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Biomedical subjects

N Roeder

Publications and source records attributed to N Roeder.

9 recordsLinked to original sources

T-cell and monocyte subsets, inflammatory molecules, rejection, and hemodynamics early after cardiac transplantation.

BACKGROUND: In the early period after cardiac transplantation, differential diagnosis of graft failure due to rejection, infection, and other causes is important but difficult. METHODS: In 22 consecutive patients undergoing heart transplantation, we prospectively determined levels of interleukin-6 as well as T-cell and monocyte subsets at eight points in time during biopsy and right heart catheterization and within 12 hr of echocardiography during the first 3 months after transplantation. RESULTS: Worse hemodynamic parameters, as characterized by dichotomization according to median values (pulmonary capillary wedge pressure >10 mmHg, mean pulmonary arterial pressure > 18 mmHg, pulmonary vascular resistance > 115 dyn x sec x cm(-5), right atrial pressure > 5 mmHg, cardiac index <3 L/min/m2, early mitral deceleration time < 135 msec, and isovolumic relaxation time <80 msec), were associated with higher levels of interleukin-6, C-reactive protein, polymorphonuclear cells, CD71+/CD14+ monocytes, and IgM levels and, in contrast, with lower levels of immunocompetence markers such as CD3+ T cells, CD4+ T cells, CD8+ T cells, CD3+/CD25+ T cells, CD4+/ CD45RO+ T cells, NK cells, and lower biopsy scores. CONCLUSION: Early after cardiac transplantation, elevated levels of inflammatory cells and soluble inflammatory molecules and lower levels of immunocompetence markers are associated with impaired allograft function in the absence of cellular rejection.

Adult

Transplant vasculopathy.

Transplant vasculopathy constitutes the major impediment to long-term survival in heart transplant recipients. Within the "response to immune injury" paradigm, it can best be understood as the resultant of an orchestrated recipient immune response to the initial allogenic stimulus by graft vascular endothelium. This response incorporates the elaboration of complex coordinated cytokine patterns and corresponding cell types including B-lymphocytes, T-helper1- and T-helper2-cells, cytotoxic T-cells, macrophages, and polymorphonuclear cells. These attack the alloantigenic vascular endothelium and lead, by complex cytokine signaling, to migration of donor smooth muscle cells from the media into the intima, associated with a switch from the contractile to a synthetic phenotype. In conjunction with recipient T-cells, macrophages, and lipids, the intimal fibroproliferative growth of the donor vessel is hereby initiated.

Animals

In vitro testing of bioprostheses: influence of mechanical stresses and lipids on calcification.

BACKGROUND: Structural valve deterioration of bioprostheses is mainly caused by the progressive development of calcification. Mechanical stresses or lipid deposits in porcine aortic leaflets have been proposed as major factors contributing to the calcification process. METHODS: A new test protocol consisting of nondestructive holographic interferometry, which allows a quantitative deformation analysis of heart valves, and accelerated dynamic in vitro calcification was used. The rapid calcification fluid contained a final combined calcium and phosphorus concentration of 130 (mg/dL)2 in barbital buffer solution. The calcification of 32 bioprostheses donated by different manufacturers (SJM Bioimplant, Biocor standard, Biocor No-React, Carpentier-Edwards SAV, Bravo, pericardial prototype) was assessed after up to 25 x 10(6) cycles by microradiography and the areas of calcification were compared with the holographic interferograms. The distribution of lipid droplets of four porcine prostheses were visualized by Sudan III stain before the calcification process. RESULTS: Most of the tested bioprostheses had areas presenting with stress concentrations, and the dynamic in vitro testing resulted in leaflet calcification corresponding to the holographic irregularities. A strong correlation between calcification and stress distribution or lipid accumulation was found (r = 0.72; r = 0.81, respectively). After 19 x 10(6) cycles, the Carpentier-Edwards SAV and the pericardial valves had significantly less calcification than other prostheses tested (p = 0.003), but the variation among individual prostheses from the same manufacturer was even more pronounced. CONCLUSIONS: Mechanical stresses or lipid accumulation seems to play an important role in the calcification process of bioprostheses. Quality control of bioprosthetic valves using holographic interferometry has the potential to predict calcification before implantation.

