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Biomedical subjects

A Haverich

Publications and source records attributed to A Haverich.

At least 91 records · Page 5Linked to original sources
PubMed2001

Homocysteine--a treatable risk factor for allograft vascular disease after heart transplantation?

Growing evidence suggests that elevated total plasma homocysteine (tHCY) levels are associated with cardiac allograft vasculopathy following heart transplantation. To assess the effect of folic acid supplementation on tHCY levels, we performed a prospective study in a cohort of 69 patients (7.0 +/- 3.2 years after heart transplantation; mean age, 55.0 +/- 9.6 years; 61 male) treated with 5 mg folic acid/day (n = 34) vs no medication (n = 35). Therapy with folic acid resulted in significantly decreased tHCY levels, from 22.6 +/- 9.6 micromol/liter to 17.3 +/- 5.5 micromol/liter (p = 0.001) within 3 months, whereas values in the control group remained unchanged. We conclude that folic acid supplementation (5 mg per day) provides a simple and effective measure to lower elevated tHCY levels in heart transplant recipients.

Aged↗
PubMed2001

Listing for lung transplantation: life expectancy and transplant effect, stratified by type of end-stage lung disease, the Eurotransplant experience.

BACKGROUND: Increased referral for lung transplantation, persistent shortage of donor lungs, and moderate transplant outcome call not only for adequate listing criteria, but also for an optimal allocation scheme. We used global cohort survival after listing and survival benefit from transplantation to study the effect of a lung allocation scheme, primarily driven by waiting time, on the different types of end-stage lung disease. METHODS: We followed all adult patients consecutively listed for first, lung-only transplantation between 1990 and 1996 (n = 1,208) for at least 2 years, with an additional 2-year follow-up after transplantation (n = 744). We used the competing risk method, the Kaplan-Meier method, and a time-dependent non-proportional hazards model to analyze waiting-list outcome and global mortality after listing, post-transplant survival, and transplant effect, respectively. Each analysis was stratified for type of end-stage lung disease. RESULTS: At 2 years, 57% of the total cohort had received lung transplants, whereas 25% had died on the waiting list. The 2-year survival post-transplant was 55%. The global mortality of the cohort, since listing, amounted to 46% at 2 years. Compared with continued waiting, patients experienced benefit from transplantation by Day 100, which lasted until the end of the 2-year analysis period. We noticed the highest global mortality rates for patients with pulmonary fibrosis and pulmonary hypertension (54% and 52%); emphysema patients had the lowest (38%). Patients with pulmonary fibrosis and cystic fibrosis had much earlier benefit from transplantation, 55 and 90 days, respectively. Transplantation also benefited emphysema patients by Day 260. CONCLUSIONS: Lung transplantation conferred transplant benefit in a Western European cohort of adults, in particular for patients with pulmonary fibrosis and cystic fibrosis, but also for patients with emphysema. The global survival rate, reflecting the real life expectancy for a newly listed transplant candidate, is poor for patients with pulmonary fibrosis and pulmonary hypertension. Allocation algorithms that lessen the impact of waiting time and take into account the type of end-stage lung disease should be developed.

Adolescent↗
PubMed2001

Iso-risk curves as a tool for clinical decision-making: donor factors and medical urgency in cardiac transplantation.

UNLABELLED: BACKGROUND; No significant improvement of overall graft survival in cardiac transplantation has occurred during the past decade, notwithstanding the identification of several prognostic donor and recipient risk factors. By translating multivariate results into iso-risk curves plots, stratified for medical urgency, we attempt to present results in a more practical manner, to be used as guidelines at the time of donor heart offer and of allocation. METHODS: We analyzed all first heart-only transplants performed in adults and carried out between January 1, 1997, and June 30, 1998 (N = 1120). Before transplant, 687 patients were at home, 233 on hospital wards, and 200 on the intensive care unit. The overall Cox model yielded 5 independent factors associated with 1-year graft outcome: donor age, donor:recipient weight ratio, medical urgency, end-stage heart disease, and transplant country. We used the significant donor variables of donor age and donor:recipient weight ratio for the iso-risk curves; we calculated relative risks for all combinations of donor age and donor:recipient weight ratio. We obtained iso-risk curves by linking equal relative risks. RESULTS: All iso-risk curves showed that with older donor age, the donor:recipient weight ratio must be higher to obtain the same relative risk for all 3 medical urgency groups. The more urgent the heart transplant candidate, the higher the course of the iso-risk curve for all donor ages. CONCLUSIONS: Iso-risk curve is an elegant tool for presenting multivariate analyses in a more practical and patient-oriented manner. The more understandable prognostic factors become the more likely we are to achieve better results in cardiac transplantation and to use more optimally donor hearts. As an example, we have demonstrated the interaction between donor age, donor:recipient size ratio, and medical urgency.

