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Axel Haverich

Publications and source records attributed to Axel Haverich.

At least 19 recordsLinked to original sources
PubMed2003

Antegrade versus retrograde perfusion of the donor lung: impact on the early reperfusion phase.

Transpulmonary thermodilution was used to evaluate the effect of flush route during harvest on hemodynamic and respiratory function of the pulmonary graft in the early post-transplant phase. Single lung transplantation was performed in two piglet groups after 24 h of cold storage. Donor organs for group A underwent antegrade perfusion, and those for group R retrograde perfusion. PaO(2), compliance (C), airway resistance (R), extravascular lung water index (EVLWI), pulmonary blood volume index (PBVI), intrathoracic blood volume index (ITBVI), capillary leak (CL), and cardiac function index (CFI) were assessed by transpulmonary thermodilution at baseline, 1, 3, and 6 h after reperfusion. EVLWI was significantly lower in group R. Compliance and PaO(2) were higher in the same group. The two groups did not differ significantly with regard to CFI, PBVI, ITBVI, and airway resistance. Retrograde perfusion of the donor lung had a positive impact on graft function during early reperfusion. Transpulmonary hemodynamic monitoring can be a powerful tool for intra- and postoperative management of transplant patients.

Animals↗
PubMed2003

Increased open probability of single cardiac L-type calcium channels in patients with chronic atrial fibrillation. role of phosphatase 2A.

BACKGROUND: The L-type calcium channel (LCC) plays a crucial role in the electrical remodeling of atrial fibrillation (AF). AF is associated with reduction of L-type calcium current density, due to a transcriptional downregulation of the pore forming alpha(1c)-subunit of LCC. However, it is unclear, whether this current reduction is related to a decrease in channel number or to alterations in channel function. Hence, we performed a single LCC analysis to assess channel gating and function in human AF. METHODS AND RESULTS: We used the cell-attached patch-clamp technique in isolated atrial human cardiomyocytes of 25 patients with sinus rhythm (SR) and 15 patients with chronic AF. Protein expression of the pore-forming alpha(1c)-subunit of LCC was reduced by 40% in AF. Single channel peak average current was 1.7-fold higher in AF than in SR, due to a 3.1-fold higher open probability of LCC. Since phosphatase 2A (PP2A) is known to preferentially reduce LCC open probability via channel dephosphorylation, we assessed whether PP2A expression or activity is reduced in AF. Okadaic acid, an inhibitor of phosphatases, increased channel open probability in SR, but not in AF. However, Western blot analysis of atrial homogenates of the same patient population revealed unchanged expression of PP2A. CONCLUSIONS: Human AF is characterized by increased single LCC activity, due to an increase of channel open probability. The blunted effect of PP2A on LCC as shown by single channel analysis may be related to a reduction of cytosolic PP2A activity or impaired local interaction between PP2A and LCC in AF.

Adrenergic beta-Agonists↗
PubMed2003

Endoluminal treatment of aortic dissection.

Aortic dissection is most often a catastrophic medical emergency which, if untreated, can be potentially fatal. The intention of therapy in patients with aortic dissection is to prevent aortic rupture or aneurysm formation as well as to relieve branch vessel ischaemia. Patients with aortic dissection are often poor candidates for anaesthesia and surgery and the surgical procedure itself is challenging requiring thoracotomy, aortic cross clamping, blood transfusion as well as prolonged hospital stay in some cases. Operative mortality is especially high in patients with critical mesenteric or renal ischaemia. The past decade has experienced the emergence of a number of interventional radiological or minimally invasive techniques which have significantly improved the management of patients with aortic dissection. These include stent grafting for entry site closure to prevent aneurysmatic widening of the false lumen as well as percutaneous techniques such as balloon fenestration of the intimal flap and aortic true lumen stenting to alleviate branch vessel ischaemia. False lumen thrombosis following entry closure with stent grafts has been observed in 86-100% of patients, whereas percutaneous interventions are able to effectively relieve organ ischaemia in approximately 90% of the cases. In the years to come, it is to be expected that these endoluminal techniques will become the method of choice for treating most type-B dissections and will assist in significantly reducing the number of open surgical procedures required for type-A dissections. The intention of this article is to provide an overview of the current status of these endoluminal techniques based on our own experience as well as on a review of the relevant literature.

