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A Haverich

Publications and source records attributed to A Haverich.

At least 73 records · Page 4Linked to original sources
PubMed2002

Endothelial anatomy of the human heart: immunohistochemical evaluation of endothelial differentiation.

OBJECTIVES: Endothelial cells play a significant role in cardiovascular physiology and the pathogenesis of numerous cardiovascular diseases. Essential phenomena such as hemostasis, inflammation and immunity require close interactions between immunocompetent and endothelial cells. However, many questions of endothelial heterogeneity regarding function and morphology at various vascular sites remain unanswered. In this study, we have created an immunohistochemical map of endothelial adhesion molecule expression at different vascular sites of the healthy human heart. The main focus was to analyze endothelial expression patterns and whether they are distinctive regarding their function at these vascular sites. We also tried to build up a relation between clinical and immunohistochemical findings. PATIENTS AND METHODS: Tissue samples from eleven different vascular locations of healthy human hearts were analyzed using immunohistochemistry. Endothelial adhesion molecules of the selectin, immunoglobulin supergene, and integrin families, some complementary cellular adhesion molecules, and von Willebrand factor were analyzed. RESULTS: Endothelial adhesion molecule expression was found to be characteristic for all vascular sites investigated. Thus, molecules involved in inflammatory reactions were predominantly expressed within the myocardial microvasculature, whereas molecules serving endothelial anchorage towards extracellular matrix components could be observed especially on endocardial and valvular surfaces. Apart from that, a parallel expression of immunologically relevant as well as integrin molecules was found to be characteristic for coronary arteries. CONCLUSIONS: To our knowledge, this is the first report on site-specific expression characteristics for all vascular sites of the human heart. Thus, our data provide important novel information, which will ultimately help to bring some light into the field of cardiac physiology.

Antibodies, Monoclonal↗
PubMed2002

In vitro engineering of heart muscle: artificial myocardial tissue.

INTRODUCTION: Myocardial infarction followed by heart failure represents one of the major causes of morbidity and mortality, particularly in industrialized countries. Engineering and subsequent transplantation of contractile artificial myocardial tissue and, consequently, the replacement of ischemic and infarcted areas of the heart provides a potential therapeutic alternative to whole organ transplantation. METHODS: Artificial myocardial tissue samples were engineered by seeding neonatal rat cardiomyocytes with a commercially available 3-dimensional collagen matrix. The cellular engraftment within the artificial myocardial tissues was examined microscopically. Force development was analyzed in spontaneously beating artificial myocardial tissues, after stretching, and after pharmacologic stimulation. Moreover, electrocardiograms were recorded. RESULTS: Artificial myocardial tissues showed continuous, rhythmic, and synchronized contractions for up to 13 weeks. Embedded cardiomyocytes were distributed equally within the 3-dimensional matrix. Application of Ca(2+) and epinephrine, as well as electrical stimulation or stretching, resulted in enhanced force development. Electrocardiographic recording was possible on spontaneously beating artificial myocardial tissue samples and revealed physiologic patterns. CONCLUSIONS: Using a clinically well-established collagen matrix, contractile myocardial tissue can be engineered in vitro successfully. Mechanical and biologic properties of artificial myocardial tissue resemble native cardiac tissue. Use of artificial myocardial tissues might be a promising approach to reconstitute degenerated or failing cardiac tissue in many disease states and therefore provide a reasonable alternative to whole organ transplantation.

Animals↗
PubMed2002

Polymerized degradable hyaluronan--a platform for stent coating with inherent inhibitory effects on neointimal formation in a porcine coronary model.

Biodegradable hyaluronan (hyaluronic acid, HA) made insoluble by self-cross-linking in the presence of N-(3-dimethylaminopropyl)-N'-ethyl carbodiimide (EDC) has been used to cover stents. The maximum polymer-mass on a 16-mm stainless steel stent is approximately 2 mg. During manual crimping and simulated application, the loss of polymerized HA is negligible. The insoluble HA coating has an advantageous inherent antiproliferative effect regarding neointimal formation after local vessel wall injury (overstretch model) and leads to a reduced inflammatory response compared to uncoated stainless-steel stents, used as control, in undiseased pig coronary arteries, over a follow-up period of four weeks. Thus, cross-linked HA stent coating warrants further research as an interactive degradable biomaterial with an inherent inhibitory effect on neointimal formation as a possible biomatrix for local drug delivery to reduce restenosis rate.

