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L W Henderson

Publications and source records attributed to L W Henderson.

At least 19 recordsLinked to original sources
PubMed1992

The effect of convection on bidirectional peritoneal solute transport: predictions from a distributed model.

A distributed model of the peritoneum has been proposed as an alternative to the standard membrane model for describing peritoneal solute transport. The effect of convection on bidirectional peritoneal solute transport is studied theoretically using the distributed model. Approximate analytical and exact numerical solutions to the distributed model yield predictions similar to those when using a membrane model of peritoneal solute transport. Difficulties in interpretation of the membrane transport parameters may arise, however, when interstitial tissue, not the capillary wall, is the dominant diffusive solute transport resistance. Under such conditions the effect of convection on peritoneal solute transport is dependent on the transport direction. Moreover, predictions from the distributed model are similar to those for a membrane model containing two transport barriers in series. Thus, both the distributed model and a membrane model containing two serial transport barriers equivalently describe the effect of convection on bidirectional peritoneal solute transport.

Animals↗
PubMed1991

Visceral peritoneum is not essential for solute transport during peritoneal dialysis.

The importance of visceral peritoneum in determining transperitoneal solute exchange was studied by determining the influence of evisceration on diffusive solute transport during peritoneal dialysis. Three series of experiments were performed in anesthetized New Zealand White rabbits. Series 1 studies compared solute transport rates from eviscerated rabbits (N = 5) with those from sham-operated controls (N = 5). Series 2 studies compared solute transport rates from eviscerated (N = 6) and sham-operated rabbits (N = 5) with application of circumferential abdominal compression to control intraperitoneal pressure and presumably maximize dialysate-peritoneum contact. Series 3 studies compared solute transport rates from sham-operated rabbits (N = 4) with and without applied circumferential abdominal compression. Transperitoneal solute exchange of creatinine and FITC-labeled neutral dextran (15 to 40 A) was equally assessed by both the dialysate to plasma concentration ratio at the end of the exchange and the diffusive permeability-area product of the peritoneum. Evisceration reduced creatinine (P less than 0.001) and dextran (15 to 30 A, P less than 0.05) transport to approximately one quarter that of controls in series 1 rabbits. When circumferential abdominal compression was applied in series 2 rabbits, however, evisceration had no effect on peritoneal solute transport rates. Moreover, circumferential abdominal compression per se had no effect on solute exchange in series 3 experiments. These findings demonstrate that the influence of evisceration on peritoneal solute transport depends on the experimental conditions. These observations further demonstrate that visceral peritoneum is not essential for solute transport during peritoneal dialysis.

Animals↗
PubMed1991

The modeling game.

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Blood Urea Nitrogen↗
PubMed1990

Hydraulically-induced convective solute transport across the rabbit peritoneum.

Transport of solutes during osmotically-induced transperitoneal ultrafiltration is less than would be predicted based upon rates of transperitoneal solute diffusion. Previous workers have hypothesized that osmotically-induced convective solute transport occurs only in small pores at the arteriolar end of peritoneal capillaries, whereas solute diffusion occurs only through large venular pores. We tested this heteroporosity hypothesis in the eviscerated New Zealand White rabbit by determining sieving coefficients (S) for creatinine, p-aminohippurate (PAH) and neutral dextran during hydraulically-induced transperitoneal ultrafiltration (N = 13). A hydraulically-induced driving force directs convective solute transport through the same capillary pores employed for diffusion; therefore S for all solutes should approach unity if the heteroporosity hypothesis is valid. S for creatinine and PAH were respectively 0.72 +/- 0.03 and 0.67 +/- 0.05, values lower than unity and not different from those previously determined during osmotically induced ultrafiltration. Mean S for dextran were relatively independent of molecular size, ranging from 0.50 at 13 A to 0.40 at 50 A. Thus, dextran S were higher than those previously determined during osmotically induced ultrafiltration yet still less than unity. Control experiments (N = 6) suggested that only surface area and not transport characteristics were altered by evisceration. These observations demonstrate that the heteroporosity hypothesis fails to completely describe both diffusive and convective transport properties of the peritoneum.