Adolescent↗
PubMed2001

Cell seeded decellularised allogeneic matrix grafts and biodegradable polydioxanone-prostheses compared with arterial autografts in a porcine model.

BACKGROUND: small diameter vascular grafts are limited by their restricted availability, early thrombosis, and requirement for anticoagulants. OBJECTIVE: to evaluate different approaches to biocompatible vascular grafts. METHODS: sixteen allogeneic acellularised arteries seeded with autologous endothelial cells were implanted to replace a segment of the common carotid artery (group I). Other animals received polydioxanone prostheses (group II: inner diameter, i.d. 4 mm, n=18; group III, i.d. 5 mm, n=20) or arterial autografts (group IV, n=8). Graft patency was evaluated by means of ultrasound duplex scanning, angiography and histology. RESULTS: patency was 54% (71%), 17% (0%), 50% (50%), and 100% (100%) in group I, II, III, and IV after 1 week (4 months), respectively. Significant differences (p<0.05) were found for group IV versus all other groups at 1 week, as well as for group IV versus groups II and III, for group II versus III, and group I versus II at 4 months. CONCLUSION: small diameter vascular grafts can be engineered from an acellular allogeneic matrix seeded with autologous cells. Patency is superior to polydioxanone prostheses but inferior to the arterial autograft.

Animals↗
PubMed2001

Heart valves from pigs and the porcine endogenous retrovirus: experimental and clinical data to assess the probability of porcine endogenous retrovirus infection in human subjects.

OBJECTIVE: Replacement of heart valves in human subjects has become a routine procedure in cardiac operations. We sought to investigate whether commercially available glutaraldehyde-fixed porcine heart valve prostheses cause porcine endogenous retrovirus infection in human subjects because recent studies revealed that human cells can be infected with porcine endogenous retrovirus. METHODS: Blood samples of 18 patients who underwent aortic or mitral valve replacement with porcine heart valves were collected 6 months to 3 years after operation and tested for porcine endogenous retrovirus by means of polymerase chain reaction and reverse transcriptase-polymerase chain reaction. In addition, we tried to trace porcine endogenous retrovirus in 3 commercially available, glutaraldehyde-fixed, porcine heart valves. RESULTS: Porcine endogenous retrovirus can be easily detected in native porcine heart valves and degrades completely within 1 week of fixation in glutaraldehyde. In all 3 commercially available porcine heart valves, no traces of porcine endogenous retrovirus were found. All blood samples showed negative test results for the porcine endogenous retrovirus genome. CONCLUSION: Our results indicate that glutaraldehyde fixation of porcine heart valves reliably prevents cross-species transmission of porcine endogenous retrovirus.

Aged↗
PubMed2001

The push-and-pull mechanism to scavenge redox-active transition metals: a novel concept in myocardial protection.

OBJECTIVE: Traces of redox-active transition metals such as iron and copper play an important role in free radical formation during postischemic reperfusion of the heart. Two studies were conducted to assess the efficacy of the complexes of desferrioxamine with zinc or gallium to prevent this aspect of reperfusion injury. METHODS: In study I, isolated working rat hearts (n = 96) were subjected to 2 hours of hypothermic arrest at 10 degrees C induced by use of St Thomas' Hospital cardioplegic solution II supplemented with desferrioxamine, zinc-histidinate, zinc-desferrioxamine, gallium-nitrate, or gallium-desferrioxamine. In study II, isolated nonworking rat hearts (n = 23) were subjected to normothermic regional (10 minutes) or global (35 minutes) unprotected ischemia. In this study, the perfusate was supplemented with gallium-desferrioxamine during preischemic and postischemic periods. RESULTS: In study I, the addition of desferrioxamine, zinc-histidinate, or gallium-nitrate to St Thomas' Hospital solution II improved postischemic aortic flow recovery. When the binary complexes zinc-desferrioxamine or gallium-desferrioxamine were added, however, functional recovery was further enhanced significantly. In study II, high-performance liquid chromatography analyses of tissue from postischemic hearts exposed to unsupplemented perfusate revealed a marked increase of malondialdehydes. In hearts perfused with perfusate supplemented with gallium-desferrioxamine, however, tissue malondialdehyde concentrations were significantly smaller, indicating reduced free radical formation. CONCLUSIONS: The data suggest synergistic protection by the complexes of the iron chelator desferrioxamine with zinc or gallium. The single components neutralize transition metals by 2 different but complementary push-and-pull mechanisms, thereby leading to an inhibition of metal-mediated site-specific free radical formation and improvement of postischemic cardiac function.

