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W von Scheidt

Publications and source records attributed to W von Scheidt.

At least 19 recordsLinked to original sources
PubMed2000

Coronary artery disease in the transplanted heart.

Coronary artery disease in the transplanted heart limits the long-term success of cardiac transplantation. Intravascular ultrasound studies reveal a dual morphology with donor-transmitted and de novo plaques. Coronary vasomotor dysfunction may occur independently of morphological alterations. The disease is characterized by the interaction of activated T lymphocytes with cytokines and donor epicardial and microvascular endothelium. Various noxious stimuli contribute to the continuing inflammatory response. Consequently, adhesion molecule expression is upregulated, leukocytes migrate into the allograft, thrombocytes accumulate, and growth factors are expressed, finally resulting in functional and morphological chronic allograft lesions. Blocking the activation of T cells, CD4+ cytokines, and adhesion molecules may prevent endothelial injury and subsequent intimal thickening. Strategies to decrease the formation of anti-endothelial and anti-HLA-DR antibodies may also be protective, as may antiproliferative drugs, augmentation of endogenous nitric oxide bioactivity, and new immunosuppressive regimens. Revascularization procedures have a limited role in treating significant focal lesions. Retransplantation, the only definitive treatment, remains ethically controversial.

Animals↗
PubMed1999

Modulation of coronary vasomotor tone by cytokines in cardiac transplant recipients.

BACKGROUND: Upon exposure to cytokines, endothelial cells may undergo profound alterations of vasomotor function. In this study, we characterized the relationship between coronary epicardial and microvascular vasomotor function and expression of specific cytokine patterns in human heart transplant recipients. METHODS: We studied 49 cardiac transplant recipients, without acute rejection or infection at an average of 6+/-3 months after transplantation. Coronary resistance vessel function was measured in an endothelium-dependent manner with acetylcholine (5 and 150 microg/5 min; intracoronary injection) and in an endothelium-independent manner with adenosine (400 and 800 microg/5 min; intracoronary injection) using an intracoronary Doppler flow wire. Simultaneous epicardial diameter changes were measured using quantitative coronary angiography. Coronary sinus and aortic serum levels of soluble interleukin (IL)-2 receptor and soluble tumor necrosis factor-a receptors (sTNF-R1 and sTNF-R2), TNF-alpha, and IL-6 were determined. Transcardiac cytokine release (coronary sinus minus aortic levels) was correlated with coronary vasomotor function. RESULTS: The highest amounts of cardiac cytokine release were observed for IL-6 (32+/-14% increase) and sTNF-R1 (26+/-13% increase). A significant inverse correlation between microvascular endothelial function and cardiac release of soluble IL-2 receptor (P=0.04) and IL-6 (P=0.03) was detected, whereas a positive correlation was observed to sTNF-R1 (P=0.004). Distal epicardial endothelial vasomotion was inversely correlated to transcardiac sTNF-R2 release (P=0.03). CONCLUSIONS: Cytokine production and activation, a common phenomenon early after heart transplantation, is related at least in part to endothelial vasomotor dysfunction of the epicardial and microvascular compartment. These results support the hypothesis that coronary endothelial dysfunction after cardiac transplantation is an immunologic phenomenon. Since endothelial dysfunction seems to be a crucial step in the pathogenesis of cardiac allograft vasculopathy, coronary cytokine suppression should be a therapeutic target of improved future immunosuppressive regimens.

Adult↗
PubMed1999

[Pharmacological testing of the reversibility of increased pulmonary vascular resistance before heart transplantation with prostaglandin I2 (prostacyclin)].

An increased pulmonary vascular resistance (PVR) or an increased transpulmonary gradient (TPG) is a risk factor for increased 3-day and 3-month mortality after heart transplantation (HTx). The reversibility of increased PVR or TPG under pharmacologic testing is supposed to indicate a decreased probability of right ventricular failure/death after transplantation. We tested the response of an increased PVR (> 2.5 Wood units, WU) and/or of an increased TPG (> 15 mm Hg) in 29 right heart catheterizations (thermodilution catheter) of 23 patients (54 +/- 8 years, mean NYHA-class 3.1 +/- 0.6, ischemic n = 8, dilated cardiomyopathy n = 15). Increasing doses of prostaglandin I2 (PGI2, mean maximum dose 13.5 +/- 6.4 ng/kg/min) were applied stepwise over at least 10 min at the maximum dose level. We analyzed any dependence of the reversibility of PVR and TPG under prostaglandin I2 on hemodynamic values, echocardiographic parameters, demographic data, and laboratory findings. A decrease of PVR to a range usually accepted as no contraindication for HTx (< or = 4 WU) was found in each patient without symptomatic systemic hypotension during application of PGI2 (baseline value: 4.7 +/- 1.3 WU, during PGI2: 2.3 +/- 0.6 WU). An unresponsive, fixed increased PVR or TPG was not observed using PGI2. In 62% of investigations, both PVR and TPG decreased below 2.5 WU and 15 mmHg, respectively. The extent of reversibility of PVR and TPG was individually different and did not depend on the mean pulmonary artery pressure, mean capillary wedge pressure, cardiac output, mean systemic artery pressure or echocardiographic parameters (EDD, FS, ES-distance), sodium, urea or bilirubin levels, medication, age of the patients or the duration of the disease. The baseline PVR correlated inversely with its percentile value during PGI2 (r = -0.76, p < 0.05). In advanced heart failure, PGI2 decreases PVR in ranges of lower risk concerning orthotopic HTx, without causing an intolerable systemic hypotension. The individual extent of reversibility of PVR and TPG under PGI2 is not influenced by basic hemodynamic parameters or the patient's demographic profile.

