Pathways for fluid loss from the peritoneal cavity.

During peritoneal dialysis, fluid is transported out of the peritoneal cavity by lymphatic and nonlymphatic pathways, thereby decreasing net ultrafiltration by 40-50% and reducing small solute clearance by 15-20%. The direct lymphatic pathway consists of the diaphragmatic lymphatics, which directly connect the peritoneal cavity to the bloodstream. The interstitial lymphatic and direct blood entry pathways convey fluid that has been driven into the interstitial space of the tissue surrounding the peritoneal cavity by the increased intraperitoneal pressure, and return it to the bloodstream. Since flow through lymphatic pathways is only a portion of the flow through all pathways, total fluid loss is greater than lymph flow. The best technique for estimating lymph flow is direct measurement by cannulation of lymphatic vessels, a technique that is not clinically feasible. The tracer disappearance technique, which measures the rate at which macromolecules leave the peritoneal cavity, is an indirect measure of fluid loss. The tracer appearance technique, which measures the rate at which macromolecules reach the blood from the peritoneal cavity, slightly overestimates lymph flow because some tracer may enter the bloodstream directly from the tissues. Much of the previous controversy over the contribution of the lymphatic pathways to total fluid loss can be resolved by understanding the differences in what these techniques measure.     

Lymphatic and nonlymphatic pathways of peritoneal absorption in mice: physiology versus pathology.

In conjunction with our studies of the pathogenesis of malignant ascites formation, we have analyzed the transperitoneal transport of macromolecules in mice. In this review, I summarize our experimental results concerning the influx (transport from the blood to the peritoneal cavity) and efflux (transport from the peritoneal cavity to the blood) of a number of different tracers [fluorescein-labeled dextrans (FITC-D), 51Cr-RBC, 125I-HSA, and 125I-fibrinogen]. We examined tracer transport in ascites tumor-bearing animals as a function of tumor growth and compared our results with transport properties obtained in normal awake mice and in mice that had received an intraperitoneal injection of a solution of 5% bovine serum albumin to simulate the protein-rich fluid accumulation associated with ascites tumor growth in the peritoneum. Our results indicate that both increased influx as well as impaired efflux are required to initiate and maintain tumor ascites fluid accumulation. To test the hypothesis that increased influx reflected increased vascular permeability, we monitored transport of intravenously injected FITC-D tracers (FITC-D) into the peritoneal cavity by fluorescence microscopy. To investigate the mechanisms involved in the decreased efflux, we determined tracer efflux rates both as the rate of appearance in the blood and as the rate of disappearance from the peritoneal cavity. We compared these transport properties for both soluble as well as particulate tracers. Our results indicate that there are additional routes of egress available to soluble macromolecules not available to particulate tracers such as 51Cr-RBC, and that in ascites tumor-bearing animals, the lymphatic pathway is shut off rather rapidly as judged by the decreased rate of 51Cr-RBC removal. By fluorescence microscopy we observed the interstitial tissue uptake of intraperitoneally injected soluble macromolecules (FITC-D) in the parietal peritoneal wall, particularly in animals with an increased intraperitoneal pressure, thereby confirming additional nonlymphatic pathways of peritoneal absorption in mice. Finally, we used the particulate tracer 51Cr-RBC to estimate the peritoneal lymphatic drainage rate, yielding a value of 1.6 microliters/min in normal awake mice based on the rate of tracer disappearance from the peritoneum.     

Role of lymphatics in peritoneal dialysis.

There is a renewed interest in understanding the precise role of lymphatics in the ultrafiltration kinetics during peritoneal dialysis. In the normal state, lymphatics draining the peritoneal cavity are the principal means of removal of intraperitoneal isosmotic fluid and macromolecules. During a hypertonic peritoneal dialysis exchange, after peak intraperitoneal volume is achieved, fluid removal proceeds at an almost linear rate, causing intraperitoneal fluid volume to reduce. The isosmotic fluid removal from the peritoneal cavity could occur through the microcirculatory capillaries or through the lymphatic capillaries draining the peritoneal cavity. Animal and human studies suggest that this fluid loss occurs primarily through lymphatics. The two indirect methods of lymph flow measurements, plasma appearance and peritoneal disappearance of tracer colloid, show conflicting results. Although direct measurement of lymph flow rates through cannulation of mediastinal lymph vessels in animals suggests a significant flow through the lymph channels in response to intraperitoneal fluid instillation, lymph flow modification at the lymph node level may prevent use of this technique to assess the precise role played by lymphatics in fluid kinetics during peritoneal dialysis. By analogy with ascites and by extrapolation from previous studies of drain volumes after infusion of isotonic and hypertonic solutions, the average daily lymph absorption rate during CAPD may be predicted to be at least 1 liter per day.     

