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Biomedical subjects

G Zünd

Publications and source records attributed to G Zünd.

At least 55 records · Page 3Linked to original sources

Tissue engineering: a new approach in cardiovascular surgery--seeding of human fibroblasts on resorbable mesh.

INTRODUCTION: In tissue engineering the material properties of synthetic compounds are manipulated to enable delivery of dissociated cells onto a scaffold in a manner that will result in in vitro formation of new functional tissue. The seeding of human fibroblasts on resorbable mesh is a precondition of a successful creation of human tissue such as autologous cardiac valves. MATERIAL AND METHODS: Polymeric scaffolds (n = 12) composed of polyglycolic acid (PGA) with a fiber diameter of 12-15 mm and a polymer density of 70 mg/ml were used as square sheets of 0.3 x 1 x 1 cm. Fibroblasts (passage 5), harvested from human foreskin, were seeded (3.4 x 10(6)) and cultured over a 3 week period on a PGA mesh. RESULTS: Microscopic examination of the seeded mesh demonstrated that the human fibroblasts were attached to the polymeric fibers and had begun to spread out and to divide. Electron microscopy showed a continuous distribution and formation of the cells throughout the "polymeric architecture". Spotlike hydrolysis of PGA fibers was observed. After 3 weeks the seeded scaffolds resembled a solid sheet of tissue. CONCLUSION: These preliminary results, successful seeding of human fibroblasts on a PGA mesh, represent a first basic step on the way to construct human tissue such as autologous cardiac valves and demonstrate that tissue engineering might be a promising new device in therapy of cardiovascular disease.

Cells, Cultured↗

[The significance of endothelial adhesion molecules in heart surgery].

Myocardial ischemia and reperfusion is a common event in cardiovascular surgery patients. The endothelium has been shown to play a key role in the injury suffered after ischemia and reperfusion. When endothelial cells became hypoxic followed by reoxygenation they become activated to express endothelial adhesion molecules followed by the migration of neutrophils into the tissue. These changes may contribute to the early postoperatively myocardial dysfunction. An increased understanding of the interaction between leukocytes and endothelium may allow to develop new therapies in future.

Animals↗

[False aneurysm in Behçet's syndrome].

HISTORY AND CLINICAL FINDINGS: A 32-year-old man developed acute right-sided sore throat, a thick voice and epistaxis. 13 years previously he had erythema nodosum, 12 and 10 year ago deep vein thrombosis. On admission he had Horner's syndrome, bulging of the gums and swelling of the paratracheal space. He had been on anticoagulation therapy with phenprocoumon since the leg vein thrombosis. INVESTIGATIONS: Computed tomography demonstrated a false aneurysm of the right internal carotid artery. 9 months later a right radial artery aneurysm occurred, which was treated surgically. An arterial cannula had previously been placed at this site for pressure monitoring. 2 months later a false aneurysm of the right femoral artery was diagnosed: it had previously been used for an intravascular intervention. As embolization to the popliteal artery occurred after sonographically controlled compression had failed and reduction of anticoagulation treatment, this aneurysm, too, was treated surgically. DIAGNOSIS, TREATMENT AND COURSE: Because of the tendency to aneurysm formation after arterial puncture and the history of venous thromboses the diagnosis of Behçet's syndrome was considered, confirmed by subsequently elucidated history of recurrent oral aphthous ulcers and folliculitis. There were no other manifestations of the syndrome. Immunosuppressive treatment was instituted after another two aneurysm recurrences were noted in the right common femoral artery. CONCLUSIONS: This case illustrates that the diagnosis of Behçet's syndrome may be made more difficult if its manifestation is primarily vascular with minimal mucocutaneous involvement. It should be considered in the differential diagnosis of recurrent arterial aneurysms in a young person.

Adult↗

Reoxygenation of hypoxic human umbilical vein endothelial cells activates the classic complement pathway.

