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P D Watson

Publications and source records attributed to P D Watson.

18 recordsLinked to original sources

Transport parameter estimation from lymph measurements and the Patlak equation.

Two methods of estimating protein transport parameters for plasma-to-lymph transport data are presented. Both use IBM-compatible computers to obtain least-squares parameters for the solvent drag reflection coefficient and the permeability-surface area product using the Patlak equation. A matrix search approach is described, and the speed and convenience of this are compared with a commercially available gradient method. The results from both of these methods were different from those of a method reported by Reed, Townsley, and Taylor [Am. J. Physiol. 257 (Heart Circ. Physiol. 26): H1037-H1041, 1989]. It is shown that the Reed et al. method contains a systematic error. It is also shown that diffusion always plays an important role for transmembrane transport at the exit end of a membrane channel under all conditions of lymph flow rate and that the statement that diffusion becomes zero at high lymph flow rate depends on a mathematical definition of diffusion.

Animals

Microvascular permeability transients due to histamine in cat limb.

We measured the protein solvent drag reflection coefficient (sigma f) and the capillary filtration coefficient (CFC) before and after adding 1 or 10 microM histamine to the recirculating fluid (20% plasma, remainder albumin and electrolytes, hematocrit of 1-2%) perfusing the isolated cat hindlimb preparation. Transient sigma f measurements were made at 3- to 15-min intervals after histamine using a modification of the steady-state integral-mass balance method. CFC measurements were made at approximately 10-min intervals after histamine in separate experiments. A 1 microM dose of histamine caused sigma f to fall from approximately 0.8 to approximately 0.3 in 2-3 min; sigma f then returned to control in approximately 20 min. CFC response to the 1 microM histamine was a peak increase approximately 2 times control and a return to control in approximately 40 min. A 10 microM dose caused sigma f to fall rapidly to near zero. In general, recovery was much slower than for the 1 microM dose, most of the limbs not returning to control by 40 min after histamine. CFC measurements after 10 microM histamine increased only approximately 5 times control even though sigma f was near zero at the same time. CFC remained above control for approximately 60 min. The combined sigma f and CFC data could be described quantitatively if histamine simultaneously opened both short-lived large gaps (approximately 1,000 A) and a longer-lived pathway that sieved protein like the normal pathway and if the numbers of channels of each pathway closed exponentially with 4- and 15-min time constants, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Filtration coefficient in cat hindlimb using protein concentration changes.

The maximum value of capillary filtration coefficient (CFC) in maximally vasodilated cat skeletal muscle is disputed. It was hypothesized that the wide range of reported values was caused by the inability of gravimetric and volumetric measurements of tissue volume to separate transcapillary filtration from vascular volume changes. Consequently, we developed a method of measuring filtration rates from changes in venous protein concentration using Evan's blue-labeled albumin in the isolated hindlimb (pentobarbital sodium anesthesia). The filtration coefficient (PFFC) calculated from these filtration rates after a step in venous pressure should not be influenced by vascular volume changes. When the perfusate flow rate through the hindlimb was greater than 15 ml.min-1.100 g muscle-1, PFFC was 0.0085 +/- 0.0015 (SD, n = 8) ml.min-1.mmHg-1.100 g muscle-1. PFFC was observed to be unvarying from 1 to 12 min after the venous pressure elevation, in contrast to CFC values, which fall during the same period. It is argued that the difference between CFC and PFFC values is caused by vascular volume changes.

Algorithms

Measurement of osmotic reflection coefficient for small molecules in cat hindlimbs.

Capillary osmotic reflection coefficients (sigma) for NaCl, urea, sucrose, and raffinose were measured in the isolated, perfused cat hindlimb using the osmotic transient technique. sigma were determined from the ratio of the maximum rate of transcapillary absorption [delta Jv(max)] to the increase in the osmotic pressure (25-35 mosmol/kg H2O) in the arterial inflow (delta pi a) produced by adding one of the molecules to an albumin-electrolyte perfusate containing isoproterenol (greater than 10(-7) M). delta Jv (max) was determined from organ weight and delta pi a from perfusate osmolalities. For each molecule, the delta Jv(max)/delta pi a ratio increased monotonically with perfusate flow rates (Q) to Q greater than 100 ml.min-1.100 g-1. This ratio was independent of the size of the delta pi a. Apparent sigma values were calculated by dividing these ratios by the capillary hydraulic capacity determined in other studies. At low Q, apparent sigma was comparable to the approximately 0.1 values found by others in skeletal muscle. At the highest Q, apparent sigma for these molecules were at least 0.5. These data are consistent with at least 50% of transcapillary water flow moving through a water-exclusive pathway.

