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Axel Haverich

Publications and source records attributed to Axel Haverich.

154 records · Page 9Linked to original sources

Surfactant function in lung transplantation after 24 hours of ischemia: advantage of retrograde flush perfusion for preservation.

OBJECTIVE: Surfactant function was shown to be impaired in clinical and experimental lung transplantation. This study was designed to define the impact of retrograde flush perfusion on graft and surfactant function after an extended period of ischemia. METHODS: Left lung transplantation was performed after 24 hours of graft ischemia in 12 pigs. In half of the grafts antegrade cold flush perfusion (Perfadex) was used for preservation. In the second group grafts were flushed in a retrograde fashion via the left atrium. Graft function was monitored for 7 hours after transplantation. Before transplantation (basal) and after 2 hours of reperfusion, bronchoalveolar lavage fluid was obtained. Minimal surface tension of bronchoalveolar lavage fluid was determined and the ratio of small and large surfactant aggregates was calculated. Lung water content was analyzed online in the reperfusion period. RESULTS: Right-sided heart failure developed in 2 animals of group 1 (antegrade perfusion) within 2 and 4.5 hours of reperfusion, respectively. All other pigs survived the observation period. PO(2)/FIO(2) (P =.001) and dynamic lung compliance (P =.001) were superior in retrogradely flushed grafts. A comparable increase of minimal surface tension was found after reperfusion in both groups. Small/large surfactant aggregate ratio after reperfusion (P =.03), as well as extravascular lung water content, was higher in the antegrade perfusion group. CONCLUSION: Retrograde flush perfusion for 24-hour lung preservation with low-potassium dextran (Perfadex) solution led to better initial graft function than the standard antegrade perfusion technique. A moderate impairment of surfactant function was found in both groups, which was more pronounced in the antegrade perfusion group.

Animals↗

Right heart support during off-pump coronary artery bypass surgery--a multi-center study.

BACKGROUND: Off-pump coronary artery bypass (OPCAB) surgery for posterior and inferior wall vessels requires heart displacement, which leads to hemodynamic instability. Based on results indicating that displacement primarily alters right heart function, this study evaluates the safety and efficacy of right heart support during OPCAB surgery to the posterior and inferior wall vessels. METHODS: In a multi-center, prospective study, 25 patients underwent multi-vessel OPCAB surgery. Right heart support was carried out using the Enabler circulatory support system (Hemodynamics Systems Ltd., Upper Yokneam, Israel). Hemodynamic measurements were recorded at baseline and during heart displacement with and without right heart support. RESULTS: No mortality was recorded. Mean graft number was 2.25 +/- 0.36. Inability to position the Enabler system occurred in five cases. Once the Enabler was properly positioned, there was no case of conversion to cardiopulmonary bypass (CPB) due to failure of the Enabler to provide adequate support. Cardiac index (CI) declined from 2.4 +/- 0.5 L/min x /m2 to 1.6 +/- 0.6 L/min x /m2 (p <0.05) during heart displacement and increased to 2.3 +/- 0.6 L/min x /m2 (p <0.05) following Enabler activation. Mean arterial blood pressure (MAP) dropped from 82 +/- 18.6 mmHg to 53.1 +/- 16.6 mmHg (p <0.001) during heart displacement and was restored to 69.8 +/- 19.4 mmHg (p <0.001) with Enabler support. CONCLUSIONS: Heart displacement caused a significant hemodynamic deterioration that was stabilized with right heart support. The Enabler system is safe and effective in facilitating multi-vessel OPCAB surgery. However, there are still serious technical problems during cannula insertion that cause an unacceptable failure rate of device utilization.

Aged↗

[Differentiation potential of human stem cells--approaches to tissue engineering and to cell transplantation].

The prospect of future clinical applications of human stem cells is one of the major arguments for the use of embryonic stem cells. Scientists are currently developing methods to culture and isolate different somatic cell types. The enormous capacity for proliferation of embryonic and certain adult stem cells combined with suitable protocols to differentiate these cells may allow the production of sufficient amounts even of those cell types which cannot be expanded in the terminal differentiated state. The ability to generate large quantities of certain somatic cells in vitro has led to the first cell transplantation-based therapeutic concepts and clinical studies. Even today comparatively simply structured in vitro-engineered tissues are applied clinically. However, to grow larger and more complex structures, a variety of problems including their vascularisation and the development of suitable matrices have to be resolved. In the long term, tissue engineering offers an as yet incalculable potential for future medical applications and may finally allow the development and clinical transplantation of complex tissues or even whole organs.