BACKGROUND: Ischemia-reperfusion injury leads to the activation and endothelial deposition of complement. We investigated whether exposure of human umbilical vein endothelial cells (HUVECs) to hypoxia and/or reoxygenation activates complement and decreases HUVEC-surface expression of the C3 regulatory proteins CD46 and CD55. METHODS AND RESULTS: HUVECs were subjected to 0, 12, or 24 hours of hypoxia (O2 = 1%) and then reoxygenated for 3 hours (O2 = 21%) in the presence of 30% human serum. C3 deposition and HUVEC-surface expression of CD46 and CD55 were evaluated by ELISA and flow cytometry. C3 deposition on HUVECs subjected to 12 or 24 hours of hypoxia followed by 3 hours of reoxygenation was significantly greater than normoxic HUVECs. Inhibition of the classic but not the alternative complement pathway during reoxygenation attenuated C3 deposition. Western blot analysis of HUVEC lysates under reducing conditions demonstrated significantly increased iC3b deposition in hypoxic/reoxygenated HUVECs compared with normoxic HUVECs. FACS analysis confirmed iC3b deposition. HUVEC-surface expression of CD46 and CD55 increases after hypoxia and/or reoxygenation. CONCLUSIONS: We conclude that (1) hypoxia and reoxygenation of HUVECs significantly increases iC3b deposition on HUVECs, (2) C3 deposition after hypoxia and reoxygenation is largely mediated by the classic complement pathway, and (3) HUVEC-surface expression of CD46 and CD55 increases after hypoxia and reoxygenation. These data demonstrate that hypoxia and reoxygenation of human endothelial cells activates the classic complement pathway despite an increase in complement C3 regulatory proteins.

Antigens, CD↗

[Aortic valve insufficiency in Crohn disease].

We report on a 39-year-old man with Crohn's disease who was admitted with cardiogenic shock after a short history of progressive dyspnea. Echocardiographic examination (transthoracic echocardiography) showed severe aortic regurgitation, mild mitral regurgitation, and enlargement of the sinus of Valsalva and of the ascending aorta at the level of the right pulmonary artery. The left ventricular ejection fraction was 30%. After aortic valve replacement, histologic examination of the ascending aorta showed chronic aortitis resembling syphilitic aortitis (serology for syphilis was negative) and HLA B27 related aortitis. The aortic valve showed deformation and thickening of the cusps by fibrous tissue without evidence of endocarditis. The patient remained well after surgery and echocardiographic examination 6 months later showed normal function of the aortic valve prosthesis. The diameter of the sinus of Valsalva and of the ascending aorta was slightly bigger, possibly indicating ongoing destruction. The left ventricular ejection fraction nearly normalized. It seems possible that this type of aortitis, characterized by its proximity to the valve ring, is another extraintestinal cardiac manifestation of Crohn's disease. The possibility of ongoing destruction of the sinus of Valsalva and of the ascending aorta after valve replacement makes regular echocardiographic control necessary.

Adult↗

New approach to patency and flow assessment after left internal thoracic artery hypoperfusion syndrome with additional saphenous vein graft to the left anterior descending artery with phase-contrast magnetic resonance angiography.

OBJECTIVE: Perioperative and early postoperative flow reduction of a left internal thoracic artery conduit is a rare complication of myocardial revascularization and may lead to the potentially fatal left internal thoracic artery hypoperfusion syndrome. It has been advocated that an additional vein graft be placed to the distal left anterior descending artery to provide sufficient myocardial perfusion. Some evidence exists, however, that this high-flow vein might lead to competing or even backward flow through the internal thoracic artery. METHODS: In the past 2 years, 21 patients received an additional vein graft to the distal left anterior descending artery for left internal thoracic artery hypoperfusion syndrome. Nineteen of these patients were available for magnetic resonance imaging. Early (< 6 months) and late (> 12 months) postoperative flow measurements, both in the left internal thoracic artery and in the saphenous vein grafts, were performed by means of conventional and a segmented k-space phase-contrast magnetic resonance angiography technique. RESULTS: Early magnetic resonance examinations indicated that all conduits had adapted to the coronary flow type with predominant diastolic perfusion. Patency rate both at the early and at the late study was 100%. No concurrent flow, flow reversal, or steal phenomena were observed. Mean flow rates were 49.2 ml/min for the left internal thoracic artery and 72.6 ml/min for the saphenous vein graft. CONCLUSION: On the basis of the flow data obtained with magnetic resonance angiography, the use of an additional saphenous vein graft as the treatment of choice in left internal thoracic artery hypoperfusion syndrome does not lead to occlusion of the artery. Conduit flow adaptation to the diastolic predominance occurs in the first 6 months after operation.