Lymphatic transport of pericardial effusate in sheep

In this report, we quantified fluid loss from the pericardial cavity during simulated saline effusions and determined what proportion of this loss occurred through lymphatics. Fifty or 100 ml of Ringers lactate solution [containing 0.5% sheep albumin and (131)I-human serum albumin (HSA)] was injected into the pericardial cavity of sheep. Pericardial pressures, systemic arterial pressures, and plasma/pericardial fluid concentrations of the radioactive tracer were measured. Lymph transport of pericardial fluid was estimated from the plasma recovery of tracer using a mass balance equation. Plasma recoveries were corrected for tracer loss using a coefficient of elimination calculated from the plasma disappearance curve of intravenously administered (125)I-HSA. Over 4 h, 27.6 +/- 4.9 (+/-SE) and 36.7 +/- 4.2 ml were lost from the pericardial cavity in the 50- and 100-ml effusion series, respectively, of which 5.2 +/- 0.8 (20.2 +/- 3.8% of volume lost) and 7.7 +/- 1.6 ml (21.5 +/- 3.3% of volume lost) could be attributed to lymphatic transport. We conclude that lymphatic transport is one of the factors that contribute to pericardial "reserve" function by helping to restore pericardial fluid volume to resting levels.     

Lymphatic versus nonlymphatic fluid absorption from the peritoneal cavity as related to the peritoneal ultrafiltration capacity and sieving properties.

In this article we discuss the role of capillary fluid absorption via Starling mechanisms (the transcapillary hydrostatic pressure gradient opposed by the colloid osmotic pressure gradient as multiplied by the capillary UF coefficient) vs. lymphatic fluid absorption as determinants of the total fluid loss from the peritoneal cavity during continuous ambulatory peritoneal dialysis (CAPD). We also mention that, under nonsteady state conditions, there is in addition some net absorption of fluid into the interstitium of tissues surrounding the peritoneal cavity. Support for the contention that nonlymphatic fluid absorption directly into the capillaries is the major mode of fluid transport from the peritoneal cavity to the blood is given by measurements of the peritoneal-to-blood clearance of tracer albumin (or other proteins). Such measurements yield clearance values of the order of 0.2-0.3 ml/min in CAPD. This represents only about 20% of the total peritoneal fluid loss rate (1.2-1.3 ml/min) in ordinary CAPD dwells. Indirect support for a relatively low lymph flow is also derived from capillary physiology. Like continuous capillary walls, the peritoneal membrane shows a bimodal selectivity towards molecules of graded molecular size. Thus, small solute transport can be described as occurring by diffusion through numerous 'small' (approximately 50 A radius) pores, whereas large solute transport is consistent with blood-peritoneal convection through smaller numbers of 'large' (radius approximately 250 A) pores. Furthermore, peritoneal sieving data are compatible with the notion that large crystalloid osmotic pressure gradients cause fluid flow through a water-exclusive ('ultra-small' pore) pathway. A three-pore model of peritoneal selectivity can explain why small solute sieving coefficients are only 0.5-0.6, even though small solute reflection coefficients are close to zero. Another important implication of the three-pore concept is that the peritoneal UF-coefficient is much higher than previously thought, emphasizing the role of capillary absorption in the fluid loss from the peritoneal cavity in CAPD. It is concluded that fluid loss from the peritoneal cavity is dominated by capillary fluid absorption. Hence, lymphatic absorption accounts for just a small fraction of the peritoneal-to-blood absorption of fluid in peritoneal dialysis.     

