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Biomedical subjects

U Losert

Publications and source records attributed to U Losert.

At least 19 recordsLinked to original sources

Animal experiments with ultra-high molecular weight polyethylene (UHMW-PE) stabilised with alpha-tocopherol used for articulating surfaces in joint endoprostheses.

Numerous investigations proved the impressive suitability of alpha-tocopherol as a stabilizer for ultra-high molecular weight polyethylene (UHMW-PE) used for endoprostheses. Regarding the biocompatibility of this new biomaterial, in-vitro celltoxicity tests gave no hint for a cyto- or genotoxic activity. In this study, animal experiments are carried out to further ensure the biocompatibility of this biomaterial. Thin UHMW-PE-films (20 x 6 x 0.23 mm3) were implanted subcutaneously into rats. Morphology and reactivity of surrounding connective tissue against either pure UHMW-PE material or UHMW-PE containing alpha-tocopherol were studied at timed intervals (2 weeks, 3 month, and 6 month after operation) in 3 groups of animals, each group comprising 10 animals. Parallel to these tests, material changes were investigated in these 3 groups of 10 animals at the same intervals after operation with the help of infrared spectroscopy (FTIR). Within the implantation time, no noteworthy oxidative degradation could be observed. The amount of lost alpha-tocopherol due to diffusion is low enough to ensure a lifetime stabilisation of the UHMW-PE. The implants were all well tolerated and definitely encapsulated already 2 weeks after operation. Presence or absence of alpha-tocopherol in the implants did not evince morphological differences. Therefore, negative consequences were not manifest in the presence of alpha-tocopherol.

Animals↗

Fetal and juvenile animal hemorheology.

The study provides information on the blood fluidity in healthy, juvenile sheep and rabbits during growth (n = 18), and shows also data from fetal rabbits and cats. In the fetal rabbit (n = 3) and cat (n = 2), whole blood viscosity (WBV; LS30, Contraves, Switzerland) and plasma viscosity (PV; OCR-D, Paar, Austria) was low (WBV (0.7 s(-1)): rabbit: 3.28/3.00/2.44; cat: 7.87/10.88; WBV (94 s(-1)): rabbit: 2.57/2.48/2.39; cat: 2.75/3.73 mPa s) (PV: rabbit: 1.10/1.10/1.05; cat: 1.27/1.39 mPa s), which was associated with a low plasma protein concentration and a low erythrocyte count despite a high erythrocyte volume. After parturition, blood viscosity increased in rabbits in parallel with hematocrit, while MCV decreased (WBV (0.7 s(-1)): 9.28 (8.07/10.88); WBV (94 s(-1)): 3.67 (3.62/3.82); PV: 1.15 (1.15/1.25) mPa s). In contrast, in the sheep, whole blood and plasma viscosity decreased after delivery (WBV (0.7 s(-1)): 1.31 (0.94/1.88); WBV (94 s(-1)): 2.45 (2.43/2.85) PV: 1.24 (1.23/1.29) mPa s). Hematocrit and MCV decreased, while erythrocyte count increased under these circumstances. In summary, whole blood viscosity was similar among fetal sheep, rabbits, and cats and is diminished compared to adult individuals to guarantee an optimal oxygen supply during a period of life in which the oxygen maintainance of the child depends on the health and the environment of the mother. However, during growth, blood viscosity rose in rabbits, while it continuously decreased in the sheep. At an unknown time point this fall in blood viscosity in lambs must reverse, since adult sheep again show a higher blood viscosity than juvenile lambs at the age of 2 months.

Analysis of Variance↗

Large interarcuate spaces in the cervical vertebral column of the tyrolean mountain sheep.

