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Biomedical subjects

Gerhard Ziemer

Publications and source records attributed to Gerhard Ziemer.

At least 19 recordsLinked to original sources
PubMed2007

Effect of biopassive and bioactive surface-coatings on the hemocompatibility of membrane oxygenators.

Postoperative complications associated with cardiopulmonary bypass (CPB) surgery and extracorporeal circulation (ECC) procedures are still a major clinical issue. Improving the hemocompatibility of blood contacting devices used for ECC procedures may ameliorate various postpump syndromes. In a simulated CPB model using human blood, we investigated the hemocompatibility, fibrinogen adsorption, and platelet receptor (GPIIb-IIIa) binding capacity of surface-modified membrane oxygenators (Jostra Quadrox). Three groups were compared: (i) biopassive protein coatings (SafeLine), (ii) bioactive heparin coatings (BioLine), and (iii) noncoated controls. During the 2 h recirculation period, plasma concentrations of activation markers for platelets (beta-thromboglobulin), inflammation (elastase), complement (C5a), and coagulation (prothrombin fragment 1+2, thrombin-antithrombin III) were lower in the groups with biopassive and bioactive coatings compared to the noncoated group (p < 0.01). These parameters did not significantly differ between the two surface-coated groups, except for complement activation: C5a levels were higher in the biopassive group compared to the bioactive group (p < 0.01). Moreover, surface-coated oxygenators showed less fibrinogen adsorption, GPIIb-IIIa binding, and platelet/leukocyte adhesion (p < 0.01). We assume that fewer fibrinogen and platelet receptor molecules bound to the surface-coated oxygenator surfaces results in fewer platelet adhesion and activation, which will significantly contribute to the improved hemocompatibility of the biopassive and bioactive oxygenators. Our results suggest that the application of bioactive oxygenators (BioLine) during CPB surgery may reduce postoperative complications for the patient more effectively than biopassive oxygenators (SafeLine).

Adsorption↗
PubMed2007

Risk of surgery for congenital heart disease in the adult: a multicentered European study.

BACKGROUND: Surgery for congenital heart disease (CHD) has changed considerably during the last three decades. The results of primary repair have steadily improved, to allow treating almost all patients within the pediatric age; nonetheless an increasing population of adult patients requires surgical treatment. The objective of this study is to present the early surgical results of patients who require surgery for CHD in the adult population within a multicentered European study population. METHODS: Data relative to the hospital course of 2,012 adult patients (age > or = 18 years) who required surgical treatment for CHD from January 1, 1997 through December 31, 2004 were reviewed. Nineteen cardiothoracic centers from 13 European countries contributed to the data collection. RESULTS: Mean age at surgery was 34.4 +/- 14.53 years. Most of the operations were corrective procedures (1,509 patients, 75%), followed by reoperations (464 patients, 23.1%) and palliative procedures (39 patients, 1.9%). Six hundred forty-nine patients (32.2%) required surgical closure of an isolated ostium secundum atrial septal defect. Overall hospital mortality was 2%. Preoperative cyanosis, arrhythmias, and NYHA class III-IV, proved significant risk factors for hospital mortality. Follow-up data were available in 1,342 of 1,972 patients (68%) who were discharged home. Late deaths occurred in 6 patients (0.5%). Overall survival probability was 97% at 60 months, which is higher for corrective procedures (98.2%) if compared with reoperations (94.1%) and palliations (86.1%). CONCLUSIONS: Surgical treatment of CHD in adult patients, in specialized cardiac units, proved quite safe, beneficial, and low-risk.

Adult↗
PubMed2007

Administration of brain natriuretic peptide improves cardiac function following operations using extracorporeal circulation in an animal model.