Algorithms

Effects of elevated venous pressure on capillary permeability in cat hindlimbs.

We investigated the effects of elevated venous pressure, Pv, (up to 140 mmHg) on the solvent drag reflection coefficient, sigma f, for protein and on the capillary filtration coefficient, CFC, in the isolated cat hindlimb perfused at constant flow. The perfusate contained 30% cat plasma and the remainder was a dialyzed albumin-electrolyte mixture. Cat red cells were added to a hematocrit of approximately 2%. sigma f was measured from the changes in hematocrit and plasma protein concentration (Integral-Mass Balance method) resulting from the fluid filtration caused by the Pv elevation. CFC was measured from the slope of the limb weight recording 2-4 min after the Pv elevation. sigma f decreased linearly from 0.807 (Pv less than 50 mmHg) to approximately 0.2 at 140 mmHg. CFC increased linearly from 0.0086 ml.min-1.mmHg-1.100 g-1 to about 0.04 over the same pressure range. A weight-independent filtration coefficient calculated from the change in hematocrit and a measurement of the initial perfusate volume gave comparable results, except at the very highest of pressures, where this coefficient was sometimes 20-40% less than CFC. Successive sigma f determinations at Pv at about 40 mmHg did not return to control after an initial measurement in which Pv was approximately 110 mmHg. Pore-theory analysis of the data suggests that the elevated Pv causes large pores to open as opposed to the stretching of small pores. Also, these large pores may remain open for a period of hours.

Animals

Blood and isoproterenol reduce capillary permeability in cat hindlimb.

In an earlier study, plasma was observed to counteract the permeability-increasing effects of blood-free perfusion when papaverine was present in the perfusate. To determine if this plasma effect was still present in the absence of papaverine, cat hindlimbs were perfused with a blood-free albumin-electrolyte solution, and capillary filtration coefficient (CFC) was measured. These data were compared with CFC values obtained when blood, plasma, or isoproterenol were present in the albumin perfusate. In separate groups of animals, CFC was observed to be 0.017 +/- 0.006 (SD, n = 26) ml X min-1 X mmHg-1 X 100 g muscle-1 during blood-free albumin perfusion, 0.012 +/- 0.002 (n = 24) when blood was present, 0.014 +/- 0.003 when isoproterenol was present, and 0.010 +/- 0.002 (n = 33) when both blood and isoproterenol were present. In a separate study, it was observed that 1) isoproterenol could reduce CFC by 11% when added to blood-free perfusate, 2) plasma had a similar but smaller and more variable effect than isoproterenol, 3) plasma had no consistent effect on CFC when added to a blood-free albumin perfusate containing isoproterenol, and 4) blood could reduce CFC significantly (P less than 0.005), from 0.014 +/- 0.003 to 0.0094 +/- 0.002 (n = 7), when added to a blood-free albumin perfusate containing isoproterenol. It was concluded that, in the absence of papaverine, the principal CFC-reducing effect of blood lay in the cell fraction and that isoproterenol had a small CFC-reducing effect under blood-free conditions. This result contrasts with the plasma effect reported earlier.

Animals

Integral-mass balance method for determination of solvent drag reflection coefficient.

We have developed the integral-mass balance (IMB) method to measure the solvent drag reflection coefficient (sigma f) for transcapillary macromolecular transport in skeletal muscle and other organs. Of course, sigma f is calculated from the cumulative amounts of water and macromolecule that move convectively across the microvascular membrane as determined from changes in hematocrit and plasma macromolecule concentration over a period of fluid filtration. We have investigated the effects of both theoretical and experimental factors that affect the validity and accuracy of the method. The effect of the following factors on sigma f determination by the IMB method were explored: low Peclet number; random-measurement errors; and systematic errors due to vascular leakage, hemolysis of red blood cells, evaporation, and osmolality changes. We found that all of these factors produced overestimations of sigma f, but their effects could be corrected. Also, appropriate experimental design could minimize these effects. Experiments using the IMB method in the isolated, perfused cat hindlimb preparation to determine sigma f for albumin and plasma proteins resulted in mean values of 0.82 +/- 0.08 (SD) (n = 7) and 0.83 +/- 0.02 (n = 4), respectively.

