The International Journal of Artificial Organs

Dialysis membranes are generally considered to be impermeable for bacterial endotoxin (lipopolysaccharide, LPS) contaminated in dialysates used for hemodialysis therapy, since LPS molecular size in aqueous media has been reported to be more than 10⁶. However, there are few reports concerning its size in dialysates. We have already presented a newly developed polyacrylamide gel electrophoresis with sodium deoxycholate (DOC-PAGE) which proves the LPS size. Using this method, therefore, we attempted to clarify the size of LPS in dialysates. We demonstrated that LPS in dialysates had roughly two different molecular sizes with DOC-PAGE and that compared to migration profiles of Salmonella LPS as controls on DOC-PAGE, one molecular size of LPS was approximately 4,000 and the other in tens of thousands. This investigation indicates the possibility of LPS transfer across dialysis membranes.

Ticlopidine, a platelet aggregation inhibitor was tested, in a double blind comparative cross-over study versus placebo, in 51 dialysed uremic patients who had increased dialyser blood clotting (> 25 fibers clotted / dialyser). At the end of a 7-day treatment period with 250 mg daily, the clearance of urea, creatinine and phosphate was determined at 30 and 210 minutes of dialysis, as well as the number of fibers clotted at the end of dialysis. Ticlopidine improved dialyser clearances for urea, creatinine and phosphate from 165 ± 41 to 182 ± 35 (p < 0.01), 135 ± 37 to 143 ± 35 (p < 0.05), and 120 ± 36 to 130 ± 35 (p < 0.05) ml/min, respectively, at 30 min of HD and a similar effect was seen after 210 min of dialysis. The number of dialyser fibers clotted after dialysis was reduced by ticlopidine therapy from 110 ± 48 to 15 ± 8 (p < 0.01). Ticlopidine reduced the initial dialysis-induced drop in leucocyte count by 20% (p < 0.05); no change in platelet or erythrocyte count was observed. Two out of 51 patients experienced an adverse reaction from ticlopidine (cutaneous haematoma and minor gingival bleeding). We conclude that ticlopidine is an efficient and safe drug for dialysed uremic patients since it can reduce blood clotting and thereby increase dialysis efficiency.

A new expandable artificial heart valve was developed for implantation by a transluminal catheter technique without using thoracotomy or extracorporeal circulation. The aim of this study was to implant the valve in isolated vessels of the descending thoracic aorta as well as in closed chest pigs, and furthermore to study the prosthesis’ mechanical stability and the valve function. The artificial valve was made by mounting a porcine aortic valve on an expandable stent. Before implantation, the stent-valve was compressed on a deflated balloon catheter and mounted inside an introducer sheath. After intravascular introduction to the descending thoracic aorta the stent-valve was discharged from the sheath. Implantation was performed by balloon inflation which expanded the stent-valve to a diameter exceeding the internal vessel's diameter. After balloon deflation the stent-valve maintained an expanded configuration ensuring a stable fixation against the vessel wall. In vitro implantations were performed in 36 isolated descending thoracic aorta specimens obtained from 80 kg pigs. Mechanical stability was evaluated by applying a downing load to the prosthesis. No displacement occurred at loads ≤ 1 kg when a large balloon (31 mm) was used for implantation. Transvalvular pressure differences between 11-47 mmHg (median) were obtained at antegrade flowrates between 5-8 1/min. Furthermore, only moderate leakage flows were measured during retrograde perfusion. In vivo implantations were performed in six 80 kg pigs. Implantation was safe and easy, and angiograph and haemodynamic evaluations revealed essentially no stenosis or regurgitation. No complications in migration, perforation, hemorrhage or thrombosis were observed. This study indicates a good mechanical stability and valve function of the new expandable artificial valves.

An alternative graft is needed for coronary bypass operations in patients lacking suitable autologous vessels. We therefore studied Denaflex™, a biologic graft, in a dog ex-vivo shunt model to determine whether heparin treatment makes this graft less thrombogenic. Comparison was also made to Bioflow™, a nonheparinized biologic graft. Fibrinogen deposition during high flow (593 ± 202 ml/min) decreased from 672 ± 467 ngl mm² in nonheparinized Denaflex grafts to 448 ± 298 ng/mm² (p<0.05) in heparinized Denaflex grafts. At low flow (117 ± 13 ml/min), heparinization of Denaflex grafts similarly decreased fibrinogen deposition from 1102 ± 601 ng/mm² to 703 ± 405 ng/mm² (p<0.05). At both flow rates fibrinogen deposition in Bioflow grafts was less than in nonheparinized Denaflex, but was similar to heparinized Denaflex grafts. Platelet deposition was not influenced by heparinization of Denaflex grafts and was similar among Denaflex and Bioflow preparations. Whether Denaflex performs acceptably in vivo as a xenograft requires extensive study.

For some time the subcutaneous (s.c.) tissue has been the target for continuous glucose measurement. The microdialysis technique permits an extracellular region approach, which has been used for about two decades for measuring various metabolites in dialysates obtained from different body regions. By connecting a s.c. implanted microdialysis probe to a flow chamber of an amperometric glucose sensor, the procedure of glucose sensing was transferred to ex vivo. Using this device it was possible to obtain, for up to 24 hours, s.c. tissue glucose profiles of healthy and diabetic people. The microdialysis theory, the calibration process and other microdialysis technique applications are discussed in this paper. Although the combination of the microdialysis technique and amperometric glucose sensing requires certain technical equipment, the combination of microdialysis and glucose sensor seems to be a promising approach to a continuously functioning glucose sensing system.

The present study was performed to evaluate the morphological response of the peritoneum and spleen to biomaterials. Silicone elastomer, knitted dacron or rubber was implanted, respectively, into a rat's peritoneal cavity and the morphology of the peritoneum and spleen was studied at 4 hours and on the 1^st, 4^th, 7^th and 21^st day after surgery. The morphological changes were identical among groups with different implanted materials. After intraperitoneal implantation of biomaterials from 4 hours and on, an infiltration of inflammatory cells was found in the slackened edematous superficial part of the peritoneum. Also noted in the spleen were stasis, vessel dilatation and fibrin deposition. With the help of scanning electron microscopy, a marked denudation and separation of the mesothelial cells, with infiltration of inflammatory cells, were observed. Peripheral leucocytes significantly increased in number one day after intraperitoneal implantation. Three weeks after intraperitoneal implantation, the materials were completely encapsulated and the morphological aberration of the peritoneum and spleen disappeared. The findings reveal the consequence and the resolution of the host-biomaterial interaction, which could contribute to the explaination of various pathophysiological alterations, including the translocation of enteric bacteria and the development of infectious complications after intraperitoneal biomaterial implantation.