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Biomedical subjects

H Reichenspurner

Publications and source records attributed to H Reichenspurner.

At least 19 recordsLinked to original sources
PubMed2006

Tracheal allograft transplantation in rats: the role of different immunosuppressants on preservation of respiratory epithelium.

BACKGROUND: Bronchiolitis obliterans is the most significant complication adversely affecting the survival of lung allograft recipients. Injury and loss of epithelium are associated with obliteration of the airway lumen. The aim of this study was to examine the effects of various immunosuppressants on airway epithelium. METHODS: Tracheae from Brown Norway donors were heterotopically transplanted into the greater omentum of Lewis (allografts) or Brown Norway (isografts) animals. Recipients were treated for 28 days with FK778 (20 mg/kg), tacrolimus (4 mg/kg), or sirolimus (2 mg/kg). Tracheal segments were evaluated for the degree of luminal occlusion as well as the type and percent of luminal epithelial cell coverage. RESULTS: All agents inhibited peritracheal infiltration and luminal obliteration. Tacrolimus- more than sirolimus-treated recipients showed partial preservation of the luminal epithelial coverage, whereas animals that received FK778 showed no respiratory epithelium. The epithelial loss was accompanied by the appearance of fibrous tissue, which replaced the mucosa. CONCLUSIONS: Tacrolimus as well as sirolimus effectively prevented the development of obliterative airway disease whereas tacrolimus and, to a lesser degree, sirolimus preserved epithelial cells as a source of protective cytokines. With FK778 significant airway obliteration was suppressed despite complete epithelial loss. Thus, FK778-treated animals displayed an epithelial-independent inhibitory effect on myofibroblast proliferation.

Animals↗
PubMed2006

FK778: new cellular and molecular mechanisms of action.

PURPOSE: The new malononitrilamide FK778 is currently being evaluated as an immunosuppressant for organ transplantation. Its main mechanism is inhibition of a pivotal enzyme of pyrimidine biosynthesis. This report revealed new mechanisms of action on different cell types involved in acute and chronic allograft rejection. METHODS: Purified Brown-Norway rat aortic endothelial cell (EC) cultures were pretreated with several concentrations of FK778. Endothelial adhesion molecule expression (ICAM-1/VCAM-1) stimulated with TNF-alpha was quantified by immunofluorescence. Purified Lewis rat lymphocytes (LC) incubated with FK778 were stimulated via TCR/CD28 signals, and CD25 expression was quantified using FACS analysis. Uridine addition was used in all assays to reverse the pyrimidine synthesis blockade. Lymphocyte-EC interaction was assessed by micromanipulator-assisted single-cell adhesion assays. Finally, smooth muscle cell (SMC) proliferation and migration was analyzed. Uridine addition was used in all assays to reverse the pyrimidine synthesis blockade. RESULTS: TNF-alpha stimulation and TCR/CD28 co-stimulation significantly increased EC ICAM-1/VCAM-1-expression and LC CD25 surface expression, respectively. These effects were dose-dependently inhibited by FK778 and were not reversed by the addition of uridine. FK778 dose-dependently attenuated LC adhesion to allogeneic EC. The dose-dependent inhibition of SMC proliferation by FK778 was abolished by uridine addition, whereas the inhibitory effect on SMC migration was not affected by uridine supplementation. CONCLUSIONS: FK778 directly reduced endothelial adhesion molecule up-regulation, inhibited lymphocyte activation, and attenuated lymphocyte-endothelium interactions, critical early steps in graft rejection. These effects were separate from the blockade of pyrimidine synthesis. The antiproliferative potency of FK778 on SMC may be an important mechanism to inhibit the fibroproliferative lesions of chronic organ rejection.

Alkynes↗
PubMed2005

[The ECG-gated 4-row multidetector CT of the heart in preoperative imaging minimal invasive coronary artery bypass grafting].