The critical phase during cardiosurgical procedures is weaning the diseased heart from the ECC (extracorporeal circulation). Post-ischaemic heart failure sometimes requires the administration of inotropic and/or vasconstrictive agents. The natriuretic peptides influence pre- and after-load through their natriuretic, diuretic and vasodilating actions. To date, there are only a few reports describing the therapeutic effect of BNP (brain natriuretic peptide) administration during cardiosurgical procedures. The aim of the present study was to evaluate the effect of BNP administration following ECC in an animal model. Surgery was performed on 20 pigs using ECC. A 30-min ischaemic episode was simulated. Following de-clamping, BNP was administered to the BNP group (n=10) by an i.v. (intravenous) bolus at 0.3 microg x kg(-1) of body weight x min(-1), followed by an infusion at a rate of 0.015 microg x kg(-1) of body weight x min(-1) for 60 min. The animals in the control group (n=10) received a saline solution instead of BNP. Haemodynamic and clinical chemistry parameters as well as the amount of catecholamines that were required were measured. All of the animals in the BNP group had a significantly better cardiac output and cardiac index at the end of the experiment. Seven out of 10 animals from the control group required catecholamines, whereas only one animal from the BNP group did. Creatine kinase levels were significantly lower in the BNP group. Systemic vascular resistance was markedly lower in the BNP group. In conclusion, administration of BNP is highly effective in treating post-ischaemic heart failure following ECC. Haemodynamics are greatly improved, and there is almost no need for pharmacological support.

Animals↗
PubMed2006

The effect of electrochemical functionalization of Ti-alloy surfaces by aptamer-based capture molecules on cell adhesion.

To improve cell seeding efficiency and cytocompatibility, we designed a new coating material for scaffolds. We used aptamers, highly specific cell binding nucleic acids generated by combinatorial chemistry with an in vitro selection called systematic evolution of exponential enrichment (SELEX). In this study, we functionalized Ti-alloy surfaces to enhance cell adhesion. By coating the material with a cell specific aptamer, working as a capture molecule, we could improve the attachment of cells effectively and avoid the limitations of the currently available materials. Aptamers, immobilized by partial electrochemical entrapment in oxide layers on Ti-alloy surfaces were able to capture cells out of a flowing suspension rapidly. This model proves that surface immobilized aptamers can greatly enhance the attachment of seeded cells. This technology opens new perspectives towards clinical application of stem cell and tissue engineering strategies.

Animals↗
PubMed2006

The arterial switch operation in Europe for transposition of the great arteries: a multi-institutional study from the European Congenital Heart Surgeons Association.

OBJECTIVES: This study analyzes the results of the arterial switch operation for transposition of the great arteries in member institutions of the European Congenital Heart Surgeons Association. METHODS: The records of 613 patients who underwent primary arterial switch operations in each of 19 participating institutions in the period from January 1998 through December 2000 were reviewed retrospectively. RESULTS: A ventricular septal defect was present in 186 (30%) patients. Coronary anatomy was type A in 69% of the patients, and aortic arch pathology was present in 20% of patients with ventricular septal defect. Rashkind septostomy was performed in 75% of the patients, and 69% received prostaglandin. There were 37 hospital deaths (operative mortality, 6%), 13 (3%) for patients with an intact ventricular septum and 24 (13%) for those with a ventricular septal defect (P < .001). In 36% delayed sternal closure was performed, 8% required peritoneal dialysis, and 2% required mechanical circulatory support. Median ventilation time was 58 hours, and intensive care and hospital stay were 6 and 14 days, respectively. Although of various preoperative risk factors the presence of a ventricular septal defect, arch pathology, and coronary anomalies were univariate predictors of operative mortality, only the presence of a ventricular septal defect approached statistical significance (P = .06) on multivariable analysis. Of various operative parameters, aortic crossclamp time and delayed sternal closure were also univariate predictors; however, only the latter was an independent statistically significant predictor of death. CONCLUSIONS: Results of the procedure in European centers are compatible with those in the literature. The presence of a ventricular septal defect is the clinically most important preoperative risk factor for operative death, approaching statistical significance on multivariable analysis.

Europe↗
PubMed2006

A new technique for the isolation and surface immobilization of mesenchymal stem cells from whole bone marrow using high-specific DNA aptamers.