Effect of intraperitoneal insulin on solute kinetics in CAPD: insulin kinetics in CAPD

The authors evaluated the transport kinetics of insulin and inulin administered intraperitoneally to six diabetic patients undergoing continuous ambulatory peritoneal dialysis. The mass transfer coefficients (MTC) calculated from dialysate to blood for 1.5% and 4.25% dextrose dialysate were (ml/min): insulin 2.9 +/- 0.9, 2.0 +/- 0.5; inulin 3.3 +/- 1.4; 2.9 +/- 1.7, respectively. The MTC for inulin calculated from blood to dialysate was 2.0 +/- 0.7 ml/min. Because insulin disappears from the peritoneal cavity at a rate similar to inulin, it suggests that insulin transport can be defined by diffusion. The derived MTC values for glucose were not altered by the addition of intraperitoneal insulin. The derived MTCs for eight diabetic to thirteen nondiabetic patients were compared. The MTC derived for urea was less among the diabetics (16.6 +/- 2.2 vs. 24.6 +/- 2.6 p less than 0.05), but there were no differences for creatinine, uric acid, glucose, inulin, and protein. The derived values were found to be normally distributed and patients in the upper quartile for one solute were generally in the upper quartile for other solutes.     

Diaphragmatic lymph vessel drainage of the peritoneal cavity.

We have studied the drainage of peritoneal fluid through the diaphragmatic lymph vessels in sheep. To measure the lymphatic flow rate, we cannulated the lymphatic vessels and timed the flow from the cannula. After we infused Escherichia coli endotoxin into awake sheep, the diaphragmatic lymph flow rate increased substantially. However, we found no increase in lymph flow in anesthetized acutely operated sheep. This indicates that studies in anesthetized animals may yield underestimates of diaphragmatic lymph flow. In sheep, many of the diaphragmatic lymph vessels drain to the caudal mediastinal lymph node. We cannulated an efferent vessel from that node in 5 sheep. Several days later we infused 100 ml/kg of Ringer's solution into the abdominal space of each awake sheep. In response, the lymph flow rate increased from 0.15 +/- 0.16 ml/min (mean +/- SD) to 0.50 +/- 0.17 ml/min. Our results are important because they demonstrate that diaphragmatic lymph flow increases substantially after fluid infusions into the abdominal space.     

Studies on lymphatic drainage of the peritoneal cavity in sheep.

In the sheep, it is possible to cannulate several of the lymphatics that drain the peritoneal cavity and assess lymphatic drainage of this serous space directly. Indwelling catheters were placed in the caudal mediastinal and thoracic ducts. The right lymph duct could not be cannulated. Lymphatic drainage of the peritoneal cavity based on the movement of 125I-albumin from the cavity into the lymph compartments was not affected by the osmolality of the dialysate but was markedly altered by anesthesia. In addition, lymphatic drainage was assessed from the disappearance of instilled 125I-albumin from the peritoneal cavity and from the appearance of intraperitoneally administered 125I-albumin in the bloodstream and compared with data from the cannulated preparations. Lymph flows derived from tracer movement into the cannulated lymph compartments and from the appearance of tracer in the bloodstream were very similar. However, calculations of lymph flows based on the disappearance of tracer from the peritoneal cavity appeared to overestimate lymphatic drainage.     

Kinetic of calcium, phosphate, magnesium and PTH variations during hemodiafiltration

Hemodiafiltration (HDF) is a technique resulting from coupling of diffusive and convective transport and thereby increase the elimination of small and middle molecules. However, may induce a convective loss from others substances such as calcium and magnesium. The aim of this study was to evaluate the effects of Ultrafiltration on the kinetics of calcium, phosphate, magnesium and parathyroid hormone. A total of thirteen patients (7 males and 6 females) on hemodialysis, were studied. Each patient was randomly dialyzed with the same dialysate calcium concentration and three different ultrafiltration rate. Schedule A: High flux hemodialysis, schedule B: HDF with 10% of weight body and schedule C: HDF with 20% of weight body. The others parameters were kept identical. Total Ultrafiltration was 2,6+/-0,9 L (9,78+/-3,78 ml/min) in A, 9,3+/-1,7 L (34,54+/-6,22 ml/min) in B and 16,3+/-3,3 L (60,94+/-12,63 ml/min) in C. Replacement fluid during dialysis was 6,85+/-1,42 and 13,65+/-2,9 L. in C and C respectively. Postdialysis total,ionized calcium and magnesium were significantly lower in schedules B and C versus A. PTH levels did not differ significantly. However, PTH changes during dialysis was -36.6+/-38.6%, 6.3+/-69.8% and 32.2+/-63.2% in A, B and C, respectively (p<0.05 A vs. C). A significant inverse correlation was found between total Ultrafiltration and postdialysis levels of total calcium (r:-0.56, p<0.001), ionized calcium (r:-0.65, p<0.001) and magnesium (r:-0.47, p<0.01). No differences were observed in pre and postdialysis phosphate levels, neither mass transfer and clearance of phosphate. We concluded that high ultrafiltration flow rates and substitution fluid without divalent cations induces a negative calcium and magnesium balance. These changes may stimulate PTH secretion during HDF. This technique did not resulted in a higher clearance or phosphate removal.     