Animals↗
PubMed2002

Induction of long-term peripheral microchimerism in non-human primates in a model of xenogeneic peripheral tolerance induction.

Xenotransplantation represents a promising solution to the ever increasing shortage of donor organs in allotransplantation. However, due to different and stronger modes of rejection, successful xenotransplantation will require different organ-protective regimes from those used in allogeneic transplantation today. Since one can not simply increase the dosage of the drugs used, immunomodulation or tolerance induction of the recipient would be the most desirable approach. Transfusion of donor leukocytes has been shown to downregulate recipient responses or even induce peripheral tolerance in small animal models. Since the infusion of donor cells represents a relatively simple approach, as one can purify and compose the inoculum exactly before infusion, we studied whether this approach can be successfully employed in a preclinical swine to non-human primate model of peripheral tolerance induction/immunomodulation. In our model, baboons underwent sequential column adsorption and complement blockade. The animals received only initial immunosuppression with cyclophosphamide. No further immunosuppression was given. Subsequently all animals received 1-3 x 10(10) porcine splenocytes i.v. Development and maintenance of chimerism was analyzed by sequential flow cytometric and PCR analyses. Other parameters studied included effects of the preparatory induction protocol. We could show that a low level of chimerism is maintained in these animals for up to 1.5 years, despite the fact that they received no additional immunosuppression after the initial one. At no time of the experiment did any animal display symptoms of poor health. Thus we demonstrate that the concept of donor leukocyte transfusion is transferable into preclinical xenotransplantation. We are currently conducting organ transplantation experiments into animals thus treated to directly analyze the immunomodulatory effect of the donor cells.

Animals↗
PubMed2001

Combined exogenous surfactant and inhaled nitric oxide therapy for lung ischemia-reperfusion injury in minipigs.

BACKGROUND: The combined application of exogenous surfactant and inhaled nitric oxide was evaluated for prevention of ischemia-reperfusion injury of the lung. METHODS: Left lungs were selectively perfused in 18 minipigs in situ with cold preservation solution. After 90 min of warm ischemia, the lungs were reperfused and the right pulmonary artery and bronchus were ligated (control group, n=6). Exogenous surfactant was instilled via bronchoscopy during ischemia (surfactant group, n=6). In a third group, surfactant was applied, followed by administration of inhaled nitric oxide (surfactant+NO group, n=6). Hemodynamic and respiratory parameters were recorded for 7 hr, and bronchoalveolar lavage fluid (BALF) was obtained before and after reperfusion for measurement of surface tension, small aggregate/large aggregate ratio, protein and phospholipid contents, and a differential cell count. RESULTS: Control group animals survived for 3.7+/-1.4 hr. In both surfactant-treated groups, five out of six animals survived the observation period (P<0.001). Dynamic compliance of the lung was decreased in control animals (P<0.001). In the surfactant+NO group, arterial PO2 was higher than in both other groups (P<0.001). BALF cell count and histology showed reduced neutrophil infiltration in surfactant+NO-treated lungs. Surface tension assessed in BALF with a pulsating bubble surfactometer was severely impaired in control animals (gammamin, 14.82+/-9.95 mN/m), but maintained in surfactant-treated (gammamin, 1.11+/-0.56 mN/m) and surfactant+NO-treated animals (gammamin, 3.90+/-2.35 mN/m, P=0.02). CONCLUSIONS: Administration of exogenous surfactant in lung reperfusion injury results in improved lung compliance. The addition of inhaled NO improves arterial oxygenation and reduces neutrophil extravasation compared with surfactant treatment alone.

Administration, Inhalation↗
PubMed2001

[Modified endothelial cells in graft vasculopathy].

