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Biomedical subjects

A Haverich

Publications and source records attributed to A Haverich.

At least 109 records · Page 6Linked to original sources

Azathioprine withdrawal in stable lung and heart/lung recipients receiving cyclosporine-based immunosuppression.

BACKGROUND: Chronic rejection is the leading cause of graft failure after (heart-) lung transplantation. Therefore, many centers maintain a triple immunosuppressive cyclosporine-based regimen including azathioprine (AZA) during the long-term course after lung transplantation. However, an increased risk of malignancies has been attributed to prolonged immunosuppression, and there is evidence that less intensive immunosuppressive regimens are feasible in the long-term course after other solid organ transplantation. Therefore, we investigated the effects of AZA withdrawal in stable lung transplant recipients. METHODS: A prospective study was performed to assess the effects of AZA withdrawal in patients who received a lung transplant more than 4 years ago with stable graft function defined by absence of rejection episodes for at least 2 years and no evidence of bronchiolitis obliterans. RESULTS: A total of 24 patients qualified for the study and 7 discontinued AZA. Despite the small number of patients, termination of the study became necessary after 12 months because significantly more grafts showed deteriorating function after withdrawing AZA (4 of 7) compared to recipients continuing a triple therapy (1 of 17; P<0.05). In recipients with deteriorating graft function conventional treatment with high-dose corticosteroids and reinstitution of AZA failed to stop the development of obliterative bronchiolitis. CONCLUSIONS: Our data reinforce the importance of a potent immunosuppressive regimen for the maintenance of stable graft function after lung transplantation.

Acute Disease↗

Engineering of human vascular aortic tissue based on a xenogeneic starter matrix.

BACKGROUND: The goal for tissue engineering of vascular grafts is the replacement of a diseased vessel with a functional and stable graft. We now introduce a new concept for the tissue engineering of vessels. The idea was to humanize a previously acellularized, but structurally intact, xenogeneic vessel by repopulation with human autologous cells. To this purpose, a gentle nondenaturing and nondeterging acellularization procedure for xenogeneic aortas was developed. This structure was reseeded with pre-expanded peripheral vascular endothelial cells (EC) and myofibroblasts using specifically designed bioreactors. METHODS: Aortas from 15-30 kg female landrace pigs were acelullarized with a 0.1% trypsin solution for between 24 and 96 hr. Human vascular cells were harvested from saphenous vein biopsy specimens. Acellularized vessels were reseeded with EC and myofibroblasts. Cell viability after reseeding was assayed by fluorescence staining. Morphologic features of the acellularized matrix and tissue engineered vessel was assayed by transmission and scanning electron microscopy and histologic analysis. Nitric oxide-synthetase activity was investigated by mass spectrometric analysis of bioreactor supernatants. The in vivo immune response was tested by subcutaneous implantation of acellularized porcine aortic tissue in a rat model. RESULTS: The acellularization procedure resulted in an almost complete removal of the original resident cells, and the 3-D matrix was loosened at interfibrillar zones. However, the 3-D arrangement of the matrix fibers was grossly maintained. The 3-D matrix was covered with a fully confluent human endothelial cell layer obtained by continuous stress challenge in the bioreactor. Myofibroblasts migrated into positions formerly occupied by the xenogeneic cells. Nitric oxide synthetase activity was maintained in the bioartificial graft. T-lymphocyte and CD18 positive leukocyte infiltrate were greatly reduced after acellularization of porcine aortic specimens after implantation in the rat. CONCLUSIONS: Porcine vessels were acellularized and consecutively fully repopulated with human EC and myofibroblasts. This approach may eventually lead to the engineering of vessels immunologically acceptable to the host using a relatively short preparation period of 2-3 weeks. We expect matrix turnover in vivo leading to a gradual assimilation of the matrix structure by the host mediated by the hosts autologous cells.

Animals↗

Impact of chronic infection with chlamydia pneumoniae on incidence of cardiac allograft vasculopathy.

Chronic infection with Chlamydia pneumoniae (CP) is associated with development of coronary disease. However, little information exists concerning CP infection and impact on posttransplant cardiac allograft vasculopathy (CAV). A total of 202 patients were investigated 5.5+/-3.1 years after cardiac transplantation (46.5+/-11.0 years; 169 male, 33 female). Assessment of CAV was performed by annual coronary angiograms. Chlamydia serology (IgG/IgA) was performed using micro-immunofluorescence. Statistics comprised analysis of variance and Kaplan-Meier analysis. A total of 152 patients were CAV positive. Elevated titers were present in 45% (IgG) and 72.8% (IgA) of patients. Generally, serostatus was not associated with development of CAV when evaluated over the total postoperative interval. However, after month 14 there was a significant trend toward lower actuarial freedom from CAV in patients with elevated IgA titers. CP seems not to play a significant role in the development of CAV early after heart transplantation but might be a predicting risk factor after the first postoperative year.

