Evidence of serial connection between the plasma volume and two interstitial fluid compartments

Background: Kinetic analysis of fluid volume shifts can identify two interstitial fluid compartments with different turnover rates, but how they are connected to the bloodstream is unknown.Methods: Retrospective data were retrieved from 217 experiments where 1.5 L of Ringer's solution (mean) had been administered by intravenous infusion over 30 min to awake and anesthetized humans (mean age 40 years). Urinary excretion and hemoglobin-derived plasma dilution served as input variables in a volume kinetic analysis using mixed models software. Possible modes of connection between the two interstitial fluid compartments and the bloodstream were judged by covariance analysis between kinetic rate constants, physiological variables, and time factors.Results: The return flow of already distributed fluid to the plasma via a fast-exchange interstitial compartment was inhibited ongoing infusion of fluid (-38 %), which was probably due to increase of the venous pressure during volume loading. Ongoing infusion also greatly retarded the entrance of fluid to the slow-exchange compartment (-85 %), which suggests that infused Ringer's first had to enter the fast-exchange compartment. A high mean arterial pressure markedly increased the urine output and, to a lesser degree, also the rate of entrance of fluid to the fast-exchange compartment. Moreover, a high blood hemoglobin concentration retarded the rate of entrance of fluid to the fast-exchange compartment. Conclusions: The fast-exchange but not the slow-exchange interstitial fluid compartment was affected by intravascular events, which suggests that only the fast-exchange compartment is directly connected to the circulating blood.