Animals

Dextran and capillary filtration coefficient in cat hindlimb.

To investigate the possible mechanisms through which dextran modifies capillary filtration coefficient (CFC), the effects of perfusion with a protein-free dextran solution were compared with those of perfusion with a Ringerlike solution. With the use of the isolated cat hindlimb, CFC was measured during perfusion at constant flow with three solutions, a control blood-albumin mixture, a Ringerlike solution called dialysate, and 3.7 g/dl dextran dissolved in dialysate. The solutions were warmed to 37-38 degrees C, bubbled with 95% O2-5% CO2, and contained 0.015 g/dl or more papaverine. CFC was calculated from the rate of limb weight gain following a step increase in venous pressure. Dextran perfusion increased CFC to 2.0 +/- 0.2 (SD, n = 8) times control, which was significantly less (P less than 0.001) than 3.1 +/- 0.6 (n = 8) times control previously reported for dialysate perfusion. The difference between the measured viscosity of dextran (1.35 cP) and dialysate (0.72) could account for this reduction. However, when a dialysate perfusion followed a dextran perfusion, CFC only increased to 2.3 +/- 0.4 (n = 8) times control. This value is also significantly less (P less than 0.01) than 3.1. This observation suggests 1) that dextran is retained within the transcapillary channel and 2) that dextran reduces CFC mainly by partially blocking the transcapillary channel rather than by increasing viscosity.

Animals

Effect of temperature on transcapillary water movement in isolated cat hindlimb.

Capillary filtration coefficient (CFC) was measured in the isolated cat hindlimb preparation, perfused at 20 ml X min-1 X 100 g muscle-1 with a perfusate containing 6 g/dl albumin and normal electrolyte concentrations, to which were added 50 ml of the cat's blood and 6 micrograms of the vasodilator isoproterenol. CFC was determined three to six times in an initial control period during which the tissue temperature (measured by a 5-mm disk thermistor implanted in a thigh muscle) was controlled near 37 degrees C. Tissue temperature was decreased to 5-10 degrees C by lowering perfusate and ambient air temperatures. About 50 min were required for tissue temperature equilibration. CFC was measured at low temperature and then again at 37 degrees C. For nine experiments, the ratio of CFC at low temperature to that in the 37 degrees C control periods averaged 87% of the ratio of water viscosity at 37 degrees C to that at low temperature. The activation energy for water calculated from these data was 5.0 kcal/mol. These results may be explained by all transcapillary water flow moving by diffusion through narrow pores or by about 90% moving by convection, with the remainder going through a lipid pathway. However, the results may be entirely due to a direct effect of temperature on the geometry of the transcapillary pathway for water movement.

Animals

Control of transcapillary water movement by vasoactive agents.

Experiments were performed to demonstrate that papaverine can increase capillary filtration coefficient, CFC, and to investigate whether this increase could be reversed by isoproterenol, norepinephrine and plasma. The study used the isolated cat hindlimb, perfused at constant flow with a recirculated blood-albumin solution. It was observed that papaverine increased CFC in a dose-dependent manner, and that this effect could be reversed by isoproterenol and norepinephrine. Norepinephrine reduced CFC even in the presence of phentolamine. Plasma, previously shown to reduce CFC when papaverine was present, was shown to have no such effect when papaverine was absent. It is argued that the CFC changes are best explained by changes in the hydraulic conductivity of the exchange vessels, rather than through changes in the perfused surface area, and that the CFC changes are similar to the permeability changes caused by inflammatory mediators and catecholamines observed by others.

Animals

Suggested criteria for vision classification on the AAMD adaptive behavior scale.

The AAMD Adaptive Behavior Scale for Children and Adults is an instrument designed to assess the degree to which an individual has adapted to his environment. While one item of the scale refers to vision, no criteria have been established to indicate degree of vision impairment on such a scale. Such criteria are suggested including a supplement which describes other visual functions. A method of assessing visual acuity in non-verbal or uncooperative patients is given.

Adaptation, Psychological