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Biomedical subjects

A Haverich

Publications and source records attributed to A Haverich.

At least 127 records · Page 7Linked to original sources
PubMed2000

Ten years experience with lung and heart-lung transplantation in primary and secondary pulmonary hypertension.

OBJECTIVE: Patients with primary pulmonary hypertension (PPHT) have a worse natural outcome compared with those with secondary pulmonary hypertension in Eisenmenger's syndrome (ES) and chronic pulmonary embolism (CPE). Lung transplantation (SLTx, DLTx, HLTx) still remains the only therapeutical option for patients with this type of endstage lung disease. METHODS: From 1988 to 1998, 63 patients underwent lung transplantation for PPHT (n=29, 9 m, 20 f, 2 SLTx, 14 DLTx, 13 HLTx), ES (n=29, 13 m, 16 f, 2 SLTx, 3 DLTx, 24 HLTx) or CPE (n=5, 2 m, 3 f, 1 SLTx, 2 DLTx, 2 HLTx). Groups were comparable for NYHA functional class, preoperative pulmonary arterial pressure, recipient and donor age, ischemic time, necessity and duration of cardiopulmonary bypass and cross-match. RESULTS: The 1-, 3- and 5-year survival was 52, 40 and 35% for the PPHT-group, 83, 78 and 74% for the ES-group and 80, 60 and 60% for the CPE-group, respectively (P=0.026, P=0.033, P=0.082 for 1-, 3- and 5-year survival). Patients following DLTx showed a lower 1-year survival rate as compared with patients after HLTx both in PPHT patients (36 vs. 62%, P=0.091) and in ES patients (67 vs. 83%, P=0.213). The incidence of bronchiolitis obliterans syndrome was 29% at 1 year and 45% at 3 years for the PPHT-group vs. 17 and 65% for the ES-group (n. s. in between groups). Excluding postoperative ventilation time (PPHT-group: 26.8+/-24.0 days vs. ES-group: 16.1+/-30.8 days, P=0. 011) and a higher incidence of infectious causes of death (PPHT-group n=8 vs. ES-group n=1, P=0.017) groups were comparable with regard to their postoperative courses. CONCLUSIONS: It is concluded, that predominantly the underlying primary disease influences graft survival after lung transplantation in patients with pulmonary hypertension compared with all other patient and procedure dependent factors. Lung transplantation in patients with PPHT requires further investigations to achieve results comparable with other indications.

Adult↗
PubMed2000

Improved right ventricular function after intracoronary administration of a C1 esterase inhibitor in a right heart transplantation model.

OBJECTIVE: Myocardial injury from ischemia can be augmented after reperfusion due to proinflammatory events including complement activation, leukocyte adhesion, and release of various chemical mediators. It has been shown that intracoronary administration of a C1 esterase inhibitor (C1 INH) significantly reduces myocardial necrosis in an experimental model of ischemia. Our study addresses the question whether the most susceptible region of the heart for ischemic injury, the right ventricle (RV), can benefit from the protective effects of C1 esterase inhibition after transplantation. METHODS: To precisely control RV volume in vivo an isovolumic model was used in which the RV volume was regulated using an intracavity high compliance balloon inserted into donor hearts of domestic pigs (34+/-4 kg). After 4 h of ischemia, donor hearts were transplanted into recipient pigs (44+/-4 kg). Treatment groups, each with six animals, consisted of C1 INH treatment or control. After opening the cross clamp, the C1 INH group animals received 20 IU/kg body weight of C1 INH intracoronary over a 5 min period. The control animals received no drug therapy. The hearts were reperfused for 60 min, and thereafter the RV balloon volume was increased in 10 ml increments until RV failure occurred. These measurements were repeated after 120 min of reperfusion. RESULTS: There was no significant difference in maximal RV developed pressure between the two groups (after 1 h, 35.7+/-5.9 vs. 40.6+/-12.7 mm Hg; after 2 h, 41.5+/-10.7 vs. 46.3+/-15.2 mm Hg; for C1 INH and control animals, respectively). However, the RV could be loaded with a significantly higher volume after both 1 h (60.0+/-20.0 ml (C1 INH) vs. 46.7+/-13.7 ml (control) balloon volume, P<0.05), and 2 h of reperfusion (70.0+/-8.9 ml vs. 60.0+/-6.3 ml; C1 INH and control animals, respectively; P<0.05). CONCLUSIONS: Intracoronary administration of a C1 INH significantly improves right ventricular function in an experimental transplant model. Thus, inhibition of the classic complement cascade may be a promising therapeutic approach for effective protection of myocardium from reperfusion injury after transplantation.

