Vital organ blood flow can be significantly compromised by microvascular gas embolism, which occurs commonly during cardiopulmonary bypass and in decompression sickness. Microbubbles adherent to biomaterials also promote clot formation within vascular grafts and ventricular assist devices. The associated untoward physiological effects may be prevented or treated using surfactant therapy. Our goal is to exploit surfactant infusion to restore or preserve blood flow and eliminated bubble adhesion by promoting gas bubble shape changes and dislodgment. We propose to investigate the relationships between surfactant physico-chemical properties, liquid, solid, and gas material properties, and interfacial stress balances in gas embolized blood vessels. We postulate that these physico-chemical and material properties are the primary determinants of 1) the liquid-bubble interfacial shape, 2) the vessel wall-bubble adhesion, 3) the perfusion pressure and 4) whether or not bubble dislodge.
Three specific aims will investigate these hypothesis: (1) to identify surfactant effects on microcirculatory blood flow that gas embolism. We postulate that surfactants administered intravascularly act at gas bubble/liquid interfaces to alter surface tension, bubble shape, and adhesion to the vessel wall. With in vivo and in vitro microcirculation experiments we will quantify the influence of intravascular surfactant administration on restoration of post-embolization tissue blood flow; (2) to quantify surfactant effects on bubble shape and adhesion in tube flow. We hypothesize that surfactants alter pressure-flow relationships and influence bubble detachment from the wall. To derive the relationships between pressure, flow, buoyancy, and surfactant properties that favor bubble detachment, we will measure surfactant-induced clearance of bubble from flow in rigid tube model blood vessels; and (3) to quantify physico- chemical properties of surfactants having therapeutic potential. We postulate that surfactant physico-chemical characteristics control the stresses and the gas-liquid interface and the adhesion characteristics at the liquid-solid-gas contact perimeter, and that these phenomena correlate with bubble shape change and detachment. Static interfacial mechanics measurements will be made to quantify the independent effects of surfactant and material properties which contribute to successful bubble dislodgment. The proposed work has been designed to utilized physiology experiments in the microcirculation in vivo and in vitro to guide a bioengineering fluid dynamics analysis of the underlying mechanical phenomena. By examining the fundamental effects of gas embolism bubbles, the proposed experiments will direct us to new clinical strategies for treatment or prevention of gas embolism.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
1R01HL060230-01A1
Application #
2765490
Study Section
Surgery and Bioengineering Study Section (SB)
Project Start
1998-12-01
Project End
2002-11-30
Budget Start
1998-12-01
Budget End
1999-11-30
Support Year
1
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Pennsylvania
Department
Anesthesiology
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
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