Publications (22)60.47 Total impact
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Article: Outcome after mitral valve operations with depressed left ventricular function.
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ABSTRACT: We retrospectively investigated 42 patients (27 men, 15 women; mean age, 67 years) with severe mitral valve incompetence and endstage cardiomyopathy (ejection fraction<30%) who were operated on between January 2002 and March 2009. Of these, 14 were in New York Heart Association class IV, and 27 were in class III. The etiology was ischemic in 18 patients and idiopathic dilated in 24. Mitral valve repair was performed in 25 patients, and 17 had mitral valve replacement. The mean logistic EuroSCORE was 33.41. The mean follow-up was 44.52 months. There were no perioperative deaths. Three patients died within 30 days postoperatively. Thirty-day mortality was lower than predicted by EuroSCORE (7.14% vs. 33.41%). The median functional class improved from 3 to 2 during follow-up. Ejection fraction improved from 24% to 42% at 6 weeks, then decreased to 33%. The midterm survival rate was 86%, and 81% after 1 and 2 years. Freedom from reoperation at 2 years was 85%; 6 patients needed reoperation for recurrent mitral regurgitation. Despite high operative risk, mitral valve surgery can be performed successfully with acceptably low mortality in patients with endstage cardiomyopathy. Patients experience substantial clinical improvement and a moderate recovery of left ventricular function.Asian cardiovascular & thoracic annals 06/2012; 20(3):292-8. -
Article: Wet-chemical approach for the cell-adhesive modification of polytetrafluoroethylene.
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ABSTRACT: Polytetrafluoroethylene (PTFE), a frequently utilized polymer for the fabrication of synthetic vascular grafts, was surface-modified by means of a wet-chemical process. The inherently non-cell-adhesive polymer does not support cellular attachment, a prerequisite for the endothelialization of luminal surface grafts in small diameter applications. To impart the material with cell-adhesive properties a treatment with sodium-naphthalene provided a basis for the subsequent immobilization of the adhesion promoting RGD-peptide using a hydroxy- and amine-reactive crosslinker. Successful conjugation was shown with cell culture experiments which demonstrated excellent endothelial cell growth on the modified surfaces.Biomedical Materials 04/2011; 6(3):035007. · 2.16 Impact Factor -
Article: Covalent RGD Modification of the Inner Pore Surface of Polycaprolactone Scaffolds.
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ABSTRACT: Scaffold production for tissue engineering was demonstrated by means of a hot compression molding technique and subsequent particulate leaching. The utilization of spherical salt particles as the pore-forming agent ensured complete interconnectivity of the porous structure. This method obviated the use of potentially toxic organic solvents. To overcome the inherent non-cell-adhesive properties of the hydrophobic polymer polycaprolactone (PCL) surface activation with a diamine was performed, followed by the covalent immobilization of the adhesion-promoting RGD-peptide. The wet-chemical approach was performed to guarantee modification throughout the entire scaffold structure. The treatment was characterized by means of chemical and physical methods with respect to an exclusive surface modification without altering the bulk properties of the polymer. RGD-modified scaffolds were tested in cell-culture experiments to investigate the initial attachment and the proliferation of three different cell types.Journal of Biomaterials Science Polymer Edition 03/2011; · 1.69 Impact Factor -
Article: Minimum cause--maximum effect: the travelogue of a bullet.
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ABSTRACT: This case report involves a 57-year-old male, accidentally shot in the chest with a small bore firearm. The bullet entered the left hemithorax, disrupting the left internal mammarian artery. It then penetrated the anterior wall of the right ventricle causing a pericardial tamponade. After leaving the base of the right heart it perforated the diaphragm, the liver, the spleen and the pancreas. Finally, it penetrated the abdominal aorta 3 cm proximally to the coeliac trunk and reached its final position paravertebrally. This case report illustrates that the management of even minimum gunshot wounds requires a maximum variety of surgical skills.Interactive cardiovascular and thoracic surgery 11/2010; 11(5):698-700. -
Article: Synthetic (glyco-)peptides of the homophilic recognition domain of E-cadherin lead to increased E-cadherin mRNA synthesis and are inductors of cell differentiation in primary lung cancer cell lines.