Serum and dialysate osteocalcin levels in hemodialysis and peritoneal dialysis patients and after renal transplantation

Serum osteocalcin (BGP), a vitamin K-dependent gamma-carboxyglutamic acid (GLA) containing bone protein, provides an index of bone turnover in patients with a variety of metabolic bone diseases. BGP increases with increasing age in both sexes, but more so in women. BGP rises above normal when the glomerular filtration rate falls below 30 ml/min. Because of its importance in bone disease, its low mol wt, and the effect of uremia, we measured BGP by RIA in serum and dialysate fluid in patients on hemodialysis (HD) or peritoneal dialysis (PD). In 32 HD patients (22 women and 10 men), serum BGP was not different pre- and postdialysis [67.5 +/- 4.4 (+/- SEM) ng/ml vs. 67.7 +/- 5.2), but was significantly elevated compared to the level in normal subjects (7.3 +/- 0.8 ng/ml). The sex difference previously reported in normal subjects was not found in patients with renal failure. The serum BGP level in 8 PD patients was 49.4 +/- 6.9 ng/ml, with a peritoneal fluid concentration of 27.6 +/- 9.3 ng/ml. The hemodialysate fluid concentration of BGP was 1.7 +/- 0.4 ng/ml, which was significantly lower than the serum BGP levels in the HD patients, the PD patients, and peritoneal fluid (P less than 0.01). A significant correlation existed among BGP, alkaline phosphatase, immunoreactive PTH, creatinine, and blood urea nitrogen. We conclude that BGP is markedly elevated in patients with renal failure, not altered in the serum by HD or PD, but very low in HD dialysate fluid. These findings may reflect a combination of impaired clearance and increased skeletal production. The difference in clearance between the peritoneal and hemodialysis fluid is compatible with the mol wt of BGP. In 15 patients who had successful kidney transplantation, serum BGP was normal despite an elevated serum PTH level.     

Evaluation of a peritoneal dialysis solution containing polymer

Glucose is used in peritoneal dialysate to produce the gradient for ultrafiltration. The peritoneal membrane's low reflection coefficient for glucose imposes a demand for high transmembrane concentrations, perhaps adding unwanted body burden of glucose. A polymer with a lower permeation rate used as an osmotic agent would circumvent this. We evaluated the mass transfer coefficient (mtc), T1/2 disappearance from the peritoneal cavity and ultrafiltration capabilities of a 900 dalton (Mn) starch derived polymer. We compared an 8% (455 mOsm/L) and a 10% (484 mOsm/L) polymer (Pol) solution to available dialysate solutions containing 2.5% (399 mOsm/L) and 4.25% (491 mOsm/L) X glucose (Glc). The dialysate compositions were otherwise similar. Using a randomized complete block design, 5 anephric dogs maintained on chronic peritoneal dialysis were studied. The mtc (ml/min) was greater for the glucose than the polymer solutions (p less than 0.05): 2.5%-13 and 4.25%-14 vs 8%-5 and 10%-6. The T1/2 disappearance (min) was also greater (p less than 0.05): 2.5% Glc-112 and 4.25% Glc-111 vs 8% Pol-281 and 10% Pol-252. Over a 180 min. period the 2.5% glucose solution generated the least volume of ultrafiltrate (ml, p less than 0.05): 2.5% Glc-113 and 4.25% Glc-589 vs 8% Pol-640; 10% Pol-912. We conclude that the lower permeation rate of the polymer yields ultrafiltration at a lower dialysate osmolality. A polymer solution may be a feasible alternative to glucose.     