Analysis of Variance↗
PubMed2001

Myocardial protection by ischemic preconditioning and delta-opioid receptor activation in the isolated working rat heart.

OBJECTIVE: delta-Opioid receptors are involved in the cardioprotective effect of ischemic preconditioning. This study was designed (1) to assess the protective capacities of ischemic preconditioning and the synthetic delta-opioid receptor agonist D-Ala(2)-D-Leu(5) enkephalin (DADLE) in a functionally oriented experimental model of ischemia and reperfusion and (2) to assess whether the effects of both protective measures are similarly blocked by naloxone, a nonspecific delta-opioid receptor antagonist. METHODS: Sixty-four isolated working rat hearts were subjected to 45 minutes of hypothermic ischemia at 30 degrees C followed by 25 minutes of normothermic reperfusion. Rats were pretreated with DADLE (1 mg/kg body weight intravenously), naloxone (3 mg/kg body weight intravenously), or a combination thereof within 60 minutes before onset of isolated heart perfusion. During the preischemic perfusion period, 8 hearts per group were preconditioned by one cycle of 5 minutes of normothermic global ischemia and subsequent reperfusion whereas another 8 served as nonpreconditioned controls. The postischemic functional recovery of hearts and their creatine kinase leakage were determined. RESULTS: Pretreatment with DADLE and ischemic preconditioning improved the postischemic recovery of aortic flow when compared with nonpreconditioning (57.7% +/- 4.0% and 60.8% +/- 4.3% vs 40.0% +/- 4.2% of preischemic baseline value, P <.001). Combined pretreatment with DADLE before ischemic preconditioning afforded additional aortic flow recovery compared with pretreatment with DADLE alone (68.6% +/- 3.3% vs 57.7% +/- 4.0% of preischemic baseline value; P =.038). With combined pretreatment, early postischemic creatine kinase release was lower than control in hearts without pretreatment (0.48 +/- 0.11 vs 0.80 +/- 0.12 IU/5 minutes per heart; P =.001). Naloxone abolished the beneficial functional effects of pretreatment with DADLE and ischemic preconditioning. CONCLUSIONS: Pharmacologic activation of delta-opioid receptors affords improvement of functional protection in isolated working rat hearts similar to that conferred by classic ischemic preconditioning. The combination of both pretreatments reduces ischemic cellular damage and further adds to postischemic functional recovery. These changes are reversed by naloxone, an observation providing evidence that ischemic preconditioning involves signaling through opioid receptors.

Animals↗
PubMed2001

Evaluation of different minimally invasive techniques in pediatric cardiac surgery: is a full sternotomy always a necessity?

STUDY OBJECTIVES: A variety of minimally invasive techniques have been recently introduced in adult cardiac surgery. Experiences with children and newborns are, however, limited. In this report, we present our first experiences with different methods of ministernotomies for closure of atrial septum defect (ASD) and ventricular septum defect (VSD) in pediatric cardiac patients. Also, the current literature for different surgical approaches is reviewed. PATIENTS AND METHODS: Twenty-five pediatric patients (range, 4 months to 12 years old) underwent elective ASD or VSD closure. Surgical access was either without division of the sternum (group A, n = 5), with partial inferior sternotomy (group B, n = 5), total sternotomy with limited skin incision (group C, n = 5), or total sternotomy with full skin incision (group D, n = 10). RESULTS: There were no severe intraoperative complications regarding exposure, cannulation, or bleeding. Conversion to full sternotomy was not necessary in any patient. Bypass time and cross-clamp time in groups A, B, and C were comparable to the standard operation (group D). However, preparation time was significantly increased in one minimally invasive group (group A vs group D, p<0.05). Despite general feasibility, the transxiphoidal access without sternotomy compromises exposure of the ascending aorta, resulting in impaired administration of cross-clamping, cardioplegia, and especially de-airing. CONCLUSIONS: Transatrial pediatric cardiac operations can be performed without or with limited sternotomy. The partial sternotomy allows uncompromised exposure of the great vessels and should be favored over the transxiphoidal approach. The operative access and perioperative risk is comparable to a classical standard surgical approach. Advantages include improved cosmetic results in combination with a high degree of safety.