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ABSTRACT: E-cadherin is one of the critical molecules involved in the metastatic process in many types of cancer. Once combined, E-cadherin exceeds the amount of membranous E-cadherin on the cellular surface by activation of intracellular signaling cascades. Studies on transformed keratinocytes of the HaCat cell line showed induction of differentiation by synthetical partial structures of the homophilic binding region of E-cadherin. The knowledge of effects in lung cancer cells is sparse. Therefore, the effects in primary lung cancer cell lines were investigated. Four primary lung cancer cell lines were incubated for 3, 6, 12, 15, 18, and 24h with synthetic partial structures (peptide and glycopeptide). The control substance was sodium butyrate. mRNA was isolated, and relative quantification of E-cadherin was performed using the Real-Time PCR. During the stimulation period, morphologic pictures were taken, and immunohistochemical staining of membranous E-cadherin was performed. Life/dead assays were used to display cell vitality. The intracellular E-cadherin mRNA amount was increased after incubation with the synthetic partial structures. Life/dead assays showed improved survival and integrated cell/cell bindings after stimulation with the partial structures. Increased cell mortality was revealed after sodium butyrate incubation. An effect mediated via E-cadherin on the cellular surface is proposed. The two synthetic partial structures of the homophilic binding region of E-cadherin increased the intracellular E-cadherin mRNA amount, cell-cell bindings, and survival of the tumor cells. Extracellular binding by synthetic partial structures to the binding region may have a beneficial influence on tumor progression in the metastatic process.Pathology - Research and Practice 07/2010; 206(7):450-7. · 1.21 Impact Factor -
Article: A follicular dendritic cell sarcoma of the mediastinum with immature T cells and association with myasthenia gravis.
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ABSTRACT: Follicular dendritic cell (FDC) sarcoma is a very rare neoplasm showing morphologic and phenotypic features of FDCs. It occurs primarily in lymph nodes but also in extranodal sites. So far, there have been no reports on FDC sarcoma associated with myasthenia gravis. In the following we will present a case of an FDC tumor of the mediastinum associated with paraneoplastic myasthenia gravis in a 39-year-old man. The tumor contained a major proportion of immature T cells, which may be connected to this patient's very unusual clinical presentation with autoimmune phenomena. Extranodal FDC sarcomas still seem hardly noticed, and their clinical and pathologic characteristics remain to be better defined.The American journal of surgical pathology 03/2010; 34(5):742-5. · 4.06 Impact Factor -
Article: Reevaluation of direct true lumen cannulation in surgery for acute type A aortic dissection.
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ABSTRACT: The optimal mode of arterial cannulation in acute type A aortic dissection is controversial. We retrospectively investigated our experience with direct true lumen cannulation as an alternative to standard cannulation procedures. From April 2004 to August 2007, 29 patients (20 men, 9 women; mean age of 63.2 +/- 12.6 years) underwent emergency operation for acute type A aortic dissection with direct true lumen cannulation. After venous drainage into the venous reservoir, the ascending aorta was completely transected in the region between the sinotubular junction and innominate artery. After visual and digital identification of the true lumen, the arterial cannula was directly inserted into the true lumen and secured with a ligature. Mean aortic cross-clamp time was 77.4 +/- 28.3 minutes, and hypothermic circulatory arrest for the distal anastomosis was 10.4 +/- 11.0 minutes. All patients survived the surgical procedure. No surgical problems were observed by applying this strategy. Mean intensive care unit stay was 4.0 +/- 3.5 days. Postoperative mean ventilation time was 43.3 +/- 41.3 hours. One patient had a prolonged postoperative course and required permanent ventilation. Two patients required temporary hemofiltration. Neurologic disorders occurred in 6 patients: 2 had severe cerebral hypoxia, and 4 had temporary hemiplegia under good regression. All patients were alive at discharge. Direct true lumen cannulation is a promising surgical strategy for emergency operations in type A aortic dissection. It is a simple, quick, and safe method to provide antegrade flow through the true aortic lumen.The Annals of thoracic surgery 05/2009; 87(4):1182-6. · 3.74 Impact Factor -
Article: Subendothelial infiltration of neutrophil granulocytes and liberation of matrix-destabilizing enzymes in an experimental model of human neo-intima.