Aortic Dissection↗
PubMed2003

Intramural hematoma of the aorta: predictors of progression to dissection and rupture.

BACKGROUND: Aortic intramural hematoma (IMH) is a variant of overt aortic dissection. The predictors of progression of IMH to dissection and rupture are still unknown, and strategies for management are not established. METHODS AND RESULTS: A multicenter study was conducted comprising 66 patients with IMH and hospital admission <or=48 hours after onset of initial symptoms. Among these, progression to aortic dissection or rupture occurred in 30 (45%) and death occurred in 13 (20%) patients within 30 days. Late progression was noted in 14 (21%) and death in 11 (17%) patients, yielding a 1-, 2-, and 5-year survival of 76%, 73%, and 43%, respectively. In a set of 9 variables, multivariate analysis identified IMH location in the ascending aorta (type A; P=0.02) and moderately ectatic aortic diameters (49+/-13 mm with progression versus 57+/-16 mm without progression; P=0.03) as independent predictors of early progression. In type A IMH, early mortality was 8% with swift surgery versus 55% without surgery (P=0.004). The risk of late progression of IMH was independently associated with age at index diagnosis (P=0.01) and absence of beta-blocker therapy during follow-up (P=0.03). Kaplan-Meier analysis confirmed improved 1-year survival of IMH with beta-blocker therapy (95% versus 67% without beta-blockers; P=0.004). CONCLUSIONS: Regardless of aortic diameter, IMH of the ascending aorta (type A) is at high risk for early progression, and, thus, undelayed surgical repair should be performed. Moreover, oral beta-blocker therapy may improve long-term prognosis of IMH independent of anatomical location.

Adult↗
PubMed2003

Anticoagulant therapy in pregnant women with mechanical heart valves.

Managing women with mechanical heart valves during pregnancy poses a particular challenge as there are no available controlled clinical trials to provide guidelines for effective antithrombotic therapy. Oral anticoagulation with coumadin-derivates administration is associated with coumarin embryopathy, and subcutaneous administration of unfractioned heparins (UFH) has been reported to be ineffective in preventing thromboembolic complications. Due to the increased risk of thromboembolic events when UFH is used, low molecular weight heparins (LMWH) were considered to be an alternative. The evidence in the literature regarding the long-term use of LMWH as the only anticoagulant after mechanical heart valve replacement is limited only to a few reports encompassing only 25 patients, with treatment failure in 20%. These data show that anticoagulation with LMWH only is neither safe nor effective in preventing thromboembolic events after mechanical heart valve replacement, in pregnant or non-pregnant women.

Anticoagulants↗
PubMed2003

Increased chimerism of bronchial and alveolar epithelium in human lung allografts undergoing chronic injury.

Chimerism on the parenchymal level has been shown for several human allografts, including liver, heart, and kidney, with the integrated recipient-derived cells most likely originating from multipotent bone marrow precursors. We investigated whether chimerism also occurs within epithelial structures of the lung. For this purpose archival tissue biopsies from seven explanted human lung allografts were obtained. We performed laser microdissection of the target structures with subsequent short tandem repeat analysis to detect chimerism within the isolated cells. We found integration of recipient-derived cells in the bronchial epithelium, in type II pneumocytes and in seromucous glands lying adjacent to larger bronchi in all lung allografts studied. Quantitative analysis revealed that the epithelial structures displaying signs of chronic injury, such as squamous metaplasia, showed a markedly higher degree of chimerism (24% versus 9.5%). We therefore conclude that in human lungs, epithelial chimerism occurs at least within bronchi, type II pneumocytes, and seromucous peribronchial glands. Although a bone marrow origin of immigrating host-derived stem cells has been suggested by previous studies in rodents, analysis of lung biopsies from bone marrow-transplanted patients (n = 3) could not prove such delineation in this study. The observation of an enhanced integration of recipient cells into chronically damaged epithelial structures suggests that extrapulmonary precursor cells are able to contribute to pulmonary regeneration.

