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Biomedical subjects

R K Reed

Publications and source records attributed to R K Reed.

At least 109 records · Page 6Linked to original sources
PubMed1990

Increased negativity of interstitial fluid pressure contributes to development of oedema in rat skin following application of xylene.

Intradermal interstitial fluid pressure (Pi) has been studied in rat skin during formation of inflammatory oedema caused by application of xylene. Pi was measured with sharpened micropipettes connected to a servocontrolled counter-pressure system. Control Pi averaged -1.3 +/- 0.6 (SD) mmHg. Following xylene application Pi decreased to -5.0 mmHg after 5 min and then increased to stabilize at about 0 mmHg at 45-60 min and later. When the transvascular fluid shifts accompanying the inflammatory reaction were prevented by inducing circulatory arrest prior to xylene application, Pi fell to -7.5 mmHg within 5 min and remained at this level throughout the observation period of 90 min. Aprotinin in large doses (80,000 KIE kg-1) before xylene application reduced the fall in Pi, whereas indomethacin had no effect. The increased negativity in Pi will add directly to a normal transcapillary net filtration pressure of about 0.5 mmHg, resulting in a 10- to 20-fold increase in this pressure. The present experiments therefore suggest that the interstitium plays an active role in oedema formation in the initial phase of xylene-induced inflammation in rat skin through the development of an increased negativity of Pi.

Animals↗
PubMed1990

Removal rate of [3H]hyaluronan injected subcutaneously in rabbits.

Hyaluronan is an important constituent of the extracellular matrix in skin, and recent studies suggest that there is a pool of easily removable ("free") hyaluronan drained by lymph. The removal rate of free hyaluronan in skin was measured from the elimination of [3H]hyaluronan, injected subcutaneously in 13 rabbits. The removal of radioactivity was determined from appearance of 3H in plasma. During the first 24 h after injection, 10-87% of the tracer entered blood, less in injectates with high concentrations of hyaluronan. The removal was monoexponential with a half-life of 0.5-1 day when concentration of hyaluronan was 5 mg/ml or less. When hyaluronan concentration was 10 mg/ml or higher, the removal was slow for about 24 h and then became similar to that in experiments with low hyaluronan concentration. Free hyaluronan at physiological concentrations is thus turned over with the same rate as serum albumin, supporting the concept that hyaluronan is removed essentially by lymph flow to be degraded in lymph nodes and liver.

Animals↗
PubMed1990

Hyaluronan in prenodal lymph from skin: changes with lymph flow.

Hyaluronan, an important structural component of the interstitial matrix in skin, is found in lymph to be subsequently degraded in lymph nodes and liver. Hyaluronan concentration and flux were measured in prenodal lymph from the hindpaw in six pentobarbital-anesthetized mongrel dogs at normal and increased transvascular fluid flux. Lymph flow and hyaluronan concentration in control averaged 16.3 +/- 15.0 (SD) microliters/min (range 6.3-46.5) and 6.16 +/- 3.78 micrograms/ml, respectively. Lymph flow was increased stepwise by raising venous pressure, and measurements were performed at each step after three consecutive and identical measurements of lymph flow and protein concentration taken 15 min apart. Hyaluronan concentration was unchanged until venous pressure was raised above 20 mmHg and then gradually fell to an average of 4.8 +/- 2.67 micrograms/ml at venous pressures around 40 mmHg. The lymphatic hyaluronan flux averaged 0.085 +/- 0.034 micrograms/min in control and 0.28 +/- 0.14 micrograms/min at the highest flows (4.3 times control), draining 2% and 10% of the total interstitial hyaluronan in the tissue in 24 h, respectively. The results suggest that at least part of the hyaluronan in skin is loosely bound and easily removed via lymph.

Animals↗
PubMed1989

Mechanisms behind increased dermal imbibition pressure in acute burn edema.

We have measured tissue pressures in excised rat skin subjected to in vitro burn injury and investigated the mechanisms behind the increased imbibition (swelling) pressure in burned skin. Skin pieces wrapped in aluminum paper were immersed into boiling hot water for 10, 30, or 60 s. Dermal imbibition pressure was measured with micropipettes and tissue osmometry as interstitial fluid hydrostatic pressure (Pif) and/or interstitial fluid colloid osmotic pressure (COPif). COPif was also measured in interstitial fluid sampled with intradermal wicks. Control values of Pif (micropipettes) and of COPif (wick fluid) averaged -1.5 mmHg and -17.5 mmHg, respectively. An increase in imbibition pressure was seen after thermal injury. After 10 s of heat exposure, the imbibition pressure gain was mainly due to a strongly negative hydrostatic pressure (Pif mean value -33.3 mmHg). Pif became slightly positive and COPif increasingly negative after longer exposure (mean Pif 0.3 and mean COPif -133 mmHg after 60-s exposure). Collagen degradation and water solubility increased with extension of the heat exposure time. Thermal degradation of collagen seems to be the main mechanism responsible for the generation of increased imbibition pressure.