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ABSTRACT: It was the objective of this study to examine the role of human neutrophil granulocytes (PMN) in an in-vitro model of human neo-intima developed for the study of atherosclerosis. Human granulocytes were subjected to a co-culture model of human endothelial and smooth muscle cells. Subendothelial lipid accumulation was achieved by addition of native LDL to the culture medium. Tissue samples were analyzed by immunohistochemistry and scanning/transmission electron microscopy, and culture supernatants were examined for the presence of interleukin-8 (IL-8), MCP-1, GRO-alpha, elastase and matrixmetalloproteinase-8 (MMP-8). Following addition of 2 mg/ml LDL, adherence, transmigration and infiltration depth of PMN was increased significantly when compared to controls. LDL challenging was paralleled by a time- and dose-dependent secretion of IL-8 from intimal smooth muscle cells. PMN infiltration was mediated by the IL-8-signalling pathway and accompanied by release of elastase and MMP-8 into the supernatant and induction of endothelial cell apoptosis. In conclusion, LDL-induced secretion of IL-8 by intimal smooth muscle cells provides a potential mechanism of PMN-recruitment into culprit lesions. The concomitant release of potent matrix-degrading enzymes and the induction of EC apoptosis may have implications for plaque destabilization and cardiovascular events.Thrombosis and Haemostasis 03/2008; 99(2):373-81. · 5.04 Impact Factor -
Article: Comparison of fondaparinux, low molecular-weight heparin and unfractionated heparin in preventing thrombus formation on mechanical heart valves: results of an in-vitro study.
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ABSTRACT: The study aim was to investigate the efficacy of three different anticoagulants in preventing thrombus formation on mechanical heart valves, using an in-vitro system. Blood samples (470 ml) were taken from young and healthy male volunteers and anticoagulated with unfractionated heparin (UFH; n=18), low molecular-weight heparin (LMWH; n=18) or fondaparinux (n=16). Bileaflet mechanical heart valves were placed in a new device--the 'Thrombosis Tester'--and exposed in a continuous circulation at a rate of 80 beats per min to the anticoagulated blood samples for a total exposure time of 60 min. Results for thrombus weight were skewed distributed and presented as log-transformed values. The weight of each valve was measured before and after 1 h of perfusion; subsequent mean (+/-SD) thrombus weights were 0.739 +/- 0.573 g for UFH, 0.789 +/- 0.099 g for LMWH, and 0.934 +/- 0.145 g for fondaparinux (p = 0.397 for comparison of all groups by ANOVA). Electron microscopy showed concordant results with regard to thrombus formation on heart valve surfaces. Fondaparinux and LMWH were as effective as UFH in preventing thrombus formation on mechanical heart valves in vitro. The 'Thrombosis Tester' proved to be a new, unique instrument for investigating the ability of anticoagulants to prevent valve thrombosis on mechanical heart valves under in-vitro conditions.The Journal of heart valve disease 12/2006; 15(6):809-14. · 0.81 Impact Factor -
Article: Neutrophil adherence to activated saphenous vein and mammary endothelium after graft preparation.