PURPOSE: Minimal invasive direct coronary artery bypass grafting (MIDCAB) or off-pump coronary artery bypass grafting (OPCAB) on the beating heart with full or mini-sternotomy are becoming more common in coronary bypass surgery of the left anterior descending (LAD). In the decision, which surgical approach (MIDCAB, OPCAB or conventional surgery with cardiopulmonary bypass) will be best used, knowledge of the anatomical field is of major importance. The aim of the study was to evaluate retrospective ECG-gated 4-row multidetector CT (MDCT) in patients planned for MIDCAB as additional imaging to coronary angiography. MATERIAL AND METHODS: The study included 25 consecutive patients. MSCT was performed as unenhanced (collimation 4 x 2.5 mm) and contrast-enhanced examination (140-170 ml, 300 mg Iodine/ml, collimation 4 x 1 mm). The evaluation included presence of LAD calcifications, distance of LAD and left internal mammarian artery (LIMA), course of LAD and LIMA, the presence or absence of bridging through myocardium or epicardial fat and the presence of pleural fibrosis. The MDCT results were correlated with intra-operative findings. RESULTS: All MDCTs could be assessed with reference to the demands. In 20/25 operations, MDCT had direct influence as to the selection of the surgical approach (11 MIDCAB, 7 OPCAB with mini-sternotomy and 5 with full sternotomy, 2 conventional surgeries). The distance of LAD and LIMA varied from 0.9 to 4.5 cm in MDCT. As to calcifications, 3/25 correlated patients had calcifications and 10 patients had no calcifications in the middle LAD. Seven patients had intraoperative fibrosis of the vessel wall without calcification of the middle LAD, which could not be detected with MDCT. Another 5 patients had single calcified plaques in the middle LAD, 4 of these had a fibrosis of the vessel and 1 had a normal vessel at surgery. In these cases, the anastomosis was done between the calcified plaques. No myocardial bridging was detected by MDCT and at surgery. Bridging of epicardial fat was shown by MDCT and at surgery in 9/25 patients and was excluded in 15 patients. In 1 patient, the LAD seemed to run superficially in MDCT, but was covered with fat as seen during surgery. The course of the LIMA was inconspicuous in all cases, no pleural fibrosis was found. CONCLUSIONS: The 4-row MDCT has proven to be adequate in addition to coronary angiography for preoperative evaluation in patients scheduled for MIDCAB and provides the surgeon with relevant information for the selection of the operative approach.

Aged↗
PubMed2004

Ross and Ross-Konno procedure in children and adolescents: mid-term results.

OBJECTIVES: The aim of the study was to analyze mid-term results of aortic root replacement with pulmonary autograft in children and adolescents in two centers. METHODS: From December 1997 through August 2003, a total of 66 patients underwent the Ross procedure in two centers. Indication for Ross procedure was predominantly aortic stenosis in 24 patients and predominantly aortic regurgitation (AR) in 22 patients. Twenty patients with severe left ventricular outflow tract obstruction (LVOTO) underwent Ross-Konno procedure. No patient had a geometric mismatch of more than 5 mm in favor of the aortic annulus. RESULTS: There was no early death. One patient died 3 months after surgery due to bacterial endocarditis. Survival on median follow-up period of 2.4 years was 98.5%. Neo-aortic regurgitation was none in 29 (44%) patients, trivial in 35 (53%) patients and mild in 2 (3%) patients. One patient (1.5%) needed aortic valve replacement because of autograft failure. Actuarial freedom from more than trivial neo-aortic regurgitation, or aortic valve replacement was 95% at 5 years follow-up. There was no patient either with recurrent LVOTO or significant aortic root dilatation. Freedom from redo was 93% at 5 years of follow-up. There had been a significant reduction (P = 0.001) and normalization in the left ventricle diastolic diameter index and left ventricle mass index, respectively, within 3-12 months after operation. Sixty-three percent of all operated patients are without medication; no one is on anticoagulation therapy. CONCLUSIONS: Our 7 years experience with the Ross and Ross-Konno operation has shown excellent mid-term results, with mortality rate approaching zero in both simple and complex left heart lesions, even in the neonates and infants. It is a procedure of choice in children with severe anomaly of the aortic valve and/or left ventricular outflow tract obstruction. The main concern is dilatation of the neo-aortic root leading to progression of AR, especially in the settings of geometric mismatch of aortic and pulmonary roots and bicuspid, regurgitant aortic valve. The risk of autograft failure in these specific subsets of patients remains to be determined.