Animals↗
PubMed1989

Estimation of capillary reflection coefficients and unique PS products in dog paw.

Lymphatic protein flux (Js) obtained in canine hindpaws at low lymph flows were used to determine the capillary osmotic reflection coefficients (sigma d) and unique permeability surface area (PS) products for total proteins, albumin, immunoglobulin (Ig)G, and IgM. This new analysis is based on the phenomenon that when maximal diffusion occurs across the capillary membrane, the Peclet number [x = Jv(1 - sigma d)/PS] attains a unique value defined only by sigma d. The diffusive flux is maximal when the relationship between protein flux and transcapillary fluid flux (Jv) changes from a curvilinear to a linear relationship. The slope of the linear portion of this protein flux relationship was used to determine sigma d as (1 - sigma d) = delta Js/(delta JvCp), where Cp is the plasma protein concentration. With the use of sigma d, the Jv at which the maximal diffusion occurred, and the corresponding Peclet number, a unique value is obtained for the PS product. Experiments performed using lymph from canine hindpaws (n = 6) yielded sigma d's (mean +/- SD) of 0.91 +/- 0.03, 0.83 +/- 0.11, 0.96 +/- 0.03, and virtually 1 for total protein, albumin, IgG, and IgM, respectively. The corresponding PS products for total protein, albumin, and IgG were 25.0 +/- 13.2, 28.4 +/- 6.6, and 14.0 +/- 7.9 microliters.min-1.100 g-1, respectively; PS for IgM was almost zero.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Interstitial exclusion of albumin in rat dermis and subcutis in over- and dehydration.

We have estimated exclusion of albumin from the interstitial matrix in rats based on measurement of albumin concentration in interstitial fluid, interstitial fluid volume (IFV), and interstitial albumin mass. Measurements were performed separately in dermis and subcutis during control, overhydration (saline infusion corresponding to 10% of body weight), and dehydration. Exclusion during control was 1.03 (SD = 0.47; n = 7 rats) and 0.85 (SD = 0.21; n = 7 rats) ml/g fat-free dry wt in subcutis and dermis, respectively. This corresponded to 44.1 and 57.8% of IFV, respectively. Collagen and hyaluronan were responsible for two-thirds and one-third of the exclusion, respectively. During overhydration the increase in albumin available volume was 70% of the increase in IFV. Both the collagen and the hyaluronan excluded compartment of the excluded volume changed when altering IFV. These data suggest that the colloid osmotic pressure in the albumin available compartment can change the volume of both the collagen and hyaluronan compartments of the excluded volume. The following changes in composition of the interstitial matrix were observed: albumin mass in subcutis decreased by 20% during dehydration and increased by 30% during overhydration, and overhydration reduced hyaluronan content by 20% in subcutis.

Animals↗
PubMed1989

Microvascular exchange and interstitial volume regulation in the rat: implications of the model.

The present work uses and extends a dynamic mathematical model [J. L. Bert, B. D. Bowen, and R. K. Reed. Am. J. Physiol. 254 (Heart Circ. Physiol. 23): H384-H399, 1988] to investigate microvascular exchange and interstitial fluid volume regulation in the rat. Alternative concepts of transcapillary exchange as well as other parametric changes were incorporated into the model. In all cases, predictions resulting from these changes did not describe the available experimental information as well as the original model. A sensitivity analysis of the model showed the microvascular exchange system to be well regulated near its normal steady-state conditions through passive readjustment of the forces participating in the volume regulation. The transient rates of fluid and protein exchange were studied in order to determine the mechanisms inherent in the model that lead to fluid volume regulation during episodes of increased venous pressure and hypoproteinemia. In addition to interstitial compliance, lymph flow characteristics, and washdown of interstitial proteins, it was found that the magnitude and direction of reabsorption played an important role in the regulation process. Edema was always associated with a permanent reversal of the reabsorptive flow.

Animals↗
PubMed1989

Microvascular exchange during burn injury: II. Formulation and validation of a mathematical model.

A mathematical model of microvascular exchange in the rat following a burn injury was developed by extending an existing model of normal microvascular exchange to include perturbations characteristic of burn injuries without fluid resuscitation. The changes anticipated for small (10% body surface area) and large (40% body surface area) burns are incorporated systematically into the model until there is no improvement in the statistical fit of the simulation predictions with the experimental data of Lund and Reed (Circulatory Shock 20:91-104, 1986). The "best fit" perturbations for the small burn include the experimentally measured changes in mean arterial pressure and injured tissue pressure as well as changes to plasma protein and fluid transport coefficients in the injured tissue. The larger burn "best fit" simulation required changes to the plasma protein transport coefficients in the intact tissues as well as all of the changes listed above. The simulation results are compared with the available experimental information on burn injuries as well as with the specific data of Lund and Reed (Circulatory Shock 20:91-104, 1986).