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ABSTRACT: Interaction of circulating leukocytes and vascular endothelium plays an important role in vasoconstriction, endothelial dysfunction, and vascular injury. Dilation procedures of grafts before coronary artery bypass graft surgery might lead to vascular injury and subsequent bypass graft disease. We analyzed in vitro the adherence of fluorescence-labeled polymorphonuclear neutrophils (PMNs) to endothelium of human saphenous vein grafts or internal mammary artery grafts after stimulation with thrombin (0.5 to 2 U/mL) or dilating procedures. Furthermore, we investigated endothelial function of prepared grafts. Thrombin stimulation resulted in a dose-dependent increase of PMN adherence to the endothelium of saphenous vein and internal mammary artery, which was attenuated by the selectin-blocking carbohydrate fucoidin or anti-P-selectin monoclonal antibody. Mechanical dilation of saphenous vein or internal mammary artery led to a marked increase in PMN adherence (65 +/- 5 versus 5 +/- 3 PMN/mm2; p < 0.01), which was significantly attenuated by fucoidin or anti-P-selectin monoclonal antibodies. Treatment of internal mammary artery with the vasodilator papaverine led to a marked increase of PMN adherence (59 +/- 8 versus 12 +/- 4 PMN/mm2; p < 0.01) when papaverine was administered directly into the vessel. However, external treatment with papaverine did not affect PMN adhesion. Endothelial dysfunction was observed in dilated venous grafts and in arterial grafts internally treated with papaverine; in contrast, external treatment did not affect endothelial function. This study showed that mechanical or pharmacologic dilation of venous or arterial coronary grafts, usually performed before anastomosis of aortocoronary bypass grafts, led to increased selectin-mediated PMN adhesion on vascular endothelium and subsequent endothelial dysfunction.The Annals of thoracic surgery 04/2006; 81(4):1262-8. · 3.74 Impact Factor -
Article: A novel in vitro model for the study of plaque development in atherosclerosis.
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ABSTRACT: For the study of atherogenesis in vitro, coculture systems have been devised, in which two or more cell types can be cultured in close contact to each other. Herein, we describe a novel in vitro model that aims at the simulation of the morphology of a normal muscular artery allowing for the study of the initial events in atherosclerosis. Using a modified fibrin gel as a scaffold for the coculture of endothelial cells (ECs) and smooth muscle cells (SMCs), we generated an autologous in vitro model with a multilayer growth of SMCs (intima-like structure) covered by an endothelium. The production of extracellular matrix (ECM) could be visualized histologically and verified by (i) ascorbic-acid dependent secretion of procollagen I into the supernatant and (ii) deposition of collagens I and III as well as laminin in the gel as assessed by immunohistochemistry. By BrdU-incorporation and Ki67 expression, the SMCs exhibited minimal proliferative activity, even when the culture period was extended to 6 weeks. Lipoprotein insudation was investigated under simulated hypo-, normo- and hypercholesterolemic conditions through addition of 0.5, 1 or 2 mg/mL LDL to the medium with subsequent time and dose dependent insudation of LDL. When human monocytes were added to the culture medium, infiltration and foam cell formation of macrophages and SMCs as well as expression of interleukin-8 (IL-8) was demonstrated. The in vitro model of the human vascular wall described herein appears to be suitable for the study of pivotal events in atherosclerotic plaque development. The applicability for long-term culture, the ability to study cell-matrix interactions and the opportunities for histomorphological and immunohistochemical examinations represent additional advantages of this model.Thrombosis and Haemostasis 02/2006; 95(1):182-9. · 5.04 Impact Factor -
Article: Comparison of cardiac troponin I versus T and creatine kinase MB after coronary artery bypass grafting in patients with and without perioperative myocardial infarction.
