Hemodynamic Effects of Lipid-Based Oxygen Microbubbles via Rapid Intravenous Injection in Rodents

Abstract

LOMs may be injected in quantities sufficient to deliver clinically meaningful volumes of oxygen but cause significant decrements in blood pressure and elevations in PVR.

Interfacial Nanoprecipitation toward Stable and Responsive Microbubbles and Their Use as a Resuscitative Fluid

“…[16][17][18] We previously showed that slow and controlled IV infusions of lipid oxygen microbubbles (LOMs) are effective at alleviating hypoxemia. [19] Moreover, during rapid injections,L OMs increased the risk of acute pulmonary vascular obstruction because of 1) the prolonged persistence of LOMs in the blood ( Figure S7), [20] and 2) the formation of lipid aggregates as aresult of lipid shedding from the LOM shells. [19] Moreover, during rapid injections,L OMs increased the risk of acute pulmonary vascular obstruction because of 1) the prolonged persistence of LOMs in the blood ( Figure S7), [20] and 2) the formation of lipid aggregates as aresult of lipid shedding from the LOM shells.…”

“…[4] However, LOMs lack sufficient stability for storage as ad rug, and are impractical for clinical use. [19] Thus,the ideal MB-based IVO 2 gas carrier should possess high storage stability,b ut be quickly cleared from the bloodstream, so that as ufficient volume of oxygen can be delivered without causing pulmonary vascular obstruction ( Figure 2A). [19] Thus,the ideal MB-based IVO 2 gas carrier should possess high storage stability,b ut be quickly cleared from the bloodstream, so that as ufficient volume of oxygen can be delivered without causing pulmonary vascular obstruction ( Figure 2A).…”

Injectable Oxygen: Interfacing Materials Chemistry with Resuscitative Science

“…Firstly, as mentioned earlier, lipid based MBs have limited shell‐life stability. Long‐term storage of LOMs led to increased size and formation of solid lipid debris, which in turn, led to a loss in injectable gas fraction and increased the risk of pulmonary obstruction and cardiac arrest . Additionally, because lipid monolayers are brittle, LOMs are prone to rupture, resulting in free gas release, when subjected to standard injection pressures exerted during rapid i.v.…”

“…For instance, the i.v. infusion of LOMs requires careful titration of the delivered gas fraction to avoid depletion of the local oxygen sink conditions within the vasculature; failure to do so results in prolonged microbubble persistence leading to pulmonary emboli and increased incidences of cardiac arrest (Figure D) Our laboratory has also shown that i.v. delivery of LOMs in a swine model of CA causes in vivo formation of lethal large gas emboli .…”

“…Such behavior likely explains the transient hypotension observed by Kheir and Black following i.v. infusion of LOMs of increasing concentrations (i.e., they may have caused transient pulmonary emboli which decreased systemic blood flow) (Figure D) . Interestingly, the authors also noted injection of concentrated DAS‐h MBs into stationary blood did not result in their immediate dissolution until a mild agitation was applied; this is not surprising because the deprotonation reaction requires proper mixing with the basic media.…”