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Biomedical subjects

A Haverich

Publications and source records attributed to A Haverich.

At least 55 records · Page 3Linked to original sources

Microcirculation of the sternum following harvesting of the left internal mammary artery.

BACKGROUND: Internal thoracic arterial grafts (ITA) in coronary artery bypass surgery provide excellent long-term patency results. Due to the elevated incidence of sternal infections following pedicled ITA harvesting, blood supply to the sternum has gained the focus of attention. This study sought to evaluate real time parameters of sternal microcirculation prior and immediately after harvesting of the ITA by a novel laser Doppler flowmetry and remission spectroscopy system (Oxygen-To-See (O2C), LEA Medizintechnik, Giessen). METHODS: 21 patients (16 males, age 63 + 4 years, mean NYHA 2.3 +/- 0.3) scheduled for coronary artery bypass grafting (CABG) were enrolled into the study. After median sternotomy, the probe was placed sequentially pre- and retrosternally for measurements of tissue oxygen saturation (sO2), hemoglobin concentration (rHb), superficial (2 mm) und deep (8 mm) blood flow. Measurements were performed and analyzed before and after surgical harvesting of the ITA with a pedicle. RESULTS: Baseline pre- and retrosternal tissue oxygen saturation (sO2) were 90 +/- 3 % and 87 + 4 %, respectively (n. s.). After left ITA harvesting, presternal sO2 remained unchanged (90 + 4 %, n. s.), whereas retrosternal sO2 decreased significantly (54 + 4 %, p < 0.001). Simultaneously, retrosternal post-capillary venous filling (rHb) increased significantly after ITA harvesting (86 +/- 2 vs. 93 + 2, p < 0.05), whereas presternal rHb remained unchanged. Retrosternal superficial and deep blood flow also decreased significantly (75 +/- 5 vs. 41 +/- 4, and 94 +/- 5 vs. 52 +/- 6) in contrast to comparable presternal blood flow before and after ITA harvesting. There were neither superficial nor deep sternal wound infections occurred in the studied patient population. CONCLUSIONS: The pedicled harvesting of ITA leads to a significant decrease of microcirculatory blood flow, retrosternal tissue oxygen saturation, and an increase in post-capillary venous filling. Parameters of microcirculation in the presternal area after ITA harvesting remained unchanged compared to baseline values. Hence, the incidence of sternal infections after ITA harvesting in coronary surgery may well be explained by a significant decrease of sternal blood supply in the retrosternal area. Further prospective randomized studies are needed to elucidate the potential role of skeletonized ITA preparation in sternal microcirculation.

Aged↗

Clinically established hemostatic scaffold (tissue fleece) as biomatrix in tissue- and organ-engineering research.

Various types of three-dimensional matrices have been used as basic scaffolds in myocardial tissue engineering. Many of those are limited by insufficient mechanical function, availability, or biocompatibility. We present a clinically established collagen scaffold for the development of bioartificial myocardial tissue. Neonatal rat cardiomyocytes were seeded into Tissue Fleece (Baxter Deutschland, Heidelberg, Germany). Histological and ultrastructural examinations were performed by DAPI and DiOC(18) staining and electron microscopy, respectively. Force measurements from the spontaneously beating construct were obtained. The constructs were stimulated with agents such as adrenalin and calcium, and by stretching. Passive stretch curves were obtained. Spontaneous contractions of solid bioartificial myocardial tissue (BMT), 20 x 15 x 2 mm, resulted. Contractions continued to week 12 (40% of BMTs) in culture. Histology revealed intercellular and also cell-fibril junctions. Elasticity was similar to that of native rat myocardium. Contractile force increased after topical administration of Ca(2+) and adrenaline. Stretch led to the highest levels of contractile force. In summary, bioartificial myocardial tissue with significant in vitro longevity, spontaneous contractility, and homogeneous cell distribution was produced using Tissue Fleece. Tissue Fleece constitutes an effective scaffold to engineer solid organ structures, which could be used for repair of congenital defects or replacement of diseased tissue.

Animals↗

Biocorrosion of magnesium alloys: a new principle in cardiovascular implant technology?

