Evaluation of gravimetric techniques to estimate the microvascular filtration coefficient

Abstract

Microvascular permeability to water is characterized by the microvascular filtration coefficient (K(f)). Conventional gravimetric techniques to estimate K(f) rely on data obtained from either transient or steady-state increases in organ weight in response to increases in microvascular pressure. Both techniques result in considerably different estimates and neither account for interstitial fluid storage and lymphatic return. We therefore developed a theoretical framework to evaluate K(f) estimation techniques by 1) comparing conventional techniques to a novel technique that includes effects of interstitial fluid storage and lymphatic return, 2) evaluating the ability of conventional techniques to reproduce K(f) from simulated gravimetric data generated by a realistic interstitial fluid balance model, 3) analyzing new data collected from rat intestine, and 4) analyzing previously reported data. These approaches revealed that the steady-state gravimetric technique yields estimates that are not directly related to K(f) and are in some cases directly proportional to interstitial compliance. However, the transient gravimetric technique yields accurate estimates in some organs, because the typical experimental duration minimizes the effects of interstitial fluid storage and lymphatic return. Furthermore, our analytical framework reveals that the supposed requirement of tying off all draining lymphatic vessels for the transient technique is unnecessary. Finally, our numerical simulations indicate that our comprehensive technique accurately reproduces the value of K(f) in all organs, is not confounded by interstitial storage and lymphatic return, and provides corroboration of the estimate from the transient technique.

A mathematical model of intestinal oedema formation

“…10-12 mmHg Cox et al (2008) and Guyton & Guyton (2000) 12 mmHg (2000), Dongaonkar et al (2011) and Unno et al (2010) 15 mmHg (low pres. )…”

Hepatic transudation barrier properties

“…The standard equations typically used to characterize steady‐state microvascular filtration were extended to study hepatic transudation, consistent with studies of transudation from the epicardium and parietal pleura . Consequently, assumptions common to all organ‐level fluid balance studies were necessary. First, the hepatic interstitial fluid compartment was assumed to behave as a well‐mixed compartment.…”

Endothelial Protrusions in Junctional Integrity and Barrier Function

“…This method, which is popular for estimating lung edema, is a gravimetric approach based on the Starling-Landis equation, in which the rate of change in interstitial fluid volume is related to the change in microvascular pressure (Dongaonkar et al , 2011). The increase in interstitial fluid volume can be determined from measurement of the tissue wet-to-dry ratio or the increase in organ weight to a steady state (Guyton & Lindsey, 1959; Drake et al , 1980).…”

“…These methods provide a fairly simple way to evaluate fluid imbalances. However, they do rely on the assumptions that interstitial fluid pressure is constant, and neglect interstitial compliance and the potential contribution of lymphatic resistance (Dongaonkar et al , 2011). …”