Occlusion of venous bypass grafts after coronary revascularization grafting represents the main reason for re-do operations. Arterial pressure as well as mechanical injury of the venous wall lead to endothelial dysfunction, causing intimal hyperplasia with luminal stenosis and eventually occlusion. In the transplanted heart, coronary artery disease limits the long-term success of cardiac transplantation. The disease is characterized by the interaction of activated immunologic cells and donor epicardical and microvascular endothelium. The ex vivo modification of endothelial cells may offer a therapeutic option to overcome both kinds of graft vasculopathy. Seeding of human endothelial cells on artificial and bioartificial acellularized vessel matrices has proven possible. The use of xenogenic matrices initially acellularized and recellularized with autologic endothelial cells and myofibroblasts may help to overcome the lack of vascular and valvular grafts with long durability. In addition, gene therapeutic methods to modify the function of such endothelial cells may offer a new therapeutic strategy, such as over-expression of nitric monoxide or inhibition of matrix metalloprotinases. First results of large animal studies show promising results and may lead to the first clinical trials in the near future.

Animals↗
PubMed2001

[A new combined surgical interventional method for univentricular palliation of congenital heart defects].

UNLABELLED: Total cavo-pulmonary anastomosis is frequently performed to palliate patients with a broad variety of congenital heart defects with functionally univentricular hearts precluding biventricular circulation. In patients with risk factors for primary repair a stepwise approach is frequently chosen with initial creation of an aorto-pulmonary shunt followed by a Glenn anastomosis or hemifontan procedure. Finally a total cavo-pulmonary connection is completed surgically. The aim of this feasibility study was to develop a combined surgical-interventional approach for creation of a total cavo-pulmonary anastomosis which reduces the number of surgical interventions, precludes extracorporeal circulation and intracardiac sutures, putting the patients at risk for subsequent rhythm disturbances. METHODS: A Glenn anastomosis was created in 10 sheep without cardio-pulmonary bypass. The superior vena cava was banded superior to the cavo-atrial junction leaving a minimal lumen for subsequent interventional balloon dilatation and implantation of a stent graft. A 15 mm Gore-Tex tube was sutured around the inferior vena cava intrapericardially to provide resistance for subsequent interventional stent implantation. Total cavo-pulmonary anastomosis was completed interventionally by dilating the banded vena cava superior and connection of the inferior vena cava to the superior vena cava by implanting an Aneurx covered stent graft. RESULTS: All animals survived the combined surgical-interventional procedure. Stent deployment was possible without causing obstruction to the hepatic veins. Neither stent dislocation nor rhythm disturbances were encountered. CONCLUSIONS: Total cavo-pulmonary anastomosis can be achieved without intracardiac sutures and cardio-pulmonary bypass by use of a combined surgical-interventional approach using the Aneurx covered stent graft.

Animals↗
PubMed2001

Retrograde versus antegrade crystalloid cardioplegia in coronary surgery: value of troponin-I measurement.

BACKGROUND: The optimal route for delivery of cardioplegia is still in debate in patients with ischemic heart disease. Cardiac troponin-I is a new marker with the potential for detection of minor differences in myocardial ischemia. METHODS: In a prospective randomized trial 58 patients undergoing elective coronary artery bypass grafting for two- or three-vessel coronary artery disease were divided into groups with antegrade (group A, n = 29) and retrograde (group R, n = 29) application of crystalloid cardioplegia (St. Thomas II). Patients with major risk factors were excluded. In addition to routine electrocardiogram monitoring, cardiac troponin-I and creatine kinase-MB activity were measured in all patients preoperatively at 2, 5, 8, 24, and 48 hours after aortic cross-clamp release, and at hospital discharge. RESULTS: In both groups, there were no differences regarding operative parameters. A significantly higher cardiac troponin-I concentration was observed in the antegrade group at 24 hours after cross-clamp (8.2 +/- 8.5 microg/L vs 3.2 +/- 3.1 microg/L; p = 0.02). Patients with subtotal stenosis or occlusion of one or more main coronary arteries showed significantly lower cardiac troponin-I levels after retrograde application. CONCLUSIONS: Lower concentrations of the cardiac troponin-I marker after retrograde application of cardioplegia indicate advantages of myocardial protection in ischemic heart disease.

Aged↗
PubMed2001

Aerosolized iloprost for severe pulmonary hypertension as a bridge to heart transplantation.