Large interarcual spaces have been described between the arcus vertebrae C5/C6 and C6/C7 in the cervical vertebral column of Nubian goats. This aperture enables direct access to spinal cord and rootlets without the need to perform a hemilaminectomy. The present study was performed in order to determine whether these large interarcual spaces can also be found in the vertebral column of the Tyrolean mountain sheep, as this small ruminant, which is anatomically very similar to the Nubian goat, is frequently used for experimental purposes at the Surgical University Clinic in Austria. The carcasses of 10 sheep (six females, four males; range of age: 2.5-6 years, range of weight: 52-89 kg) were dissected and the vertebral column was exposed. All 10 sheep showed elliptic openings between the fourth cervical and the first thoracal vertebrae. Three sheep had additional openings between the first and the second thoracal vertebrae. All openings were covered solitarily by the ligamentum flavum and under this ligamentum lay the spinal cord without any further osseous or ligamentous protection. These findings are not mentioned in the common textbooks of veterinary anatomy and deserve attention, as they can be a step forward towards non-traumatic experimental surgery on the spinal cord.

Animals↗

Activation of nuclear factor-kappa B significantly contributes to lumen loss in a rabbit iliac artery balloon angioplasty model.

BACKGROUND: To investigate the contribution of inflammation to postangioplasty lumen loss, we used an adenoviral gene therapy approach to inhibit the central inflammatory mediator nuclear factor-kappaB (NF-kappaB) by overexpression of its natural inhibitor, IkappaBalpha. METHODS AND RESULTS: The adenovirus carrying human IkappaBalpha was applied immediately after balloon dilatation by a double-balloon catheter in a rabbit iliac artery restenosis model. Immunohistochemistry of IkappaBalpha revealed that mainly smooth muscle cells of the media but also cells of the adventitia were transduced and expressed the transgene IkappaB alpha for >/= 8 days. At this time point, intercellular adhesion molecule-1 (30%) and monocyte chemotactic protein-1 (50%) expression, as well as recruitment of macrophages into the wounded area (90%), were significantly reduced in IkappaB alpha-treated vessels. In addition, expression of inhibitor of apoptosis proteins was reduced and the percentage of apoptotic cells was increased compared with control-treated contralateral vessels. Animals killed 5 weeks after treatment exhibited a significantly reduced degree of lumen narrowing (P<0.02) on the side treated with adenovirus IkappaBalpha. The lumen gain of approximately 40% was due to positive remodeling. CONCLUSIONS: From these data, we conclude that balloon angioplasty-induced activation of NF-kappaB contributes to lumen loss likely via induction of an inflammatory response and a decrease in the rate of apoptosis. These data show for the first time that inflammation mediated by NF-kappaB is involved in postangioplasty lumen narrowing. Specific and more potent inhibitors of NF-kappaB might therefore be a useful therapeutic measure to improve clinical outcome after balloon dilatation.

Adenoviridae↗

Biocompatibility and performance of the Wallstent and several covered stents in a sheep iliac artery model.

PURPOSE: To compare the biocompatibility and performance of various stent-grafts to those of a bare stent in an ovine model with a subchronic (3 months) endpoint. MATERIALS AND METHODS: Three different types of stent-grafts (ePTFE/nitinol, n = 8; polyester/nitinol, n = 8; and polycarbonate urethane/cobalt-alloy, n = 8) and a bare stent as a control (Ni-Co-Ti-steel-alloy, n = 8) were implanted in the iliac arteries in eight female sheep. One type of each stent-graft was implanted per animal, two implants at each side. The implantation sites for each type varied from animal to animal. Angiographic control and intravascular ultrasound (IVUS) imaging were performed before and after implantation, after 2 months, and before explantation at 3 months and were used to characterize patency and to assess intimal hyperplasia. After 3 months, the implants were retrieved and subjected to histologic evaluation (after methacrylate embedding, cutting, and histologic staining) to characterize the biologic response. RESULTS: Implantation was technically successful in all procedures. At 2 and 3 months after implantation, all segments in which stents had been implanted were patent. Marked neointima formation was found in the polyester-covered stent-graft that showed significant luminal narrowing of 50%, compared to the ePTFE-covered (24%) and polycarbonate urethane-covered endoprostheses (22%), as well as the bare stent (Wallstent; 9%; P < .001). A minimal inflammatory vessel wall reaction was demonstrated for the polyester-covered and ePTFE-covered endoprostheses; the polycarbonate urethane-covered stent-graft's response was demonstrable but not significantly different from that of the Wallstent. At 3 months, the ePTFE-covered stent-graft showed incomplete (>90%) endothelial coverage; in the other endoprostheses, complete but partially immature endothelialization was found. CONCLUSION: All stent-grafts induced an inflammatory vessel wall reaction with neointimal hyperplasia. The polyester-covered endoprosthesis caused a marked reaction with 50% luminal stenosis. Endothelialization was retarded with the ePTFE-covered stent-graft. The bare stent performed best in regard to neointimal formation and caused the least inflammatory response.