Adult mesenchymal stem cells (aMSCs) are a stem cell population present in bone marrow, which can be isolated and expanded in culture and characterized. Due to the lack of specific surface markers, it is difficult to separate the MSCs from bone marrow directly. Here, we present a novel method using high-specific nucleic acids called aptamers. Porcine MSCs were used as a target to generate aptamers by combinatorial chemistry out of a huge random library with in vitro technology called systematic evolution of ligands by exponential enrichment (SELEX). After cloning and sequencing, the binding affinity was detected using a cell-sorting assay with streptavidin-coated magnetic microbeads. We also used 12-well plates immobilized with aptamers to fish out MSCs from the cell solution and a fluorescein isothiocyanate-labeled aptamer to sort MSCs from bone marrow using high-speed fluorescence-activated cell sorting. The cells showed high potency to differentiate into osteogenic, as well as into adipogenic, lineages with typical morphological characteristics. Surface marker staining showed that the attached cells were CD29(+), CD44(+), CD45(-), CD90(+), SLA class I(+), SLA DQ(-), and SLA DR(-). Compared with existing methods, this study established a novel, rapid, and efficient method for direct isolation of aMSCs from porcine bone marrow by using an aptamer as a probe to fish out the aMSCs. This new application of aptamers can facilitate aMSC isolation and enrichment greatly, thereby enhancing the rate of aMSC-derived cells after in vitro differentiation for various applications in the emerging field of tissue engineering and regenerative medicine.

Animals↗
PubMed2006

Results of surgery for Ebstein anomaly: a multicenter study from the European Congenital Heart Surgeons Association.

OBJECTIVE: Since most centers' experience with Ebstein anomaly is limited, we sought to analyze the collective experience of participating institutions of the European Congenital Heart Surgeons Association with surgery for this rare malformation. METHODS: The records of all 150 patients (median age 6.4 years) who underwent surgery for Ebstein anomaly in the 13 participating Association centers between January 1992 and January 2005 were reviewed retrospectively. Patients with congenitally corrected transposition were excluded. RESULTS: Most patients (81%) had Ebstein disease type B or C and significant functional impairment (61% in New York Heart Association class III or IV) and 16% had prior operations. Surgical procedures (n = 179) included valve replacement (n = 60, 33.5%), valve repair (n = 49, 27.3%), 1(1/2) ventricle repair (n = 46, 25.6%), palliative shunt (n = 13, 7.26%), and other complex procedures (n = 11, 6.14%). There were 20 hospital deaths (operative mortality 13.3%) after valve replacement in 5 patients, valve repair in 3, 1(1/2) ventricle repair in 7, palliative procedures in 3, and miscellaneous procedures in 2. Younger age and palliative procedures were univariate risk factors for operative death, but only age was an independent predictor on multivariable analysis. CONCLUSIONS: Most patients coming to surgery presented in childhood and were significantly symptomatic. More than half underwent valve replacement or repair, but a considerable proportion had severe disease necessitating 1(1/2) ventricle repair or palliative procedures. Operative mortality did not differ significantly among repair, replacement, and 1(1/2) ventricle repair but was associated with palliative procedures for severe disease early in life, young age being the only independent predictor of operative death.

Adolescent↗
PubMed2006

Peripheral arteries: treatment with antibodies of platelet receptors and reteplase for thrombolysis--APART trial.

PURPOSE: To prospectively compare the safety and efficacy of combination therapy with the glycoprotein IIb/IIIa antagonist abciximab plus the third-generation thrombolytic agent reteplase versus those of therapy with the standard thrombolytic agent urokinase plus abciximab. MATERIALS AND METHODS: The study was approved by the local ethics committee, and patient informed consent was obtained. Patients with peripheral arterial occlusions less than 60 days old (n=120) were enrolled in the study: 50 patients (32 men, 18 women; mean age, 67 years; range, 23-88 years) received reteplase plus abciximab and 70 patients (36 men, 34 women; mean age, 68 years; range, 28-88 years) received urokinase plus abciximab. Study end points were the rate of major complications at 30 days, therapeutic success, and survival without open surgery or major amputation at follow-up. Fisher exact test was used to compare treatment groups with respect to dichotomous variables, and the event-free-survival probabilities were calculated with the Kaplan-Meier method. For the comparison of the lengths of occlusions among the groups, a two-sample t test was used. RESULTS: Therapeutic success (P=.7) did not differ between the groups, whereas the time required for thrombolysis was lower in the urokinase-plus-abciximab group (P=.001). Patients who received reteplase plus abciximab tended to develop more minor complications (mainly bleeding events) (P<.001). During long-term follow-up (2-4 years), no group differences were observed. The reocclusion rate was 48% (22 of 46) in the reteplase-plus-abciximab group and 45% (29 of 64) in the urokinase-plus-abciximab group. Only two of 120 major amputations were counted in the follow-up period. CONCLUSION: The proposed regimen resulted in only a limited number of major complications, and the low amputation rate in both groups may be attributed to abciximab.

