VARIATIONS IN FLOW DYNAMICS IN CEREBRAL CAPILLARY BEDS

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The rate of local cerebral blood flow (LCBF) varies six-fold or more among CNS structures in the awake conditions. The possible causes of the dissimilarities and alterations in LCBF include differences in the volume of perfused capillaries per unit tissue volume and variations in the linear velocity of blood flow within the capillaries. We propose to investigate these variations in LCBF in rats under contol and LCBF altering conditions and hypothesize that: 1) these dissimilarities in LCBF are mainly the result of differences in the local volumes of perfused capillaries; 2) the percentage of perfused capillaries within local capillary beds normally varies among CNS structures and this percentage changes when LCBF is altered; and 3) the modulation of LCBF involves increasing ("recruiting") and decreasing ("retiring") the percentage of perfused capillaries when LCBF is moderately altered but involves not only capillary recruitment-retirement but also changes in linear flow velocity of intracapillary blood when LCBF is markedly altered. To test these hypotheses, LCBF will be altered in four groups of experimental rates by exposing them to gas mixtures of varying 02 and C02 contentt and in one group by pentobarbital anesthesia. The following parameters will be measured in control rats and the five experimental groups using radiotracer distribution techniques, quantitative autoradiography, image analysis and light micrographic morphometry: 1) LCBF, 2) local cerebral glucose utilization; 3) local volumes of perfused microvessels (perfused "capillary" volume); 4) local blood-brain transfer constants of four compounds; 5) mean local capillary transit time; 6) mean local capillary length; 7) mean linear velocity of intracapillary blood flow (linear flow velocity); 8) local capillary volume, and 9) percentage of perfused "capillaries." If the variations in LCBF are mainly due to differences in the local volume of perfused capillaries (first hypotheses), then there should be a close correlation between our experimentally determined values of LCBF and perfused "capillary" volume, and also between our estimates of LCBF and local blood-brain transfer constants, which are functions of perfused capillary surface area; moreover linear flow velocity should be similar in all brain areas. If changing LCBF alters the percentage of perfused capillaries (second hypotheses), then the percentages of perfused "capillaries" assessed from our data should shift in parallel with LCBF changes. Comparisons of the changes in LCBF with the variations in perfused "capillary" volume, linear flow velocity, and percentage of perfused "capillaries" will indicate the relative importance of each of these modes of varying blood flow with small and large shifts in LCBF and provide the testing of our third hypothesis.