Animals↗
PubMed1989

Unilateral nephrectomy and glomerular solute transport in the dog.

The influence of compensatory hyperfunction that occurs following unilateral nephrectomy on glomerular solute transport was determined in awake, unanesthetized dogs by renal clearance studies. Two groups of dogs were studied using different test solutes: group I (N = 5) using inulin, iothalamate, creatinine and sodium p-aminohippurate; and group II (N = 6) using creatinine, neutral dextran (3000 to 50,000 daltons) and sodium p-aminohippurate. Compensatory hyperfunction, as assessed by the increase in creatinine clearance per kidney, was 43 +/- 7% and 39 +/- 11% in the group I and II dogs, respectively. The inulin to creatinine and iothalamate to creatinine clearance ratios in the group I dogs were 0.93 +/- 0.07 and 1.00 +/- 0.04 before unilateral nephrectomy. The respective values after unilateral nephrectomy of 0.86 +/- 0.04 and 0.89 +/- 0.05 were lower but not statistically different. In the group II dogs, dextran to creatinine clearance ratios (dextran fractional clearance) over the molecular weight range studied also did not change significantly following unilateral nephrectomy. The magnitude of the change in dextran fractional clearance following unilateral nephrectomy was qualitatively consistent with that predicted by previous models of glomerular macromolecular transport based on membrane pore theory. A lack of quantitative agreement with these models, however, precluded a calculation of the changes in glomerular functional parameters following unilateral nephrectomy. Significant alterations in fractional clearance for neutral macromolecules do not occur following unilateral nephrectomy in the dog.

Animals↗
PubMed1989

Dialysate to blood transport of macromolecules during peritoneal dialysis.

Asymmetrical transport of macromolecules between plasma and the peritoneal cavity results primarily from unidirectional lymphatic removal from the peritoneal cavity. Recent work suggests, however, that macromolecular transport across the peritoneal-plasma barrier via the capillary wall (i.e., the peritoneal membrane) may also be asymmetrical. We determined the diffusive and convective transport properties for creatinine, p-aminohippurate, and neutral dextran (13-40 A) across the peritoneal membrane in the dialysate to blood direction during peritoneal dialysis using isotonic and hypotonic solutions in awake New Zealand White rabbits. Values of the diffusive permeability-area product that were calculated during the isotonic exchange were similar to, yet somewhat smaller than, those previously determined in the blood to dialysate direction for all test solutes. Solute reflection coefficients that were calculated during the hypotonic exchange were variable, yet the resulting mean solute reflection coefficient values for all the test solutes were similar to those previously determined in the blood to dialysate direction. We conclude that asymmetrical peritoneal transport of macromolecules with radii less than 40 A is not due to asymmetrical transport across the peritoneal membrane.

Animals↗
PubMed1989

Prevention of heparin-resistant thrombotic occlusion of hollow-fiber hemodialyzers by synthetic antithrombin.

Because heparin anticoagulation during hemodialysis with hollow-fiber devices is associated with progressive loss of volume of fiber bundles subsequent to thrombotic occlusion, we examined the antithrombotic and antihemostatic effects of the irreversible synthetic thrombin inhibitor D-phenylalanyl-L-prolyl-L-arginyl-chloromethylketone (FPRCH2Cl) during repeated exposure of cupramonium cellulose hollow-fiber hemodialyzers in an extracorporeal blood circuit in baboons. By contrast with full anticoagulating doses of heparin, FPRCH2Cl (100 nmol/kg/min) decreased both the loss of fiber bundle volume (19.1% +/- 7.0% vs 6.4% +/- 3.6% p less than 0.01) and deposition of 111In-labeled platelets within the dialyzer (15.7 +/- 5.9 x 10(9) vs 3.2 +/- 1.2 x 10(9) platelets; p less than 0.01). Additionally, blood markers of thrombus formation in vivo (i.e., plasma beta-thromboglobulin, platelet factor 4, and fibrinopeptide A) remained at low levels throughout infusion of FPRCH2Cl, whereas levels were elevated during heparin therapy (p less than 0.01 in each case). FPRCH2Cl, but not heparin, prolonged bleeding times (p less than 0.001) without affecting the capacity of platelets to aggregate in response to the presence of either collagen or adenosine diphosphate ex vivo. Complement activation by the dialyzer was not affected by FPRCH2Cl. We conclude that the progressive loss of dialyzer hollow fibers is a platelet-dependent, thrombin-mediated process that, although resistant to heparin, is interrupted by the synthetic antithrombin FPRCH2Cl.