Coronary Vessels↗

In situ repair of aortobronchial, aortoesophageal, and aortoenteric fistulae with cryopreserved aortic homografts.

PURPOSE: The surgical treatment of fistulae that originate from aortic aneurysms or prosthetic aortic grafts carries a high mortality rate. We investigated whether in situ repair with cryopreserved aortic homografts would improve the outcome. METHODS: Between April 1994 and June 1996, 11 patients (mean age, 62 +/- 10 years) with aortobronchial, aortoesophageal, or aortointestinal fistulae originating from mycotic aneurysms (five of 12) or prosthetic aortic grafts (six of 12) underwent in situ replacement of the thoracic (seven of 10) or abdominal (four of 10) aorta with homografts. Emergency surgery was performed in eight of 11 patients (73%). RESULTS: The hospital mortality rate was 9%; there was one sudden cardiac death on the seventh postoperative day. The mean hospital stay was 42 +/- 26 days (range, 21 to 90 days). After surgery, antibiotics were given for 38 +/- 6 days (range, 28 to 42 days). Neither reinfection, suture line rupture, nor anastomotic aneurysms were observed by magnetic resonance angiography, computed tomography, angiography, or transesophageal echocardiography after 14.3 +/- 8.2 months (range, 6 to 31 months). In one patient, percutaneous vascular stent placement was necessary after 18 months for an anastomotic stenosis of a thoracic homograft. CONCLUSIONS: In situ repair with cryopreserved aortic homografts seems to be a promising step in the treatment of aortobronchial, aortoesophageal, and aortointestinal fistulae. This technique has a low operative mortality rate and may prevent reinfection.

Aged↗

Temporary loss of cardiac autonomic innervation after the maze procedure.

OBJECTIVE: Blunted sinus node response to exercise has been reported after the maze operation. We suggested the autonomic vegetative function of the heart to be disturbed after the maze procedure. METHODS: 17 patients, mean age 63 +/- 15 years, with chronic atrial fibrillation for 49 +/- 46 months (range 5-65) underwent the maze procedure during mitral valve surgery. Bicycle stress test, 24-h electrocardiography and heart rate variability were analysed in 11 patients after three and in six after 14 +/- 3 months. Spectral analysis within two frequency bands, vector analysis of the main circular resultant and influence of orthostasis and Valsalva manoeuvre on different R-R intervals were calculated. RESULTS: One patient died from a perioperative ischaemic stroke. At follow-up, all patients were in sinus rhythm. Heart rate reached 84 +/- 14%, the mean circular resultant was 60 +/- 48%, the ratio of the longest to the shortest R-R interval during the Valsalva manoeuvre was 92 +/- 8% and the ratio of maximal to minimal R-R interval after orthostasis was 98 +/- 4% of the age-adjusted normal value. Maximal workload was 116 +/- 31 watts. All patients had abnormal heart rate variability. Heart rate variability was significantly more blunted after three months, than after 14 months (P < 0.05). The minimal heart rate and the difference between the maximal and the minimal heart rate during the 24-h electrocardiography were significantly correlated to the number of normal physiological tests (r = -0.52; P < 0.05; r = 0.71; P < 0.005); for the maximal heart rate, there was a positive trend only (r = 0.44; P = 0.07). CONCLUSIONS: Early after the maze procedure, a nearly total denervation of the sinus node is present, similar as seen after heart transplantation, with partial restoration of the autonomic function after one year. The exercise capacity of the patients was satisfactory.

Adult↗

Hypoxia enhances induction of endothelial ICAM-1: role for metabolic acidosis and proteasomes.