Abciximab↗
PubMed2006

Use of the implantable loop recorder in children and adolescents.

INTRODUCTION: Recurrent but infrequent syncopes represent a diagnostic challenge, since they frequently remain unexplained despite extensive investigations. This applies specifically for patients who carry an increased risk of potentially lifethreatening arrhythmias, either due to congenital cardiac disease or primary electrical disorders. Implantable loop recorders permit long-term electrocardiographic monitoring. Experience with these devices is still limited in children. PATIENTS AND METHODS: Between January 1999 and August 2005, 12 patients underwent implantation of a loop recorder in our tertiary referral centre. The mean age was 10.9 years, with a range from 2 to 17 years. Of the patients, 6 had structural disease, 3 had primary electrical abnormalities, and 3 had no cardiovascular disease. RESULTS: Resyncope occured in 9 of the 12 patients. Arrhythmic origin of the syncope was diagnosed in 4 of these patients. The events recorded were ventricular fibrillation in 2, intermittent asystole in 1, and pacemaker-syndrome in the other patient. Malignant arrhythmia was ruled out in the remaining 5 patients. There were no complications related to implantation of the loop recorder, and the mean duration until explantation was 8.3 months. CONCLUSIONS: Based on our experience, we suggest that implantation of a loop recorder represents an additional tool for a selected group of children. Due to its invasive nature, it should be restricted to patients at high risk, or those in which there is substantial clinical suspicion of the likelihood of serious arrhythmias when conventional testing has been inconclusive. In this cohort, implantation of the loop recorder either helps to establish the correct diagnosis, or to exclude an arrhythmic event, thus avoiding unnecessary escalation of therapy and providing reassurance for the family.

Adolescent↗
PubMed2006

Blood cell and plasma protein repellent properties of star-PEG-modified surfaces.

The implantation of biomaterials, medical devices or prostheses can instigate a rejection response or initiate an undesirable adsorption of plasma proteins, as well as blood cells on the implant surface, thus triggering diverse defense mechanisms against the supposed pathologic invader. The extent of this inflammatory reaction depends in part on the biocompatibility of the used materials or coatings. Although adsorption and coagulation responses can appear during the total in vivo lifetime of the implant, they are initially and crucially formed within the first 2-4 weeks of implantation. This early phase is of decisive importance for the consecutive in-growth and healing process. The present study was intended to elucidate the effects of blood contact to surfaces modified with reactive six-arm star-shaped poly(ethylene glycol-stat-propylene glycol) pre-polymers (Star PEG). Taken together, for Star-PEG-covered substrates we could demonstrate a profound reduction of various blood-biomaterial interactions compared to non-coated substrates, indicating the promising potential of this material as future coating for biomaterials with blood contact.

Adsorption↗
PubMed2005

Suppression of ICAM-1 in human venous endothelial cells by small interfering RNAs.

OBJECTIVE: Cardiopulmonary bypass-mediated release of proinflammatory cytokines promotes the transendothelial migration of leukocytes. Among others, intercellular adhesion molecule (ICAM) is essential for this migratory process within the venous bypass graft, which finally contributes to a diminished early patency rate by thickening of the intima. Small interfering ribonucleic acids (siRNAs) are efficient and specific modulators of endogenous gene expression. This study describes the application of siRNAs to suppress ICAM-1 expression on the surface of human venous endothelial cells. METHODS: Primary cultures of human venous endothelial cells were either transfected with ICAM-1 siRNA, with a scrambled control siRNA or cultured without transfection. ICAM-1 expression was analyzed with or without TNF-alpha stimulation by flow cytometry. RESULTS: Upon TNF-alpha stimulation, cells transfected with ICAM-1 siRNA showed a six- to seven-fold decreased ICAM-1 expression compared to untransfected cells or cells transfected with the scrambled control siRNA. CONCLUSIONS: This is the first report that ICAM-1 expression can be effectively silenced by siRNAs on endothelial cells from human saphenous veins. This new technology may render novel therapeutic concepts to reduce early graft failure by protecting venous bypass grafts against early intra- or postoperative leukocyte infiltration.