Preexisting pulmonary hypertension in pediatric patients is associated with poor outcome after cardiac transplantation because of donor right ventricular dysfunction. To avoid a combined heart-lung transplantation in a 17-year-old patient, we used an intensified pretreatment with intravenous prostacyclin and dobutamine combined with an inhalative therapy with the aerosolized prostacyclin-analog Iloprost. With this regimen, the patient was hemodynamically stabilized for the waiting period of 21 days after which an uneventful cardiac transplantation was performed.

Adolescent↗
PubMed2001

Minimally invasive removal of a dislocated stent from the right atrium after previous CABG.

Repeat sternotomy after previous open heart operations constitutes a serious risk factor for cardiac injury, particularly in the presence of a patent internal thoracic artery. We report a case of successful minimally invasive removal of a dislocated subclavian vein stent entangled in the tricuspid valve in a patient 5 years after coronary artery bypass surgery.

Aged↗
PubMed2001

Impact of vascular branching sites on focal progression of allograft vasculopathy in transplanted hearts.

BACKGROUND: Cardiac allograft vascular disease (CAVD) represents one of the most accelerated progressing coronary syndromes in the human heart. A variety of risk factors have been identified over recent years; however, little is known about the influence of physical forces. As a model for differences in focal blood flow dynamics, we analyzed progression of intimal hyperplasia at vascular bifurcational sites using intravascular ultrasound (IVUS). METHODS: The most diseased vascular sites ("worst sites") in 59 coronary arteries were assessed (30 MHz, motorized pull back) in 25 consecutive heart transplant recipients at baseline (52.8+/-15.3 days postoperatively) and after 1 year of follow up (360.5+/-24.9 days). Progression of intimal hyperplasia was compared between branching and non-branching lesions as well as in focal relation to the position of the flow divider. RESULTS: A total of 41 (69.5%) worst sites were identified at branching locations. Progression of intimal hyperplasia was found to be significantly more severe at bifurcational sites with an increase in plaque area by 1.5+/-1.8 mm(2) in branching versus 0.4+/-0.6 mm(2) in non-branching lesions (P=0.015). The highest rate in focal progression was found at the opposite site of the flow divider with an increase in maximal intimal thickness by 0.3+/-0.23 mm (180 degrees ) as compared to 0.11+/-0.15 mm (90 degrees, P<0.001) and 0.15+/-0.15 mm (P=0.014) at 270 degrees. CONCLUSIONS: Using serial intravascular ultrasound examinations, vascular branching sites could be identified to be predisposing locations not only for a donor related arteriosclerosis, but also for progression of intimal hyperplasia within transplanted hearts. The highest regional increase in intimal thickness was found at the outer wall of the flow divider, suggesting focal shear or wall stress to be involved in pathogenesis.

Coronary Disease↗
PubMed2001

Flush perfusion with low potassium dextran solution improves early graft function in clinical lung transplantation.

OBJECTIVES: We have previously demonstrated experimentally an amelioration of reperfusion injury of the lung after preservation using low potassium dextran (LPD) solution compared to Euro-Collins (EC) solution. Now we report on early graft function in 106 lung transplant recipients of LPD or EC preserved grafts. METHODS: Initial graft function was assessed by measurement of lung compliance and oxygenation index 2 h after transplantation. Length of stay on the intensive care unit and hours of mechanical ventilation were compared. Correlation of donor oxygenation, ischemic time, type of transplant, recipient age and sex as well as initial lung compliance and oxygenation with early postoperative course were calculated. RESULTS: Dynamic lung compliance was significantly (P<0.05) improved in the LPD group. PO(2)/fiO(2) was comparable in both groups (303+/-122 mmHg LPD, 282+/-118 mmHg EC). Mechanical ventilation was used for 321+/-500 h in the EC group and 189+/-365 h in the LPD group (P=0.006). Intensive care therapy was required for 17.2+/-23.7 days in the EC group and 10.4+/-16 days in the LPD group (P=0.012). Significantly higher lung function parameters were obtained in extubated recipients of LPD preserved grafts 2 weeks after TX. Thirty day graft survival was improved in the LPD group (P=0.045). In the EC group, 30 day mortality was 14.2 and 8% in the LPD group. CONCLUSIONS: A reduction of perioperative mortality and morbidity suggests that LPD solution has superior early graft function compared to lung preservation using EC solution.