Intercellular adhesion molecule 1 (ICAM-1) is an important molecule in promotion of polymorphonuclear neutrophil transendothelial migration during inflammation. Coincident with many inflammatory diseases is tissue hypoxia. Thus we hypothesized that combinations of hypoxia and inflammatory stimuli may differentially regulate expression of endothelial ICAM-1. Human endothelial cells were exposed to hypoxia in the presence or absence of added lipopolysaccharide (LPS) and examined for expression of functional ICAM-1. Although hypoxia alone did not induce ICAM-1, the combination of LPS and hypoxia enhanced (3 +/- 0.4-fold over normoxia) ICAM-1 expression. Combinations of hypoxia and LPS significantly increased lymphocyte binding, and such increases were inhibited by addition of anti-ICAM-1 antibodies or antisense oligonucleotides. Hypoxic endothelia showed a > 10-fold increase in sensitivity to inhibitors of proteasome activation, and combinations of hypoxia and LPS enhanced proteasome-dependent cytoplasmic-to-nuclear localization of the nuclear transcription factor-kappa B p65 (Rel A) subunit. Such proteasome activation correlated with hypoxia-evoked decreases in both extracellular and intracellular pH. We conclude from these studies that endothelial hypoxia provides a novel, proteasome-dependent stimulus for ICAM-1 induction.

Acidosis↗

Hypoxia enhances stimulus-dependent induction of E-selectin on aortic endothelial cells.

In many diseases, tissue hypoxia occurs in conjunction with other inflammatory processes. Since previous studies have demonstrated a role for leukocytes in ischemia/reperfusion injury, we hypothesized that endothelial hypoxia may "superinduce" expression of an important leukocyte adhesion molecule, E-selectin (ELAM-1, CD62E). Bovine aortic endothelial monolayers were exposed to hypoxia in the presence or absence of tumor-necrosis factor alpha (TNF-alpha) or lipopolysaccharide (LPS). Cell surface E-selectin was quantitated by whole cell ELISA or by immunoprecipitation using polyclonal anti-E-selectin sera. Endothelial mRNA levels were assessed using ribonuclease protection assays. Hypoxia alone did not induce endothelial E-selectin expression. However, enhanced induction of E-selectin was observed with the combination of hypoxia and TNF-alpha (270% increase over normoxia and TNF-alpha) or hypoxia and LPS (190% increase over normoxia and LPS). These studies revealed that a mechanism for such enhancement may be hypoxia-elicited decrements in endothelial intracellular levels of cAMP (<50% compared with normoxia). Addition of forskolin and isobutyl-methyl-xanthine during hypoxia resulted in reversal of cAMP decreases and a loss of enhanced E-selectin surface expression with the combination of TNF-alpha and hypoxia. We conclude that endothelial hypoxia may provide a novel signal for superinduction of E-selectin during states of inflammation.

1-Methyl-3-isobutylxanthine↗

Interleukin-4 and interleukin-13 differentially regulate epithelial chloride secretion.

Intestinal epithelia are in intimate contact with subepithelial and intraepithelial lymphocytes. When stimulated, mucosal lymphocytes generate cytokines that act locally and influence functional aspects of many cell types. We have previously defined functional epithelial receptors for interferon-gamma, interleukin (IL)-4, and a recently described IL-4-like cytokine IL-13. In this study, we examine the ion transport properties of T84 cells, a crypt-like epithelial cell line, following exposure to IL-4 and IL-13. Basolateral exposure of epithelial monolayers to both IL-4 and IL-13 attenuated epithelial barrier function and increased paracellular flux of a dextran marker by greater than 65% in a dose- and time-dependent fashion. Stimulated Cl- secretion, as measured by epithelial short circuit current, however, was diminished only by IL-4 and not IL-13, demonstrating cytokine specificity in this epithelial function. Decreased Cl- secretion following IL-4 exposure was associated with diminished Cl- channel activity and IL-4 pretreatment of epithelia decreased expression of the cystic fibrosis transmembrane regulator. Finally, stimulated fluid transport across cultured epithelia was diminished following exposure to IL-4, but not IL-13. These results indicate that while post-receptor signaling events induced by IL-13 and IL-4 may be similar, end point function is cytokine-specific.

1-Methyl-3-isobutylxanthine↗

[Analysis of early and late results of surgically treated Wolff-Parkinson-White syndrome].