OBJECTIVES: To develop and test a new concept of the degradation kinetics of newly developed coronary stents consisting of magnesium alloys. METHODS: Design of a coronary stent prototype consisting of the non-commercial magnesium based alloy AE21 (containing 2% aluminium and 1% rare earths) with an expected 50% loss of mass within six months. Eleven domestic pigs underwent coronary implantation of 20 stents (overstretch injury). RESULTS: No stent caused major problems during implantation or showed signs of initial breakage in the histological evaluation. There were no thromboembolic events. Quantitative angiography at follow up showed a significant (p < 0.01) 40% loss of perfused lumen diameter between days 10 and 35, corresponding to neointima formation seen on histological analysis, and a 25% re-enlargement (p < 0.05) between days 35 and 56 caused by vascular remodelling (based on intravascular ultrasound) resulting from the loss of mechanical integrity of the stent. Inflammation (p < 0.001) and neointimal plaque area (p < 0.05) depended significantly on injury score. Planimetric degradation correlated with time (r = 0.67, p < 0.01). CONCLUSION: Vascular implants consisting of magnesium alloy degradable by biocorrosion seem to be a realistic alternative to permanent implants.

Absorbable Implants↗

Acellular scaffold implantation--no alternative to tissue engineering.

OBJECTIVE: Degradation mechanisms of cardiovascular bioprostheses may play an important role in bioartificial implants. The fate of acellular implanted and cellular cardiovascular scaffolds was examined in an in vivo model. METHODS: Decellularized or native ovine carotid artery (CA, n=42) and aorta (AO, n=42) were implanted subcutaneously into rats for 2, 4 and 8 weeks. Immunohistochemical methods were used to monitor repopulation. Desmin-vimentin, CD31-, CD4- and CD18-antibodies for myocytes, endothelium, and inflammatory cell-infiltration, respectively. Calcification was detected by von-Kossa staining. Cell density was quantified by DNA-isolation. RESULTS: Acellular AO and CA matrices showed progressive calcification. Cellular AO and CA matrices trigger a strong inflammatory reaction which subsides after two weeks. CA scaffolds are revascularized progressively, whereas AO biocomposites degenerate. Calcification is less pronounced in cellular AO scaffolds and lacking in CA. CONCLUSION: Acellular bioartificial implants demonstrate degradation mechanisms similar to currently applied cardiovascular bioprostheses. Cellularized viable implants are promising clinical alternatives.

Animals↗

Carboxyfluorescein diacetate succinimidyl ester facilitates cell tracing and colocalization studies in bioartificial organ engineering.

BACKGROUND: We demonstrate a method that includes colocalization studies to analyze cell suspensions after isolation and to characterize 3-dimensional grafts consisting of cells and matrix in vitro and in vivo. MATERIALS AND METHODS: Neonatal rat cardiomyocytes were labelled by CFDA-SE after harvest. Cells in the isolated cell suspension, the embodied cells in the seeded scaffolds were characterized measuring features such as viability and distribution of the cell types. RESULTS: Selective cell count revealed high yields of viable cardiomyocytes. After seeding cells in collagen matrix, viability of the cells decreased gradually in the time process in vitro. Histology of implanted bioartificial myocardial tissue detected viable cardiomyocytes within the graft. CONCLUSION: Using colocalization histology we could label and track cells within the bioartificial myocardial tissue graft in vitro and post implant and assess viability and distribution.

Animals↗

Role of inflammation and ischemia after implantation of xenogeneic pulmonary valve conduits: histological evaluation after 6 to 12 months in sheep.

OBJECTIVE: Commercially available biological heart valve prostheses undergo degenerative changes, which finally lead to complete destruction. Here we evaluate the role of inflammation and ischemia after implantation of xenogeneic heart valve conduits (XPC) generated by novel concepts of tissue engineering. METHODS: Acellularized (a-)XPC and autologus re-seeded (s-)XPC were implanted into sheep. Samples were taken as follows: after acellularization (n = 2), after re-seeding (n = 2), 6 months (seeded/non-seeded: n = 3/5), 9 months (n = 2/5), and 12 months (n = 3/2) post implantation. Five native porcine conduits served as control. Using histological methods, samples were evaluated for pathological changes and existence/density of microvessels. RESULTS: Prior to implantation a-XPC were completely free of cells. Six months after implantation, leaflets and pulmonary arteries of s-XPC and a-XPC showed good endothelial surface coverage. Microvessel density within the myocardial cuffs and pulmonary vessel walls were comparable to control in all grafts. However, 6, 9 and 12 months after implantation pathological severe microvessel ingrowth, calcification and cellular infiltrations were observed on a-XPC and s-XPC valves, whereas myocardial cuffs and XPC-artery walls showed only mild degenerative alterations. CONCLUSIONS: Inflammatory reactions play a pivotal role in the degeneration of a-XPC and s-XPC. Thus, since ischemia seems to have little or no influence on this process, inflammation inductive factors should be the center of interest.