Animals↗
PubMed2000

ACE-gene polymorphism is associated with the development of allograft vascular disease in heart transplant recipients.

BACKGROUND: Cardiac allograft vascular disease is (CAVD) the most important cause of death following heart transplantation (HTX). Although in the past, researchers focused predominantly on mechanisms of endothelial injury, the possible role of recipient-related and genetically determined factors has not been studied in detail. METHODS: Stimulated by recent observations in native coronary artery disease, we analyzed the potential impact of angiotensin-converting enzyme (ACE) polymorphism (insertion/deletion [I/D], intron 16) on development and progression of CAVD. We characterized genotype in 146 patients 1 to 12 years after HTX (121 men; mean age, 46.2+/-11.3 years; observation period, 6.1+/-3.8 years) and correlated genotype to the onset and progression of CAVD, defined as luminal obstruction > 50%. RESULTS: We found allelic frequencies to be 28.8% (n = 42) for ACE-DD, 49.3% (n = 72) for ACE-DI, and 21.9% (n = 32) for ACE-II. Differences in actuarial freedom from vasculopathy were significant 6 years after transplantation, with 84.6% for ACE-II compared with 54.4% for ACE-DD. We observed intermediate results for ACE-DI genotype (77.3%, p = 0.015). CONCLUSIONS: In this large cohort study, we demonstrated a close relationship between the recipient-related ACE-D genotype and development of advanced CAVD. These observations suggest that gene-environment interactions might be clinically important in coronary vasculopathy after HTX.

Actuarial Analysis↗
PubMed2000

[Harvesting the vena saphena magna for aortocoronary bypass operations--is the subcutaneous suture necessary?].

BACKGROUND: The need for stitching the subcutaneous layers after saphenous vein graft harvest for coronary artery bypass is discussed controversially. METHODS: We conducted a prospective study to determine whether subcutaneous stitches reduce the incidence of hematoma, infection and wound dehiscence after saphenous vein graft harvest in patients undergoing coronary artery bypass grafting. Patients were randomized either to group 1 (n = 100, subcutaneous suture) or group 2 (n = 46, without subcutaneous suture). Leg wounds were examined for hematoma, wound dehiscence, necrosis or secretion preoperatively and on day 2 and 5 after surgery. Furthermore, leg circumferences were measured at distinct areas. RESULTS: There were no significant differences in the incidence of wound complications. Especially, leg circumferences and incidence of hematomas (group 1: 36% versus group 2: 39%) as well as the length of hospital stay (group 1: 6.8 days versus group 2: 6.2 days) did not differ significantly. CONCLUSIONS: The subcutaneous suture following saphenectomy is unnecessary. A deterimental effect of an additional subcutaneous suture could not be demonstrated.

Aged↗
PubMed2000

Productive infection of primary human endothelial cells by pig endogenous retrovirus (PERV).