Alloys↗

Neovascularisation of the testes by experimental omentotesticulopexy.

With the currently used surgical procedures, surgical correction of extreme forms of high undescended testes is associated with an atrophy rate of 10% to 30%. In this experimental study in two groups of Sprague-Dawley rats of pubescent age, we examined whether fixation (pexy) of an omental flap on the testis (omentotesticulopexy = OMTX) permits preservation of the viability of the parenchyma. A left-sided OMTX was performed in group 1 with the animals under general anaesthesia. An omental flap was prepared. The tunica albuginea of the testis planned for OMTX was pierced with a needle (26 x 23 G) within an area with a diameter of 1 cm; a puncture distance of 2 mm was used. The omental flap was then fixed using absorbable monofilament 6-0 interrupted sutures. Six weeks later the spermatic vessel was transected at this site. The right testis was left untouched throughout the procedure; it remained in situ. In group 2 only the spermatic vessel on the left side was severed. The right testis was not manipulated and remained in situ. After a total of 10 weeks both testes were removed from all rats and fixed in formalin. Standardised haematoxylin and eosin staining was performed and histological sections were obtained. The size of the testicles, Leydig-cell count, viability, and calcified areas within the tissue were determined for all testicles. Student's t-test was used for statistical evaluation. The study showed that OMTX leads to neovascularisation in the area of fixation and that viability can be preserved within this area.

Animals↗

Epinephrine application via an endotracheal airway and via the Combitube in esophageal position.

OBJECTIVE: To compare plasma concentrations and cardiovascular effects of epinephrine after application via a conventional endotracheal airway and via the esophageal lumen of a new emergency airway, the esophageal tracheal Combitube. DESIGN: Prospective, randomized study. SETTING: Center for Biomedical Research, University of Vienna. SUBJECTS: Fourteen juvenile swine received either an endotracheal tube (Group A) or a Combitube in esophageal position (Group B). INTERVENTIONS: In Part I of the study, epinephrine was administered during spontaneous beating of the heart; in Part II, epinephrine was administered during cardiopulmonary resuscitation, using a ten-fold higher dosage in Group B, respectively. MEASUREMENTS: Plasma epinephrine levels were measured 1, 2, 3, 5, 7, 10, 15, and 30 mins after application. Systolic arterial blood pressure and cardiac output in Part I, and end-tidal CO2 and coronary perfusion pressure in Part II were recorded. MAIN RESULTS: In Part I, increased levels of plasma epinephrine and systolic arterial pressure were maintained significantly longer in Group B when compared with Group A. In Part II, no significant differences between the groups were found with regard to plasma epinephrine levels and hemodynamic variables. CONCLUSION: Epinephrine applied via the esophageal lumen of the Combitube in a ten-fold higher dosage has similar effects on plasma epinephrine levels and hemodynamic variables compared to endotracheal administration.

Animals↗

[Distraction osteogenesis with a fully implantable system. Experimental study].

