Biomedical subjects

Ernst Wolner

Publications and source records attributed to Ernst Wolner.

At least 19 recordsLinked to original sources

PubMed2007

Endocrine function is not impaired in patients with a continuous MicroMed-DeBakey axial flow pump.

OBJECTIVES: Pulsatile blood flow has been regarded to be of importance for the regulation of endocrine organs. A new generation of continuous flow mechanical blood pumps is now available for clinical application. Patients with implanted MicroMed-DeBakey axial pumps show nonphysiologic low-pulsatile blood flow profiles, and therefore it appeared to be of interest to evaluate their possible effect on the endocrine system. METHODS: Eight male patients and 1 female patients (mean age, 51 +/- 10 years) with end-stage left-sided heart failure were implanted with a MicroMed-DeBakey axial pump. After a mean period of 67 +/- 19 days, basal pituitary hormone concentrations and their responses to a bolus injection of hypothalamic releasing hormones were tested. In addition, thyroid hormones, testosterone, and plasma and urinary catecholamine levels were measured at baseline. RESULTS: Administration of the hypothalamic releasing hormones revealed normal responses of all pituitary hormones (adrenocorticotropic hormone, thyroid-stimulating hormone, luteinizing hormone, and prolactin), except for growth hormone, the response of which was slightly impaired (10.2 +/- 6.8 vs 19.9 +/- 6.5 ng/L, P < .05). Also, the cortisol response to the corticotropin-releasing hormone-stimulated adrenocorticotropic hormone release was normal, as were basal concentrations of thyroid hormones (triiodothyronine, thyroxine, free triiodothyronine, and free thyroxine), testosterone, and urinary catecholamines. CONCLUSIONS: Implantation of a continuous flow axial pump with low-pulsatile blood flow profile appears to have no major effect on the hypothalamic-pituitary-endorgan system and sympathoadrenal functions. This finding is reassuring for the growing number of patients treated with this convenient new pump and could contribute considerably to their prognosis and quality of life.

Catecholamines↗

PubMed2006

Ten-year follow-up of a prospective, randomized trial of BT563/bb10 versus anti-thymocyte globulin as induction therapy after heart transplantation.

BACKGROUND: Alloantigen-activated T cells express high-affinity interleukin-2 receptor (IL-2R). Specific blockade of this receptor has been associated with lower rejection episodes in clinical transplantation when compared with placebo. The first short-term results of the newer IL-2R antagonists are becoming available but little is known about the long-term effects of these drugs. The aim of the study was to compare the clinical efficacy of the IL-2R antagonist BT563 with polyclonal rabbit anti-thymocyte globulin (ATG) in heart transplant recipients. METHODS: Forty patients undergoing cardiac transplantation were randomly assigned to receive either BT563 or rabbit ATG as induction therapy, combined with triple immunosuppression thereafter. Ten-year surveillance for rejection, infection, allograft vasculopathy and tumorgenicity was performed. Allograft rejection and vasculopathy were assessed by endomyocardial biopsy and coronary angiography, respectively. Screening for infection included blood, urine or tracheobronchial cultures and serology. RESULTS: No difference was detected in terms of 10-year survival between the two groups (50% for the IL-2R group and 70% for the ATG group, p = 0.16). Actuarial incidence of severe rejection was significantly higher in the IL-2R group (55% vs 10% at 10 years post-operatively, p = 0.028; 55% vs 5% during the first month post-operatively, p = 0.0005). Patients receiving ATG had a higher incidence of viral infection. Freedom from allograft vasculopathy was significantly higher in the ATG group (80% vs 60%, p = 0.031). CONCLUSIONS: BT563/BB10 is less effective than ATG for prevention of both acute allograft rejection and allograft vasculopathy after cardiac transplantation. Clinically relevant infections or tumorgenicity were not increased with the use of ATG.

Adult↗

PubMed2006

Granulocyte-based immune response against decellularized or glutaraldehyde cross-linked vascular tissue.