The potential risk of viral transmission in the setting of xenotransplantation has gained major attention. Different porcine cell types have been shown to release retroviral particles, which are infectious for human cell lines in vitro. However, there are only a few data on whether PERV (pig endogenous retrovirus) is able to infect primary human cells. In this study we have analyzed endothelial cells, vascular fibroblasts, mesangial cells, mononuclear cells, hematopoetic stem cells and bone marrow stromal cells for PERV transmission. We now provide evidence for primary human endothelial cells, vascular fibroblasts, and mesangial cells to be susceptible to PERV transmission. PERV infection was productive in endothelial cells and mesangial cells. Our data confirm and extend former reports concerning the PERV infection of human cells. The PERV infection of different primary human cells represents further significant evidence for a viral risk during xenotransplantation. In this context, special attention should be directed towards productive infection of human endothelial cells: in the setting of xenotransplantation this cell type will have close contact with porcine cells and PERV particles.

Animals↗
PubMed2000

Primary porcine enterocyte and hepatocyte cultures to study drug oxidation reactions.

1. Primary porcine hepatocytes and enterocytes were isolated and cultured in Williams' E medium for up to 10 days to investigate potential organ differences in the metabolism of the immunosuppressive compound tacrolimus (FK 506) and of two investigational drugs (KC11346 and KC12291). Using LC-MS (FK506) and HPLC-FL (KC 11346/12291) a number of metabolites with identical mass and/or identical retention time could be detected. 2. In the case of tacrolimus hepatocytes and enterocytes produced the same spectrum of metabolites, e.g. bisdemethyl-tacrolimus, demethyl-tacrolimus, demethyl-hydroxy-tacrolimus and hydroxy-tacrolimus, albeit at varying intensities. 3. Treatment of enterocyte cultures with dexamethasone increased the overall metabolite formation very significantly (up to 36 fold). 4. The metabolism of tacrolimus was also studied with preparations of insect cells, that express specifically high levels of individual human cytochrome P450 (CYP) isoenzymes. All metabolites could be generated with microsomal preparations specifically expressing CYP3A4, but hydroxy-tacrolimus was exclusively produced by CYP3A5. 5. In the case of the investigational drugs KC 11346 and KC 12291 only three metabolites were formed by cultured enterocytes whereas hepatocytes produced 10 and 20 metabolites, respectively. 6. When assessed at the protein level CYP1A and CYP3A were expressed in cultures of porcine enterocytes for up to 10 days but porcine hepatocytes expressed additionally CYP2C9/10. 7. In conclusion, primary enterocytes and hepatocytes can be successfully cultured for several days while maintaining mono-oxygenase activity and may therefore be used as a tool for studying intestinal and hepatic metabolism.

Animals↗
PubMed2000

Tissue engineering of vascular grafts: human cell seeding of decellularised porcine matrix.

OBJECTIVES: To develop a biocompatible and mechanically stable vascular graft combining human cells and a xenogenic acellular matrix. DESIGN/MATERIALS: Decellularised matrix tubes were obtained by enzymatic cell extraction of native porcine aortas. Endothelial cells and myofibroblasts were isolated from human saphenous veins and grown in cell cultures. The inner surface of the tubes was seeded with endothelial cells or myofibroblasts and exposed to pulsatile flow. RESULTS: After cell extraction, the absence of cellular components, as well as the maintenance of matrix integrity, was demonstrated by means of light microscopy and scanning electron microscopy. Furthermore, the porcine matrix was successfully seeded with human endothelial cells, which grew to a monolayer under flow conditions. Stable biomechanical properties were achieved at physiological perfusion pressures in vitro. CONCLUSIONS: Cellular components can be extracted from native porcine blood vessels. Vascular grafts can be generated in vitro of animal acellular matrix and human cells.

Animals↗
PubMed2000

Proximal aortic dissection late after aortic valve surgery: 119 cases of a distinct clinical entity.

