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Multiple factors have been implicated in the hematologic response to erythropoietin (EPO). The authors studied 54 hemodialysis patients; 44 received 1.5 g of iron intravenously, 16 received oral iron for 12 weeks, and 24 were treated with EPO. Some patients received these treatments in sequence. The factors evaluated were serum albumin, protein catabolic rate, serologic evidence of hepatitis B or C, parathormone (PTH), and aluminum levels. Red cell production was expressed as milliliters of red blood cell increase per day per kilogram of body weight. For patients receiving EPO, hematologic response was normalized to 50 U/kg/dialysis. Of the patients on oral iron, 31% had a good response (hematocrit greater than or equal to 30%). Of the patients who received iron intravenously, 50% had a good response (hematocrit greater than or equal to 30%). All patients treated with EPO responded well, except for one patient who did not respond to doses of EPO up to 200 U/kg/dialysis. The response to intravenous iron dextran was more rapid than the response to oral iron or EPO. Nutritional factors (serum albumin and protein catabolic rate), serologic evidence of hepatitis, elevated PTH levels, or elevated aluminum levels did not significantly affect the response to iron supplementation or EPO treatment.

An attempt was made to develop a tracheal or bronchial stent for nonsurgical implantation using a bronchoscope. Titanium-nickel alloy composed of 50% by weight of each metal has unique thermal shape-memory properties, with a transition temperature of 20 degrees C. Each stent consists of one wire with a diameter of 0.9 mm. It is 30 mm long with a cross-sectional profile resembling a horseshoe. The stent is designed to sustain the airway only at the cartilage rings. Tracheal cartilages of dogs were broken to make a tracheomalasia model, and 10 stents were implanted in 10 animals. The stents were made straight by cooling in liquid nitrogen and then inserted into the region of tracheomalasia. Once in place, they were warmed and recovered their initial shape. The animals were killed between 1 week and 6 months after implantation, and then examined. Nine of the ten stents were located in the implanted area. In one dog, the stent had been displaced into the bifurcation. Microscopic observation showed that the wires were gradually covered with epithelium. At 6 months, 58% were covered with epithelium.

Tumor necrosis factor alpha (TNF) is a mediator of injury in the critically ill. Its small molecular size (17 kd) should allow its clearance during continuous hemodiafiltration (CHD). The authors studied TNF extraction in 12 critically ill patients (APACHE II score 26.3 mean; range, 19-34) receiving CHD. Tumor necrosis factor levels were measured in prefiltered and filtered blood and ultradiafiltrate at 0.4 and 24 hours of therapy. Before CHD, mean plasma TNF levels were 261 pg/ml (95% confidence interval [CI]: 184-578) and 291 pg/ml (95% CI: 0-589) after 24 hours. There were no statistically significant differences between prefilter and postfilter TNF levels. Most ultradiafiltrate samples (74%) contained demonstrable TNF (mean, 314 pg/ml; 95% CI: 67-561). Daily TNF excretion was a mean of 15.9 micrograms (+5.6 standard error [SE]), with a mean daily clearance of 27.5 L (95% CI: 2.5-52.5). The authors conclude that significant amounts of TNF are excreted in the ultradiafiltrate during CHD. This observation may provide a rationale for use of similar therapies in critically ill patients in the absence of conventional indications for dialytic support.

Continuous monitoring of pump performance is essential and effective for optimal driving of a pulsatile blood pump. The authors contrived a practical method for continuous estimation of blood volume in a pump by measurement of electrical impedance (Z). This method was evaluated with the air-driven, diaphragm type pump. The pump was made from polyurethane and had two metal connectors at the inlet and the outlet ports. Z was measured by charging the alternating current (50 kHz, 0.4 mA) between two connectors as electrodes. In in vitro tests, Z reached maximum value during full-empty and minimum value at full-fill. The blood volume calculated by an empirical equation of Z was linearly related to the real blood volume (r = 0.99). In in vivo tests with goats, pump output estimated by this method was linearly related to pump output measured with an electromagnetic flowmeter and effectively evaluated pump performance. For calibration, this method needed only to measure Z at full-fill. This method was useful as a controller of a full-fill to full-empty drive. It was concluded that this method is a practical estimate of pump performance, even if implantable diaphragm type pumps are used, and easily applicable to any kind of pulsatile pump.

In a retrospective study of 330 animals with total artificial hearts (TAH), 103 (31%) had microbially infected thrombi (MIT). The incidence of MIT approximated 75% in the animals surviving more than 100 days. The most common pathogen isolated from animals with MIT was Pseudomonas. Most thrombi appeared to have originated from valve junctions and connectors. Methods to prevent MIT should be aimed at eliminating thrombus formation by improved design and materials and controlling the route of bacterial colonization. These findings suggest that bacterial interaction with the thrombus, device-related bacterial colonization, host immunomodulation, and gut barrier function after TAH implantation need further study.