Cells, Cultured↗
PubMed2005

Gene expression changes in leukocytes during cardiopulmonary bypass are dependent on circuit coating.

BACKGROUND: Cardiopulmonary bypass (CPB) results in a systemic inflammatory response. Leukocytes play a crucial role in inflammatory reactions. Their gene expression profile in the context of CPB is unknown. METHODS AND RESULTS: In a prospective, randomized, and double-blind clinical trial, 12 male patients underwent elective coronary artery bypass grafting with either heparin-coated (group H) or protein-coated (group P) CPB circuits. Oligonucleotide microarray analyses of 22,283 genes were performed on circulating leukocytes, collected immediately before surgery and 6 hours after CPB. Microarray results were validated with real-time polymerase chain reaction. All patients had uneventful surgery, and no significant differences between groups were observed during the clinical course. Multiple statistical analyses with different methods were performed. Compared with preoperative expression at a threshold value of P<0.01, postoperative expression revealed 814 upregulated and 1187 downregulated genes in group H compared with 99 upregulated and 231 downregulated in group P (P<0.001). Fifty genes exhibited a >4-fold increase and 27 exhibited a >4-fold decrease in group H, whereas only 7 genes exhibited upregulation and 7 revealed downregulation in group P. Microarray-pathway-profile-finder analyses determined 1405 upregulated and 1454 downregulated pathways in group H compared with 552 upregulated and 818 downregulated pathways in group P (P<0.01). Pathways related to inflammatory response exhibited highest z scores in group H, reflecting cellular inflammatory activation. CONCLUSIONS: Heparin coating resulted in a more profound alteration in leukocyte gene expression when compared with protein coating. Microarray analyses present an innovative approach for the evaluation and understanding of inflammatory reactions associated with CPB.

Aged↗
PubMed2005

The GP IIb/IIIa inhibitor abciximab (ReoPro) decreases activation and interaction of platelets and leukocytes during in vitro cardiopulmonary bypass simulation.

OBJECTIVE: Cardiopulmonary bypass (CPB) induces a systemic inflammatory response and increases expression of the platelet activation marker P-selectin which mediates binding of platelets to leukocytes. Inhibition of the platelet GP IIb/IIIa receptor during CPB has been shown to protect platelets without increasing bleeding complications and is assumed to reduce the inflammatory response. The aim of this study was to investigate the effect of the GP IIb/IIIa inhibitor abciximab (ReoPro) on the function and interaction of platelets and leukocytes during experimental CPB. METHODS: Heparinized (3 U/ml) fresh whole blood of healthy volunteers was treated before continuous in vitro circulation in a well established CPB model with 3.2 microg/ml abciximab (n=6) or left untreated as control (n=6). Measurements were made before (baseline) and after 30 and 60 min of circulation and comprised: percentage of platelets expressing P-selectin and percentage of platelet-bound leukocytes (flow cytometry), release of the leukocyte activation marker PMN-elastase (ELISA), and platelet and leukocyte counts. RESULTS: Abciximab almost completely prevented a CPB-induced increase of platelet P-selectin and platelet-leukocyte binding after 30 and 60 min of circulation, and significantly inhibited release of PMN-elastase after 30 min of circulation. Furthermore, abciximab significantly inhibited a CPB-induced decrease of platelet and leukocyte counts. CONCLUSIONS: Abciximab inhibits CPB-induced activation, interaction and consumption of platelets and leukocytes in vitro. GP IIb/IIIa inhibition should be considered as a promising approach not only to conserve platelet function but also to inhibit pro-inflammatory events during CPB in vivo.

Abciximab↗
PubMed2005

Forty years of clinical aprotinin use: a review of 124 hypersensitivity reactions.

Since its clinical introduction, the anaphylactic potential of aprotinin has been a major concern. World wide, its use is expanding so there is an increased chance that patients have reexposure from various sources. The risk of anaphylaxis is approximately 2.8% in reexposed patients. From 1963 to 2003, 124 cases of aprotinin-induced anaphylaxis were reported in 61 publications. Eleven patients died. The reexposure interval was less than 3 months in 72% (38 of 53 patients). This review looks at the profile of patients at risk so preventive measures may be taken. Past and future exposures have to be taken into account before any aprotinin administration.

