynamics and transport mechanics. Herein we review literature relevant to understanding of the key gas-liquid interface interactions inciting injury at the molecular, organelle, cellular and tissue levels, including clot formation, cellular activation, and adhesion events. We review the fluid physics and transport dynamics of surfactant-based interventions to reduce tissue injury from gas embolism. In particular, we focus on experimental research and computational and numerical approaches which demonstrate how surface-active chemical based intervention, based on competition with blood-borne or cell surface-borne macromolecules for surface occupancy of gas-liquid interfaces, alters cellular mechanics, mechanosensing and signaling coupled to fluid stress exposures occurring in gas embolism. We include a new analytical approach for which an asymptotic solution to the Navier-Stokes equations coupled to the convection-diffusion interaction for a soluble surfactant provides additional insight regarding surfactant transport with a bubble in a non-Newtonian fluid.

Iatrogenic air embolism: pathoanatomy, thromboinflammation, endotheliopathy, and therapies

“…Endothelial and pulmonary cellular injury and lung edema are the result of thromboinflammatory changes provoked by the release of damage-associated molecular patterns, normally not exposed to the innate immune system but recognized by the pattern recognition receptors when cell and tissue damage occur. Innate upstream systems like complement, toll-like receptors, and others induce downstream release (e.g., from the complement C5a-C5aR1 axis) of innumerable of inflammatory vasoactive mediators such as thromboxane, leukotrienes, cytokines, and coagulation factors with resultant increase in alveolocapillary permeability ( 1 , 3 , 12 , 30 , 35 – 37 , 79 , 80 ).…”

“…It has also been shown that bubble volumes as small as 10 nL may persist for more than 35 minutes, which can significantly impede the delivery of oxygen to areas such as the brain and heart. It has been proposed that a diameter of 250 µm represents a threshold at which CBF is completely impaired ( 37 ). At these obstruction threshold values, variable reduction of CBF and cerebral function are likely and may explain the protean manifestations and the delayed response of HBOT ( 2 , 3 , 29 ).…”

“…The increase in cytoplasmic calcium is thought to disrupt adherens junctions, leading to loss of tight junctions between endothelial cells, increased endothelial permeability, and perivascular edema. Moreover, air emboli have been demonstrated to increase tissue factor levels and complement component 3 (C3) activation, leading to thromboinflammation ( 37 , 121 ). (Created with ).…”

“…The stretching of the Syn4 causes the transient receptor potential vanilloid (TRPV) Ca2+ channels to open and allow Ca2+ to enter the cell. This interferes with the function of the endothelium, thereby causing capillary leak ( 30 , 37 , 121 ).…”

“…The glycocalyx executes this regulation through deformation forces which are visibly imposed by the bubble that execute protective forces over HA in the underlying cell membrane and interfacial interaction with HS which causes TRPV activation. Thus, HA functions as a cushion-like barrier between the active air-liquid interface along with the underlying glycocalyx components as opposed to functioning as an activating entity ( 30 , 37 , 39 , 121 ). The crosstalk between thrombosis and inflammation, which is initiated by the bubbles at the endothelial level is mediated by a complex interaction of hemostatic and inflammatory pathways, in particular, the complement system ( Figure 8 ).…”