![]() This method of determining viscosity was chosen because of its relevance to distribution of surfactant in the upper airways that is controlled by gravity as well as by airflow upon inhalation. The kinematic viscosity can be converted to dynamic (absolute) viscosity by multiplying by the density of the fluid. Time required for fluid to drain by gravity through a viscometer tube was measured, and this time was converted to a value of kinematic viscosity using a calibration constant supplied by the manufacturer and verified in our laboratory using standard fluids. The sizes correspond to different ranges of viscosity with some overlap that were suitable for our measurements. Kinematic viscosity measurements were made with Cannon-Manning semi-microviscometers (State College, PA) sizes 100, 150 and 200. Light microscopy of the different mixtures was carried out to find whether correlations existed between viscosity and the microstructure of surfactant dispersions. Our aim was to measure and characterize the viscous properties of therapeutic surfactants with and without polymers under a range of conditions. Survanta and Infasurf were selected not only because they are both in widespread clinical use but also because their viscosities differ appreciably, as previously reported. In the event that some of these mixtures have lower viscosity than the surfactant itself, then the lowered viscosity may be a contributing factor to the in vivo improvements in lung function previously attributed to enhanced surface activity. For this reason, we measured surfactant viscosity in the presence or absence of the polymers that we have found to be beneficial including those concentrations of surfactant and polymer that may be clinically relevant. Of concern is whether added polymers would increase viscosity of therapeutic surfactants to the degree that distribution of surfactant in the lung might be affected. Although the viscosity of a variety of surfactants has been studied, changes in viscosity after addition of polymers have not been investigated. Benefits include improvements in surface activity and lung function. Our previous work and that of others have shown the benefits in vitro and in vivo of adding an ionic polymer like hyaluronan (HA), or nonionic polymers like polyethylene glycol (PEG) or dextran to exogenous surfactant. The distribution of surfactant into the small airways and the alveoli, occurring in the remaining dozen or so generations, is controlled by differences in surface tension of various fluids and components in the pulmonary system (Marangoni flow), or by surface viscosity, not by bulk viscosity and therefore not studied. A lower value allows a more uniform and rapid distribution of the instilled surfactant with less initial loss due to coating of the upper airways. The early stage of surfactant distribution, occurring in the upper one-third of approximately 18 generations or bifurcations of the airway system, is rapid and controlled mainly by surfactant bulk viscosity. Viscosity is believed to influence the rate, extent and uniformity of distribution of surfactant in the lungs. ![]() The viscosity of lung surfactant is dependent on its molecular composition, its microstructure, the interactions between components and the environmental conditions. Aggregation of surfactant vesicles caused by polymers may therefore not only improve surface activity as previously shown, but may also affect viscosity in ways that could improve surfactant distribution in vivo. Effects of polymers on viscosity correlate with changes in size and distribution of surfactant aggregates and the apparent free volume of liquid as estimated by light microscopy. Addition of hyaluronan at clinical surfactant concentrations slightly increased Infasurf viscosity and produced little change in Survanta viscosity. However, the addition of polyethylene glycol and dextran to surfactants at clinically used concentrations can substantially lower viscosity. Our results indicate that at lower surfactant concentrations, the addition of any polymers increased the viscosity. The measurements were carried out over a range of surfactant concentrations using two concentrations of polymers at two temperatures. In this study, we have measured the viscosities of Survanta and Infasurf with and without the addition of polyethylene glycol, dextran or hyaluronan. Although the viscosity of surfactants has been investigated, the viscosity of surfactant polymer mixtures has not. The addition of various polymers to pulmonary surfactants improves surface activity in experiments both in vitro and in vivo.
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