Animals↗

The ex-vivo-shunt-model: novel approach for assessing the thrombogenicity of vascular implants.

OBJECTIVE: Disadvantages associated with commercially available vascular implants necessitate alternative strategies to develop new vascular prostheses. Although many tissue characterizing strategies have been defined, no valid test for thrombogenicity exists. Here we introduce a novel concept for thrombogenicity testing of vascular implants METHODS: Silastic tubes were implanted into the carotid arteries of 12 sheep. After placing these shunts, tc99m-labeled platelets were administered and test-vessels were put in between the shunts. Native autologous (n=6), as well as native/acellularized allogeneic (n=6/n=6), and xenogeneic (n=6/n=6) carotid arteries and allogeneic (n=6/n=6) and xenogeneic (n=6/n=6) carotid arteries reseeded with allogeneic endothelial-cells, fibroblasts and myocytes were evaluated. Number and time course of intra-operatively deposited platelets were evaluated with a Geiger-counter; certain areas of platelet deposition located, envisioned and characterized by a gamma-camera and scanning electron-microscopy afterwards. RESULTS: Counter results revealed no significant different platelet depositions when comparing silastic tubes with either autologous or allogeneic native carotid arteries. However, starting 5 minutes after placement, acellularized/reseeded allogeneic (p=0.001/p=0.00004), and xenogeneic (p=0.0001/p=0.01) carotid arteries showed significantly more platelet depositions than native autologous carotides. Moreover, it was possible to show that almost no platelets adhere to native vessels or silastic tubes, thus proving the test method itself. CONCLUSION: The Ex-Vivo-Shunt-Model is a valid method to measure and envision the intrinsic thrombogenicity of vascular implants.

Anastomosis, Surgical↗

No evidence for productive PERV infection of baboon cells in in vivo infection model.

OBJECTIVES: The discovery that pig endogenous retroviruses are infectious for human cells in vitro lead to vehement discussions about the possible risk of infection after clinical xenotransplantation. Since PERV transmission to non-human primate cells in vitro has been observed, similar to human cells, infection studies in non-human primates should represent the best model to analyze a potential PERV transmission after xenotransplantation. However, it is still open to discussion, whether non-human primate cells can be infected productively-similar to human cells- and whether those species are suitable to analyze PERV infection risks in vivo. METHODS: In vitro, only few cell types can be tested for susceptibility. We developed a pig to baboon cell transplantation model with special emphasis on B-cell effective immunosuppression, removal of anti Gal-alpha 1,3-Gal-antibodies, inhibition of the complement cascade and long term survival of transplanted cellular grafts. This model allows us to investigate in vivo, whether any baboon cell types may be permissive for productive PERV infection. The xenograft recipients were investigated for up to 535 days post transplantation. Gal-alpha 1,3-Gal-antibody and complement levels were monitored. Potential PERV transmission was analyzed, not only in PBMC, but in a variety of tissue samples as well as in serum and plasma samples by PCR, RT-PCR and by detection of RT-activity. Moreover, potential PERV specific immune responses were studied by a highly sensitive Western-Blot-assay. RESULTS: Despite several days of extremely low levels of Gal-alpha 1,3-Gal-antibody and complement, and despite of long term xenochimerism, no evidence for PERV infection was obtained in any of the tested tissues or in the tested serum samples. CONCLUSION: This study supplies further evidence for a low susceptibility of baboons towards productive PERV infection after xenotransplantation.

Animals↗

[Anticoagulation in pregnant women after artificial heart valve replacement: is low-molecular-weight heparin an alternative?].