Continuous venous-venous hemofiltration for the treatment of fluid overload in continuous ambulatory peritoneal dialysis patients

Fluid overload is not infrequent in continuous ambulatory peritoneal dialysis (CAPD) patients. In our experience, extemporaneous continuous venous-venous hemofiltration (CVVHF) was able to correct fluid imbalances refractory to high dose diuretics and hypertonic solutions. We treated 8 of 52 patients (5 females, 3 males, mean age 52 years) on CAPD from 4 to 36 months and with fluid overloads of up to 10 kg. A Biospal SCU/CAVH flat-sheet high-flux hemodialyzer employed for 10 h produced an ultrafiltration rate (QB:150 ml/min) of 11.12 +/- 4.97 ml/min. With an isotonic replacement solution, the filter provided sufficient extraction of small molecules so that CAPD could be interrupted during CVVHF. The procedure appeared well tolerated. This approach reduced the use of hypertonic dialysate, which is not devoid of side effects on ultrafiltration capacity of the peritoneal membrane.     

Effect of the direction of dialysate flow on the efficiency of continuous arteriovenous haemodialysis

We have investigated the effect of the direction of the dialysate flow during continuous arteriovenous haemodialysis. Under similar conditions countercurrent flow was more efficient than concurrent flow in terms of both urea clearance (mean +/- SEM), 23.5 +/- 0.5 compared to 18.4 +/- 0.4 ml/min (p less than 0.001) and creatinine clearance, 21.1 +/- 0.5 compared to 15.6 +/- 0.4 ml/min (p less than 0.001). There was a greater drop in pressure along the blood compartment of the haemodiafilter during countercurrent flow, 16 +/- 0.8 compared to 13 +/- 0.3 mm Hg (p less than 0.05) during concurrent flow, and this was associated with a greater ultrafiltration rate, 7.2 +/- 0.6 compared to 6.0 +/- 0.5 ml/min. The differences in diffusion, back diffusion and convection between the two systems resulted in a net gain of lactate/bicarbonate and a net loss of chloride during countercurrent dialysate flow, and a net loss of lactate/bicarbonate with a gain of chloride during concurrent flow. These losses would have to be corrected in the clinical setting of patients who had been continuously treated by these systems for several days.     

Evaluation of pre- and postdilutional on-line hemodiafiltration adequacy by partial dialysate quantification and on-line urea monitor.

On-line highflux hemodiafiltration (HDF) is a clinically interesting and effective mode of renal replacement therapy, which offers the possibility to obtain an increased removal of both small and large solutes. The fundamental role of urea kinetic monitoring to assess dialysis adequacy in conventional hemodialysis has been widely studied. Both direct measurement of the urea removed by the modified direct dialysate quantitation (mDDQ) based on partial dialysate collection (PDC) and dialysate-based urea kinetic modeling (DUKM) using urea monitor have been advocated. The validity of this assessment tool in the patients with on-line HDF remained unclear. The aims of this investigation were (1) to compare the delivered Kt/V, urea mass removal (UMR), solute removal index (SRI) and normalized protein catabolic rate (nPCR) between pre- and postdilutional high-flux HDF; (2) to verify and compare the efficiency of pre- and postdilutional HDF using DUKM with on-line dialysate urea sensor, and mDDQ with partial dialysate collection. During both mode of HDF, the paired analysis urea removed and Kt/V showed no significant difference. Using mDDQ, mean values for predilutional mode were as follows: Kt/V 1.53 +/- 0.01 UMR, 16.8 +/- 0.3 g/session; urea clearance 178 +/- 18 ml/min; SRI 75.5 +/- 7.7%; urea distribution volume (V) 28.3 +/- 1.2 liters; nPCR 1.34 +/- 0.18 g/kg/day; on the other hand, mean values for postdilutional mode were Kt/V 1.58 +/- 0.01; UMR 17.10 +/- 0.28 g/session; urea clearance 184 +/- 21 ml/min; SRI 77.2 +/- 3.5%; urea distribution volume, 27.8 +/- 1.5 liters; nPCR 1.34 +/- 0.19 g/kg/day. The mean value of urea generation rate was 5.82 +/- 1.12 mg/min during HDF. Our results showed that dialysis adequacy was achieved with both high-volume predilutional HDF and postdilutional HDF. These two modes of HDF provided similar and adequate small solute clearance. In addition, we found that on-line analysis of urea kinetics is a reliable tool for quantifying and assuring delivery of adequate dialysis.     