Aortic Valve

[Proinflammatory cytokines and cardiac pump function].

In situations of depressed myocardial function, the role of immunological mechanisms has been studied recently. In different pathophysiological situations, such as chronic heart failure, open heart surgery with extracorporal circulation, cardiac transplantation, myocardial infarction and angina pectoris, patterns have been described with elevation of proinflammatory cytokines, such as tumor necrosis factor-alpha, interleukin-1, interleukin-6, and reversible myocardial dysfunction, which may represent a final common pathway. The available data suggest a modulation of important determinants of pump function, i.e., contractility, preload, afterload, and heart rate, by cytokines. Potential mechanisms include the beta-adrenoceptor- and nitric oxide pathway, as well as a direct impact on intracellular calcium homeostasis. Interventional strategies based on this understanding are beginning to emerge.

Animals

Heart surgery in patients aged eighty years and above: determinants of morbidity and mortality.

Escalating medical costs, limitation of resources and the necessity to provide cost-effective medical care have created a need for systematic risk stratification and cost-benefit analyses in the background of an ongoing discussion. Results of heart surgery in octogenarians have been evaluated in a prospective single-center, study since 1990. 101 consecutive patients (55/ 101 = 54.5% female) aged 80 years and above (median: 81 years; interquartile range [IQR]: 80.0-82.5, total range [TR]: 80-92 years) undergoing open heart surgery at our institution between January 1990 and March 1996 were included into this prospective study. Prior to surgery, most patients were severely symptomatic being in functional NYHA classes either III (56.4%) or IV (31.7%). 61/101 (60.4%) patients underwent isolated coronary artery bypass grafting (CABG), 23 (22.8%) had aortic valve replacement (AVR), 14 patients (13.9%) had CABG combined with AVR or double valve replacement and 3 (3.0%) had mitral valve repair. Follow-up (median: 23.0 months. IQR: 10.5-39.0, TR: 1-72) was focused on long-term morbidity and quality of life. The impact of preoperative and operative risk factors on morbidity and mortality was determined by uni- and multivariate statistical analysis. The 30-days overall mortality in this study was 7.9%. The postoperative course was uneventful for 27 (26.7%) of our patients. Univariate risk factors of postoperative mortality were: left main stem disease (p < or = 0.044), ejection fraction < 45% (p < or = 0.006), preoperative intensive care unit (ICU) (p < or = 0.002), urgent or emergency operation (p < or = 0.034). The only independent predictor of operative mortality was preoperative ICU-stay (p < or = 0.008). Significant risk factors for the number of postoperative complications in the multivariate analysis were: prior stroke (p < or = 0.04), diabetes mellitus (p < or = 0.02), New York Heart Association (NYHA) class IV symptoms (p < or = 0.002) and prolonged cross-clamping time (p < or = 0.001). Mean postoperative length of stay in the ICU was 3.9 +/- 3.9 days. Late morbidity was not related to postoperative complications. Cumulative survival was 87.9%, 79.5% and 72.9% at one, two or five years, respectively. After hospital discharge, 67/93 patients (82.8%) were in NYHA functional class I or II. Cardiac surgery in very elderly patients can be performed with acceptable operative risk and a favorable long-term outcome. The individual patient risk-profile including significant co-morbid conditions and severity of the heart disease predicts not only survival but the extent of perioperative morbidity.

Aged

[Internal quality assurance--Munster experiences].

Medical data monitoring is an effective tool to insure high quality and efficient performance of health care providers. In the Department of Thoracic and Cardiovascular Surgery of the University of Muenster this is based on a comprehensive data management system. This system has been custom tailored to enable optimal monitoring of quality, performance and cost aspects based on access to all available data. Data acquisition is achieved online and allows for continuous data analysis. This data monitoring is the basis for objective quality control of medical performance as well as for the evaluation of the impact of politically induced economic restrictions on the quality of care.

Cardiovascular Surgical Procedures

Heart transplant candidates at high risk can be identified at the time of initial evaluation.