Animals↗
PubMed1989

Microvascular exchange during burn injury: III. Implications of the model.

The present work investigates the implications of the predictions of a dynamic mathematical model of microvascular exchange following a nonresuscitated burn injury in a rat (Bert et al.: Circulatory Shock 28:199-219, 1989). Transport coefficients, transmicrovascular pressures, and the resultant fluid and protein fluxes were examined in order to assess their quantitative importance to the dynamic behavior of small (10% body surface area) and large (40% body surface area) burns. Edema accumulation in the injured tissue is dependent not only on events occurring in that tissue but is influenced strongly by interaction with the plasma and the noninjured tissue compartments.

Animals↗
PubMed1988

Transcapillary albumin extravasation in rat skin and skeletal muscle: effect of increased venous pressure.

Plasma-to-tissue transport of radioactively labelled albumin has been used to study the effect of increased venous pressure on transcapillary albumin transport. Venous pressure was increased by inflating a balloon catheter in the inferior caval vein. Plasma-to-tissue transport of albumin was taken as the extravascular distribution space (EValb) for 125I-labelled human serum albumin (I-HSA) after 1 h. Venous pressure was increased from 2 to 20 mmHg in the experimental group. Interstitial fluid volume (IFV) was measured as the extravascular distribution space for 51Cr-EDTA. In control EValb was 9.24 X 10(-3) ml g-1 d. wt (SD = 1.28, n = 8) and 3.67 X 10(-3) ml g-1 d.wt (SD = 0.94, n = 8) in skin and skeletal muscle, respectively. Increasing venous pressure raised EValb and IFV in skin and skeletal muscle, but the increase in EValb was about 3 and 5% of the rise in IFV, resulting in capillary reflection coefficients for albumin of 0.94 in skin and 0.98 in skeletal muscle. The low transcapillary albumin transport relative to water transport is compatible with a two-pore model of transcapillary exchange where large pores (250 A) accounts for less than 5.5 and 2.5% of the total capillary filtrate of fluid in skin and skeletal muscle, respectively.

Animals↗
PubMed1988

Hyaluronan in the rat with special reference to the skin.

The total hyaluronan content has been determined in rats. The animals were frozen and sectioned in a cryostat before digestion with papain and pronase. The hyaluronan content was determined by a specific radioassay and it was found that 250 g rats contained 40-60 mg of the polysaccharide. The recovery from the preparation procedure was close to 100%, as determined from tracer experiments. More than half of the hyaluronan was found in skin, approximately one quarter in the skeleton and supporting structures and less than one tenth in skeletal muscle. Based on calculated lymph flow and lymph concentration of hyaluronan, it seems that a significant fraction of the total hyaluronan in skin (greater than 1%) is removed via the lymphatics in a 24 h period. An attempt was made to isolate undegraded hyaluronan from rat skin by gentle methods giving full recovery in order to estimate the molecular weight of the polysaccharide. Hyaluronan was recovered quantitatively, but as determined from added tracer, it had been degraded. Correction for the estimated degradation gave a molecular weight of several millions for the endogenous hyaluronan.

Animals↗
PubMed1988

Microvascular exchange and interstitial volume regulation in the rat: model validation.

A dynamic mathematical model is formulated and used to describe the distribution and transport of fluid and plasma proteins between the circulation, interstitial space of skin and muscle, and the lymphatics in the rat. Two descriptions of transcapillary exchange are investigated: a homoporous "Starling model" and a heteroporous "plasma leak model." Parameters used in the two hypothetical transport mechanisms are determined based on statistical fitting procedures between simulation predictions and selected experimental data. These data consist of interstitial fluid volume and colloid osmotic pressure measurements as a function of venous pressure for muscle and interstitial colloid osmotic pressure vs. venous pressure for skin. The values determined for the transport parameters compare well with data in the literature. The fully determined model is used to simulate steady-state conditions of hypoproteinemia, overhydration, and dehydration, as well as the dynamic response to changes in venous pressure and intravascularly administered protein tracers. Comparisons between the simulation predictions and experimental data for these various perturbations are made. The plasma leak model appears to provide a better description of microvascular exchange.

Algorithms↗
PubMed1988

Acute postburn edema: role of strongly negative interstitial fluid pressure.