Aprotinin↗
PubMed2005

Thrombospondin 1 as possible key factor in the hemocompatibility of endocoronary prostheses.

Intracoronary stenting has markedly improved the patency of native coronary arteries after percutaneous transluminal coronary angioplasty (PTCA). Advances in stent technology and design, including drug releasing stents, have contributed to reduce the long-term restenosis rate. However, stenosis caused by neointimal hyperplasia, vascular remodeling and thrombosis is still a major problem after endocoronary stent procedures. This study focuses on differential gene expression of circulating peripheral blood cells after 90 min exposure to stents to search for initially activated cellular pathways, which may foster restenosis. Fresh human whole blood (1 IU heparin/ml), taken from non-medicated healthy volunteers, was incubated under flow conditions in an in vitro closed-loop stent-testing model (modified Chandler-Loop). Differential gene expression compared to resting conditions and to the experimental controls was investigated by a DNA-microarray technique encoding for over 17,000 genes simultaneously. As expected, a large variety of genes showed differential gene expression. Interestingly, Thrombospondin 1 (TSP-1), which plays a key role in initial immune defense, was found to be the most markedly up-regulated gene. We propose TSP-1 expression as an early indicator for the activation of immune responses following intracoronary stenting. After clarifying the participation of TSP-1 in vivo, future studies will therefore focus on TSP-1 as a potential prognostic factor, which may also help to develop and control new surface materials with an improved biocompatibility.

Adult↗
PubMed2005

Prophylaxis of thromboembolic complications after the Fontan operation (total cavopulmonary anastomosis).

OBJECTIVES: Thrombotic events have been reported as a major cause of morbidity after the Fontan procedure. There is no consensus concerning the postoperative mode and duration of anticoagulation prophylaxis. In a retrospective study, we evaluated the results of a prophylactic regimen on the basis of the surgical technique, potentially predisposing risk factors, and specific sequelae. METHODS: We evaluated 142 surviving patients after total cavopulmonary anastomosis (mean follow-up was 91.1 +/- 43.9 months). Prophylactic antithrombotic treatment was initiated in 86 patients with partial prosthetic venous pathway with acetylsalicylic acid; 45 patients with complete autologous tissue venous pathway or partial prosthetic venous pathway received no anticoagulation, and 11 patients received warfarin sodium (Coumadin). During long-term follow-up, 22 patients (12 after acetylsalicylic acid medication) crossed over to warfarin. RESULTS: Thrombotic events occurred in 10 patients (7%), with systemic venous thrombus formation in 8 (5.6%), stroke in 2 (1.4%), and a peak incidence during the first postoperative year. Eight of 10 patients were receiving heparin therapy mainly for prolonged postoperative immobilization. During follow-up, none of the 74 patients receiving acetylsalicylic acid and 1 of 40 patients without medication presented with thrombus formation. Under warfarin medication, 1 of 28 patients had an asymptomatic thrombus. Expected freedom from a thromboembolic event was 92% at 5 years and 79% at 10 years. There was no association with coagulation factor abnormalities. Protein-losing enteropathy was present in 4 of 10 patients. CONCLUSION: A prophylactic anticoagulation strategy that considers the surgical technique and potential predisposing circumstances proved effective in the prevention of late thrombotic complications after total cavopulmonary anastomosis. There is no need for routine anticoagulation during long-term follow-up after Fontan-type surgery in pediatric patients.

Anticoagulants↗
PubMed2005

Hypoplasia of the left heart with discordant ventriculoarterial connections.

We report the rare combination of a severely hypoplastic left ventricle and discordant ventriculoarterial connections, with associated subpulmonary obstruction of the left ventricular outflow tract. The long tortuous arterial duct originated at an acute angle from the aorta, suggesting that the subpulmonary obstruction developed early in fetal life. Residual flow via the hypoplastic left ventricle to the pulmonary circulation after insertion of an aortopulmonary shunt resulted in haemodynamic deterioration, which was instantly reversed by closing the pulmonary trunk.

Coronary Vessel Anomalies↗