Adolescent↗
PubMed2004

Heart transplantation in a patient with multiple sclerosis and mitoxantrone-induced cardiomyopathy.

We describe a 30-year-old man with end-stage heart failure after therapy with mitoxantrone for multiple sclerosis. A successful orthotopic heart transplantation was performed when intensified medical therapy failed to improve the patient's hemodynamics. In spite of the severe underlying disease he did well on dual immunosuppression with methylprednisone and cyclosporine. Neurologic symptoms remained stable throughout the procedure and, after 2 months, he resumed preoperative ambulatory status. Eight years after the operation, the patient is now in New York Heart Association (NYHA) Class I status. Using canes, he is able to walk short distances. Repeated urinary tract infections caused by Escherichia coli became a problem, but have been controlled by long-term oral antibiotic prophylaxis with trimethoprim.

Adult↗
PubMed2003

Neurological and neuropsychological examination and outcome after use of an intra-aortic filter device during cardiac surgery.

Cerebral embolization of particles after cardiac surgery is frequently associated with neurological deficits. Aortic crossclamp manipulation seems to be the most significant cause of emboli release during cardiac surgery. The goal of this study was to demonstrate whether the use of an intra-aortic filter device has an effect on the magnet resonance imaging (MRI) and functional neurological outcome. Twenty-four patients undergoing cardiosurgical procedures using cardiopulmonary bypass (CPB) were selected: coronary artery bypass graft (CABG) surgery (n = 17), aortic valve replacement (AVR) surgery (n = 4) or combined procedures (n = 3). Patients were evaluated by diffusion weighted MRI of the brain, neurological examination and neuropsychological assessment regarding alertness as well as divided and selective attention before and five to seven days after surgery. The patients were divided into two groups. In group I, 12 patients received a filter through a modified 24 F arterial cannula immediately before the aortic crossclamp was released. Filters remained in the aorta until CPB was discontinued. Intraoperatively, bilateral middle cerebral artery transcranial Doppler (TCD) was monitored at baseline, at the beginning of CPB, at a timepoint when the aorta was crossclamped, when the filter was inserted and while the crossclamp was switched to partial clamping until the CPB was discontinued. TCD was used for detection of microembolic signals (MES). The captured material in the filter was examined histologically. Twelve patients served as controls without aortic filtration (group II). The MRI of the brain did not show any diffusion alterations in either group before or after surgery. No patient developed a focal neurological deficit or stroke. Intraoperative quantitative MES detection revealed a four to tenfold increase in patients of group I compared with group II (5-6 versus 0.5-1 MES/min) during the filter dwell time. There was no consistent pattern regarding the neurobehavioural sequelae. Filters showed arteriosclerotic debris in 75% of the patients. The use of the intra-aortic filter device did not show a positive effect on neurological, neuroradiographical and neuropsychological outcomes. The increase of the MES rate in group I patients may be due to microbubbles generated as microcavitations by the filter or the aortic filter cannula. The intra-aortic filter was able to capture atheromatous material in 75% of the patients.

Aorta, Thoracic↗
PubMed2002

Midterm results and quality of life after minimally invasive vs. conventional aortic valve replacement.

