Heart capillary permeability to lipid‐insoluble molecules

Abstract

2. The method used to study the exchange was the 'indicator diffusion' technique. It consists in a rapid arterial injection of a mixture containing a diffusible and a non-diffusible molecule, followed by a rapid split collection of the venous outflow, up to 30 sec. The fractional extraction, E, of the diffusible substance was obtained by comparing the relative concentrations of both tracers in injected medium and in each venous sample.3. E for [3H]water was the highest (0.90 + 0.03), and it did not vary with flow. All other molecules had values for E that decreased as flow increased.4. Capillary permeability constant, P, was estimated from PS = -F In(1-E), in which S is the surface area of exchange and F is the blood perfusion rate. To test the validity of the equation, E was measured at different blood perfusion rates. It was found that the equation did not apply at relatively low flows for the more diffusible substances. 5. The average values of P estimated for inulin, sucrose, glucose, glycerol and urea were 0x27, 0-8, 1D0, 1-5 and 3-1 x 105 (cm/sec), respectively. The ratio P/D (in which D is the free diffusion in water constant) was the same for all these substances. This can be interpreted as showing that if pores exist in the capillary endothelium, they must be larger than 80-100 A diameter. It is concluded that the pores could actually be the intercellular slits as previously suggested by electron microscope studies. Endothelial cell participation in the exchange appears to be small except for [3H]water.

Alterations of myocardial capillary permeability by albumin in the isolated, perfused rabbit heart.

“…g-1, PS for 51Cr-EDTA and [57Co]cyanocobalamin appeared to become independent of the perfusion rate. PS for 22Na was still increasing even at the highest flows tested, and hence the best estimate ofPS was only an underestimate since flow rather than diffusion limited transcapillary exchange (Alvarez & Yudilevich, 1969;. -').…”

“…These studies have demonstrated that permeability-surface area products (PS) measured for highly diffusible solutes are influenced by the coronary blood flow (Yudilevich & Martin de Julian, 1965;Alvarez & Yudilevich, 1969; Yipintsoi, Tancredi, Richmond & Bassingthwaighte, 1970;Ziegler & Goresky, 1971;Laughlin & Diana, 1975;Guller, Yipintsoi, Orvis & Bassingthwaighte, 1975). However, as originally shown by Alvarez & Yudilevich (1969) myocardial PS estimates for less diffusible solutes tended to become independent of flow at high perfusion rates. A fact often overlooked is that PS measurements only define the true capillary diffusion capacity of an organ if there is no flow limitation of transcapillary solute exchange (see review of Crone & Christensen, 1979).…”

“…sec1) in the rabbit heart does not appear to differ significantly from Pinunn (0 27-0{36 x 10-5 cm . sec') measurements in dog hearts (Alvarez & Yudilevich, 1969;Laughlin & Diana, 1975).…”

Noninvasive Quantitative Assessment of Pulmonary Blood Flow with 18F-FDG PET

“…Although the distribution of water and, hence, 15 O-H 2 O has repeatedly been shown to be flow limited rather than diffusion limited, even at high blood flow (28,29), the tracer permeabilitysurface area product for glucose and, hence, 18 F-FDG is substantially lower than that of water (29,30). The latter data suggest that 18 F-FDG is a diffusion-limited tracer, even at relatively low blood flow (20-40 mLÁmin 21 Á100 g 21 ) (29). Furthermore, because PBF may exceed 2,000 mLÁmin 21 Á100 g 21 , it may largely overcome the blood flow of other organs (23,24), whereas myocardial blood flow at exercise in humans amounts to 200-250 mLÁmin 21 Á100 g 21 (31).…”

An integrative model of coupled water and solute exchange in the heart

“…Using Crone's method for estimating the product of capillary permeability and surface area (PS), Alvarez and Yudilevich (3) observed that the ratios of solute permeability to free diffusion coefficient (P/D) were very nearly the same for urea, glycerol, glucose, sucrose, and inulin. This fact was confirmed by other researchers using the same technique (10,45), and refinements of the methods for tracer analysis have not changed the observation (9).…”