Interstitial fluid hydrostatic pressure (Pif) was measured with micropipettes during the acute edema generation that followed thermal skin injury in rats. Intradermal Pif was reduced from normal level of -1 mmHg to very negative values after thermal injury. The strongly negative Pif reflects a tissue imbibition pressure created by the thermal injury. The magnitude and duration of this pressure was dependent on the extent of the injury and the availability of fluid. After in vivo injury to 10 and 40% of the total body surface area (TBSA), mean intradermal Pif was temporarily reduced to -20 and -31 mmHg, respectively. Intravenous fluid infusion resulted in a rapid return of Pif to slightly positive values. Fluid available for transfer from the circulation was reduced by inducing the injury after killing the animal (postmortem injury) and even more by the subcutaneous insertion of a plastic barrier: this led to more pronounced reductions in Pif to average minimum values of -95 and -135 mmHg, respectively. Our data show that increased tissue imbibition pressure and increased net filtration pressure (tissue mechanisms) are responsible for a major part of the acute fluid shifts into thermally injured skin. Vascular mechanisms (permeability changes and intravascular pressure) are involved in the postburn edema development but are clearly less important than hitherto believed.

Animals↗
PubMed1987

Transcapillary colloid osmotic pressures in injured and non-injured skin of seriously burned patients.

Thermal skin injury is accompanied by rapid and excessive oedema formation implicating a dramatic increase in the transcapillary fluid transport. In order to clarify the pressure changes occurring across the microvasculature after a thermal skin injury we have measured colloid osmotic pressures (COP) in interstitial fluid (COPi) of injured and non-injured skin as well as in plasma (COPp) from patients suffering major cutaneous burns. Interstitial fluid was collected with a wick-technique and analysed for COP. Measurements were performed as early as 6 h and continued until 56 h after injury. A severe hypoproteinaemia occurred in all patients with a marked reduction in COPp down to about 10 mmHg. Up to 12h post-burn we found a higher COPi in injured skin than in plasma. The first measurement of COPp averaged 9.8 mmHg as compared to an average COPi of 11.1 and 9.3 mmHg in injured and non-injured skin respectively. Measurements performed later than 12h showed a return of the transcapillary COP gradient towards the normal direction (COPp greater than COPi). The gradient was considerably less than in a normal situation. Based on the present observations of transcapillary COP it is suggested that colloids should be withheld until the transcapillary COP gradient returns to the normal direction.

Adult↗
PubMed1987

Measurement of interstitial fluid pressure in dogs: evaluation of methods.

Interstitial fluid pressure (IFP) was measured with two acute (micropipettes and wick-in-needle) and two chronic methods (perforated and porous capsules) in dog skin/subcutis. In control conditions all techniques gave similar mean pressures, approximately -2 mmHg. Overhydration induced by intravenous Ringer infusion, 10% of body wt, caused two to three times greater increase in pressure recorded with chronic than with acute methods but 2 h after the end of the infusion all methods gave similar pressures. An almost opposite pattern was observed during dehydration induced by peritoneal dialysis with hypertonic glucose. The fall in pressure recorded with the perforated capsule exceeded that of the porous capsule, both exceeding the pressure reduction measured with the acute methods by a factor of 2-5. The difference between pressures measured with both acute methods and the perforated capsule increased in the 90 min following dialysis. Acute overhydration or dehydration as well as aspiration from or infusion into perforated capsules caused a pressure gradient between lumen, capsule wall, and surrounding skin. We propose that the transient pressure differences recorded by acute vs. chronic methods during changes in hydration result from different physical properties of the capsule lining compared with that of the surrounding skin, in addition to a possible osmometer effect of the capsule lining.

Animals↗
PubMed1987

Volume-pressure relationship (compliance) of interstitium in dog skin and muscle.

The relationship between changes in interstitial fluid volume (IFV) and pressure (IFP) during over- and dehydration was estimated in hindlimb skin and skeletal muscle of 17 dogs. IFV was measured as the extravascular distribution volume of 51Cr-EDTA after nephrectomy and IFP with micropipettes, wick-in-needle technique (WIN), and perforated capsules. Control IFP (micropipettes) averaged -1.7 +/- 0.5 (n = 17) and 0.0 +/- 1.0 mmHg (SD; n = 17) in skin and muscle, respectively, not different from corresponding WIN and capsule pressures in subcutis. Control IFV was 0.93 +/- 0.34 (n = 17) and 0.42 +/- 0.11 ml/g dry wt (SD; n = 17) in skin and muscle, respectively. Peritoneal dialysis with 20% glucose reduced IFV by 27% in skin and by 44% in muscle, whereas micropipette IFP fell gradually by approximately 4 mmHg in skin and muscle. Compliance during dehydration was 7.6 and 12.5% change in IFV per millimeter Hg fall in IFP (micropipettes) in skin and muscle, respectively, whereas compliance in subcutis based on perforated capsule pressure was 2.0% change in IFV per millimeter Hg. The maximal increase in IFP during overhydration was approximately 2 mmHg in both skin and muscle. Skin and muscle compliance in dogs did not differ significantly from that of rats and cats. We conclude that the difference in compliance among previous studies mainly results from different methods for IFP measurement but is probably also influenced by the state of hydration before altering IFV.

Animals↗