Supporting structures derived from biological tissue have been used in numerous tissue-engineering applications. This study focuses on the immune response of human leukocytes toward decellularized or glutaraldehyde (GA) cross-linked vascular tissue in vitro. Porcine and human pulmonary roots were sterilized with antibiotics, decellularized or cross-linked with GA. Proteins of the vascular tissue were extracted and the migratory response of human leukocytes toward protein extracts was examined using an in vitro migration chamber. Transmigrated leukocytes were counted and subsets (lymphocytes, monocytes, granulocytes) analyzed by flow cytometry. Decellularization significantly reduced the migration of monocytes compared to native porcine tissue. Although the proportion of transmigrating lymphocytes was much lower, decellularization again reduced the migratory response. Surprisingly, after decellularization granulocyte migration was still significantly higher than the negative control. Results comparable to those obtained with porcine material were found when human tissue was used for the experiments. Interestingly, migratory behavior toward extracts of GA-fixed porcine tissue was similar to that of decellularized specimens. We have shown that decellularization of vascular tissue reduces lymphocyte and monocyte recruitment comparable to cross-linking treatment. However, the migration of granulocytes, which are also known to be strongly involved in early inflammatory reactions, could be abolished neither by decellularization nor by fixation with GA.

Animals↗

PubMed2006

Transposition of the supraaortic branches for extended endovascular arch repair.

BACKGROUND: Supraaortic branches limit extended application of endovascular aortic repair. For this purpose, we applied extensive reconstructions. METHODS: Between October 2002 and March 2005, 11 patients (mean age 72.3 years) presented with acute or chronic aortic diseases originating from the aortic arch (arch aneurysms n=8, type B dissections n=3). Treatment was by autologous sequential transposition of the left carotid artery into the brachiocephalic trunk and of the left subclavian artery into the already transposed left common carotid artery in nine patients and by additional reconstruction of the brachiocephalic trunk in two patients. Endovascular stent-graft placement was successfully performed thereafter. RESULTS: Procedure-related mortality was 0%. At completion angiography, all reconstructions were fully patent. One patient had a small type Ia endoleak that resolved spontaneously within one week. Mean follow-up was 18 months (1-29 months). One patient underwent redo stent-graft placement after 25 months due to a type III endoleak. The remaining patients had normal follow-up CT scans with regular perfusion of the supraaortic branches without any signs of endoleaks. CONCLUSIONS: Extended application of this technique will enable safe and effective treatment of a highly selected group of patients by avoiding conventional repair.

Acute Disease↗

PubMed2006

Inflammation and postinfarct remodeling: overexpression of IkappaB prevents ventricular dilation via increasing TIMP levels.

OBJECTIVE: Nuclear factor-kappa B (NF-kappaB) orchestrates genes involved in inflammation and extracellular matrix (ECM) remodeling following myocardial infarction (MI). The objective of the present study was to investigate the effect of overexpression and mode of function of IkappaB, the natural inhibitor of NF-kappaB, on ECM remodeling in a rat model of MI. METHODS: MI was induced in male Sprague-Dawley rats by ligation of the left anterior descending coronary artery (LAD) and was followed by adenovirus-mediated intramyocardial transfection of IkappaB (n = 26) or LacZ reporter genes (n = 26). Sham-operated animals (n = 14) served as controls. RESULTS: In transthoracic echocardiography 49 days after MI, systolic and diastolic left ventricular dimensions were reduced while fractional shortening was preserved in the treatment group. Additionally, evaluation on the isolated heart showed an attenuated downward shift of pressure-volume relationships in the IkappaB group compared to LacZ. NF-kappaB p65 DNA binding activity was diminished both at 5 and 49 days post-MI in the treatment group. Five days post-MI in the treatment group, protein levels of tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta were significantly reduced by 72.6% and 73.2%, respectively, compared to LacZ (p<0.05). In parallel, matrix metalloproteinase (MMP)-2 and MMP-9 levels were reduced 5 days post-MI, with MMP-9 still being decreased 49 days post-MI (p<0.01). In contrast, tissue inhibitors of metalloproteinases (TIMP)-1, -2, and -3 were increased compared to LacZ (p<0.01 and p<0.05, respectively) 5 days post-MI. After 49 days, TIMP-2, -3, and -4 expressions were significantly elevated (p<0.05). CONCLUSION: Reducing NF-kappaB activity via IkappaB overexpression after MI positively influences ECM remodeling by reducing MMP-2 and -9 levels while increasing TIMP-1, -2, -3, and -4 levels. Therefore, IkappaB overexpression prevents ventricular dilation and consequently preserves cardiac function.