BACKGROUND: This study compares early and mid-term results as well as the quality of life (QOL) between the minimally invasive and conventional aortic valve replacement (AVR). METHODS: Between 7/97 and 4/01, 70 patients (mean age 64.3 +/- 1.3 years) underwent minimally invasive AVR (group M) through an L-shaped ministernotomy. The results were compared to those of 70 conventional AVR (group C) patients during the same period. Patients were equally matched according to age, sex, ejection fraction, valvular lesion, and valve prosthesis. In groups M and C, follow-up was 98.5 % and 95.4 % complete and averaged 34.0 +/- 10.3 and 33.1 +/- 12.9 months, respectively. RESULTS: There were no hospital deaths in group M but two deaths in group C (p = n. s.). Conversion to full sternotomy was necessary in two group M patients. Cross-clamping time (71 +/- 15 min vs. 58 +/- 18 min), cardiopulmonary bypass time (105 +/- 22 min vs. 84 +/- 24 min), and time of surgery (228 +/- 45 min vs. 184 +/- 48 min) were significantly longer in group M. No statistically significant differences between the two groups for postoperative ventilation time, transfusion rate, ICU stay or length of hospital stay were recorded. At the end of follow-up, 98.5 % vs. 96.9 % of the patients were free of thromboembolism (p = n. s.), 100.0 % vs. 96.9 % were free of endocarditis (p = n. s.), and 98.5 % vs. 100.0 % were free of reoperation (p = n. s.) in group M compared to group C. Survival was 97.0 % vs. 91.9 % (p = ns). No differences in any of the 8 QOL categories, in patient satisfaction with the operative result or in judgment of the cosmetic aspect were noted among groups. CONCLUSIONS: This study has failed to show any advantage of minimally invasive AVR in early or midterm follow-up.

Adult↗
PubMed2002

Bronchial epithelial cell B7-1 and B7-2 mRNA expression after lung transplantation: a role in allograft rejection?

Obliterative bronchiolitis is commonly interpreted as chronic rejection and involves the bronchial and bronchiolar epithelium. Upregulation of major histocompatibility complex (MHC) II on bronchial epithelial cells (BEC) had been hypothesised to be an important trigger of a bronchus directed rejection response. More recently, the additional expression of the costimulatory molecules B7-1 (CD80) and B7-2 (CD86) on antigen presenting cells were found to play an important role in the activation of T-lymphocytes in transplant rejection. The role of the expression of these molecules by BEC is unclear. BEC obtained by bronchial brushing and bronchoalveolar lavage fluid (BALF) cells from lung transplant recipients were studied and evaluated for messenger ribonucleic acid (mRNA) expression of B7-1 and B7-2 by semi-quantitative reverse transcriptase-polymerase chain reaction. Significantly elevated B7-1/glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA ratios were found in BEC from patients examined during the first 3 months after lung transplantation. Interestingly, in a small group of patients with bronchiolitis obliterans syndrome the B7-1/GAPDH and B7-2/GAPDH ratios were significantly elevated for BEC, whereas no differences were found for the BALF cells. In summary, B7 messenger ribonucleic acid expression by bronchial epithelial cells may play a role in (chronic) lung allograft rejection.

Adult↗
PubMed2002

Cell transplantation--a potential therapy for cardiac repair in the future?

