Intratracheal instillation of PFC liquid has been shown to improve pulmonary mechanics and support gas exchange in animals and humans with respiratory insufficiency. During this process, PFC is detected in the blood; the effect of physicochemical properties of PFC liquids and physiologic factors on uptake have not been quantitated previously. The purpose of this study was to evaluate the relative influence of physiochemical (PFC vapor pressure - VP, relative lipid solubility - PFC lipid α) and physiologic(surface area - SA, blood flow - Q, blood lipid content - L) factors on the rate and magnitude of blood PFC uptake. A closed system, temperature and flow controlled, recirculating table top circuit was designed; PFC liquids (LiquiVent®, APF 140M, or RIMAR 101) were circulated countercurrent to sheep blood through membranes (Sci-Med™) in separate experiments. APF 140M was compared to Rimar 101 and LiquiVent® to assess the effect of PFC VP (mmHg) and PFC lipid α, respectively. The effect of SA (M2) was assessed by comparing LiquiVent® uptake across two membranes. Q (ml/min) was changed and Intralipid™ was added to blood to assess the effect of Q and L (mg/gm), respectively, on LiquiVent® blood uptake. Serially sampled blood was analyzed by electron capture gas chromatography to measure blood PFC content (μgm PFC/gm blood). Peak PFC content (Cpeak) and the time constant (τ. min) associated with time to equilibration were analyzed to evaluate magnitude and rate of PFC uptake (*p< 0.01).

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These data demonstrate that the magnitude of uptake is directly related to relative PFC lipid solubility and blood lipid content. The rate of uptake is inversely related to relative PFC lipid solubility and blood lipid content and directly related to surface area and blood flow. Whereas it was anticipated that an increase in vapor pressure, thus driving force for uptake, would increase Cpeak and reduce t, we speculate that Cpeak decreased due to a 6x decrease in relative PFC lipid solubility which offset the 4x increase in vapor pressure. These in vitro studies suggest that the dynamics of PFC uptake in vivo is likely to reflect PFC physicochemical, blood lipid, and ventilation/perfusion profiles.

(Supp in part and consultation with Alliance Pharm Corp, Hoechst-Marion-Roussel)