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ABSTRACT: Cardiac troponins have shown to be specific markers of myocardial injury. The aim of this prospective study was to compare patterns and kinetics of troponin I and T after coronary artery bypass grafting (CABG) with or without perioperative myocardial infarction (PMI). 119 patients (male/female: 96/23, age 64 +/- 10 years) underwent first time elective CABG. Preoperative mean ejection fraction was 55.8% +/- 15.6%. The mean number of grafts was 3.1 +/- 1.1/patient, in 85.7% the internal mammary artery was used. Cardiac troponin I (cTnI) and T (cTnT) levels, total serum activities of creatine kinase (CK) and creatine kinase isoenzyme MB (CK-MB) were measured before operation, at arrival on the intensive care unit (ICU), and 6, 12, 24, 48, and 120 h after unclamping of the aorta. Twelve lead electrocardiograms (ECGs) were recorded preoperatively and at days 1, 2, and 5. Perioperative data and postoperative cTnI and cTnT levels were correlated statistically. Two patients died due to refractory myocardial failure in the early postoperative period. For further evaluation, patients were divided in two groups according to postoperative ECG changes (group I: patients without PMI, n = 107; group II: patients with PMI, n = 10: six of them with Q-wave and four of them with non-Q-wave PMI). Calculated best cutoff values for cTnI and cTnT were 8.35 microg/l and 0.768 microg/l in ROC (receiver-operator characteristic) analysis. Serum concentrations of cTnI, and cTnT were in the normal range preoperatively and increased significantly after surgery in both groups. In both groups, cTnI reached its medium peak level after 24 h (group I: 2.7 microg/l, 95% confidence interval [CI]: [2.1,3.2]); group II: 70.5 microg/l). CTnT reached its medium peak level in group I without PMI after 48 h (0.298 microg/l, 95% CI: [0.254,0.354]), in group II with PMI not until 120 h (3.0 microg/l) postoperatively. In group II serum level of both troponins remained considerably high at 120 h (cTnI median = 10.75 microg/l, cTnT median = 3 microg/l). Release patterns of cTnI and cTnT after CABG are different: cTnI reaches its postoperative peak value earlier and declines more quickly than cTnT. After uncomplicated CABG, serum levels of both cardiac troponins remain continuously low. Elevated concentrations reflect perioperative myocardial ischemia or infarction. CTnT shows a different release pattern in patients with or without myocardial infarction.Herz 12/2004; 29(7):658-64. · 0.92 Impact Factor -
Article: [Cultivation of human cells on polymer covered biomaterial--a new concept to improve the implant characteristics. Results of an in-vitro-investigation].
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ABSTRACT: Calcific degeneration with the resulting need for operative replacement remains the major drawback of bioprostheses. Previous studies have shown that cellular surface seeding decreases calcium uptake in vitro and in vivo, but complete coverage remains difficult to achieve. A new approach is presented, masking glutaraldehyde residues with a covalently bound polymer layer thus facilitating cell seeding. The aim of this study was to evaluate different polymers for their ability to promote surface cell adhesion and formation of complete monolayers. Ten ultrathin polymers, covalently bound to glass and exhibiting different physicochemical characteristics (thickness, molecular weight, hydrophilic properties, electrical charge) were seeded with human endothelial cells. Four of the ten polymers were also seeded with fibroblasts. As a reference, both cell types were seeded on glass surface. Quality of cell growth and coverage was evaluated by light and scanning electron microscopy. Five of ten polymers and glass exhibited excellent growth and complete surface coverage after 2 weeks, two allowed less cell adherence than glass reference, and three showed only poor cellular growth without adherence. Scanning electron microscopy demonstrated an intact monolayer for the five polymers with excellent cell coverage. Fibroblasts grew well on glass but not on the four tested polymers. No correlation was found between molecular weight, thickness, hydrophilic or charge characteristics of the polymers. Several ultrathin polymers, seeded with human endothelial cells, permit complete monolayer formation, but without any apparent correlation to physicochemical characteristics. Polymers covalently bound to biologic tissue appear as a promising approach to prevent calcific degeneration of bioprostheses.Herz 06/2004; 29(3):341-7. · 0.92 Impact Factor -
Article: Kultivierung humaner Zellen auf polymerbeschichteten Bioimplantaten—ein neues Konzept zur Verbesserung der Implantateigenschaften
