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P D Watson

Publications and source records attributed to P D Watson.

At least 37 records · Page 2Linked to original sources

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↗

Anoxia and capillary filtration coefficient in the isolated cat hindlimb.

Isolated cat hindlimbs were perfused from a reservoir with an albumin-blood mixture at a constant flow of 20 ml X min-1 X 100 g muscle-1 while alternately bubbling the perfusate with either 95% O2-5% CO2 gas mixture or a 95% N2-5% CO2 mixture for 50- to 60-min periods. Capillary filtration coefficient (CFC), vascular resistance (R), and perfusate O2 content were measured in each period. The arterial O2 content fell from fully equilibrated to 0.25 vol% during the use of N2. R fell from about 6 mmHg X min X 100 g X ml-1 during O2 bubbling to approximately 1.0 with N2. CFC averaged 0.012 +/- 0.002 ml X min-1 X mmHg-1 X 100 g muscle-1 (SD, n = 6) during the 1st O2 period, rising to 0.016 +/- 0.002 (n = 4) in the 3rd O2 period 4 h later. CFC fell by 5% (P less than 0.001) during the periods of N2 bubbling. Papaverine was present in two experiments without effect on the CFC data. It was concluded that CFC was not meaningfully influenced by vascular resistance or anoxia, a finding that is inconsistent with the concept of local metabolic control of CFC by precapillary resistance vessels.

Animals↗

Effect of plasma and red blood cells on water permeability in cat hindlimb.

Capillary filtration coefficient (CFC) was measured to investigate the effect of blood in the perfusate of an isolated, maximally vasodilated cat hindlimb. CFC was measured during perfusion with several different perfusates: a blood-albumin mixture, albumin alone, a plasma-albumin mixture, and a plasma-albumin mixture containing varying volumes of red blood cells. In some experiments the plasma was ultrafiltered to remove low-molecular-weight components. It was found that perfusion with albumin alone usually raised CFC above the level found with the blood-albumin mixture, plasma could reduce the CFC when CFC was elevated above that value obtained with the blood-albumin mixture, ultrafiltered plasma failed to reduce CFC when CFC was elevated, and the red cell content of the perfusate had no influence on CFC over the hematocrit range of 0-20% when the plasma solute concentrations were kept constant. It was concluded that the reduction of CFC by blood was caused by a small molecule (less than 10,000 mol wt) present in plasma.

Animals↗

Effects of blood-free and protein-free perfusion on CFC in the isolated cat hindlimb.

To investigate the effects of blood and protein on capillary filtration coefficient (CFC), isolated cat hindlimbs were perfused at constant flow from a reservoir containing one of three perfusates: 1) an electrolyte solution also used for dialyzing bovine serum albumin (BSA) and hence labeled dialysate, 2) dialyzed 6.5-7.0 g/100 ml BSA, labeled albumin, and 3) albumin plus cat blood, labeled control. CFC during control perfusion averaged 0.0137 +/- 0.003 (SD, n = 26) and increased slowly with time. CFCs with dialysate and albumin were 3.1 +/- 0.56 (n = 11) and 1.7 +/- 0.52 (n = 15) times control, respectively. However, the ratio in a particular experiment depended on control CFC, the ratio being low when the control CFC was low and high when control CFC was high. The data can be explained if water flow occurs through two types of transcapillary pathways, one having a hydraulic capacity constant from animal to animal and insensitive to blood and protein, the second varying in hydraulic capacity and requiring blood and protein for its normal values.

Animals↗

Colloid osmotic pressure changes in isolated isogravimetric cat hindlimb.

The development of osmotic pressure, following the addition of bovine serum albumin (BSA) to the perfusate, was measured in an isogravimetric cat hindlimb fully dilated with papaverine. The changes in colloid osmotic pressure were followed by recording the changes in venous pressure (PVI) necessary to maintain constant weight. Capillary filtration coefficient (CFC) and vascular compliances were calculated from weight changes following steps in venous pressure. Venous BSA levels reached arterial within 1 min, and PVI reached a new steady state 13.1 +/- 0.9 (SE) min (n = 9 in 6 limbs) after adding BSA. This apparent delay in the development of the osmotic pressure agrees with earlier reports. However, when the BSA was added under constant venous pressure conditions, the fluid reabsorption reached its maximum rate within 1.5 min. The data suggest that the BSA is osmotically fully effective after the capillary washin. The slowness of the rise of PVI in the isogravimetric state is probably caused by the time necessary to absorb sufficient fluid from the interstitium to raise the capillary pressure to a level that balances the increased oncotic pressure. A mathematical model supports this explanation.

Animals↗

Early kinetics of large molecule transport between plasma and lymph in dogs.

Using a mathematical model in which the interstitial space resembled a gel filtration column, Watson and Grodins (Microvasc. Res. 16: 19-41, 1978) predicted that molecules larger than serum albumin should have an early approach to steady state in lymph faster than that of serum albumin. This hypothesis was tested in dogs anesthetized with pentobarbital sodium by use of radiolabeled albumin and fibrinogen and a fluorescent dextran and by collecting lymph from cannulas in the prepopliteal lymphatics of the hind paws. The steady-state lymph-plasma concentration ratios (R), measured chemically, were 0.24 +/- 0.02 (SE, n = 16) for albumin and 0.040 +/- 0.004 (n = 16) for fibrinogen. In 5 h, albumin and fibrinogen tracers had reached approximatly 25 and 50% of their steady-state levels, respectively. The dextran (mol wt 1.5 x 10(5)) behaved like fibrinogen. The data support the hypothesis that the interstitium has nonrestricting pathways, and that there are gel regions that have a low permeability to very large molecules.

Animals↗

Exclusion of plasma proteins in interstitium of tissues from the dog hind paw.

Exclusion of plasma albumin and fibrinogen from portions of the extravascular sucrose space in tissues of the hind paw of anesthetized dogs was studied by use of radioactive traces. Thirty hours after a bolus injection of the labeled proteins, tracer concentrations were measured in plasma, prenodal popliteal lymph, and samples of hind paw skin, tendon, muscle, and toe pad. In a few experiments, constant plasma levels of tracer sucrose were maintained for 2 h before terminal sampling. In all experiments a vascular volume marker was given 15 min before termination. A linear correlation was found between the amounts of extravascular protein tracers in the tissue samples and their concentrations in lymph from the same paw, as would be expected if their actual interstitial concentrations were closely related to their lymph concentrations. For albumin, the extravascular distribution volume calculated at lymph concentration was less than the sucrose space for all tissues except toe pad. For fibrinogen, the extravascular distribution volume was less than albumin and sucrose for all tissues except skin. Differences in pattern and degree of exclusion may reflect the differences in interstitial gel-phase composition and structure.

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↗