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Biomedical subjects

A Haverich

Publications and source records attributed to A Haverich.

At least 19 recordsLinked to original sources
PubMed2006

Inhibition of complement activation by pexelizumab reduces death in patients undergoing combined aortic valve replacement and coronary artery bypass surgery.

OBJECTIVE: We sought to evaluate the effects of pexelizumab, a C5 complement inhibitor, on death and myocardial infarction in patients undergoing combined aortic valve replacement and coronary artery bypass grafting surgery. METHODS: The Pexelizumab for Reduction in Myocardial Infarction and Mortality in Coronary Artery Bypass Graft surgery trial, a phase III prospective, randomized, double-blind, placebo-controlled study, enrolled 3099 patients at 205 centers. The primary end point was the composite of death, myocardial infarction, or both at postoperative day 30 in patients undergoing coronary artery bypass grafting without valve surgery. Postoperative myocardial infarction was defined as a creatine kinase MB fraction value of 100 ng/mL or greater, Q-wave myocardial infarction with a creatine kinase MB fraction value of 70 ng/mL or greater, or new Q-wave evidence of myocardial infarction by postoperative day 30. Because patients undergoing coronary artery bypass grafting with a valve procedure were not included in the primary population, separate analysis of death and myocardial infarction was conducted in 218 patients undergoing combined aortic valve replacement and coronary artery bypass grafting surgery. RESULTS: Of the 353 patients randomized to any valve procedure, 106 (61%) underwent combined aortic valve replacement and coronary artery bypass grafting in the pexelizumab treatment group compared with 112 (63%) patients in the placebo group. Coronary artery bypass grafting was performed with 1 or more internal thoracic artery grafts in 139 (64%) patients and with 1 or more saphenous vein grafts in 179 (82%) patients. There were 4 (3.8%) deaths in the pexelizumab group versus 11 (9.9%) in the placebo group by postoperative day 30 and 6 (5.7%) deaths in the active group versus 16 (14.4%) in the placebo group by postoperative day 180 (P =.107 and P =.043, respectively, Fisher exact test). The incidence of myocardial infarction 30 days after surgical intervention was identical in the 2 groups, but the study was not designed to detect differences in this cohort of patients. CONCLUSIONS: Inhibition of complement activation by pexelizumab resulted in a decreased mortality at 180 days among 218 patients who underwent combined aortic valve replacement and coronary artery bypass grafting surgery. Additional studies are warranted to confirm this decrease in mortality with pexelizumab in combined aortic valve replacement and coronary artery bypass grafting procedures.

Aged↗
PubMed2006

Severe obstructive calcifications affecting the descending and suprarenal abdominal aorta without coexisting peripheral atherosclerotic disease--coral reef aorta.

The case of a 58-year-old woman with leg claudication due to a very rare form of atherosclerosis affecting the descending thoracic and abdominal aorta--known as coral reef aorta--without involvement of the femoro-distal vessels is reported. The patient was treated with a polyester bifurcation graft from the proximal descending aorta to both common iliac arteries via a left dorsal mini-thoracotomy and a second left retroperitoneal approach. This unusual approach was chosen instead of direct aortic replacement in order to prevent paraplegia. In case of future visceral or left renal malperfusion the diseased artery can be connected to the prosthesis directly or by the use of an additional bypass graft. This would not be the case with a conventional axillo-bifemoral graft.

Anastomosis, Surgical↗
PubMed2006

Clinically applicable 7-Tesla magnetic resonance visualization of transplanted human adult stem cells labeled with CliniMACS nanoparticles.

BACKGROUND: Intra-myocardial transplantation of bone marrow derived cells is currently under clinical evaluation as a therapy for heart failure. A major limitation of all clinical studies for myocardial restoration through cell transfer is the inability to track the fate of the transplanted cells. We present a clinically applicable technique using advanced ultra high-field 7-Tesla (7T) magnetic resonance imaging (MRI) of nanoparticle-labeled transplanted human EPCs in porcine ischemic hearts. METHODS: CD133 positive cells were isolated from bone marrow by magnetic bead selection. Positive cells (5 - 8 x 10 (6) cells) were transplanted into porcine ischemic myocardium (n = 8). Control animals (n = 3) received a medium injection. MRI on a 7T scanner was performed to demonstrate the distribution of the EPCs. RESULTS: CD133+ cells were identified on gradient echo images (T(1)-weighted) within the myocardium 4 weeks after transplantation. CONCLUSIONS: Magnetically labeled EPCs transplanted for therapeutic neovascularization or reduction of infarct size in myocardial ischemia can be visualized by MRI at high-field strengths.