Adolescent↗
PubMed2003

In vivo repopulation of xenogeneic and allogeneic acellular valve matrix conduits in the pulmonary circulation.

BACKGROUND: Approaches to in vivo repopulation of acellularized valve matrix constructs have been described recently. However, early calcification of acellularized matrices repopulated in vivo remains a major obstacle. We hypothesised that the matrix composition has a significant influence on the onset of early calcification. Therefore, we evaluated the calcification of acellularized allogenic ovine (AVMC) and xenogenic porcine (XVMC) valve matrix conduits in the pulmonary circulation in a sheep model. METHODS: Porcine (n = 3) and sheep (n = 3) pulmonary valve conduits were acellularized by trypsin/EDTA digestion and then implanted into healthy sheep in pulmonary valve position using extracorporeal bypass support. Transthoracic echocardiography (TTE) was performed at 12 and 24 weeks after the implantation. The animals were sacrificed at week 24 or earlier when severe calcification of the valve conduit became evident by TTE. The valves were examined histologically and biochemically. RESULTS: All AVMC revealed severe calcification after 12 weeks with focal endothelial cell clustering and no interstitial valve tissue reconstitution. In contrast, after 24 weeks XVMC indicated mild calcification on histologic examination (von Kossa staining) with histologic reconstitution of valve tissue and confluent endothelial surface coverage. Furthermore, immunohistologic analysis revealed reconstitution of surface endothelial cell monolayer (von Willebrand factor), and interstitial myofibroblasts (Vimentin/Desmin). CONCLUSIONS: Porcine acellularized XVMC are resistant to early calcification during in vivo reseeding. Furthermore, XVMC are repopulated in vivo with valve-specific cell types within 24 weeks resembling native valve tissue.

Animals↗
PubMed2003

Methylene blue: the drug of choice for catecholamine-refractory vasoplegia after cardiopulmonary bypass?

OBJECTIVES: Vasoplegia is a frequent complication after cardiopulmonary bypass that often requires the application of norepinephrine. In a number of cases, however, vasoplegia is refractory to norepinephrine. The guanylate cyclase inhibitor methylene blue could be an attractive treatment alternative in such cases. This study examines the results of methylene blue therapy for norepinephrine-refractory vasoplegia after cardiopulmonary bypass. METHODS: A total of 54 patients with norepinephrine-refractory vasoplegia after cardiopulmonary bypass were treated with methylene blue (2 mg/kg) administered intravenously through a period of 20 minutes. The effects on hemodynamics, norepinephrine dosage, and clinical outcome were evaluated. RESULTS: Three patients (5.6%) died during the hospital stay. A clinically relevant increase in systemic vascular resistance and a decrease in norepinephrine dosage were observed in 51 patients within 1 hour after methylene blue infusion. Four patients (7.4%) had no response to methylene blue. No adverse effects related to methylene blue were observed. CONCLUSIONS: A single dose of methylene blue seems to be a potent approach to norepinephrine-refractory vasoplegia after cardiopulmonary bypass for most patients, with no obvious side effects. Guanylate cyclase inhibitors could be a novel class of agents for the treatment of norepinephrine-refractory vasoplegia after cardiopulmonary bypass. A controlled clinical trial is now needed to evaluate the role of methylene blue in this situation.

Cardiopulmonary Bypass↗
PubMed2003

Influence of scaffold thickness and scaffold composition on bioartificial graft survival.