BACKGROUND: Besides systemic hypertension and Marfan syndrome, only previous aortic valve replacement (AVR) is independently associated with proximal (type A) aortic dissection. Little, however, is known to date about the characteristic features of this clinical entity. METHODS: Clinical, prognostic and predisposing profiles in 119 cases of dissection and/or aneurysm occuring 1 month to 16 years after routine AVR were analyzed comprising 62 cases from our database and 57 reported cases. RESULTS: Dissection after AVR has been observed in 0.6% of all routine AVR procedures in the past four decades. With clinical signs, symptoms and anatomical features different from classic aortic dissection post-AVR dissection is a distinct clinical entity with a high intraoperative mortality of 44% and a 30-day and 5-year survival of 62% and 43%, respectively. Aortic regurgitation and a thin and/or fragile aortic wall at AVR, however, predict late dissection. Using a prediction model, the risk of late dissection can be stratified based on information obtained during AVR surgery. CONCLUSIONS: Aortic dissection following AVR is likely to represent a distinct clinical entity which can be predicted and possibly prevented at AVR.

Aged↗
PubMed2000

[Primary leiomyosarcoma of the pulmonary artery--a case report].

A case of a primary pulmonary leiomyosarcoma originating in the right pulmonary artery in a 61-year-old woman is reported. Patient's complaints were non-specific and after non-invasive diagnostics a chronic thromboembolic event was suspected to have occurred a long time ago. During a heart catheter investigation prior to planned surgical embolectomy a small specimen was taken from the pulmonary artery. Histological examination revealed malignant the tumour and by immunohistological staining its smooth muscle differentiation was confirmed. Complete resection of the tumour was achieved by radical surgery, including pneumonectomy and extensive resection of pulmonary vessels with subsequent implantation of a Goretex prosthetic. There was no evidence of recurrence or metastasis of the primary leiomyosarcoma of the pulmonary artery in a 14-month follow-up period after operation.

Biopsy↗
PubMed2000

Low-potassium dextran solution ameliorates reperfusion injury of the lung and protects surfactant function.

OBJECTIVE: This study was designed to compare the effect of lung preservation with low-potassium dextran solution and Euro-Collins solution on reperfusion injury and surfactant function by using an in situ model of warm ischemia. METHODS: The left lungs of 6 minipigs were selectively perfused with Euro-Collins solution. In an additional 6 animals low-potassium dextran solution was used for flush perfusion. After 90 minutes of warm ischemia, the lungs were reperfused, and the contralateral pulmonary artery and bronchus were clamped. Hemodynamic and respiratory measurements were obtained for 7 hours of reperfusion. Surface tension of bronchoalveolar lavage and surfactant small and large aggregates were determined before perfusion (right lung) and after 2 hours of reperfusion (left lung). RESULTS: In the group receiving Euro-Collins solution, right heart failure developed within 215 +/- 39 minutes of reperfusion. An increase in minimal surface tension (P =.03), surfactant small aggregates/large aggregates ratio (P =.003), and bronchoalveolar lavage protein content (P =.012) were found after 2 hours of reperfusion. In the group receiving low-potassium dextran solution, all minipigs survived (P =.0001). Dynamic lung compliance (P =.034) and oxygen tension/inspired oxygen fraction ratios were higher (P =. 0001). Lung water content was lower (P =.049). The increase of minimal surface tension (P =.02) and bronchoalveolar lavage protein concentration (P =.015) were significantly less. CONCLUSION: Preservation of the lung with Euro-Collins solution leads to a reduction of physical surfactant function during reperfusion. Low-potassium dextran solution protects surfactant function and metabolism, thereby reducing reperfusion injury of the lung.

Animals↗
PubMed2000

Cellular dedifferentiation of endothelium is linked to activation and silencing of certain nuclear transcription factors: implications for endothelial dysfunction and vascular biology.