Cell Culture Techniques↗

Heart and heart-lung transplantation: standards and improvements.

Standards and new developments of thoracic organ transplantation are reviewed with particular focus on current treatment strategies, alternatives to transplantation, and xenotransplantation. The current indications for heart, single and bilateral sequential lung, and heart-lung transplantation as well as the technical aspects of each procedure are presented. Criteria for transplant recipients and absolute and relative contraindications are pointed out. Criteria for donor selection are also reviewed. The results of single, double-sequential, and heart-lung transplantation over the past 10 years as reported by the International Society for Heart and Lung Transplantation Database are stated. In addition, the experience of the lung and heart-lung transplantation program at the Hannover Medical School is reviewed, including the current immunosuppression regimens. This experience includes 1075 heart,heart-lung, and lung transplantations since 1983. The 1- and 5-year actuarial survival rates for heart transplant recipients are 81% and 70%, for heart-lung recipients 76% and 61%, and for single and double lung transplant recipients 77% and 59%, respectively. During the past decade there has been continuous improvement in the results of heart, lung, and heart-lung transplantation. Alternatives to thoracic organ transplantation, living-related lobar transplantation, new antirejection agents, and xenograft transplantation are areas for continuing and future investigation.

Heart Failure↗

Glucose metabolism, energetics, and function of rat hearts exposed to ischemic preconditioning and oxygenated cardioplegia.

We examined changes induced during ischemia-reperfusion on myocardial metabolism and function by oxygenated warm cardioplegia (CP) and ischemic preconditioning (IP). The postischemic hemodynamic recovery was comparable and significantly better in IP and CP groups, than in untreated hearts (e.g., LVDP recovery was threefold that of the control). The IP hearts reached a pH plateau earlier during ischemia and at considerably higher pH value (pH approximately 6) compared to the other groups (pH approximately 5.5). Postischemic phosphocreatine (PCr) and ATP recoveries were comparable and better in protected groups (approximately 72% and approximately 30% vs approximately 25% and approximately 10% in control, p < 0.0001). Preischemic glycogen was significantly reduced in IP to 49% and increased in CP hearts to 127%. However, the lactate levels at the end of ischemia were similar in all the groups, indicating glucose utilization from extracellular space during ischemia in IP hearts. Thus, similar hemodynamic protection by CP and IP is observed despite increased energy depletion during ischemia in IP. IP and CP protection is expressed through better energetic status and by higher recovery of the TCA cycle activity or enhanced mitochondria-cytosol transport of alpha-ketoglutarate on reperfusion in addition to metabolic changes during ischemia. Glycogen store recovered significantly better in IP than in CP and Control. These results exhibit similar and improved postischemic hemodynamic protection by CP and IP. Increased recovery of postischemic glycogen pool is a protective feature of IP, whereas slightly higher lactate metabolism during reperfusion is a protection component of CP.

Adenosine Triphosphate↗

No evidence for infection of human embryonic stem cells by feeder cell-derived murine leukemia viruses.

Until recently, culture and expansion of nondifferentiated human embryonic stem cells (hESCs) depended on coculture with murine embryonic fibroblasts. Because mice are known to harbor a variety of pathogens, such culture conditions implicate the risk of xenozoonoses. Among these pathogens, endogenous retroviruses, including murine leukemia viruses (MuLVs), are of special importance. It is well known that some strains cause pathogenic (e.g., leukemic) effects and that xenotropic, polytropic, and amphotropic MuLVs are able to infect human cells. In view of potential clinical applications of hESC lines, it is therefore imperative to investigate potential infection of hESCs by mouse feeder cell-derived viruses. As a first step towards a comprehensive infection risk assessment, we have analyzed embryonic fibroblasts derived from different mouse strains for expression and release of xenotropic, polytropic, and amphotropic MuLVs. Moreover, several hESC lines have been investigated for expression of specific receptors for xenotropic/polytropic MuLVs, as well as for MuLV infection and expression. Evidence for expression of humantropic MuLVs was found in cultures of mouse embryonic fibroblasts (MEFs). Moreover, expression of specific receptors for xenotropic/ polytropic MuLV on human HEK293 and hESC lines and infection after coculture with an MuLV-producing mink cell line could be demonstrated. In contrast, no evidence of MuLV transmission from MEFs to human HEK293 cells or to the hESC lines I-3, I-6, I-8, and H-9 has been obtained. Our results suggest that recently established hESC lines are free of MuLV infections despite long-term close contact with MEFs.

Animals↗