Adult↗

Cardiac allograft vascular disease after orthotopic heart transplantation: methylenetetrahydrofolate reductase gene polymorphism C677T does not account for rapidly progressive forms.

BACKGROUND: Recently, homocysteine (HCY) levels have been suggested to be a risk factor in cardiac allograft vascular disease (CAVD). As plasma levels are partially under genetic control, we investigated the influence of the methylenetetrahydrofolate reductase (MTHFR) polymorphism on HCY levels and development of CAVD in heart transplant (HTX) recipients. METHODS: Genotyping and assessment of fasting HCY levels were performed in a cohort of 146 HTX recipients and correlated to the onset and progression of CAVD, assessed by serial angiography. RESULTS: Actuarial freedom from CAVD did not differ significantly between the genotypes. However, patients positive for CAVD presented with higher HCY levels than CAVD-negative individuals (21.0+/-9.4 vs. 18.2+/-6.6 micromol/L, P=0.046). CONCLUSIONS: There is some evidence that plasma HCY might be involved in development of CAVD. However, polymorphism of the MTHFR gene could not be shown to be related to severity of allograft vascular disease.

Adult↗

Endoluminal grafting of abdominal aortic aneurysms: experience with the Talent endoluminal stent graft.

The aim of this study was to evaluate the Talent endoluminal stent graft (TESG) in treating abdominal aortic aneurysms (AAA). The TESG is a polyester-covered nitinol endograft (proximal diameters 20-38 mm and iliac limb diameters 8-22 mm). Twenty-two men were treated with the TESG via bilateral femoral arteriotomies. Pre-implantation, coil embolization of various vessels arising from the aneurysm was performed in 6 patients. Plain radiographs and spiral CT angiograms (CTA) were carried out at 7 days, 3, 6, and 12 months following TESG implantation or re-intervention. Median aortic and iliac diameters were 27 mm (range 20-34 mm) and 14 mm (range 10-19 mm). The corresponding graft diameters were 30 mm (range 24-38 mm) and 14 mm (range 12-20 mm). No patient was rejected purely on the basis of too large aortic or iliac diameters. Eight patients required custom-made grafts. Graft implantation was successful in all patients. There were no blood transfusions, distal embolic episodes, or conversions to open surgery. Re-intervention was necessary in 1 patient. Complications included one fatal myocardial infarction, one inguinal hematoma, and two superficial wound infections. The aneurysm thrombosed completely following implantation in 14 patients and at 3 or 6 months in 4 other patients. One patient with endoleak is awaiting his 3-month control and 2 patients show tiny endoleaks but reduction of aneurysm size. The mean aneurysm size decreased significantly from 58 +/- 10 to 53 +/- 13 mm (p < 0.0005). Due to the large sizes available and the option of custom-made grafts, the TESG helps widen the spectrum of patients who can be treated with endoluminal grafting. The treatment is associated with a significant reduction in aneurysm size.

Aged↗

Vascular remodeling in cardiac allograft vasculopathy.

Growing evidence suggests that vascular remodeling processes contribute significantly to the amount of luminal obstruction in coronary artery disease. Recently changes in vascular geometry in the form of positive (compensatory enlargement) as well as negative remodeling (constrictive changes) could be demonstrated in transplanted hearts as well. For further characterization intravascular ultrasound provides an excellent insight into time-related changes (by serial follow-up examinations) and into longitudinal spatial relationships within vessels (motorized pullback with 3-D reconstruction). Focused on time-related changes a decrease in total vessel volume within the first year after transplantation as compared to a slight compensatory enlargement in patients 'late' after HTX could be demonstrated. Regarding focal luminal obstruction, local constrictive changes (negative remodeling) were identified to be the most important predictor of severity of stenosis. It is concluded that changes in vascular geometry are of major importance in focal stenosis as well as in a general luminal loss of coronary arteries within transplanted human hearts. These observations might be of special interest regarding pathophysiology and potential therapeutic interventions in this unique form of an accelerated coronary syndrome.

Coronary Angiography↗

Cardiac allograft vasculopathy--coronary interventions and surgical options.