Distraction osteogenesis using external or intraoral devices is an established method for lengthening the human mandible. In this preliminary study on sheep, a completely implanted device for mandibular lengthening is presented. After osteotomy of the mandible, the electromechanical device was fixed to the mandible and the power and control unit were inserted subcutaneously in the neck region. After a healing period of 5 days, the device was activated magnetically and allowed calibrated distraction steps of 0.04 mm/h, achieving a total of 1.0 mm per day. With this method, it was possible to lengthen the mandible automatically over a period of 14 days without transmucosal activation. In our study, this newly designed internal device was successfully used for distraction osteogenesis, and a maximum mandibular lengthening of 13.6 mm was achieved. Further research is necessary to achieve progression to human clinical application in the near future.

Animals↗

Microspheres based detoxification system: in vitro study and mathematical estimation of filter performance.

Because of the closed plasma (secondary) circuit in the Microspheres based Detoxification System (MDS), a convective blood purification system, the same amount of filtrated plasma is backfiltrated into the blood circuit. Therefore, there is no direct way to determine the ultrafiltrate production rate, which is an important factor of efficiency. The only possible way to estimate the filtration properties of the filter is to consider pressure values. In this study the pressure distribution in the filter was investigated in vitro. To explain the results and to calculate inaccessible parameters, a mathematical model was established which also considered the asymmetric behaviour of the filter membrane. The result was a linear pressure gradient, agreement with the measurements was reasonably good (calculated primary pressure loss differs <13% from measured value when using mean measured filter resistance as model parameter). Linear pressure distribution offers the possibility of easily calculating the filtration length, a parameter which can be used to estimate the filter condition. The comparison between calculated filtration and backfiltration rates offers an instrument of control for these values.

Adsorption↗

Gene transfer with IL-4 and IL-13 improves survival in lethal endotoxemia in the mouse and ameliorates peritoneal macrophages immune competence.

Systemic anti-cytokine therapies have been unsuccessful in preventing mortality from gram-negative bacteremia in humans partly because of the failure to neutralize pro-inflammatory cytokines at sites of exaggerated production. In an attempt to deliver anti-inflammatory cytokines to organs directly, gene transfer was employed. Thirty-six BALB/c mice were injected intraperitoneally with cationic liposomes containing plasmids encoding the human interleukin-4 (hIL-4) or IL-13 gene. Both, hIL-4 and hIL-13 mRNA were detected by reverse transcription-polymerase chain reaction analysis in the liver and the spleen of the animals. Fourty-eight hours after the in vivo gene transfer, these 36 mice and 18 mock-transfected mice, were challenged with a lethal dose of E. coli lipopolysaccharide with D-galactosamine (D-GalN). Gene transfer with hIL-4 reduced the serum tumor necrosis factor (TNF)-alpha production in response to endotoxin/D-GalN by 80% from 113.1 pg/ml in mock-transfected animals to 22.2 pg/ml (p < 0.05); human IL-13 gene transfer reduced serum TNF-alpha levels by 90% (113.1 pg/ml to 11.6 pg/ml; p < 0.05). Survival was improved from 20% to over 83% in both treatment groups (p < 0.001). Our data demonstrate a potent in vivo anti-inflammatory action of both IL-4 and IL-13. In addition, the immune functions of peritoneal macrophages are significantly ameliorated in both treatment groups, with IL-13 demonstrating better macrophage immune modulation than IL-4 (p < 0.05).

Animals↗

Experimental laparoscopic and thoracoscopic discectomy and instrumented spinal fusion. A feasibility study using a porcine model.