Adult Stem Cells↗
PubMed2006

[In vivo detection of integration of grafted cells after myocardial transplantation].

Myocardial transplantation of myocytes and bone marrow derived cells is currently under clinical evaluation as an alternative therapy of heart failure. One of the main problems of all clinical studies performed so far is the inability to track the fate of the transplanted cells. The aim of our study was the development of a potentially clinically applicable approach, which allows for detection of the transplanted cells without need for collection of tissue samples. Fetal canine cardiomyocytes were labelled with the non-toxic fluorescent membrane dye Vybrant CM-DiI and delivered into the free wall of the left ventricle of adult mongrel dogs. For subsequent tracking of the cellular graft, the dogs underwent a second operation in which an intra-vital microscope was mounted above the exposed heart within the thorax. A special computer software eliminated artefacts caused by myocardial contraction. Two months after transplantation, the fluorescent graft was macroscopically visible by intra-vital microscopy using a 10x magnification. Histological studies served as microscopic control and confirmed the existence of DiI-labelled cells at the site of injection. Connexin 43 immunoreactivity was visible at junctional complexes between donor and recipient cells, suggesting morphologic and functional coupling as a result of gap junction formation. Our results demonstrate that in vivo detection of transplanted cells in the heart is feasible. Further technical adjustments should allow for thoracoscopic/endoscopic application of this method, making it appropriate for use in other organs and in clinical studies.

Animals↗
PubMed2006

Isolation of bovine cardiomyocytes for reprogramming studies based on nuclear transfer.

The goal of this study was to establish and validate a protocol for preparing bovine cardiomyocytes from slaughterhouse material for nuclear transfer experiments. The cardiomyocyte was selected because it is a terminally differentiated cell and strongly expresses a unique subset of genes which can be monitored during the reprogramming period. A total of 39 trials were conducted, and an optimized protocol was developed yielding individual contractile cardiomyocytes from 3-5-month-old bovine fetuses The basic protocol involves stabilization of bovine heart tissue for transportation from the slaughterhouse to the laboratory by perfusion with Custodiol. This was followed by an enzymatic dissociation with collagenase in calcium-free medium and yielded individual contractile rod-shaped cardiomyocytes. Subsequent addition of Ca2+ caused the cardiomyocytes to round up which was an essential pre-condition for drawing them into glass transfer pipettes for delivery into the perivitelline space and for efficient electrofusion with cytoplasts derived from in vitro matured bovine oocytes. The use of cardiomyocytes maintained at 37 degrees C in nuclear transfer, resulted in a significantly reduced proportion of blastocysts compared to adult fibroblasts (14.0% versus 32.7%). Storage of cardiomyocytes at 4 degrees C prior to nuclear transfer was not compatible with blastocyst development. It is expected that this system will be valuable for investigating the reprogramming of gene expression which occurs after somatic cell nuclear transfer.

Animals↗
PubMed2006

Improved outcome of chronic hepatitis B after heart transplantation by long-term antiviral therapy.

Chronic hepatitis B progresses to cirrhosis in the majority of immunosuppressed patients. The outcome of long-term antiviral therapy in HBV-infected organ transplant recipients is unknown. In 1996, we included 20 heart transplant (HT) recipients in a pilot trial to treat chronic hepatitis B with famciclovir. At that time, bridging fibrosis or cirrhosis was evident in 15 individuals (75%). From 1998 onwards, patients were switched to lamivudine in case of primary or secondary virological nonresponse to famciclovir. Adefovir or tenofovir became available at our centre for HT recipients in 2002. After 103 months, one patient was still on famciclovir showing a complete virological response. Sixteen patients were switched to lamivudine after 0.5-4 years of famciclovir therapy. Six of those showed a long-term response to lamivudine therapy lasting for up to 7 years. Lamivudine resistance developed in the remaining 10 patients (63%), in 4 of them successful rescue therapy (adefovir n = 3, tenofovir n = 1) could be initiated. Only one hepatocellular carcinoma developed, which was successfully treated by locoregional ablative therapy. Nine patients died (45%), with lamivudine-resistance-related liver failure as the cause of death in five cases. Significant improvement of Ishak fibrosis scores could be demonstrated in six of the seven patients with more than two sequential liver biopsies available. Long-term antiviral therapy of chronic hepatitis B can lead to regression of liver cirrhosis in patients after organ transplantation, unless viral resistance occurs. This study demonstrates the urgent need for further antivirals to overcome antiviral resistance.