Cardiac Surgical Procedures↗
PubMed2001

Early clinical experience with the On-X prosthetic heart valve.

BACKGROUND AND AIM OF THE STUDY: The study was designed to investigate the clinical performance of the On-X prosthetic heart valve in a multicenter experience. METHODS: Between September 1996 and September 1999, 301 patients (56% males) underwent isolated On-X valve replacement (184 isolated aortic (AVR), 117 isolated mitral (MVR)) at 11 European centers under a standardized protocol. Average age at implant was 60.2 years. Office or hospital follow up was required by the protocol; average follow up on all patients was 11 months. RESULTS: Thirty-day mortality in the study was 2.2% for AVR and 6.0% for MVR, with valve-related mortality of 0.5% for AVR. There were eight late deaths (0.7%/pt-yr AVR and 2.3%/pt-yr MVR). Two of these deaths were sudden, and thus possibly valve-related (one AVR, one MVR). Early total valve-related morbidity was 3.5% for AVR and 2.6% for MVR. In total, 13 thromboembolic events occurred; one early event in AVR resulted in death (0.5%), and one transient early event occurred in MVR (0.9%). There were 11 late events (seven AVR (1.7%/pt-yr) and four MVR (1.8%/pt-yr)), for a two-year freedom from thromboembolism of 96.6% after AVR and 97.1% after MVR. Three late bleeding events occurred, all after AVR (0.7%/pt-yr and 98.9% free at two years). Major paravalvular leaks requiring reoperation occurred on two occasions early (one AVR (0.5%), one MVR (0.8%)) and once late in MVR (0.5%/pt-yr). Late minor, untreated paravalvular leaks occurred in three AVR patients (0.7%/pt-yr) and in one MVR patient (0.5%/pt-yr). Prosthetic endocarditis occurred four times (two AVR (0.5%/pt-yr), two MVR (0.9%/pt-yr)), all within the first 12 months of surgery. Actuarial freedom from all valve-related events at two years was 88.7% for AVR and 88.1% for MVR. NYHA class was improved in 75.8% of AVR patients and 70.6% of MVR patients at two years after surgery. CONCLUSION: These early results indicate that the On-X valve provides satisfactory clinical outcome in the immediate postoperative period, and that the valve is both safe and effective.

Actuarial Analysis↗
PubMed2001

[Replacement of the ascending aorta with aortic valve reimplantation: indications, technique and results].

The main cause of aortic valve insufficiency is a dilatation of the sinotubular junction in patients with an ascending aortic aneurysm. Morphologically preserved aortic valve cusps represent an ideal condition for preservation and reconstruction of the aortic valve with an simultaneous replacement of the ascending aorta with a Dacron graft. This report presents the results of 140 patients, who underwent such surgery since 1993 in our institution. Indications for surgery, operative technique and different outcome parameters are discussed. Intra- and perioperative morbidity and mortality are low and quality of life excellent. Reoperation due to progressive aortic valve insufficiency was necessary in 2.1% of patients during follow-up. When compared with the standard operation (composite replacement utilizing a mechanical valve), patients with aortic valve reconstruction demonstrate similar results with regard to hospital stay and functional improvement. However, bleeding complications and thromboembolic events are significantly reduced in patients undergoing valve reconstruction. Due to these long-term results combined with excellent stress hemodynamics and improvement in LV function, aortic valve reconstruction currently represents our standard operative strategy in this patient group.

Adolescent↗
PubMed2000

Systemic inflammatory response in cardiac allograft vasculopathy: high-sensitive C-reactive protein is associated with progressive luminal obstruction.

