IN-VIVO DIFFUSION OF IMMUNOGLOBULIN-G IN MUSCLE - EFFECTS OF BINDING,SOLUTE EXCLUSION, AND LYMPHATIC REMOVAL

Previously, we demonstrated that immunoglobulin G (IgG), dissolved in an isotonic solution in the peritoneal cavity, transported rapidly int o the abdominal wall when the intraperitoneal tip) pressure was >2 cmH (2)O. We hypothesized that this was chiefly caused by convection and t hat diffusion of IgG was negligible. To investigate the role of diffus ion, we dialyzed rats with no pressure gradient across the abdominal w all muscle for 2 or 6 h with an ip isotonic solution containing I-125- labeled IgG. At the end of the experiment, ment, the animal was euthan ized and frozen and abdominal wall tissue was processed to produce cro ss-sectional autoradiograms. Quantitative densitometric analysis resul ted in IgG concentration profiles with far lower magnitude than profil es from experiments in which convection dominated. In other in vivo ex periments, we determined the lymph flow rate to be 0.8 x 10(-4) ml min (-1).g(-1) and the fraction of extravascular tissue (theta(s)) availab le to the IgG to be 0.041 +/- 0.001. An in vitro binding assay was use d to determine the time-dependent, nonsaturable binding constant: 0.00 65 min(-1) x duration of exposure. A non-steady-state diffusion model that included effects of theta(s), time-dependent binding, and lymph f low was fitted to the diffusion profile data, and the IgG diffusivity within the tissue void was estimated to be 2 x 10(-7) cm(2)/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 cmH(2)O, but diffusion may not be n egligible. Furthermore, nonsaturable binding must be accounted for in the interpretation of tissue protein concentration profiles.