PURPOSE: Adult human myocardium cannot regenerate because cardiac muscle cells do not reenter the cell cycle. Myoblasts, cardiomyocytes, and stem cell-derived cardiomyocytes have been transplanted in experimental settings to replace lost myocardial tissue. The purpose of this paper is to review the experimental data about cell transfer onto myocardium and to highlight the advantages of the particular cell types used. BACKGROUND AND METHODS: Myoblasts or satellite cells are precursor cells attached to skeletal muscle fibers. The transfer of these cells onto damaged myocardium was demonstrated successfully in several animal models. Because myoblasts can be expanded in culture, a large number of cells can be obtained from only a small skeletal muscle specimen. These cells could be delivered locally by injection within a damaged myocardial area or by coronary infusion. However, only one group has been able to show an improvement in myocardial function after myoblast transfer. The second type of cells used experimentally for cell transfer were fetal cardiomyocytes. Fetal cardiomyocytes retain the ability to divide and therefore can be expanded in culture. The cells were integrated into the myocardial tissue, differentiated into normal cardiac muscle cells, and formed intercellular connections with host myocardial cells. The transplantation of these cells onto cryo-injured myocardium resulted in improved cardiac function in several animal models. Stem cell-derived cardiomyocytes can be selected from embryonic stem cells. These cells still divide and differentiate into different cardiac muscle cells (atrial, ventricular, and pacemaker). After transplantation into damaged myocardium in mice, they formed stable grafts and survived for at least 7 weeks. The selection of these cells has to be performed with care to prevent teratoma formation originating from single undifferentiated cells attached to the transferred cells. Recent experimental studies revealed the ability of bone marrow stem cells to differentiate into cardiomyocytes. These cells were transplanted into damaged myocardium via coronary perfusion. They survived for at least 4 weeks and showed differentiation toward cardiac muscle cells. The functional benefit of bone marrow stem cells, however, has not been clearly demonstrated, and there is a possibility of tumor formations originating from these cells. DISCUSSION: Myoblasts and bone marrow stem cell-derived cardiomyocytes would permit autologous cell transfer onto the myocardium. These cells can be easily obtained and expanded in culture. Gene transfer is also possible, and there are no ethical proscriptions against an autologous cell transfer. However, the integration and final differentiation of these cells in the heart tissue is not clear yet. Fetal cardiomyocytes, on the other hand, are integrated in the myocardial tissue, improve cardiac function, and can be expanded in culture. Their transfer would be allogenic, making immunosuppression necessary. Stem cell-derived cardiomyocytes could be used to replace all 3 types of cardiac muscle cells, and they can be expanded in culture. The possibility of teratoma formation makes a 100%- selection mandatory. At present, ethical concerns against working with human embryonic stem cells are a factor to be considered. CONCLUSIONS: Cell transfer therapy has been shown to improve myocardial function in animal experiments. This finding indicates that a reduced myocardial function can be improved by cell transfer therapy. Stem cell-derived cardiomyocytes in particular, either of embryonic or bone marrow cell origin, would allow for selective replacement of pacemaker cells or atrial or ventricular cardiomyocytes.

Heart Diseases↗
PubMed2001

Single vessel revascularization with beating heart techniques -- minithoracotomy or sternotomy?

OBJECTIVE: The purpose of the study was to evaluate the best surgical approach in off-pump single vessel revascularization of the left anterior descending coronary artery (LAD). METHODS: In 256 patients a single left internal mammary artery (LIMA) to LAD bypass was performed with beating heart techniques through a left anterior minithoracotomy (minimally invasive direct coronary artery bypass (MIDCAB), n=129) or a full sternotomy (off-pump coronary artery bypass (OPCAB), n=127). RESULTS: In the OPCAB group, significantly more severe comorbidities (P=0.001) and redo-operations were noted (P<0.001). Conversion to sternotomy or CPB was necessary in five MIDCAB patients and one OPCAB patient. No cerebrovascular accident was seen in both groups. There was no hospital death in MIDCAB- and two deaths in OPCAB procedures (P=ns). There was a significant reduction in time of surgery (P=0.028) and coronary occlusion (P=0.009) in the OPCAB group. No differences in postoperative ventilation time, ICU stay and length of hospital stay were recorded between groups. Wound infections occurred in six MIDCAB patients (4.7%) and one OPCAB patient (0.8%). Early postoperative reoperation due to graft failure was necessary in three patients after MIDCAB and two patients after OPCAB (P=ns). Confirmed by angiography, the early graft patency rate was 96 and 98%, respectively (P=ns). CONCLUSIONS: Both beating heart techniques showed good results with low hospital mortality, low early complications and comparable angiographic results. Nevertheless, MIDCAB is a challenging technique as demonstrated by the longer times of surgery and coronary occlusion with a tendency towards a higher risk of conversion and wound infection. Thus, this technique should only be performed in selected patients with favourable coronary anatomy. Through a sternotomy approach, single vessel revascularization can be performed safely off-pump even in high-risk patients.

