In vivo diffusion of immunoglobulin G in muscle: effects of binding, solute exclusion, and lymphatic removal

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Abstract
Previously, we demonstrated that immunoglobulin G (IgG), dissolved in an isotonic solution in the peritoneal cavity, transported rapidly into the abdominal wall when the intraperitoneal (ip) pressure was >2 cmH2O. We hypothesized that this was chiefly caused by convection and that diffusion of IgG was negligible. To investigate the role of diffusion, we dialyzed rats with no pressure gradient across the abdominal wall muscle for 2 or 6 h with an ip isotonic solution containing125I-labeled IgG. At the end of the experiment, the animal was euthanized and frozen and abdominal wall tissue was processed to produce cross-sectional autoradiograms. Quantitative densitometric analysis resulted in IgG concentration profiles with far lower magnitude than profiles from experiments in which convection dominated. In other in vivo experiments, we determined the lymph flow rate to be 0.8 × 10−4ml ⋅ min−1 ⋅ g−1and the fraction of extravascular tissue (θs) available to the IgG to be 0.041 ± 0.001. An in vitro binding assay was used to determine the time-dependent, nonsaturable binding constant: 0.0065 min−1 × duration of exposure. A non-steady-state diffusion model that included effects of θs, time-dependent binding, and lymph flow was fitted to the diffusion profile data, and the IgG diffusivity within the tissue void was estimated to be 2 × 10−7cm2/s, a value much higher than that published by other groups. We also demonstrate from our previous data that convection of IgG through tissue dominates over diffusion at ip pressures >2 cmH2O, but diffusion may not be negligible. Furthermore, nonsaturable binding must be accounted for in the interpretation of tissue protein concentration profiles.