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ABSTRACT: Hintergrund und Ziel:Kalzifikation und Degeneration stellen die Hauptprobleme im Langzeitverlauf nach Implantation biologischer Prothesen dar. In Vorluferstudien konnte gezeigt werden, dass sich durch eine Bedeckung der Oberflche des Biomaterials mit Zellen eine Reduktion der Calciumaufnahme erzielen lsst. Allerdings ist eine vollstndige Oberflchenbesiedelung schwer zu erreichen. Daher wurde das Konzept der kovalenten Bindung von Polymeren an die Oberflche des Implantats und der sich daran anschlieenden Zellbesiedelung entwickelt. Ziel der aktuellen Studie war die Austestung verschiedener Polymere auf ihre Fhigkeit, die Adhrenz humaner Zellen zu frdern, so dass sich ein intakter Monolayer ausbildet.Material und Methodik:Zehn an Glas gebundene ultradnne Polymere mit unterschiedlichen physikochemischen Eigenschaften wurden mit humanen Endothelzellen und vier von diesen zehn Polymeren mit Fibroblasten besiedelt. Das Wachstumsverhalten wurde mit dem der Zellen auf einer Glasoberflche verglichen. Das Wachstum wurde photographisch im Phasenkontrastmikroskop und in der Elektronenmikroskopie dokumentiert.Ergebnisse:Bei fnf der zehn Polymere sowie auf Glas zeigten sich ein exzellentes Wachstum und eine vollstndige Zellbedeckung nach 2 Wochen, bei zwei Polymeren nahm die Zelladhrenz nach 1 Woche wieder ab, und drei zeigten bis auf einzelne nicht im Zellverbund wachsende Zellen kein Wachstum. In der Elektronenmikroskopie der fnf Polymere mit exzellentem Wachstum konnte ein intakter Monolayer dargestellt werden. Fibroblasten wuchsen gut auf Glas, jedoch auf keinem der vier getesteten Polymere. Es wurde keine Korrelation zwischen den physikochemischen Eigenschaften und dem Zellwachstum gefunden.Schlussfolgerung:Ultradnne Polymere knnen mit humanen Endothelzellen besiedelt werden, jedoch ohne Korrelation zwischen den physikochemischen Eigenschaften und dem Wachstumsverhalten der Zellen. Die kovalente Bindung von Polymeren an biologisches Gewebe mit anschlieender Zellbesiedelung hin zur kompletten Oberflchenbedeckung erscheint als viel versprechender Ansatz, um die kalzifizierende Degeneration biologischer Implantate zu verhindern.Background and Purpose:Calcific degeneration with the resulting need for operative replacement remains the major drawback of bioprostheses. Previous studies have shown that cellular surface seeding decreases calcium uptake in vitro and in vivo, but complete coverage remains difficult to achieve. A new approach is presented, masking glutaraldehyde residues with a covalently bound polymer layer thus facilitating cell seeding. The aim of this study was to evaluate different polymers for their ability to promote surface cell adhesion and formation of complete monolayers.Material and Methods:Ten ultrathin polymers, covalently bound to glass and exhibiting different physicochemical characteristics (thickness, molecular weight, hydrophilic properties, electrical charge) were seeded with human endothelial cells. Four of the ten polymers were also seeded with fibroblasts. As a reference, both cell types were seeded on glass surface. Quality of cell growth and coverage was evaluated by light and scanning electron microscopy.Results:Five of ten polymers and glass exhibited excellent growth and complete surface coverage after 2 weeks, two allowed less cell adherence than glass reference, and three showed only poor cellular growth without adherence. Scanning electron microscopy demonstrated an intact monolayer for the five polymers with excellent cell coverage. Fibroblasts grew well on glass but not on the four tested polymers. No correlation was found between molecular weight, thickness, hydrophilic or charge characteristics of the polymers.Conclusion:Several ultrathin polymers, seeded with human endothelial cells, permit complete monolayer formation, but without any apparent correlation to physicochemical characteristics. Polymers covalently bound to biologic tissue appear as a promising approach to prevent calcific degeneration of bioprostheses.Herz 04/2004; 29(3):341-347. · 0.92 Impact Factor -
Article: Ultrathin polymer monolayers for promotion of cell growth on bioprosthetic materials -- evolution of a new concept to improve long term performance of biologic heart vales.
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ABSTRACT: Reoperation of aldehyde tanned bioprotheses due to calcific degeneration remains their major drawback. Based on experiments studying mechanisms and factors that influence the time phase, extent and progression of calcification and evaluating the efficiency of anticalcification treatments and the effects of surface seeding with vital cells a new concept to avoid calcification emerged: masking aldehyde-residues with a covalently bound polymer that supports surface cell seeding. Different covalently bound polymers were tested for their suitability to grow cells. Dense cell growth was achieved on some polymers but without correlation to physico-chemical properties. Ultrathin coating of biological materials appears a promising approach to achieve lining with vital cells.Bio-medical materials and engineering 02/2004; 14(4):419-25. · 1.23 Impact Factor -
Article: Clopidogrel and aspirin in the prevention of thromboembolic complications after mechanical aortic valve replacement (CAPTA).