Cardiopulmonary Bypass↗
PubMed2001

Tacrolimus versus cyclosporine after lung transplantation: a prospective, open, randomized two-center trial comparing two different immunosuppressive protocols.

BACKGROUND: The need for better immunosuppressive protocols after lung transplantation led us to investigate tacrolimus (Tac) in combination with mycophenolate mofetil (MMF) and steroids or cyclosporine (CsA) in combination with MMF and steroids in a prospective, open, randomized trial after lung transplantation. METHODS: Between September 1997 and April 1999, 50 lung transplant recipients were randomized to receive either Tac (n = 26) or CsA (n = 24) in combination with MMF and steroids. All patients underwent induction therapy with rabbit antithymocyte globulin (ATG) for 3 days. Freedom from acute rejection (AR), patient survival, infection episodes, and side effects were monitored. RESULTS: There was no difference in patient demographics between the two groups. Six-month and 1-year survival was similar (84.6% and 73.1% in the Tac group vs 83.3% and 79.2% in the CsA group). Freedom from AR at 6 months and 1 year after lung transplantation was slightly higher in the Tac group (57.7% and 50% vs 45.8% and 33.3%, p = not significant [n.s.]), whereas the number of treated rejection episodes per 100 patient days in the Tac group was significantly lower (0.225 vs 0.426, p < .05). Four patients in the CsA group had to be switched to Tac. Two patients in the CsA group had to be retransplanted. Incidence of infections was similar in both groups with a trend toward more fungal infections in the Tac group (n = 7 vs n = 1, p = n.s.). CONCLUSIONS: The combination of Tac and MMF seems to have slightly higher immunosuppressive potential compared with CsA and MMF. The effectiveness of Tac as a rescue agent is not paralleled with undue signs of overimmunosuppression.

Acute Disease↗
PubMed2001

Standard heparin, low molecular weight heparin, low molecular weight heparinoid, and recombinant hirudin differ in their ability to inhibit transduction by recombinant adeno-associated virus type 2 vectors.

Recombinant adeno-associated virus type 2 (rAAV) is a promising vector for in vivo gene therapy. Transduction by rAAV requires binding to heparan sulfate proteoglycan on the cell surface, and heparin can block this binding. Because heparin is administered to most patients undergoing cardiovascular gene transfer in order to prevent thrombotic events, it is important to identify anticoagulants which do not interfere with rAAV transduction. Therefore, we examined the influence of different anticoagulants on rAAV transduction in vitro. rAAV transduction was inhibited by 40.5 +/- 7.9% at heparin concentrations of 0.1 U/ml, and by 81.7 +/- 3.6% at 1.0 U/ml. The low molecular weight (LMW) heparin tinzaparin inhibited rAAV transduction by 20.2 +/- 3.8% at 0.1 U/ml and 37.1 +/- 1.8% at 1.0 U/ml. The inhibitory effect was significantly weaker compared with heparin at 1.0 U/ml, (P < 0.01). The LMW heparinoid danaparoid inhibited rAAV transduction by 8.8 +/- 3.5% at 0.1 U/ml (P < 0.01 compared with heparin). In contrast, recombinant hirudin did not interfere at all with rAAV transduction. In summary, the results demonstrate that inhibition of rAAV transduction by heparin occurs rapidly and at therapeutically used concentrations. LMW heparinoids and above all recombinant hirudin might be alternatives for heparin when vascular gene transfer with rAAV requires transient anticoagulation.

Anticoagulants↗