The results of surgical procedures for termination of Wolff-Parkinson-White (WPW) Syndrom were assessed in 59 patients undergoing operation between January, 1980 and December, 1993. All cases of WPW were refractory to medical treatment and 14 of 58 patients had one or several syncopes, and 4 of them had to be reanimated. The surgical treatment of these patients was a dissection of an accessory atrioventricular pathway. 15 patients required additional heart operation. A total of 60 accessory pathways were diagnosed preoperatively, 64 were located intraoperatively. The reoperation rate was 3% (2 patients) due to persistent WPW. Incidence of total AV block after the operation was 7% (4 patients). In the late postoperative stage, 12 patients developed supraventricular tachycardias, but none of these cases required a surgical treatment. The actuarial survival rate after 10 years was 100% and after 14 years 96%. We conclude that surgical dissection of accessory pathways offers a good alternative in cases of unsuccessful catheter ablative procedure or in cases of additional heart operation.

Adolescent↗

Hypoxic stress alone does not modulate endothelial surface expression of bovine E-selectin and intercellular adhesion molecule-1 (ICAM-1).

UNLABELLED: Hypoxemia is a common event in many vascular diseases, especially vascular ischemia. Since endothelial cells of blood vessels are exposed to conditions within the vascular space and leucocytes play a key role in ischemia/reperfusion injury, we hypothesized that endothelial exposure to hypoxia may regulate expression of surface proteins important in leucocyte-endothelial interactions, such as E-selectin and intercellular adhesion molecule (ICAM-1). In this study, we used isolated bovine aortic endothelial monolayers to examine endothelial surface alterations of E-selectin and ICAM-1 induced by tumor necrosis factor-alpha (TNF-alpha), lipopolysaccharide (LPS) and hypoxia using a whole cell enzyme-linked immunosorbent assay (ELISA). Bovine endothelial exposure to TNF-alpha (50 ng/mL) induced a time dependent increase (range 0-24h) in specific E-selection surface expression. Endothelial exposure to hypoxia alone (pO2 approximately 3 mmHg, range 0-24 h), however, failed to elicit endothelial E-selectin expression. Endothelial exposure to LPS brought about a dose- and time-dependent (range 0.5 ng/mL and 2-8 h) increase in specific ICAM-1 surface expression (max. 3.5 +/- 0.15-fold increase over no cytokine control at 10 ng/mL, 4 h). Hypoxia (pO2 approximately 3 mmHg, 8h), however, did not induce ICAM-1 surface expression over normoxia levels. IN CONCLUSION: i) bovine endothelial E-selectin and ICAM-1 surface expression are regulated molecules, ii) hypoxia, per se, does not regulate surface expression of either E-selectin or ICAM-1. These results suggest that hypoxic endothelia may require additional external signals for generation of adaptive inflammatory responses.

Animals↗

[Retrospective analysis of early and late results following surgical intervention in supraventricular arrhythmia].

The results of surgical procedures for treatment of supraventricular tachycardias were assessed in 65 patients undergoing operation between January, 1980 and December, 1993. Indications for intervention were WPW (59 patients), atrial fibrillation (5 patients) and atrial flutter (1 patient). All cases of WPW were refractory to medical treatment and 14 of 58 patients had one or several syncopes, 4 of whom had to be resuscitated. The surgical treatment of these patients was dissection of an accessory atrioventricular pathway. 15 of these patients underwent heart operation for a different indication at the same time. A total of 60 accessory pathways were diagnosed preoperatively, while 4 were located intraoperatively. The reoperation rate was 3% (2 patients) due to persistent WPW. Incidence of total AV block after the operation was 7% (4 patients). In the late postoperative stage, 12 patients developed supraventricular tachycardias, but none of these cases required surgical treatment. The actuarial survival rate after 10 years was 100%, and after 14 years 96%. We conclude that surgical dissection of accessory pathways offers a good alternative in cases of unsuccessful catheter ablative procedures or in cases of concomitant heart surgery. In 6 patients with mitral valve surgery, associated chronic atrial fibrillation was found. A concomitant Maze-procedure was performed for the purpose of surgically converting the atrial fibrillation to a stable sinus rhythm. The early postoperative results are promising.