Thrombosis Research 02/2003; 109(2-3):131-5. · 2.44 Impact Factor -
Article: Aprotinin inhibits leukocyte-endothelial cell interactions after hemorrhage and reperfusion.
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ABSTRACT: The serine protease inhibitor aprotinin has been successfully used to reduce blood loss in patients undergoing cardiac operations. We studied aprotinin for its ability to modulate leukocyte-endothelial cell interactions after ischemia and reperfusion. The effects of aprotinin on leukocyte-endothelial cell interactions were observed by intravital microscopy in the rat mesenteric microcirculation and immunohistochemical analysis. The inflammatory cascade (leukocyte rolling, firm adherence, and transmigration) was studied after thrombin stimulation and after hemorrhage and reperfusion. Intravenous bolus administration of aprotinin treatment (20,000 U/kg) significantly reduced leukocyte rolling from 55 +/- 8 to 17 +/- 3 cells/min (p < 0.01) and adherent cells from 12 +/- 2 to 7 +/- 1.4 cells (p < 0.05) along the venous endothelium of the rat mesentery after thrombin activation. In addition, aprotinin pretreatment significantly inhibited transmigration of leukocytes from 11.3 +/- 1.2 to 6.0 +/- 1.1 cells (p < 0.05) through the microvascular endothelial wall. Similarly, aprotinin decreased leukocyte-endothelium interaction after hemorrhagic shock. Moreover, immunohistochemistry demonstrated that aprotinin significantly attenuated P-selectin expression by the intestinal vascular endothelium. CONCLUSIONS. Our data demonstrate that aprotinin potently inhibits recruitment of leukocytes in the microvasculature by interfering with endothelial cell-polymorphonuclear neutrophil interaction, and is a potent endothelial protective agent in clinically relevant doses. Thus, aprotinin pretreatment may be useful for primary prevention of inflammatory tissue injury mediated by ischemia-reperfusion injury such as shock, trauma, open heart operation, or other extensive vascular surgical procedures.The Annals of Thoracic Surgery 01/2003; 75(1):210-5; discussion 215-6. · 3.74 Impact Factor -
Article: Cardioprotective effects of the serine protease inhibitor aprotinin after regional ischemia and reperfusion on the beating heart.
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ABSTRACT: Early coronary reperfusion of the ischemic myocardium is a desired therapeutic goal to preserve myocardium. However, reperfusion itself contributes to an additional myocardial injury (ie, reperfusion injury), which has been attributed to neutrophil infiltration with subsequent release of proteases and oxygen-derived radicals. We studied the effects of the serine protease inhibitor aprotinin (Trasylol) on myocardial ischemia and reperfusion in a rat model. The effects of aprotinin (5000 and 20,000 U/kg) were examined in vivo in a rat model of regional myocardial ischemia (20 minutes) and long-term reperfusion (24 hours). Cardioprotecive effects were determined by means of measurement of creatine kinase and myeloperoxidase activity within the myocardium, as well as histochemical analysis. Aprotinin (20,000 U/kg) administrated 2 minutes before reperfusion significantly attenuated myocardial injury expressed as creatine kinase washout compared with that seen in vehicle-treated rats (65 +/- 25 vs 585 +/- 98 creatine kinase difference in units per 100 mg, P <.01). Administration of 5000 U/kg of the protease inhibitor resulted in partial inhibition of myocardial reperfusion injury. Moreover, cardiac myeloperoxidase activity in the ischemic myocardium, a marker of neutrophil accumulation, was significantly reduced after aprotinin treatment. Histologic analysis of the reperfused myocardium demonstrated reduced polymorphonuclear leukocyte infiltration and reduced tissue injury. Furthermore, aprotinin treatment resulted in decreased induction of cardiac myocyte apoptosis compared with that seen in vehicle-treated rats. Inhibition of serine proteases with aprotinin appears to be an effective means of preserving ischemic myocardium from reperfusion injury, even after 24 hours of reperfusion. Aprotinin might exert cardioprotection through inhibition of polymorphonuclear leukocyte-induced myocardial injury and inhibition of reperfusion-induced apoptosis of cardiac myocytes.Journal of Thoracic and Cardiovascular Surgery 11/2002; 124(5):942-9. · 3.41 Impact Factor -
Article: Simvastatin inhibits inflammatory properties of Staphylococcus aureus alpha-toxin.