2-Aminopurine↗
PubMed2005

[Cardiac surgery in elderly patients].

Due to demographic changes in average life expectancy, the age of patients undergoing cardiac surgery is increasing. We have reviewed the literature to analyse whether and how far octogenarians benefit from cardiac surgical procedures. Different studies analysed the outcome of patients in different age groups after cardiac surgery. Octogenarians can undergo cardiac surgical procedures at a reasonable risk. The perioperative mortality and other postoperative complications are strongly dependent on comorbidities rather than on patients' age. Elderly patients benefit from improved functional status and quality of life.

Age Factors↗
PubMed2005

[Tissue engineering for heart valves and vascular grafts].

Current prosthetic substitutes for heart valves and blood vessels have numerous limitations such as limited durability (biological valves), susceptibility to infection, the necessity of lifelong anticoagulation therapy (prosthetic valves), and reduced patency in small-caliber grafts, for example. Tissue engineering using either polymers or decellularized native allogeneic or xenogenic heart valve/vascular matrices may provide the techniques to develop the ideal heart valve or vascular graft. The matrix scaffold serves as a basis on which seeded cells can organise and develop into the valve or vascular tissue prior to or following implantation. The scaffold is either degraded or metabolised during the formation and organisation of the newly generated matrix, leading to vital living tissue. This paper summarises current research and first clinical developments in the tissue engineering of heart valves and vascular grafts.

Animals↗
PubMed2005

Outcome following single vs bilateral lung transplantation in recipients 60 years of age and older.

AIMS: The significant shortage of donor organs in lung transplantation necessitates a careful selection of lung transplant recipients. The outcome of lung transplant recipients aged 60 years and older has not been analyzed systematically. METHODS: We retrospectively reviewed our experience with older recipients. Between January 1999 and July 2003, 248 patients underwent lung transplantation at our institution, of which 18 were aged 60 years and older (7.3%, range 60-66, mean 62 +/- 1.1). RESULTS: Eleven (61%) of the recipients 60 years and older received a single (SLTx) and seven (39%), a bilateral lung transplant. Donor age in the single transplant cohort was 30 +/- 4 years. It was 33 +/- 3 years in bilateral patients. Posttransplant ventilation time was significantly different among groups, with 282 +/- 32 hours after bilateral and 56 +/- 13 hours after transplant (P < .05). Also significantly longer was the length of the ICU stay in the bilateral group. First PaO2 in the ICU was not different among the two groups. The 1-year survival in the single transplant group was significantly better compared to the bilateral group with 73% versus 43%, respectively. CONCLUSIONS: The 1-year survival following lung transplantation in patients older than 60 years is markedly reduced compared to recipients under 60 years of age. If a lung transplant is considered in a recipient above the age of 60 years, a single transplant should be favoured. If that is not indicated, patients over 60 should be very carefully selected for bilateral transplant.

Aged↗
PubMed2005

Shuttle of lentiviral vectors via transplanted cells in vivo.

Lentiviral vectors have turned out to be an efficient method for stable gene transfer in vitro and in vivo. Not only do fields of application include cell marking and tracing following transplantation in vivo, but also the stable delivery of biological active proteins for gene therapy. A variety of cells, however, need immediate transplantation after preparation, for example, to prevent cell death, differentiation or de-differentiation. Although these cells are usually washed several times following lentiviral transduction, there may be the risk of viral vector shuttle via transplanted cells resulting in undesired in vivo transduction of recipient cells. We investigated whether infectious lentiviral particles are transmitted via ex vivo lentivirally transduced cells. To this end, we explored potential viral shuttle via ex vivo lentivirally transduced cardiomyocytes in vitro and following transplantation into the brain and peripheral muscle. We demonstrate that, even after extensive washing, infectious viral vector particles can be detected in cell suspensions. Those lentiviral vector particles were able to transduce target cells in transwell experiments. Moreover, transmitted vector particles stably transduced resident cells of the recipient central nervous system and muscle in vivo. Our results of lentiviral vector shuttle via transduced cardiomyocytes are significant for both ex vivo gene therapy and for lentiviral cell tracing, in particular for investigation of stem cell differentiation in transplantation models and co-cultivation systems.