Biological scaffolds exhibit advantageous properties for tissue engineering of small diameter vessels. The influence of their extracellular matrix (ECM) components during in vivo repopulation is unknown. We implanted different xenogenic vascular matrices in a rat model to determine the influence of scaffold-thickness and ECM composition on in vivo repopulation. Decellularized ovine jugular vein (JV, n=42), carotid artery (CA, n=42) and aorta (AO, n=42) were implanted subcutaneously in the neck of adult male rats. Animals were sacrificed 2, 4 and 8 weeks after implantation. Cell and matrix morphology of explanted scaffolds were characterized by hematoxylin-eosin and pentachrome staining. Monoclonal anti-rat-CD31 was used to identify revascularization. Quantification of cell density was done by DNA-isolation. THICKNESS OF IMPLANTED XENOGENIC SCAFFOLDS VARIED ACCORDING TO THE MATERIAL USED (AO: 3.0-3.8mm; CA: 0.7-0.88mm; JV: 0.35-0.61mm). Immunohistology revealed complete repopulation of AO, CA, and JV scaffolds with endothelial cells and myofibroblasts within 2 weeks. After 8 weeks of implantation, AO scaffolds were completely covered by an endothelial monolayer and showed signs of a central matrix degeneration. JV scaffolds were completely degenerated at this stage. In contrast, CA scaffolds showed preserved ECM with a normal myofibroblast population and endothelial cell coverage.

Animals↗
PubMed2003

Technical advances of pulmonary thromboendarterectomy for chronic thromboembolic pulmonary hypertension.

OBJECTIVE: To minimize the side-effects of circulatory arrest times and profound hypothermia in patients undergoing pulmonary thromboendarterectomy (PTE) for chronic thromboembolic pulmonary hypertension (CTEPH). METHODS: Between March 2000 and June 2002, 30 patients (in New York Heart Association (NYHA) class III or IV) were operated for CTEPH using our modified technique. It includes moderate hypothermic (28-32 degrees C), total cardiopulmonary bypass (CPB) and simultaneous selective antegrade cerebral perfusion and occlusion of the bronchial arteries by introducing an occlusive balloon catheter into the descending aorta. The preoperative pulmonary vascular resistance in the cohort was 873+/-248dynes/s/cm(-5). RESULTS: Mean total CPB, cross-clamp times and duration of anterograde cerebral perfusion were 132+/-40, 98+/-21 and 21+/-10min, respectively. Mean core temperature 29.5+/-1.9 degrees C. The duration of postoperative mechanical ventilatory support was 34+/-44h and the mean stay in the ICU was 5+/-9 days. Seven patients had mild to moderate lung reperfusion injury, one transient neurological dysfunction. Three patients (10%) died during their hospital stay, two for multiorgan failure and one for persistent pulmonary hypertension. All patients had a significant pulmonary hemodynamic improvement and all achieved NYHA class I (P<0.01) status 4 weeks after discharge, remaining stable at a median follow-up time of 16 months (range, 1-29 months) postoperatively. CONCLUSIONS: These technical advances improve neurological outcome, control back-bleeding from bronchial arteries and avoid prolonged rewarming phases in patients undergoing PTE.

Chronic Disease↗
PubMed2003

In-situ topical cooling of lung grafts: early graft function and surfactant analysis in a porcine single lung transplant model.

OBJECTIVE: Improvement of organ preservation is essential to facilitate acceptance of marginal donor lungs for transplantation. Thus, recruiting non-heart-beating donors (NHBD) may be one reasonable strategy to augment the organ-pool especially in the field of pulmonary transplantation. Topical cooling (TC) of donor lungs could provide fast organ-protection and is an available procedure even in smaller centers. In this study transplanted lung function and surfactant activity in same lungs, which were preserved by TC, were assessed following transplantation. METHODS: Twelve porcine allogeneic single lung transplants were performed. Six lungs that were flush preserved through the antegrade route served as controls. The other six lungs were preserved by TC for 30 min after induction of cardiac arrest by repeated application of cold saline (8 degrees C) to both pleural cavities. Lungs of both groups were stored in LPD solution for 24 h at 8 degrees C. After transplantation, the recipient's right bronchus and right pulmonary artery were clamped. Major endpoints included early graft function over a period of 7 h. Hemodynamic measures and respiratory functions were recorded in 30-min intervals. Surfactant function was determined before transplantation and 2 h after reperfusion by broncho-alveolar lavage fluid analysis. RESULTS: Only four animals of the control-group survived the 7 h reperfusion period. Right heart failure occurred in two animals after 150 and 240 min of reperfusion. All six animals in the TC group survived the observation period. Pulmonary vascular resistance (p<0.01), pulmonary artery pressure (p=0.03), and lung tissue water content remained significantly lower in topically cooled allografts (p=0.01) vs. controls. Surfactant function after transplantation was comparable in both groups with a trend towards lower protein contents (p=0.07) in the broncho-alveolar fluid of grafts after TC. CONCLUSIONS: In-situ TC seems to be a reliable strategy to preserve lungs for up to 24 h. It even surpasses the results of LPD-perfused grafts in hemodynamic function and survival time.