Amino Acid Chloromethyl Ketones↗
PubMed1988

Peritoneal dialysate volume determined by indicator dilution measurements.

Dialysate volume was simultaneously determined by two different indicator dilution technique as a function of dwell time in a rabbit model of peritoneal dialysis using isotonic, hypertonic and hypotonic solutions. After a single injection of a large molecular weight index solute (SIIS) to the dialysis solution at a known concentration, the first indicator dilution technique determined dialysate volume by the change in the index solute concentration. In the second technique, dialysate volume was determined after multiple injections of a different index solute (MIIS) by measuring the change in concentration of the index solute two minutes after its injection into the dialysis solution. The volumes determined by SIIS were similar during isotonic, but larger during both hypertonic and hypotonic exchanges, than those determined by MIIS. Drained volume was dependent upon the peritoneal catheter used, was not different from that determined by MIIS, but was significantly smaller than that determined by SIIS. The present results suggest that systematic errors in volume measurements when using indicator dilution result from the loss of the index solute from the peritoneal cavity and are greater for SIIS than for MIIS. A model for fluid transfer during peritoneal dialysis showed that dialysate volumes determined by SIIS were useful, however, when estimating the rate of fluid movement across the peritoneal membrane.

Animals↗
PubMed1988

Dialysate volume measurements required for determining peritoneal solute transport.

Solute transport parameters for the peritoneal membrane have been previously determined using dialysate volumes measured by the indicator dilution method. Recent work has shown that the indicator dilution volume (IDV) exceeds true dialysate volume (TV) because the indicator or index solute is lost from the peritoneal cavity. A peritoneal transport model that includes significant solute loss from the peritoneal cavity is here described. Theory suggests that simultaneous measurements of both IDV and TV are required to calculate solute transport parameters for the peritoneal membrane when solutes are lost from the peritoneal cavity. The magnitude of systematic errors incurred by the use of either IDV or TV alone was determined in the calculated diffusive permeability-area product (PA) for creatinine during a two hour exchange in a rabbit model of peritoneal dialysis. IDV was measured using dextran (2 X 10(6) daltons) and TV by the dilution of multiple injections of Evans blue-albumin complex. Best estimates of PA using either or both volume measurements were determined in the blood to dialysate direction with isotonic (N = 9) and hypertonic (N = 7) solutions and in the dialysate to blood direction with isotonic (N = 4) and hypotonic (N = 4) solutions. Systematic errors in PA using either IDV alone or TV alone were small with either isotonic or hypertonic solutions but were increased with hypotonic solutions. Moreover, systematic errors were larger when using TV alone thaN IDV alone. When solute transport parameters for the peritoneal membrane are approximately determined employing only a single volume measurement, the use of IDV leads to less systematic error than TV.

Animals↗
PubMed1988

Adequacy of dialysis.

(1) There is no single measurement of adequacy in dialysis available now, and there likely never will be. (2) With present knowledge, it is rational to model patients for removal of both small and middle molecules. Minimum weekly clearances for urea and for a middle molecule the size of Vitamin B12 should be 120 and 30 liters per week per 1.73 m2 respectively. (3) In prescribing a dialysis treatment, a Kt/v urea greater than 1 should be targeted, a value of under 0.8 is unacceptable. (4) Attention to the nutritional status of the patient is important, and one should strive for a PCR of 1.1 to 1.3 g/kg/day. (5) Studies on living cells (for example, platelets) and systems (for example, CNS function) are valuable if there is doubt as to the patient's status. (6) Assessments of treatment stresses and quality of life should be used in monitoring dialysis patients. (7) In clinical trials of different treatment methods, it is important to equate findings to solute clearance profiles and to include studies on functions of cells or systems and to measure the impact of the treatment upon quality of life.