The increasing discrepancy between the numbers of patients selected for cardiac transplantation and the available donor organs requires validation of markers of high risk at the time of initial evaluation that may help to determine which patients profit from aggressive therapy. We retrospectively examined the case records of 91 heart transplant candidates selected out of a total of 140 consecutive patients referred for evaluation. Of these 91 patients, 48 were transplanted during follow-up. Of the remaining 43 patients, 25 died after a mean survival time of 1.6 +/- 2.5 months. The causes of death were pump failure in 18 (72%) and sudden cardiac death in 7 (28%). Multivariate analysis identified 4 out of 26 parameters at initial evaluation that distinguished the 25 nonsurvivors from the 18 survivors. These were: mean arterial pressure (P = 0.03), pulmonary capillary wedge pressure (P = 0.002), mean pulmonary artery pressure (P = 0.001), and fractional shortening (P = 0.007). The mode of death could not be predicted. We conclude that there are prognostic markers at initial evaluation that allow more restrictive selection of patients for cardiac transplantation and mechanical bridging.

Adult

[Operations in limited left ventricular pump function].

The proportion of patients with left ventricular dysfunction (LVD) undergoing open heart surgery is increasing. In this patient group, the perioperative risk is elevated because of the preexisting pathophysiology. Detailed evaluation, interdisciplinary differential therapeutic considerations on the basis of the comparative benefit rationale as well as hemodynamic, antiischemic and antiarrhythmic optimization is mandatory. To plan the operation in patients with coronary artery disease, the issue of reversibility of LVD has to be resolved by sophisticated viability testing. The ultimate decision on revascularization versus aneurysmectomy and scar excision has to be met by the operating surgeon. If the patient's hemodynamics is severely compromised, the perioperative risk may be too high and cardiac transplantation, possibly with mechanical bridging, should be considered. If, in addition, intractable malignant tachyarrhythmias are encountered, antitachycardia operation and defibrillator implantation may be performed. During extracorporeal circulation which is associated with a systemic inflammatory response syndrome the compensatory potential is reduced in patients with LVD, and therefore, the risk of complications such as low-output syndrome, respiratory and renal failure is elevated. Advances in the understanding of pathophysiological mechanisms, an individualized preoperative tailored medical and mechanical therapy for preparation of the operation, anesthesiologic management, cardioprotection and postoperative intensive care have contributed to improvement of outcome in this patient group. Specifically patients with documented evidence of myocardial viability such as angina have profited from surgical revascularization as compared to medical therapy in large scale prospective trials. Perioperative mortality has been lowered to 2-20%. In the absence of angina and presence of overt heart failure and arrhythmias, however, the postoperative 3- and 5-year prognosis of 60% and 35%, respectively, continues to be reduced. Improvement of ejection fraction, angina class, functional capacity and quality of life has been documented in all studies. In conclusion, cardiac operations in patients with left ventricular dysfunction can nowadays be performed with a reasonable risk-benefit ratio, if a careful individualized preoperative evaluation and optimal pre-, intra-and postoperative management is performed.

Coronary Disease

[Cost/benefit relations in heart transplantation].

The expanding role of cardiac transplantation as well as mechanical and antiarrhythmic bridging requires a critical reflection of the economic impact of these therapeutic modalities. Based on assumptions from the pertinent literature, cardiac transplantation requires costs of about 55,000 DM per year of life gained by the procedure. Even if a maximum social and professional reintegration percentage of about 60% is assumed, it does not seem possible to perform the procedure without additional costs to the health care system. The consequences of this are the following: 1) Cardiac transplantation should only be performed by centers experienced in all aspects of terminal heart failure care including a heart failure program, high-risk conventional surgery program, mechanical and antiarrhythmia bridging program, and qualified post transplant care program. 2) In order to evaluate potentially cost-saving therapeutic strategies in cardiac transplantation, multicenter trials have to be conducted which require a continuous scientific working group and research data organization based on the consensus of all participating transplant centers. 3) An improved professional reintegration program is necessary. 4) The ethical foundation for offering cardiac replacement to patients, namely, the responsibility for the individual person's well-being, has to be emphasized by physicians active in the field. 5) The society as a whole, not the group of physicians active in the field, has to debate and decide on how many resources should be spent in this field of health care. 6) Since potential cardiac transplant recipients are, to a large extent, recruited from patients suffering from coronary artery disease, it is essential to incorporate a primary preventive perspective into this high-technology field of medicine.

Adult