BACKGROUND: Response to immunologic and nonimmunologic injury has been reported to initiate the development of cardiac allograft vasculopathy (CAVD). Although histopathologic examinations reveal signs of focal inflammation, little is known about the systemic inflammatory response in this accelerated coronary syndrome. METHODS AND RESULTS: Therefore, we investigated high-sensitive C-reactive protein (CRP) in a large cohort of heart transplant (HTX) recipients (n=102, 90 male, mean age 45.2+/-11.5 years, 6.1+/-3.3 years after HTX) in correlation with a progression of luminal obstruction as assessed by serial coronary angiography (defined as an increase of focal stenosis >/=30% or detection of a new lesion) after a mean interval of 1.8+/-1.0 years. Patients with signs of an acute rejection or infection were excluded. In the entire group, CRP levels ranged from 0.2 to 12.7 mg/L (mean 2.6+/-2.7 mg/L). Patients with progressive CAVD (n=35) presented with significantly higher levels of CRP (4.1+/-3.3 mg/L) than did those with a nonprogressive course (n=67) (1.8+/-1.9 mg/L, P:=0.001). These observations were independent of the initial indication for HTX (atherosclerotic disorder versus cardiomyopathy, P:=0.18) and the severity of CAVD at baseline examination (P:=0.12). CONCLUSIONS: Progressive cardiac allograft vasculopathy is accompanied by a systemic inflammatory reaction, which gives further insight into the pathogenesis of this coronary syndrome and may well serve as an indicator for patients at risk.

C-Reactive Protein↗
PubMed2000

Tissue engineering of pulmonary heart valves on allogenic acellular matrix conduits: in vivo restoration of valve tissue.

BACKGROUND: Tissue engineering using in vitro-cultivated autologous vascular wall cells is a new approach to biological heart valve replacement. In the present study, we analyzed a new concept to process allogenic acellular matrix scaffolds of pulmonary heart valves after in vitro seeding with the use of autologous cells in a sheep model. METHODS AND RESULTS: Allogenic heart valve conduits were acellularized by a 48-hour trypsin/EDTA incubation to extract endothelial cells and myofibroblasts. The acellularization procedure resulted in an almost complete removal of cells. After that procedure, a static reseeding of the upper surface of the valve was performed sequentially with autologous myofibroblasts for 6 days and endothelial cells for 2 days, resulting in a patchy cellular restitution on the valve surface. The in vivo function was tested in a sheep model of orthotopic pulmonary valve conduit transplantation. Three of 4 unseeded control valves and 5 of 6 tissue-engineered valves showed normal function up to 3 months. Unseeded allogenic acellular control valves showed partial degeneration (2 of 4 valves) and no interstitial valve tissue reconstitution. Tissue-engineered valves showed complete histological restitution of valve tissue and confluent endothelial surface coverage in all cases. Immunohistological analysis revealed cellular reconstitution of endothelial cells (von Willebrand factor), myofibroblasts (alpha-actin), and matrix synthesis (procollagen I). There were histological signs of inflammatory reactions to subvalvar muscle leading to calcifications, but these were not found in valve and pulmonary artery tissue. CONCLUSIONS: The in vitro tissue-engineering approach using acellular matrix conduits leads to the in vivo reconstitution of viable heart valve tissue.

Animals↗
PubMed2000

High level benzodiazepine and ammonia clearance by flat membrane bioreactors with porcine liver cells.

The onset of hepatic encephalopathy is a multifactorial process in which endogenous benzodiazepines and hyperammonemia play a pivotal role. The treatment of comatose states in liver failure is one of the major functions of a bioartificial liver. A controlled study demonstrating the capacity of a large scale bioartificial liver to detoxify benzodiazepines could be a crucial prerequisite to break this circle of events leading to coma. The aim of this study was therefore to expose the bioreactor to high levels of benzodiazepines and ammonia for evaluation of its detoxifying capacity. We have developed a novel and unique device reconstructing the plate architecture of the liver. Porcine hepatocytes were co-cultured with non-parenchymal cells. We investigated benzodiazepine metabolism using diazepam as model drug. The bioreactor was also loaded with high levels of ammonia and ammonia clearance as well as urea secretion with ammonia challenge were investigated. Albumin secretion was analysed in parallel as a control viability and tissue specific secretory parameter. The results clearly show that the velocity of diazepam turnover increases between day 1 and 2 and stabilises at high levels. Typical diazepam metabolites including temazepam, N-desmethyl-diazepam and oxazepam were generated. Cell specific functions, including albumin secretion, were comparable to an in vivo liver. We conclude that the flat membrane bioreactor used as bioartificial liver has the potential to detoxify diazepam and ammonia at significant amounts. Maintenance of monoxygenase activities in vitro is one of the strongholds of the bioreactor concept presented in this study.

Albumins↗