We report on the case of a 24-year-old pregnant woman with acute mechanical mitral valve thrombosis due to a treatment failure of low molecular weight heparin (LMWH) for permanent anticoagulation following mechanical valve replacement. Initially, our patient was put on oral warfarin for anticoagulation, but when her pregnancy was perceived the anticoagulation regimen was switched to daily subcutaneous administration of LMWH in order to minimize the risk of warfarin-induced embryopathy. During her 24th week of gestation she developed acute life-threatening pulmonary edema and hemodynamic instability, which was caused by an acute thrombosis of her artificial mitral valve. In an emergency operation the thrombozed valve was replaced by a porcine biological heart valve. The patient recovered uneventfully and gave birth to a healthy child in her 35th gestational week by cesarean section. In addition we discuss the rationale of different anticoagulation regimens with regard to maternal and fetal outcome with special consideration of LMWH as an alternative strategy to oral anticoagulation during pregnancy in women with mechanical heart valves.

Anticoagulants↗

Triple valve replacement in a patient with severe carcinoid heart disease.

We report on the case of a 34-year-old male patient suffering from end-stage carcinoid heart disease with severe tricuspid, pulmonary and mitral valve regurgitation. In addition, a persisting foramen ovale was present. The primary carcinoid tumor was never discovered. However, urine 5-hydroxy-indole-acetic-acid (5-HIAA) were consistently elevated after the first diagnosis of carcinoid disease and after eight years of medication with Octreotide and Interferon alpha-2b our patient developed significant cardiac insufficiency mainly due to severe valvular dysfunction. Ultimately, mechanical tricuspid, mitral and pulmonary valve replacement was performed. Twelve hours following the operation the patient had to be returned to the operating room for persisting intrathoracic hemorrhage. He recovered uneventfully and was discharged from hospital on day 37. Twelve months following triple valve replacement the cardiac status recovered from preoperative NYHA-IV to NYHA-I.

Adult↗

A novel bioartificial myocardial tissue and its prospective use in cardiac surgery.

BACKGROUND: Congenital heart defects such as atrial septal defect, ventricular septal defect, double outlet ventricles and the hypoplastic left heart syndrome as well as ischemic heart disease are associated with aplastic, defective or necrotic myocardial structures. In many of these instances patch closure, reconstruction of the defect or revascularization is required. We have developed a contractile bioartificial myocardial tissue, which offers new perspectives for various reconstructive surgical interventions, including congenital heart surgery. METHODS: Neonatal rat cardiomyocytes were seeded in vitro in a commercially available collagen scaffold. Histological examination and ultrastructural evaluation were performed. Protein and mRNA analysis were carried out by two-dimensional electrophoresis and reverse transcription-polymerase chain reaction (RT-PCR). Force measurements of contractions from the spontaneously beating or the pharmacologically stimulated bioartificial myocardial patch were obtained. RESULTS: A solid matrix of 20 x 15 x 2 mm with spontaneous contractions resulted 36 h after cardiomyocyte seeding. Histology showed a tight mesh of collagen fibrils. Two-dimensional electrophoresis and RT-PCR revealed cardiotypical proteins (actin, tropomyosin, creatine kinase, ventricular light chain) and mRNA (myosin heavy chain, Connexin 43). The elasticity curve during passive stretch was similar to that of myocardium. Contractile force increased after topical administration of Ca(2+) and adrenaline. However, stretch led to the highest levels of contractile force. CONCLUSIONS: Our novel contractile bioartificial tissue can be engineered in vitro and may open novel avenues for myocardial tissue replacement in congenital and reconstructive heart surgery. From the current standpoint autologous or allogeneic cells would be preferred over xenogeneic sources.

Animals↗

Acute dissection of the ascending aorta: first results of emergency valve sparing aortic root reconstruction.