We investigated the gene expression of the nuclear transcription factors c/EBPalpha, GATA-2, and the silencer Oct-1 in conjunction with the gene expression of all major cytochrome P450 genes and of eNOS in cultures of endothelial cells of the rat. The purity of cultured endothelial cells was also confirmed by flow cytometry measurements of PECAM-1, a surface antigen of endothelial cells. Taken collectively, the gene expression and flow cytometry studies provide strong evidence for c/EBPalpha, GATA-2, and Oct-1 to play a key role in the cellular dedifferentiation of endothelial cells; gene expression of eight individual CYP genes in conjunction with protein activity could be significantly increased upon treatment with Aroclor 1254, a well-documented chemical inducer of a battery of genes. Nevertheless, the gene expression of c/EBPalpha, GATA-2, and most of the CYP genes was dramatically reduced (up to 90%) in cell cultures lacking PECAM-1 expression; in strong contrast, expression of the silencer Oct-1 was massively increased (approximately 14-fold). We thus conclude activation of the silencer Oct-1 to be strongly correlated with loss of PECAM-1 and eNOS gene expression, e.g., loss of cellular differentiation and endothelial function; in conjunction, gene expression of all major P450 isoforms was dramatically reduced in cultures of dedifferentiated endothelial cells. This process of cellular dedifferentiation and endothelial dysfunction was accompanied by down-regulation of endothelial specific transcription factors.

Animals↗
PubMed2000

Myocardial "hybrid" revascularisation with minimally invasive direct coronary artery bypass grafting combined with coronary angioplasty: preliminary results of a multicentre study.

OBJECTIVE: To expand the benefits of the minimally invasive direct coronary artery bypass (MIDCAB) concept to patients with multivessel disease, a hybrid procedure combining surgical revascularisation of the left anterior descending artery with interventional procedures for additional coronary lesions has recently been introduced. Preliminary results in patients undergoing this hybrid procedure are presented. DESIGN AND PATIENTS: Since December 1996, 35 patients (29 male, 6 female, mean (SD) age 56.7 (17) years) underwent a hybrid revascularisation performed as a primary MIDCAB procedure for grafting of the left anterior descending artery with the left internal mammary artery, followed by staged angioplasty and stenting of additional coronary lesions. RESULTS: After MIDCAB grafting the postoperative course was uneventful in all patients. Coronary reangiography after a median of seven days revealed patent and functioning left internal mammary artery grafts in all patients. Applying subsequent percutaneous transluminal coronary angioplasty and occasional stenting (n = 14), a total of 47 lesions were treated successfully. Procedure related complications did not occur. All patients remained free from angina and no stress ECG changes were recorded. CONCLUSIONS: The preliminary results of this hybrid approach to myocardial revascularisation suggest that this is a safe and effective procedure for complete revascularisation in selected patients with multivessel disease. Elderly and reoperative patients with significant comorbidity may benefit especially from such hybrid procedures by avoiding cardiopulmonary bypass and mid sternotomy.

Adult↗
PubMed2000

Progression of cardiac allograft vascular disease as assessed by serial intravascular ultrasound: correlation to immunological and non-immunological risk factors.

OBJECTIVE: To characterise the severity and progression of cardiac allograft vascular disease (CAVD) in a large patient cohort, and to evaluate possible immunological and non-immunological risk factors for progression. DESIGN: A prospective observational study using intravascular ultrasound. SETTING: Two university hospitals. PATIENTS AND MAIN OUTCOME MEASURES: Changes in focal plaque, lumen, and total vessel area (worst site method) were assessed at baseline and after 12.1 (2.8) months (mean (SD)) of follow up in a cohort of 96 patients (79 male, 17 female; mean age 48.7 (9.6) years; time post-transplant 26.0 (32.4) months). RESULTS: Overall, the mean (SD) intimal index of worst sites increased by 6.7 (8.8)%. The increase in the first 12 months was 7.5 (9.4)%, v 5.9 (8.0)% after the first year (NS). Analysing immunological and non-immunological risk factors (age, underlying disease, sex, donor age, immunosuppression, cytomegalovirus, rejection episodes, cholesterol), low density lipoprotein (LDL) cholesterol was found to be the most important predictor of severe progression (as defined by an increase in intimal index of >/= 15% (p = 0.01). CONCLUSIONS: Progression of CAVD is characterised by a continuing increase in intimal hyperplasia, especially within the first year after heart transplantation. LDL cholesterol is an important predictor of major progression.

Adult↗