Animals↗

PubMed2006

Long-term neurocognitive function after mechanical aortic valve replacement.

BACKGROUND: Mechanical aortic valves are a possible source of microemboli potentially causing cerebral injury. Therefore, the long-term impact of mechanical aortic valve replacement on neurocognitive function is uncertain. METHODS: In this prospective, contemporary study, we followed 32 consecutive patients (aged 51 +/- 8 years; range, 38 to 70; EuroSCORE [European System for Cardiac Operative Risk Evaluation] 4.4 +/- 1.7) undergoing isolated aortic valve replacement with a mechanical prosthesis. A cohort of age- and sex-matched patients (n = 28, aged 50 +/- 7 years) served as nonsurgical controls. After aortic valve replacement, neurocognitive function was serially reevaluated at 7-day (n = 32), 4-month (n = 31), and 3-year (n = 29) follow-up. Neurocognitive function was measured by means of P300 auditory evoked potentials. RESULTS: Before the operation, P300 peak latencies were comparable between surgical patients (361 +/- 32 ms) and nonsurgical controls (365 +/- 33 ms, p = 0.783). In patients undergoing aortic valve replacement, P300 peak latencies were prolonged 7 days after surgery (380 +/- 32 ms) as compared with before the operation (361 +/- 32 ms, p < 0.0001) and as compared with nonsurgical controls (364 +/- 34 ms, p = 0.002). At 4-month (369 +/- 30 ms, p = 0.752) and 3-year (370 +/- 31 ms, p = 0.825) follow-up, P300 peak latencies normalized as compared with before operation and as compared with nonsurgical controls (4-month follow-up 363 +/- 31 ms, p = 0.832; 3-year follow-up 366 +/- 32 ms, p = 0.432). We found no difference in patients with different valve types. CONCLUSIONS: Despite previous assumptions based on the potential occurrence of microemboli in patients with mechanical valves, mechanical aortic valve replacement has no adverse long-term impact on neurocognitive function. This finding is only valid for patients with a comparable age range undergoing isolated aortic valve replacement.

Adult↗

PubMed2006

Late vascular complications after extracorporeal membrane oxygenation support.

BACKGROUND: Extracorporeal membrane oxygenation support through the groin vessels is an established treatment option for patients with life-threatening conditions, resistant to medical treatment. However, because of critical status and type of vascular access, late vascular complications are a potential risk. METHODS: From January 1998 through December 2004, 174 adults (mean age, 45 +/- 19 years) undergoing either cardiac surgery (n = 54, 31.4%) or lung transplantation (n = 120, 68.6%) were supported with extracorporeal membrane oxygenation. Data were prospectively collected and retrospectively analyzed. Follow-up extended up to 60 months (mean, 30 +/- 10 months). Multivariable regression analysis was used to identify predictors of late vascular complications. RESULTS: Hospital survival was 57.3%. A total of 12 hospital survivors (12.2%) experienced late vascular complications. All late vascular complications were local stenosis at the former arterial cannulation site. Treatment was done by means of femorofemoral crossover bypass (n = 3), iliofemoral bypass (n = 1), thromboendarterectomy (n = 3), and percutaneous transluminal angioplasty (n = 5). We experienced no limb loss during follow-up. Predictors for long-term vascular complications were technical problems during extracorporeal membrane oxygenation explantation (p = 0.002; odds ratio, 23.2) and history of peripheral vascular disease (p = 0.015; odds ratio, 3.1). CONCLUSIONS: Extracorporal membrane oxygenation support is associated with the development of late vascular complications at the femoral access site. In selected patients alternative cannulation sites should be considered.

Adult↗

PubMed2006

Management of central coronary sinus ruptures using the pericardial patch repair technique.