Animals↗
PubMed2003

In vivo model for cross-species porcine endogenous retrovirus transmission using tissue engineered pulmonary arteries.

OBJECTIVE: Acellularised porcine scaffolds have been successfully used for cardiovascular tissue engineering. However, there is concern about the possibility of porcine endogenous retrovirus (PERV) transmission. In this study we developed an in vivo model for cross-species PERV transmission. METHODS: In vitro autologous repopulated porcine pulmonary arteries (n=6) were implanted in sheep in orthotopic position. Blood samples were collected regularly up to 6 months after implantation and tested for PERV by means of polymerase chain reaction and reverse transcriptase-polymerase chain reaction. Explanted tissue engineered pulmonary arteries were tested for PERV sequences. RESULTS: PERV DNA was detectable in acellularised porcine scaffolds. No PERV sequences were detectable 6 months after implantation of in vitro repopulated acellularised porcine pulmonary arteries and in all tested peripheral blood samples. CONCLUSIONS: Acellularised porcine matrix scaffolds can be used for cardiovascular tissue engineering of autologous grafts without risk of PERV transmission.

Animals↗
PubMed2003

Hypothermic circulatory arrest during ascending and aortic arch surgery: the theoretical impact of different cerebral perfusion techniques and other methods of cerebral protection.

Operations on the thoracic aorta using hypothermic circulatory arrest are still associated with significant morbidity and mortality due to neurological complications. During the last decades, different cerebral protection techniques have been introduced into clinical practice to reduce the incidence of such complications. Furthermore clinical as well as basic researches have been performed to improve the outcome after these operations. Currently different cerebral perfusion methods are in clinical use and the superiority of one or the other method is a matter of controversial discussion. This review has been undertaken to evaluate the theoretical impact of these different methods of cerebral protection. Based on the experience of the authors the pros and cons are discussed with clinical and experimental reports from the literature.

Aorta↗
PubMed2003

Functional endurance capacity and exercise training in long-term treatment after heart transplantation.

OBJECTIVE: The aim of this study was to investigate the influence of cardiac denervation on endurance exercise capacity in heart transplant recipients (HTR) in comparison to patients with coronary artery disease (CAD). METHODS: We performed two successive incremental tests and a 30-min constant load test (CLT) in 20 HTR (55 +/- 7 years old, 4.9 +/- 2.2 years after transplantation) and in 13 patients with CAD (58 +/- 8 years). RESULTS: Maximal workload in HTR was 106 +/- 25 W (163 +/- 41 W; p < 0.01). In CLT at anaerobic threshold of 55 +/- 6 W (97 +/- 34 W; p < 0.01), lactate increased from 0.9 +/- 0.2 (1.0 +/- 0.2) to 2.9 +/- 1.3 (3.3 +/- 1.3) after 10 min and to 3.1 +/- 1.6 (3.4 +/- 1.5; NS) mmol. l(-1) after 30 min, confirming that the anaerobic threshold reflects a steady state. The CLT kinetics of heart rate (+6 beats in HTR and in CAD between 10th and 30th min) and lactate are comparable in HTR and CAD, demonstrating that endurance kinetics are not influenced by cardiac denervation.

Aged↗