Permselectivity of the peritoneal membrane

To investigate the osmotic barrier characteristics of the peritoneal membrane during conditions similar to peritoneal dialysis in man, yet transperitoneal fluid movement was measured in 20 cats following intraabdominal placement of isotonic saline and hypertonic solutions of NaCl, glucose, raffinose, and inulin. Also, isooncotic solutions of hemoglobin and albumin and two sulfated high-molecular-weight dextrans were investigated. Transperitoneal fluid movement was measured by a volume recovery method. Oncotic pressures of test solutions and plasma were measured by osmometry. Peritoneal osmotic conductances were calculated from the rate of transperitoneal water movement and the difference in osmotic pressures between the test solution and isotonic saline. The average glucose osmotic conductance per unit body surface are was found to be 2.3 +/- 0.18 x 10(-3) ml . min-1 . mm Hg-1 . m-2, in good agreement with previous reports, and the glucose osmotic reflection coefficient (sigma) was estimated to be 0.02. All the osmotic conductances measured could be fitted to a peritoneal equivalent pore radius of approximately 6 nm according to current hydrodynamic theories. The peritoneal membrane filtration coefficient was estimated to be 0.12 ml . min-1 . mm Hg-1 . m-2, of which 0.5-1% was found to be due to transcellular water flow. In conclusion the results of this study indicate that the peritoneum is a highly selective membrane with restrictive properties comparable to those reported for continuous capillary beds.     

Transvascular passage of macromolecules into the peritoneal cavity of normo- and hypothermic rats in vivo: active or passive transport?

During the last decades there has been a debate regarding whether transvascular protein transport is an active (transcytosis) or a passive (porous) process. To separate cooling-sensitive transcytosis from passive transport processes between blood and peritoneal fluid, we induced hypothermia in rats in vivo, reducing their body temperature to 19 degrees C. Control rats were kept at 37 degrees C. Either human albumin, or IgG, or IgM, or LDL, radiolabeled with (125)I, was given intra-arterially together with (51)Cr-EDTA. During tracer administration, a 2-hour peritoneal dialysis dwell was performed. Clearance of the tracers to dialysate, and the permeability-surface area coefficient (PS) for (51)Cr-EDTA and glucose were assessed. During cooling, mean arterial blood pressure (MAP) was reduced to 40% of control and plasma viscosity increased by 48.5%, while peritoneal blood flow was reduced to 10%. At 19 degrees C, clearance of albumin to dialysate fell from 9.30 +/- 1.62 (SEM) to 3.13 +/- 0.28 microl/min (p < 0.05), clearance of IgG from 6.33 +/- 0.42 to 2.54 +/- 0.12 microl/min (p < 0.05), clearance of IgM from 3.65 +/- 0.33 to 1.10 +/- 0.12 microl/min (p < 0.05), and clearance of LDL from 3.54 +/- 0.20 to 0.73 +/- 0.06 microl/min (p < 0.05). The fall in PS for (51)Cr-EDTA was from 0.320 +/- 0.01 to 0.075 +/- 0.003 ml/min (p < 0.05), and that for glucose from 0.438 +/- 0.02 to 0.105 +/- 0.01 ml/min (p < 0.05). Tissue cooling reduced large solute transport largely in proportion to the cooling-induced reductions of MAP (to 40%), and the concomitant increase in viscosity (to 67%), i.e. to approximately 20-30% (0.40 x 0.67) of control, though LDL clearance was reduced further. The fall in small solute PS, in excess of the viscosity effect, mirrored the fall in peritoneal blood flow occurring during hypothermia. In conclusion, the good correlation of predicted to calculated changes suggests that the overall transendothelial macromolecular passage in vivo occurs passively, and not due to active processes.     

