Capillary filtration coeficient, CFC, measures the filtration ability of a whole organ capillary bed. The accepted view for skeletal muscle is that CFC is controlled mainly by changes in the tone of precapilary smooth muscle, which is regulated in turn by the local metabolic environment. However, many investigators, including ourselves, cannot reproduce some or all of the findings which led to the metabolic control hypothesis. It is proposed to investigate the causes of the divergence in results and/or interpretation using the isolated perfused cat hindlimb. The principal experimental differences are 1) whole blood vs. low hematocrit perfusates, 2) the presence or absence of the animal in the perfusion circuit, 3) constant pressure vs. constant flow perfusion, and, perhaps the most important, 4) the method of determining CFC. CFC is determined by calculating a rate of weight increase at some variable, and frequently undefined, time following a step increase in venous pressure. But, as the rate of weight increase falls with time (for reasons which are mainly unknown in well-hydrated, maximally-vasodilated skeletal muscle), the period chosen in which to measure the rate of weight increase is critical. In addition to studying the factors listed above, it is proposed to investigate why the rate of weight increase varies with time using the same preparation. By the use of perfusates with differing protein concentrations and other factors, the possible role of protein in the fall of the rate of weight increase will be studied. In addition, as one group has proposed that the decreasing rate is caused by a low compliance tissue compartment, this hypothesis will be tested by using different rates of filtration and different hydration states with low protein perfusates and stop-flow techniques. These proposed experiments will resolve many of the differences described above, and will significantly improve our understanding of the nature of filtration at the capillary wall, a very basic and illunderstood process in microcirculatory physiology. Such knowledge will aid the treatment of such disorders as edema and circulatory shock.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL024314-09
Application #
3337588
Study Section
Cardiovascular and Pulmonary Research B Study Section (CVB)
Project Start
1979-08-01
Project End
1989-06-30
Budget Start
1987-09-15
Budget End
1989-06-30
Support Year
9
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of South Carolina at Columbia
Department
Type
Schools of Medicine
DUNS #
111310249
City
Columbia
State
SC
Country
United States
Zip Code
29208
Watson, P D (1995) Permeability of cat skeletal muscle capillaries to small solutes. Am J Physiol 268:H184-93
Watson, P D; Garner, R P; Ward, D S (1993) Water uptake in stimulated cat skeletal muscle. Am J Physiol 264:R790-6
Hamilton, M T; Ward, D S; Watson, P D (1993) Effect of plasma osmolality on steady-state fluid shifts in perfused cat skeletal muscle. Am J Physiol 265:R1318-23
Watson, P D (1993) Sieving of electrolytes at capillary wall of cat skeletal muscle by osmotic water flow. Am J Physiol 265:H1869-74
Watson, P D; Wolf, M B (1992) Transport parameter estimation from lymph measurements and the Patlak equation. Am J Physiol 262:H293-8
Watson, P D; Wolf, M B (1989) Filtration coefficient in cat hindlimb using protein concentration changes. Am J Physiol 256:H186-94
Wolf, M B; Watson, P D; Porter, L P (1989) Effect of adenosine on capillary filtration coefficient in the isolated cat hindlimb. Microvasc Res 37:357-62
Wolf, M B; Watson, P D (1989) Measurement of osmotic reflection coefficient for small molecules in cat hindlimbs. Am J Physiol 256:H282-90
Edwards, D; Berry, J J (1987) The efficiency of simulation-based multiple comparisons. Biometrics 43:913-28
Wolf, M B; Watson, P D; Scott 2nd, D R (1987) Integral-mass balance method for determination of solvent drag reflection coefficient. Am J Physiol 253:H194-204

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