BACKGROUND: Intraoperative coronary sinus rupture is a rare event; however, it carries potential mortality and its' management is technically challenging. A repair technique should provide adequate bleeding control while avoiding narrowing or stricture of the coronary sinus. METHODS: We retrospectively review our experience with a new pericardial patch repair technique. From January 1996 to May 2005 four cases of intraoperative coronary sinus injury were identified. Three female patients and one male patient with a mean age of 74 +/- 4 years underwent valve replacement and/or coronary artery bypass on cardiopulmonary bypass. A double pericardial patch technique sandwiched with human fibrin glue was used to cover the defect. RESULTS: In all patients treated with this method, the injury could be treated successfully. All patients were extubated on the first postoperative day and median intensive care unit stay was 3 days. Drains could be removed after 4 days median. Median hospital stay was 13 days. After a median follow-up of 33 months all patients are alive without any echocardiographic signs of impairments of the coronary sinus. CONCLUSIONS: We conclude that the pericardial patch technique is a safe and technically feasible technique for repair of central coronary sinus ruptures. Excellent bleeding control and, in our experience, no consecutive complications were observed.

Aged↗

PubMed2006

Treatment of acute type a dissection by percutaneous endovascular stent-graft placement.

Acute type A dissections are a life threatening condition requiring immediate surgical intervention to avoid aortic rupture or pericardial tamponade. Success of surgical intervention is markedly limited in those patients with advanced age, neurological deficits, and multiple co-morbidities at the time of treatment. We report the successful endovascular stent-graft treatment in a patient suffering from an acute type A dissection. Due to the presence of multiple comorbidities the patient was considered too high risk for surgical treatment.

Acute Disease↗

PubMed2006

Cystic formation of the foramen ovale mimicking a right atrial myxoma.

A 65-year-old woman presented with shortness of breath, stenocardia, and tachycardia. She underwent several steps of examination. Echocardiography showed a suspicious formation in the right atrium extending into the inferior caval vein. The lesion was suspicious for a myxoma, a thrombus, or a malformation. Intraoperatively this formation presented as a cystic formation connected to the right atrial wall in the area of the foramen secundum and filled with blood and five calcified thrombi. We hypothesize that a slit-like opening in the foramen ovale produced a valve-like mechanism bulging parts of the septum secundum and produced this cystic formation.

Aged↗

PubMed2006

Invited commentary.

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Disease Susceptibility↗

PubMed2006

The incidence of reoperations in pacemaker recipients.

OBJECTIVE: To evaluate the incidence of reoperation due to complications or battery depletion in patients who underwent endocardial permanent pacemaker implantation during an 8-year period. METHODS: All pacemaker implantation and related procedures from January 1996 to June 2003 were retrospectively collected and entered into a database. During this time period a total number of 3856 operations with 2242 primary implantations and 1614 redo operations were performed at our department. As 809 patients were referred from another hospital, where the primary operation was done, these patients were excluded from further analysis. The mean follow-up time was 48 months, ranging from 6 to 96 months. RESULTS: A total of 547 patients underwent 805 reoperations during this 8-year period. The most common cause for reoperation was lead malfunction, which occurred in 326 patients (8.4%). Atrial leads were affected more commonly (206 patients, 63%) than ventricular leads (120 patients, 37%). Eighty percent of lead failure occurred during the first 3 months after implantation and was due to dislocation of the lead, whereas the remaining 20% occurred more than 3 months after implantation and were caused by lead fracture, insulation failure, and exit block. Elective replacement indication of a pacemaker was necessary in 312 patients (8%), and pacemaker pocket erosion or infection required reoperation in 167 patients (4%). CONCLUSION: Permanent pacemaker implantation is now accepted as a highly effective and safe procedure. However, cost effectiveness and the relatively simple procedure have to be weighed against the need of reoperations due to system malfunction or replacement indication.

Aged↗

PubMed2006

Decellularization does not eliminate thrombogenicity and inflammatory stimulation in tissue-engineered porcine heart valves.