To explore the safety and the effectiveness of laparoscopic and thoracoscopic spinal surgery, an acute/non-survival animal trial was performed in 5 pigs using rigid and flexible endoscopes, flouroscopy, a holmium-YAG laser, and prototype instruments and implants. Our study aimed to approach the intervertebral disc space and spinal canal using laparoscopic and thoracoscopic techniques and to explore the potential and limits for endoscopic anterior spinal decompression and fusion. In a lateral recumbency access was provided to the anterolateral aspect of the lumbar spine from L1/2 to L7/S1, the thoracic spine was accessible from T2/3 to the diaphragmatic insertion. Complete disc space emptying with penetration into the spinal canal could be performed, epidural bleeding could be controlled by a hemostatic sponge, however bleeding restricted visualization for further endoscopic manipulation in the spinal canal. Intervertebral fusion was accomplished at T6/7, L4/5 and L7/S1 using small fragment plates with 3.5 mm screws and iliac bone grafts or prototype carbon fiber cages. On post mortem examination we found no dural tears and no nerve root damage, all animals had stabilized fusion sites and good implant position. We conclude that minimally invasive thoracoscopic and laparoscopic approaches to the spine are feasible and safe to perform disc decompression and implant placement for spinal fusion. In addition to currently performed laparoscopic interbody fusion, also plate fixation to reestablish lordosis of the lumbar spine is feasible at least in the porcine model. Careful disc decompression must be performed prior to implant introduction to prevent iatrogenic disc protrusion and spinal cord or nerve root compression. However, further surgical exploration of the spinal canal using these techniques does not provide adequate visualization of epidural spaces and therefore must be regarded as unsafe.

Animals↗

Experimental bifurcation aneurysm: a model for in vivo evaluation of endovascular techniques.

An experimental aneurysm model for in vivo testing of endovascular techniques is described. The aneurysm is produced surgically in the neck of the rabbit by partial anastomosis of the left to the right common carotid artery, thus creating an arterial bifurcation. Subsequently, a venous pouch is sutured into the artificial bifurcation. The size of the arteries, coagulation profile and hemodynamic features in this aneurysm model closely mimic human conditions. Surgical technique and our preliminary experience with this model are discussed.

Animals↗

Early effects of catecholamine therapy on mucosal integrity, intestinal blood flow, and oxygen metabolism in porcine endotoxin shock.

OBJECTIVE: To determine the early effects of therapy of endotoxin (ET) shock with epinephrine, norepinephrine, or dopexamine on splanchnic circulation, oxygen metabolism, sigmoid mucosal pHi, bacterial translocation, and morphologic integrity of the ileal, colonic, and sigmoid mucosa. SUMMARY BACKGROUND DATA: Conflicting concepts exist concerning the catecholamine therapy of septic shock, but little is known about the effects of catecholamine treatment on splanchnic circulation and mucosal integrity. METHODS: ET shock was induced in pigs by ET infusion over 30 minutes, and animals were studied for 4 hours. All animals were resuscitated with fluid. To mimic the treatment of septic shock in humans, mean arterial pressure was maintained in two groups at >70 mm Hg with the administration of epinephrine or norepinephrine. A third group of animals received dopexamine at 7 microg/kg per minute. Systemic and splanchnic blood flow and oxygen metabolism were studied, sigmoid colon mucosal pHi was obtained tonometrically, and bacterial translocation was determined by culture of portal venous blood, mesenteric lymph nodes, liver, spleen, and lung specimens. Histologic sections of ileal, colonic, and sigmoid mucosa were morphometrically examined for therapy effects. RESULTS: All investigated catecholamines increased cardiac output and systemic oxygen delivery, whereas intestinal blood flow and oxygen delivery remained unchanged. Sigmoid mucosal pHi decreased in all study animals, but the decrease was most pronounced in the epinephrine group. Pigs receiving epinephrine also showed >40% damage of the mucosa of the ileum and colon, whereas animals receiving ET alone, norepinephrine, or dopexamine showed only moderate lesions with signs of restitution. No animal showed bacterial translocation. CONCLUSIONS: Systemic hemodynamics and oxygen metabolism data do not reflect intestinal perfusion. Norepinephrine or dopexamine administration in ET shock causes no additional impairment of intestinal integrity. Epinephrine therapy, in contrast, is associated with a significant reduction of mucosal pHi and considerable early mucosal damage. Its application in septic shock is hazardous.

Animals↗