Pericardial fluid absorption into lymphatic vessels in sheep

We estimated the volumetric lymphatic clearance rate of pericardial fluid in sheep. In the first group of studies, 125I-human serum albumin (HSA) was injected into the pericardial cavity and after 4 h, various lymph nodes and tissues were excised and counted for radioactivity. Several lymphatic drainage pathways existed defined by elevated 125I-HSA in the middle and caudal mediastinal, intercostal, and the cardiac nodes located near the root of the aorta. In a second group of experiments, the plasma recovery of intrapericardially administered tracer was compared in sheep with intact lymphatics and in animals in which thoracic duct lymph was diverted and other relevant lymphatics ligated. The 4-h plasma recoveries were reduced significantly from an average of 12.2 +/- 3. 4% injected dose in the lymph-intact group to 3.0 +/- 1.1% injected dose in the diverted/ligated group (an inhibition of approximately 75%). In order to estimate the volumetric clearance of pericardial fluid through lymphatics in conscious sheep, 125I-HSA was administered into the pericardial cavity to serve as the lymph flow marker. 131I-HSA was injected intravenously to permit calculation of plasma tracer loss and tracer recirculation into lymphatics. From mass balance equations, total pericardial clearance into lymphatics averaged 1.50 +/- 0.43 ml/h or approximately 1.13 ml/h if one was to assume that the average 25% recovered plasma tracer in lymph diverted/ligated animals was due to nonlymphatic transport. In conclusion, mediastinal lymphatic pathways remove a volume equivalent to the pericardial volume (8.1 +/- 1.1 ml) every 5.4 to 7. 2 h.     

Enhancement of peritoneal transport in rats by disrupting stagnant fluid films

Dialysate comes into contact with the active membrane and remains in contact until the fluid is refreshed. This design exaggerates stagnant fluid films. Dialysis rate studies were done to evaluate transport when stagnant fluid films were disrupted. Following anesthesia, 30 mL of commercial 1.5% glucose dialysate containing 100 mg% urea and 25 mg% inulin warmed to 37.5 C were instilled. Dialysate was sampled at 5, 15, 30, 45, and 60 min after instillation. Experimental rats were vibrated at 25 Hz throughout the study. Diffusive mass-transfer coefficients (MTC mL/min 1000 cm2) were calculated, and control and vibrated group means were tested for differences using Student's t-test. The mean MTC values for control (n = 10) and vibrated groups (n = 12), respectively, were: urea 0.8 +/- 0.04, 1.4 +/- 0.2, p less than 0.01; glucose 0.4 +/- 0.03, 0.6 +/- 0.03, p less than 0.01; insulin 0.2 +/- 0.01, 0.2 +/- 0.01, p = NS. Disrupting stagnant fluid films augments peritoneal transport.     

Role of molecular charge in disruption of the blood-brain barrier during acute hypertension

Acute hypertension disrupts the blood-brain barrier and may neutralize the negative charge on cerebral endothelium. The goal of this study was to determine the effects of molecular charge on permeability of the blood-brain barrier during acute hypertension. Intravital fluorescent microscopy and fluorescein-labeled dextrans were used to evaluate disruption of the blood-brain barrier during acute hypertension in rats. Disruption of the blood-brain barrier was quantitated by calculating clearance of neutral dextran and of anionic dextran sulfate in two groups of rats. Pressure in pial venules, which are the primary site of disruption of the blood-brain barrier during acute hypertension, was measured using a servo-null device. When systemic arterial pressure was increased from 87 +/- 5 (mean +/- SEM) to 188 +/- 5 mm Hg, clearance of neutral dextran increased from 0.04 +/- 0.01 to 4.38 +/- 0.72 ml/sec x 10(-6). When systemic arterial pressure was increased from 91 +/- 4 to 181 +/- 3 mm Hg, clearance of anionic dextran sulfate increased from 0.02 +/- 0.01 to only 0.70 +/- 0.23 ml/sec x 10(-6). Increases in pial venular pressure were similar in the two groups. Thus, similar increases in systemic arterial pressure and pial venular pressure during acute hypertension produce less disruption of the blood-brain barrier to anionic dextran sulfate than neutral dextran. The findings suggest that 1) the net negative charge of cerebral vessels may be preserved during acute hypertension, and 2) molecular charge is an important determinant of the severity of disruption of the blood-brain barrier during acute hypertension.