Despite improved results early after heart transplantation (HTX) obstructive allograft vasculopathy still remains the leading cause of death late after HTX. Studies in the past, focused on angioplasty (PTCA), presented with disappointing results. Using intravascular ultrasound an extensive early recoil could be shown to be the major cause for re/rest-stenosis in dilated lesions. Stimulated by these observations, stent implantation was recently shown to be an effective therapeutical alternative in focal luminal obstruction in graft coronary arteries. Treatment of 41 patients in a single center experience (75 lesions, 85 stents) resulted in a success rate of 98%; no acute or subacute stent thromboses were observed (protocol with ASS and Ticlopidine). Control angiography revealed a 6-month restenosis rate of 14.1% defining stent implantation as the method of choice for relief of focal luminal obstruction. Only limited experience is available regarding the surgical approach with coronary artery bypass grafting. In selected patients (focal obstruction not suitable for interventional therapy, adequate peripheral vessels) it might represent a therapeutical alternative.

Angioplasty, Balloon, Coronary↗

Simultaneous treatment of thoracic and infrarenal aortic aneurysm using a combination of conventional surgery and endoluminal stent grafting.

INTRODUCTION: Patients with multiple aortic aneurysms represent a small subgroup with the need for extensive surgical treatment at considerable risk. Endovascular treatment in combination with conventional operation is possible. We demonstrate a case with simultaneous exclusion of aneurysms of the descending thoracic and the infrarenal aorta to outline the technical obligations. CONCLUSION: Simultaneous exclusion of a thoracic and an abdominal aneurysm can be performed successfully by conventional infrarenal aortic replacement with bifurcated dacron prosthesis and endovascular implantation of a thoracic stent-graft within one operation.

Anastomosis, Surgical↗

Minimally invasive coronary artery revascularization on the beating heart.

BACKGROUND: The quality of surgical beating heart revascularization is frequently questioned, especially when the surgical access is limited. Nevertheless, the number of off-pump coronary procedures is expanding worldwide. METHODS: Since getting started with minimally invasive direct coronary artery bypass to anterior myocardial vessels in June 1996, 306 patients received left internal mammary artery grafting through an anterior minithoracotomy. Risk increasing comorbidities were present in 168 of them. Particular attention was paid to early postoperative angiographic results and complications. RESULTS: The 30-day mortality summed up at 1.0% and was limited to patients with additional risks for conventional bypass grafting. Early postoperative control angiographies in 232 patients confirmed a global patency rate of 97.8%, revealing in addition four unexpected malinsertions to diagonal branches. In surviving patients major complications like myocardial infarction, stroke, or multiorgan failure were completely absent. CONCLUSIONS: Minimally invasive direct coronary artery bypass grafting appears to allow for a safe and effective revascularization of the left anterior descending artery by use of the left internal mammary artery. Especially patients with risk increasing comorbidities should benefit from this approach, provided the surgical indication based on a dominating left anterior descending artery lesion. Angiographic minimally invasive direct coronary artery bypass results seem to fulfill the expectations generated by results obtained in conventional left internal mammary artery grafting and appear to be superior to interventional means.

Aged↗

Effects of minimal invasive coronary artery bypass on pulmonary function and postoperative pain.

BACKGROUND: Minimally invasive direct coronary artery bypass (MIDCAB) requires substantially smaller incisions than conventional coronary artery bypass grafting (CABG). We investigated whether this fact may lead to less postoperative pain and improved pulmonary function. METHODS: Preoperative and postoperative (days 1, 3, and 5) pulmonary function and postoperative pain were assessed in 15 patients undergoing MIDCAB (group A) by using a standardized score and were compared with 15 patients admitted for CABG (group B). RESULTS: Total operation time (140 minutes versus 189 minutes; p<0.001) and duration of mechanical ventilation (300 minutes versus 840 minutes; p<0.001) were significantly less in group A. Pulmonary function was comparable between the 2 groups on postoperative day 1 (POD 1). Vital capacity was significantly greater in group A on POD 3 (59.7% versus 40.6%; p<0.001) and on POD 5 (74.4% versus 53.9%; p<0.001). Similar results were found for forced expiratory volume in 1 second (group A versus B on POD 3: 56.3% versus 42.2%; p<0.05; and on POD 5: 68.4% versus 55.5%; p<0.01). Postoperative pain was significantly higher in group A (POD 1: score 5.5 versus 3.6; POD 3: 4.0 versus 2.9; p<0.01). CONCLUSIONS: MIDCAB procedures lead to better preservation of pulmonary function compared with conventional CABG despite greater postoperative pain.

Aged↗

Mini-sternotomy for off-pump coronary artery bypass grafting.

The number of off-pump coronary artery bypass grafting procedures without cardiopulmonary bypass is steadily increasing. We report on a new, minimally invasive surgical approach for off-pump coronary revascularization in multivessel disease. A distal sternotomy is performed to gain access to the left and right internal thoracic arteries and to reach the left anterior descending coronary artery, diagonal branches, and right coronary artery for off-pump revascularization.

Coronary Artery Bypass↗