Animals↗
PubMed2005

[Preliminary clinical experience with the Ventrica automatic distal anastomosis system in coronary surgery].

The surgical treatment of coronary lesions is based on bypassing the anatomical lesions with autologous vascular grafts. This procedure has traditionally been "invasive", requiring a micro-surgery technique, institution of extra-corporeal circulation, as well as temporary cardiac arrest with a cardioplegic solution. Recently, an automatic distal anastomosis procedure has been developed (Ventrica, Medtronic Inc.), based on a magnetic coupling with two implanted intravascular magnets, allowing easy connection between the graft and the coronary artery. The immediately obvious advantages are the time saved, ease of use, reproducibility and reliability. The learning curve is fast. Furthermore, the use of this automatic process does not compromise a manual anastomosis in case of implantation failure. The immediate post-operative results, as well as angiography immediately and at 6 months are all satisfactory. This technique is applicable for multiple revascularisations, all types of autologous grafts, terminal or sequential bypasses, as well as nearly all types of coronaries. The contribution to beating heart, closed thorax coronary surgery seems equally promising.

Aged↗
PubMed2004

[Biological vascularized matrix (BioVaM): a new method for solving the perfusion problems in tissue engineering].

A new technique is presented to harvest an acellular matrix from a porcine small bowel segment preserving the mesenteric arterial and venous pedicles. Reseeding of this biological vascularized matrix (BioVaM) with functional cells, i.e. smooth muscle and urothelial cells isolated from the urinary tract, and resurfacing of its vascular structures with endothelial precursor cells results in a vascularized tissue engineered graft for reconstruction and augmentation of the urinary bladder. First promising short term implantation experiments using a porcine model for the evaluation of early graft perfusion after vascular anastomosis are presented.

Animals↗
PubMed2004

Acute aortic dissection versus aortic root aneurysm: comparison of indications for valve sparing aortic root reconstruction.

OBJECTIVES: To prove whether different indications for valve sparing aortic root reconstruction may have an impact on the outcome and longevity of the repair. METHODS: From July 1993 to March 2003, the reimplantation technique for valve sparing aortic root reconstruction was applied to 232 patients. In 44 patients, indication for operation was acute aortic dissection type A (AADA). These patients were compared with 44 randomised patients operated for aortic root aneurysm (root) by matched pair analysis with respect to age, gender, time point of operation and presence of Marfan's syndrome. Peri- and post-operative courses with focus on survival and valvular stability were analysed. RESULTS: Pre-operative grade of aortic insufficiency was 2.4+/-1 in root vs. 1.5+/-1.7 in AADA (P = 0.004) Mean CPB-time (214+/-60 vs. 171+/-42 min;P < 0.001), aortic cross clamp time (158+/-40 vs. 129+/-39 min; P = 0.001) and stay on ICU (5.2+/-9 vs. 1.7+/-1 days; P = 0.034) were longer for AADA, while hospitalisation was comparable (14+/-10 vs. 14+/-7 days; P = 0.88). Five patients (11.4%) from AADA died peri-operatively compared to no patient from root (P = 0.055). None of the early deaths were valve-related. Re-thoracotomy rate was 6.8% for both groups. Mean follow-up was 19+/-21 months for AADA vs. 28+/-21 months for root (P = 0.038) Survival at 3 years was 88+/-5% for AADA and 100% for root (P = 0.028). Freedom from valvular reoperation was 97+/-2.7% for root and 97+/-3% for AADA at 3 years (P = 0.44). At last investigation, mean grade of aortic insufficiency for AADA was 0.2+/-0.3 compared to 0.3+/-0.3 for root (P = 0.34) CONCLUSIONS: Regardless of the underlying indication, the aortic valve preserving reimplantation technique can be performed with favourable functional results.

Acute Disease↗