To clarify further the extent, pathways, and significance of convective transport during peritoneal dialysis, acute transport studies were conducted in which five continuous ambulatory peritoneal dialysis (CAPD) patients underwent 6 hr dialyses (2 L infusate with 2.25% dextrose) on 2 successive days, with multiple sampling of both blood and peritoneal dialysate. Concentrations of permeants (urea, creatinine, uric acid, beta 2 microglobulin, and apolipoprotein A) and a radiolabeled marker (125I-polyvinyl pyrollidone [PVP]) were determined at 20-30 min intervals in dialysate and every 90 min in plasma. Intraperitoneal volumes and lymphatic flows were calculated from rates of dilution and disappearance of 125I-PVP. Intratreatment lymphatic flow rate averaged 76 +/- 15 ml/hr. Although lower than observed in small animal models and reported by some clinical groups, this level of lymphatic drainage was still sufficient to decrease net patient weight loss by approximately 50% and to resorb approximately 15% of metabolites in the peritoneal cavity, independent of molecular weight. Transcapillary ultrafiltration ranged from 7.4 +/- 1.5 ml/min at 10 min into the exchange to 1.3 +/- 1.5 ml/min at 345 min. Reverse ultrafiltration, from the peritoneal cavity back through capillary vasculature to the patient, was not observed in any patient in this study.

Blood flow with an arteriovenous access is limited by the resistance of the catheters and hemofilters or dialyzers in the extracorporeal system. Resistance data from manufacturers are varied as to the test conditions used, however, making it difficult to select optimum components. Furthermore, the same size catheters may have varying inner diameters, resulting in large differences in flow resistance. The pressure at various flow rates was determined using a water manometer. The pressure/flow relationship for catheters gave a curve, whereas the logarithmic function resulted in a straight line with a slope of 1.48. The pressure/flow relationship for hemofilters and dialyzers was a straight line with an intercept close to the origin. The data in the tables for flow resistance at 50 and 100 ml/min can be used to compare the various components, and to estimate flow in a given extracorporeal system.

To clarify the roles of endothelin (ET: vasoconstrictor) and platelet activating factor (PAF: vasodilator) in hemodialysis (HD), intradialytic changes in those substances were compared by a crossover study between HD with regenerated cellulose (RC) and polymethylmethacrylate (PMMA) membranes using currently developed radioimmunoassay methods. Hemodialysis patients demonstrated higher plasma ET values than normal controls, and hypertensive HD cases showed the highest levels. Although ET decreased significantly during the initial stage of HD with both membranes, the decreasing rates were greater in the group with intradialytic hypotension than those in the normotensive group. Plasma PAF did not differ among normal controls, hypertensive HD, and normotensive HD patients. Platelet activating factor tended to increase during HD in both hypotensive and normotensive groups; however, the increasing rates were greater in HD with RC than those with PMMA. These results indicate that the decrease in ET may partially contribute to the initiation of HD induced hypotension. Because PAF is an intracellular mediator, and there is an intradialytic increase in PAF with RC membrane, PAF should be regarded as one of the indices of membrane biocompatibility.

Interleukin-1 (IL-1) was measured in the plasma and in mononuclear cell (MC) lysates from patients on maintenance hemodialysis (HD) using either cuprophan (CU) or polysulfone (PS) membranes. Basal plasma levels of IL-1 in HD patients were significantly higher than those of uremic patients on conservative treatment or of healthy subjects. In 10 patients on conservative treatment, plasma levels of IL-1 increased significantly after 3 and 6 months of HD. During a single HD session, plasma IL-1 fell to 21% (CU) and 22% (PS) of pre-HD levels. Hemodialysis patients had a significantly higher intracellular IL-1 content than normal controls. During HD, a further increase was seen regardless of the membrane employed. A parallel in vitro study showed that IL-1 produced during HD requires at least 24 hours to be released, and that both CU and PS are able to bind and clear IL-1.

This study was initiated to investigate the use of the Gianturco intravascular stent in prolonging dialysis access graft patency after angioplasty. Stents were placed in 25 patients with follow-up to date of 0.5-8 months. The stent used was 1.5 x 3 cm and consisted of two units connected by a single strut. In Phase 1, the strut was rigid, and the stent had no barbs. The rigidity of the stent and stent migration caused problems. In Phase 2, an articulated strut design was used, and in Phase 3, barbs were added. These modifications solved the previously noted problems. No anticoagulation was used, and clotting was not a significant problem. The duration of patency for the total group was not significantly better than for control groups. However, there were no losses with the modified stent design used in Phases 2 and 3 with follow-up to date of 0.5-5.5 months. Further study of this treatment modality appears warranted.