Adolescent↗

The internal mammary artery malperfusion syndrome: incidence, treatment and angiographic verification.

Internal mammary artery (IMA) malperfusion syndrome is caused by an acute imbalance between myocardial demand and nutritional support through the mammary artery. In a consecutive series of 2326 isolated myocardial revascularizations-with at least one IMA to the left anterior descending branch (LAD) in 91.3% (2125/2326)-we identified 45 patients (1.9%) with a perioperative course suggesting IMA malperfusion syndrome. Additional saphenous vein graft to the distal segment of the LAD was performed during normothermic ventricular fibrillation in all patients. Hospital mortality was 4.4% (2/45), intra-aortic balloon pumping was required in 15.5% (7/45) and anterior myocardial infarction occurred in 28.8% (13/45). Coronary angiography was performed in all survivors between 3 and 24 months postoperatively. Wide patent IMA graft and patent saphenous vein graft were observed in 56% (24/43), narrowed but patent IMA graft and patent vein graft in 35% (15/43), while patent vein graft and not visualized IMA in 7% (3/43); in one patient with severely diseased peripheral LAD, no flow could be demonstrated in the IMA graft or in the additional vein graft (1/43, 2.4%). No major differences were found between early and late coronary angiography in these patients. Additional vein graft to distal LAD is the treatment of choice in acute IMA malperfusion syndrome. Despite patent vein graft with superior blood flow, early and late postoperative IMA flow to LAD is maintained in the majority of patients.

Adult↗

Surgical aspects of popliteal artery entrapment syndrome: 26 years of experience with 26 legs.

The authors present their experience in diagnosis, therapy and follow up of the Popliteal Artery Entrapment Syndrome (PAES) during the last 26 years. PAES appears most frequently in young athletic male patients. From 1967 to 1993, 20 patients, 17 male (85%) and 3 female (15%), with 26 entrapment legs were treated. Average age at the time of the first symptoms was 33.5 years and at the time of diagnosis 38.5 years. Six patients suffered from PAES on both legs. In 5 of the 24 operated cases a re-operation was necessary. One case required a third operation. To reduce the postoperative complication rate, surgical technique was chosen according to the anatomical situation. If there was only slight disease of the popliteal wall, the current surgical technique consisted in decompressing the artery and replacing it in the orthotopic position through a direct entrance with the patient in the prone position. If there was severe disease of the popliteal wall, an autologous venous bypass from the popliteal artery segment I to segment III should be done with the patient supine. In our opinion, a primary catheter lysis therapy, which can be indicated for stenosed arteries, should not be done for peristenotic aneurysms. Successful therapy of PAES largely depends on early diagnosis that has been confirmed by CT scan.

Adolescent↗

Prediction of early cardiac morbidity and mortality following aorto-iliac reconstruction: comparison between clinical scoring systems, echocardiography and dipyridamole-thallium scanning.

Preoperative cardiac assessment may be difficult in patients with aorto-iliac and/or peripheral vascular disease because of severe physical limitation due to the disease itself, advanced age, locomotor problems or because of beta-blocker usage. 216 patients with aorto-iliac occlusive disease were studied; several cardiac risk scoring systems were determined for each patient. Preoperative echocardiography was performed in 182 patients and thallium-scanning in 63 patients. The results from the preoperative risk factor evaluations, echocardiographies and thallium examinations were correlated individually with the postoperative observed cardiac complications. Overall mortality was 2.8% (4 patients died from myocardial infarction). A total of 13 major postoperative cardiac events (10 myocardial infarctions and 3 life-threatening arrhythmias) were registered. No statistical correlation could be identified between the patient's clinical examination nor the scoring system and the occurrence of postoperative cardiac complications. 12 events occurred out of 13 patients who were shown to have a reversible defect on the preoperative thallium scan. These patients also presented hypokinesia or akinesia on the preoperative echocardiography. Thallium imaging and echocardiography represent a valid preoperative test to evaluate the risk of cardiac morbidity and mortality in vascular patients. Coronary angiography is recommended in patients suffering from progressive and/or unstable angina.

Aged↗