OBJECTIVE: Acute dissection of the ascending aorta requires immediate surgical intervention. In this study, we report our first results with valve sparing aortic root reconstruction removing all the diseased tissues. METHODS: From August 1995 to December 2000, 22 patients with acute aortic dissection of the ascending aorta (Stanford type A) underwent valve sparing aortic root reconstruction. Their ages ranged from 20 to 76 years (52+/-15, 68% males). Dissection was found in the ascending aorta (3 patients) or both in the ascending aorta and aortic arch (19 patients; 86%). Course and length of hospitalization, echocardiographic and clinical follow-up, complications and mortality were analysed. RESULTS: Mean cardiopulmonary bypass time was 212+/-56 min (134-352 min), mean aortic cross clamp time was 157+/-24 min (114-205 min). In patients undergoing additional arch replacement (n=19), circulatory arrest was 35+/-18 min (11-75 min). After reconstruction, intraoperative echocardiography showed aortic insufficiency (AI) grade 0 in 16 patients (84%) and grade 1 in three patients (16%). Stay in intensive care unit was 2.1+/-0.7 days, and postoperative hospitalization was 21+/-14.4 days. There were three perioperative deaths (14%). Mean post-operative follow-up was 18.4+/-18 months (0.4-65.4 month). One patient died 10 months postoperatively. At follow-up, no patient suffered AI grade 2 or higher, and no reoperation for aortic valve failure was necessary. All patients presented with a favorable exercise tolerance being in New York Heart Association functional class I or II. CONCLUSION: Valve sparing aortic root reconstruction in patients with type A dissection can be performed with acceptable intraoperative mortality and morbidity and excellent results during follow-up. The complete resection of the diseased aorta is particularly appealing.

Acute Disease↗

Restoration of blood flow and evaluation of corresponding angiogenic events by scanning electron microscopy after a single dose of VEGF in a model of peripheral vascular disease.

The angiogenic effect of vascular endothelial growth factor (VEGF) has typically been assessed by indirect methods, including microsphere injection and angiography. Here, we use 3-D scanning electron microscopy (SEM) to directly visualize patterns of angiogenesis after a single bolus administration of VEGF in a model of peripheral vascular ischemia. Hind limb ischemia was induced by subcutaneous turniquet implantation in adult Wistar rats. The control group (group A, n = 10) was left untreated, group B (n = 10) received a single dose of VEGF (50 microg) injected in the peroneus muscle. LASER Doppler was applied for blood flow measurements. Animals were sacrificed on day 14 after ischemia induction and vascular casting was performed. Angiogenetic events such as 'tiny lateral sprouts', arcus formations', confluences and the angle of sprouting were assessed by SEM. Significant capillary sprouting was observed in both groups. VEGF-treated limbs demonstrated higher degrees of capillary growth (P = 0.01) and flow recovery (P = 0.028). 3-D-SEM showed sprouts to be more frequent in group B. Tiny lateral sprouts, which always left the mother vessel at an angle of 90 degrees and which were of small diameter and lacked imprints of endothelial cell nuclei, were more frequent in the VEGF-treated group (P = 0.018). Arcus formation was significantly higher in the treated group (P = 0.02). We have developed a simple and effective experimental model of ischemia. For the study of angiogenic phenomena, 3-D imaging of the microvasculature offers a direct and conclusive method for the study of angiogenic events.

Animals↗

Traveling after heart transplantation.

BACKGROUND: With evolving medical techniques and post-operative care, the quality of life after cardiac transplantation is improving over the recent years. However, the need for continuous immunosuppressive therapy may result in restrictions from some social and recreational activities, including traveling. The aim of this study was to analyze traveling activities and complications in a large cohort of heart transplant recipients, with the intention to develop adequate safety and behavioral guidelines. METHODS: Using a standardized questionnaire, 103 consecutive patients (pts) were asked to report about time and destination of their traveling activities, predominant activities, as well as potential travel-related complications. Documented rejection episodes as well as laboratory data are listed. RESULTS: Feedback was 97% (of 103 pts asked). Out of 100 pts who responded, [82 males, 18 females, mean age 52.3 +/- 12.4 yr, 6.9 +/- 3.8 yr post-heart transplantation (HTX)] 95 reported on traveling activities (95%). Concomitant disease was present in form of diabetes (n=8), renal insufficiency (n=5) and cardiac allograft vasculopathy (n=12). Mean cumulative traveling time was 120 +/- 125 d (3-560 d). Except from domestic journeys, 79 pts chose destinations within Europe, and 29 to overseas countries. Complications were reported by 15 of 95 pts (15.8%), being mostly small accidents and febrile episodes. Rejection episodes or other life threatening events were not observed. There was no significant correlation between observed complications and gender, age, time post-HTX, immunosuppression or comorbidities. CONCLUSIONS: Traveling after HTX appears to be safe and favorably improves quality of life, if certain precautions are met.

Adult↗