Humans↗
PubMed1987

Complement activation during hemodialysis: laboratory evaluation of hemodialyzers.

A laboratory method that facilitates delineation of the complement-activating characteristics of various dialyzers under defined conditions has been developed. Results obtained by circulating reconstituted human serum through these devices and measuring time-dependent production of both C3a and C5a antigens are entirely consistent with previous clinical observations. For example, the complement-activating potential of dialyzer membranes could be described as high (cuprammonium cellulose), moderate (cellulose acetate), or low (polycarbonate or polyacrylonitrile). Furthermore, these techniques provided the opportunity to identify membrane characteristics that are not readily defined by clinical studies alone. Specifically, membranes that transported and absorbed C5a antigen were readily identified by these methods. Additionally, laboratory evaluation provided the unique ability to define the efficiency of complement activation taking place on the membrane surface. Results of these investigations are compatible with a hypothetical model that not only describes the properties of a typical dialyzer membrane but may be generally applicable to other biomaterials as well.

Acrylic Resins↗
PubMed1987

A novel bioassay to predict the clinical response to cryofiltration treatment. A preliminary report.

Phagocytosis by normal human mononuclear monocytes grown in vitro was examined after incubation with known concentrations of aggregated human gamma-globulin (AHG) and in plasma obtained from patients suffering from immunologic diseases. When the phagocytes were pretreated with AHG, an inverse relationship between amounts of AHG and phagocytosis of radiolabeled Candida albicans was found. Inhibition of phagocytosis by patient plasma was independent of other laboratory determinations including antinuclear antibody, C3, C4, CH50, DNA-binding and circulating immune complexes. Plasma from 5 patients subjected to cryofiltration treatment (CFT) demonstrated less inhibition after than before CFT. This lessened inhibition of phagocytosis in vitro correlated with the clinical response due to CFT. The response to CFT could not be predicted by the conventional laboratory parameters investigated. Improvement between pre- and post-CFT plasma estimated by using the present bioassay may provide a quantitative description of which patient may benefit from plasmapheresis treatment procedures.

Biological Assay↗
PubMed1987

Biocompatibility of artificial organs: an overview.

Papers that are presented in this symposium on biocompatibility of foreign surfaces used in artificial organs are commented upon and set in an overall context of the biocompatibility of foreign surfaces to blood. A working formulation of the events comprising lack of biocompatibility of hemodialysis membranes to the complement system is given as a possible model to which other foreign surfaces may be compared.

Animals↗
PubMed1987

Molecular size dependence of peritoneal transport.

The nature of the barrier between blood and peritoneal dialysate was studied by determining peritoneal solute transport rates as a function of molecular size using neutral dextrans, polymers with different molecular weights but uniform chemical composition. Transport rates for creatinine, p-aminohippurate (PAH), and neutral dextran (3,000 to 50,000 daltons) were measured during peritoneal dialysis in the awake rabbit using sequential isotonic and hypertonic dialysis solutions. The permeability-area product (PA) for the peritoneum was determined from the dependence of the dialysate concentration on time during the isotonic exchange. The dependence of PA on molecular size showed no additional hindrance by the peritoneum as molecules of larger size were considered. By accounting for convective solute transport during the hypertonic exchange, the solute reflection coefficient (sigma) and PA were simultaneously determined. The values of PA for creatinine and PAH were similar to those determined during the isotonic exchange, and sigma values for creatinine and PAH were 0.18 +/- 0.20 and 0.14 +/- 0.14, respectively. Dextran sigma values (3,000 to 22,000 daltons) were near unity (0.9 to 1.0) and relatively independent of molecular size, suggesting substantial hindrance to convective transport for this size range. This work demonstrates that the paradoxical transport properties of an "open" diffusive yet "tight" convective peritoneal barrier are primarily reflective of the unique structural properties of this biologic tissue and are not related to test solute heterogeneity.

Animals↗