Adolescent↗
PubMed2001

Coronary artery bypass grafting surgery without the routine application of blood products: Is it feasible?

OBJECTIVE: Fresh frozen plasma (FFP) substitution is currently standard practise in cardiac surgery. In this study we investigate whether elective coronary artery bypass grafting (CABG) surgery is feasible without the administration of blood products compared to the substitution of fresh frozen plasma. PATIENTS AND METHODS: From September 1997 to April 1998, 120 consecutive patients underwent CABG surgery at our institution. In the FFP group patients (n=60; men, n=43; women, n=17; mean age: 64+/-8.5 years) received 4 units of fresh frozen plasma (FFP) intraoperatively. In comparison, patients in the control group (n=60; men, n=44; women, n=16; mean age: 65+/-7.5 years) did not receive FFP. Main endpoints included perioperative hematologic parameters, blood loss, and the amount of blood products that were administered. RESULTS: Intraoperatively, the substitution of packed red blood cells (pRBC) in the FFP group was significantly higher compared with the control group (0.63+/-0.94 units/patient vs. 0.12+/-0.38 units/patient, P=0.001). Postoperatively, patients in the FFP group required significantly more pRBC products than patients in the control group (0.78+/-1.09 vs. 0.42+/-0.77, P=0.024). There were no significant differences in hemoglobin (FFP group: 99+/-11.1 g/dl; control group: 105+/-13.5 g/dl) and hematocrit levels (FFP group: 30+/-3.39%; control group: 32+/-4%). Also, no significant differences regarding the postoperative blood loss was observed between groups (FFP group: 588+/-224 vs. control group: 576+/-272 ml/24 h). CONCLUSIONS: This study clearly demonstrates that the avoidance of routine intraoperative FFP administration does not lead to an increase in blood loss postoperatively compared to patients that received FFPs. Furthermore, we did not observe increased requirements for postoperative FFP infusion in patients that did not receive FFPs intraoperatively.

Aged↗
PubMed2001

Valve sparing aortic root reconstruction versus composite replacement -- perioperative course and early complications.

OBJECTIVE: In patients with aneurysm of the ascending aorta, dilatation of the sinotubular junction is the major cause of aortic valve regurgitation. Valve sparing aortic root replacement in patients without valvular structural defects offers a new form of treatment. The aim of this study was the assessment of the perioperative course and early complications of this method compared to composite replacement in a large single center cohort. METHODS: From 1992 to 1999, valve sparing replacement of the ascending aorta (recon) has been performed in 78 patients, while 269 patients underwent replacement by a composite graft (comp). A comparison of matched pairs (n=52) with respect to age, gender, presence of Marfan's syndrome, aortic dissection as well as date of surgery, was chosen. Aortic insufficiency was 2.8+/-0.7 for recon vs. 2.2+/-1.1 for comp preoperatively. Course and length of hospitalization, echocardiographic follow-up, complications, and mortality were compared at 1-year follow-up. RESULTS: There were no operative deaths. During follow-up, one patient (2%) died 5 months postoperatively (recon) vs. two patients (3.9%) in the comp group. Bypass-time (123+/-31 vs. 153+/-31 min, P<0.0001) and cross-clamp-time (82+/-22 vs. 120+/-23 min, P<0.0001) were significantly shorter in comp. Stay in ICU (1.9+/-1.6 for recon vs. 2.3+/-2.1 days for comp) and post-op hospitalization (18.3+/-5.7 vs. 21.2+/-11.1 days) were comparable. Improvement of NYHA-class was significant after both operations (recon 2.6+/-0.8 vs. 1.3+/-0.5 and for comp 2.4+/-0.6 vs. 1.5+/-0.7, both P<0.0001). One patient (1.9%) in the recon group had to be reoperated for valve failure. Thrombembolic or bleeding complications were observed in 6 patients (12%) in comp, zero in recon (P=0.027). CONCLUSION: Valve sparing aortic root reconstruction is feasible with low perioperative morbidity and mortality and good early results. Major advantages of recon are significant reduction of thrombembolic and anticoagulation related complications as opposed to longer cross-clamp and bypass times as well as a valve failure in one patient. Further follow-up is needed to confirm our data in a long-term perspective.

Aorta↗