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ABSTRACT: Simvastatin, a 3-hydroxy-methylglutaryl coenzyme A reductase inhibitor, has been shown to lower serum cholesterol levels in clinical use. Moreover, statins exert beneficial effects in vascular diseases by inhibition of leukocyte rolling, adherence, and transmigration. The aim of this study was to determine if pretreatment with simvastatin attenuates Staphylococcus aureus alpha-toxin-induced increase in leukocyte-endothelial interactions during exotoxemia. The effects of simvastatin on leukocyte-endothelial cell interactions were observed by intravital microscopy in the rat mesenteric microcirculation. Simvastatin (50 or 100 microg/kg) was administered 18 hours before the study. Activation of microcirculation was induced by bolus administration of 40 microg/kg S aureus alpha-toxin. Exotoxemia resulted in a significant and time-dependent increase in leukocyte rolling, adherence, and transmigration of leukocytes as well as P-selectin expression on the intestinal vascular endothelium. Pretreatment with simvastatin significantly inhibited exotoxin-induced leukocyte rolling from 71+/-10 to 14+/-4.7 cells/min (P<0.01) and adherence from 14+/-3.5 to 0.4+/-0.2 cells (P<0.01). In addition, simvastatin pretreatment significantly inhibited transmigration of leukocytes from 10.5+/-1.2 to 4.2+/-0.9 (P<0.05) cells. Immunohistochemical detection of endothelial cell adhesion molecule P-selectin showed a 50% decrease in endothelial cell surface expression after simvastatin treatment. Furthermore, simvastatin treatment resulted in enhanced expression of endothelial cell NO synthase III in the intestinal microcirculation. These results demonstrate that simvastatin interferes with exotoxin-induced leukocyte-endothelial cell interactions, which may be relevant in various infectious diseases. Statin treatment may offer a new therapeutic strategy for these clinical conditions.Circulation 10/2002; 106(16):2104-10. · 14.74 Impact Factor -
Article: Annexin V does not represent a diagnostic alternative to myoglobin for early detection of myocardial infarction.
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ABSTRACT: Annexin V is a calcium binding protein, which is widely present in various cells and tissues. Due to an early release reaction after myocardial injury the determination of annexin V might be useful for the rapid diagnosis of acute myocardial infarction. An enzyme-linked immunosorbent assay was used to measure annexin V in comparison to myoglobin in samples from healthy individuals, patients suffering from acute or chronic liver, renal, and pulmonary diseases as well as acute coronary syndromes and aortocoronary bypass surgery. Increased myoglobin and annexin V concentrations were observed 80 and 140 (maximum) minutes after myocardial ischemia induced by percutaneous transluminal coronary angioplasty. For the diagnosis of myocardial infarction annexin V (cutoff-level: 5.9 microg/L) showed a slightly higher sensitivity than myoglobin (annexin V: 74.5%; myoglobin: 59.6%), but specificity was much lower (annexin V: 39%; myoglobin: 82.5%). The area under the curve of a ROC analysis demonstrated that annexin V cannot be used as an early marker for the diagnosis of acute coronary syndromes. Increased annexin V levels are induced by several diseases, leading to a low specificity for the diagnosis of a myocardial injury.Clinical laboratory 02/2002; 48(9-10):517-23. · 0.90 Impact Factor
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Institutions
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1998–2012
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Johannes Gutenberg-Universität Mainz
- Department of Cardiothoracic and Vascular Surgery
Mainz, Rhineland-Palatinate, Germany
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2006
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Martin-Luther-Universität Halle-Wittenberg
- Poliklinik für Innere Medizin III (Kardiologie, Angiologie)
Halle, Saxony-Anhalt, Germany
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