BACKGROUND AND AIM OF THE STUDY: In tissue engineering of heart valves using decellularized xenogenic valves, it has been suggested that cell elimination would result in a biologically inert matrix. The aim of this in-vitro investigation was to evaluate different decellularization methods in regard to the completeness of cell removal, inflammatory response, and thrombocyte activation. METHODS: Decellularized porcine Synergraft valves were compared with porcine pulmonary conduits decellularized with Triton X-100, sodium deoxycholate, Igepal CA-630 and ribonuclease. Completeness of decellularization was evaluated with staining for nuclei and alpha-Gal epitope. Decellularized heart valves with and without seeding with endothelial cells (ECs) were incubated with human platelet-rich plasma and stained for CD41 and PAC-1 to evaluate thrombocyte activation. Samples were processed for laser scanning microscopy (LSM) and scanning electron microscopy (SEM). Migration of human monocytic cells towards extracted valve proteins was tested. RESULTS: In contrast to the Synergraft, complete cell removal and elimination of the alpha-gal epitope was achieved with the new decellularization method. Numerous adherent and activated platelets were found on the decellularized matrix. This was inhibited by seeding with ECs. Even in completely cell-free valve tissue extracellular matrix proteins attracted human monocytic cells as in early inflammation, depending on whether porcine or human tissue was used. CONCLUSION: Important differences were found in the decellularization efficacy of treatment methods. However, even complete elimination of cells and their remnants did not result in a biologically inert matrix. The decellularized porcine heart valve matrix has the potential to attract inflammatory cells and to induce platelet activation. These findings suggest that it will be important to control the different inflammation-stimulating factors if porcine tissues are to be used successfully in tissue engineering.

Animals↗

PubMed2006

Apoptosis-specific activation markers in on- versus off-pump coronary artery bypass graft (CABG) patients.

BACKGROUND: The relation of epithelial/endothelial apoptosis and secretion of death-inducing receptors (DIR) in comparison to vascular adhesion molecules is not known in patients undergoing the On- versus Off-pump coronary artery bypass graft (CABG) procedure. METHODS: 30 patients were prospectively included in the study (On- vs. Off-pump CABG, each n = 15). Serum samples were obtained prior to, and 30 minutes, 60 minutes and 24 hours after CABG operation. ELISA was utilized to detect caspase-cleaved cytokeratin-18 (CK18) by means of M30 antibody, soluble VCAM-1, soluble ICAM-1, and soluble DIR TNFR-1 and CD95. RESULTS: Soluble caspase-cleaved CK18 was increased and leveled to initial values at 24 hrs. sICAM-1 showed a significant decrease at 30 minutes and 60 minutes in comparison to preoperative values. sTNFR-1/sCD95 showed a rise that was not significant to preoperative values. CONCLUSION: These results indicate for the first time that epithelial/endothelial apoptosis is occurring in patients undergoing bypass operation, irrespective of the CABG procedure selected.

Apoptosis↗

PubMed2005

Donor total lung capacity predicts recipient total lung capacity after size-reduced lung transplantation.

BACKGROUND: Size-reduced lung transplantation has only recently undergone widespread use, especially in highly urgent cases. However, it is still not considered standard procedure at most centers. It has the potential to alleviate the donor organ shortage by allowing the use of oversized grafts for small and pediatric recipients. Limited data exist on pre-operative parameters predicting functional outcome after lung transplantation in general, especially after size-reduced lung transplantation. METHODS: All 98 patients undergoing primary lung transplantation during a 2-year period, including 27 size-reduced lung transplantations, were analyzed retrospectively. Pre-operative functional parameters were-after correction of estimated values according to the amount of size reduction-correlated with post-operative functional assessment. Actual and predicted total lung capacity (TLC) of transplant recipients and predicted TLC of donors was compared with the best post-operative TLC achieved within 12 months after transplantation. RESULTS: Size-reduced lung transplantation was performed in 27 cases. Downsizing was achieved by lobar transplantation (n = 9), split-lung transplantation (n = 2) or peripheral segmental resection (n = 16). There was a statistically highly significant (p < 0.01) correlation between donor TLC and best recipient TLC achieved after transplantation (Pearson's correlation coefficient = 0.675). No statistically significant correlation was seen between pre-operative recipient actual TLC and best post-operative TLC (p = 0.87; Pearson's correlation coefficient = 0.415). In standard lung transplant recipients post-operative TLC was correlated with both donor predicted TLC (p < 0.01; Pearson's correlation coefficient = 0.509) and actual pre-operative recipient TLC (p < 0.01; Pearson's correlation coefficient = 0.667). CONCLUSIONS: Post-operative recipient TLC in size-reduced lung transplantation can be predicted by donor TLC rather than pre-operative recipient TLC.

