Pulmonary Gas Trapping Differences Among Animal Species in Response to Intravenous Infusion of Perfluorocarbon Emulsions

Abstract

In animals, increased lung volume and a concomitant failure of lungs to collapse normally upon autopsy can occur following intravenous injection of higher vapor pressure perfluorocarbons (PFCs) administered as emulsions. Responses vary considerably depending on the PFC, dose and animal model. The study objective was to examine animal species differences with respect to this apparent pulmonary gas trapping (PGT) phenomenon which has not been observed in human clinical trials. A dose-related increase in postmortem lung volume following treatment with either a concentrated perflubron emulsion or Fluosol was observed. It was most pronounced in pigs, rabbits and monkeys, and essentially nonexistent in mice and dogs. No clear effects on arterial blood gases were seen in most species, but PaO2 levels were reduced transiently in monkeys given the highest PFC doses. Reversibility of pulmonary effects occurred more rapidly with perflubron emulsions than with Fluosol. Vacuolated mononuclear cells, reflecting the presence of PFC particles in the lung, and alveolar distention varied between species, but no lesions or edema were observed. Species differences in collateral ventilation, airway morphology and pulmonary intravascular macrophages may influence their sensitivity and contribute to the interspecies differences in response to intravenously administered PFC emulsions.

Initial Investigation of Acoustic Droplet Vaporization for Occlusion in Canine Kidney

“…Compared to rabbits, dogs have been found to be less sensitive to the higher dosage of PFC emulsion (up to 12 mL/kg) (Leakakos et al 1994). It has been reported that several important factors, such as the number of pulmonary intravascular macrophages, collateral ventilation, transpulmonary pressure and the airway geometry may contribute to these species-related responses (Leakakos et al 1994).…”

“…It has been reported that several important factors, such as the number of pulmonary intravascular macrophages, collateral ventilation, transpulmonary pressure and the airway geometry may contribute to these species-related responses (Leakakos et al 1994). As indicated in arterial blood samples, respiratory acidosis was observed in both the IV and transcutaneous experiments as a result of repeated droplet injections.…”

Insight into Pulmonary Gas Trapping as an Index of Airway Responses in Small Laboratory Animals

“…Further, the apparatus for measuring ELGV is much less expensive (hundreds of dollars) than the equipment for noninvasive or invasive pulmonary function measurements (tens of thousands of dollars) in small laboratory animals. Finally, investigators from academic [28,38,39], government [40], and pharmaceutical [27,41,42] laboratories have used the ELGV measurement to advance their research. Thus, I believe the ELGV measurement is a costeffective alternative approach for assessing in vivo airway mechanics in small laboratory animals and for examining novel therapies for treating human lung disease.…”

Assessment of the biodistribution of an [18F]FDG‐loaded perfluorocarbon double emulsion using dynamic micro‐PET in rats

“…For example, lung retention of microbubbles within the pulmonary microvasculature is a size‐dependent phenomenon . The formulation of transpulmonary, micron‐sized emulsions can minimize certain types of PFC‐related bioeffects . Additionally, the pharmacokinetics of sonosensitive PFC particles are directly related to the time window between vascular administration of the particles and the application of ultrasound to activate the particles.…”