Adolescent↗

PubMed2005

Tissue engineering of heart valves: decellularized porcine and human valve scaffolds differ importantly in residual potential to attract monocytic cells.

BACKGROUND: Tissue-engineered or decellularized heart valves have already been implanted in humans or are currently approaching the clinical setting. The aim of this study was to examine the migratory response of human monocytic cells toward decellularized porcine and human heart valves, a pivotal step in the early immunologic reaction. METHODS AND RESULTS: Porcine and human pulmonary valve conduits were decellularized, and migration of U-937 monocytic cells toward extracted heart valve proteins was examined in a transmigration chamber in vitro. Homogenized tissue specimens were size fractionated by SDS-PAGE. The decellularization procedure effectively reduced the migration of human monocytes toward all heart valve tissue. However, only the antigen reduction of human pulmonary valves abolished the monocytic response (wall, 0.88+/-0.19% versus 30.20+/-3.93% migrated cells [mean+/-SEM]; cusps, 0.10+/-0.06% versus 10.24+/-1.83%) and was significantly lower (P<0.05) than that of the decellularized porcine equivalent (wall, 5.03+/-0.14% versus 24.31+/-2.38%; cusps, 3.18+/-0.38% versus 10.24+/-1.83%). SDS-PAGE of the pulmonary heart valve tissue revealed that considerable amounts of proteins with different molecular weights that were not detected in the human equivalent remain in the decellularized porcine heart valve. CONCLUSIONS: We describe for the first time that the remaining potential of decellularized pulmonary heart valves to attract monocytic cells depends strongly on whether porcine or human scaffolds were used. These findings will have an important impact on further investigations in the field of heart valve tissue engineering.

Animals↗

PubMed2005

Effect of laser perforation on the remodeling of acellular matrix grafts.

Autologous cells migrate only slightly into acellular matrix grafts. This study was carried out in small-diameter, allogeneic matrix grafts to investigate the effects on cell repopulation and remodeling caused by increased wall porosity induced by laser perforation. Allogeneic ovine carotid arteries were decellularized by dye-mediated photooxidation (Photofix). Matrix grafts (10 cm x 4 mm i.d.) were perforated with holes of 50 microm diameter at a density of 50 holes/cm(2) using a Ti-sapphire laser. The grafts were implanted in the carotid arteries of 10 sheep and were compared to nonperforated grafts implanted contralaterally. The prostheses were retrieved after 6 weeks or 3 or 6 months following implantation and were evaluated by histologic examination, immunohistochemical staining, and scanning electron microscopy. All grafts, except one of the perforated specimens, remained patent. Perforated implants, examined at 6 weeks, showed faster recellularization with endothelial cells than did the corresponding contralateral controls. Perforated grafts, examined at 6 months, showed a significantly thicker neointima and clear signs of neovascularization: endothelial cells, basal lamina, elastic fibers, circular and longitudinally orientated smooth muscle cells in comparison to nonperforated specimens. Repopulation of the decellularized matrix with host cells was higher in the perforated than in the nonperforated prostheses. These results suggest that the increased matrix porosity induced by laser perforation promotes graft remodeling and reconstitution with host cells.

Animals↗

PubMed2005

Successful treatment of an aortoesophageal fistula after emergency endovascular thoracic aortic stent-graft placement.

We report the case of a 57-year-old man who underwent emergency stent-graft placement in August 2003 due to a contained rupture of a distal descending aortic aneurysm. After 1 month the patient was readmitted with chest pain as well as swallowing disorders. A computed tomographic scan revealed a fistula between the distal esophagus and the excluded aneurysm sac. The patient was treated by an esophagectomy, a cervical esophagostomy, as well as a feeding gastrostomy. The infectious parietal thrombus was partially debrided and the aneurysm sac was filled with vancomycin. After 3 months continuity was reinstalled with a pedicled isoperistaltic transverse colonic conduit. The patient recovered uneventfully. At a 3 month follow-up, he showed no signs of infection. However, he is still being treated with antibiotic therapy of ciprofloxacin for a minimum of 1 year.

Aortic Aneurysm, Thoracic↗