Dose-Response Relationship, Drug↗
PubMed1999

Combination therapy with tacrolimus and mycophenolate mofetil following cardiac transplantation: importance of mycophenolic acid therapeutic drug monitoring.

BACKGROUND: Interest has recently been expressed in tacrolimus and mycophenolate mofetil (MMF), two potent immunosuppressants, for a variety of transplant indications. The efficacy of this combination was assessed as primary therapy following cardiac transplantation. METHODS: Forty-five patients were enrolled; 15 into Phase I and 30 to Phase II of the study. Intravenous tacrolimus was administered for 2-3 days to all patients prior to conversion to oral therapy; target blood concentrations were 10-15 ng/mL. Treatment also consisted of steroids and MMF. During Phase I, a fixed 2 g/day dose of MMF was given whilst doses were adjusted according to mycophenolic acid (MPA) plasma levels during Phase II (target range 2.5-4.5 microg/mL). Mean follow-up was 696 +/- 62 days and 436 +/- 88 days for Phases I and II, respectively. RESULTS: Phase I: Patient survival was 100%. Rejection was diagnosed in 66.7% of patients (mean number of episodes per patient 1.33 +/- 1.18). Retrospective analyses indicated that whereas mean MPA plasma levels >3.0 microg/mL were not associated with rejection, no correlation was found with tacrolimus blood concentrations. Phase II: A survival rate of 96.7% was evident, one patient having died from aspergillosis. Diagnoses of rejection were made in 10.0% of patients (0.10 +/- 0.31 episodes per patient) and confounding factors were present in all 3 cases. MPA trough levels were 1.0 +/- 0.3 microg/mL at this time. Resolution was apparent following pulse steroid therapy. Steroids were successfully withdrawn from all patients who completed 6 months' treatment. CONCLUSIONS: Combination therapy with tacrolimus and MMF is associated with suppression of acute myocardial rejection; however, this is dependent upon routine therapeutic drug monitoring.

Adolescent↗
PubMed1999

Functional significance of cardiac reinnervation in heart transplant recipients.

BACKGROUND: There is accumulating evidence of structural sympathetic reinnervation after human cardiac transplantation. However, the functional significance of reinnervation in terms of exercise capacity has not been established as yet; we therefore investigated the influence of reinnervation on cardiopulmonary exercise testing. METHODS: After orthotopic heart transplantation 35 patients (mean age, 49.1 +/- 8.4 years) underwent positron emission tomography with scintigraphically measured uptake of C11-hydroxyephedrine (HED), lung function testing, and cardiopulmonary exercise testing. Two groups were defined based on scintigraphic findings, indicating a denervated group (n = 15) with a HED uptake of 5.45%/min and a reinnervated group (n = 20) with a HED uptake of 10.59%/min. RESULTS: The two study groups did not show significant differences with regard to anthropometric data, number of rejection episodes, preoperative hemodynamics, and postoperative lung function data. The reinnervated group had a significant longer time interval from transplantation (1625 +/- 1069 versus 800 +/- 1316 days, p < .05). In transplant recipients with reinnervation, heart rate at maximum exercise (137 +/- 15 versus 120 +/- 20 beats/min, p = .012), peak oxygen uptake (21.0 +/- 4 versus 16.1 +/- 5 mL/min/kg, p = .006), peak oxygen pulse (12.4 +/- 2.9 versus 10.2 +/- 2.7 mL/min/beat, p = .031), and anaerobic threshold (11.2 +/- 1.8 versus 9.5 +/- 2.1 mL/min, p = .046) were significantly increased in comparison to denervated transplant recipients. Additionally, a decreased functional dead space ventilation (0.24 +/- 0.05 versus 0.30 +/- 0.05, p = .004) was observed in the reinnervated group. CONCLUSIONS: Our study results support the hypothesis that partial sympathetic reinnervation after cardiac transplantation is of functional significance. Sympathetic reinnervation enables an increased peak oxygen uptake. This is most probably due to partial restoration of the chronotropic and inotropic competence of the heart as well as an improved oxygen delivery to the exercising muscles and a reduced ventilation-perfusion mismatching.

Adult↗
PubMed1999

Endothelin in coronary endothelial dysfunction early after human heart transplantation.

BACKGROUND: Cytokines and growth factors released as part of the immune response to alloantigenic stimuli are capable of regulating endothelin-1 expression in the allograft. Endothelin plays a significant role as a modulator of coronary vascular reactivity in the early stages of atherosclerosis and may be important as a participant in and marker for cardiac allograft vasculopathy. METHODS: We characterized a possible relationship between morphological and functional coronary changes, transcardiac plasma endothelin level and myocardial endothelin-mRNA expression in 33 cardiac transplant recipients in the early, stable phase 5+/-3 months after orthotopic heart transplantation. Coronary microvascular function was determined as endothelium-dependent with acetylcholine and endothelium-independent with adenosine using intracoronary Doppler-FloWire. The percentage of the epicardial diameter changes was measured using quantitative coronary angiography. Intravascular ultrasound was performed to quantify intimal hyperplasia. Cardiac endothelin uptake or release was determined by measuring plasma endothelin levels in the coronary sinus and aorta. Myocardial endothelin-gene expression was determined using semiquantitative RT-PCR. RESULTS: The aortic endothelin levels were significantly increased in transplant recipients compared to nontransplanted patients (11.8+/-2.2 vs 7.2+/-0.9 fmol/mL; P < 0.001). Endothelin uptake was noticed in the majority of patients, and the amount of endothelin uptake was correlated to microvascular (r = 0.37; P < 0.05) and epicardial (r = 0.41; P < 0.03) endothelium-dependent vasodilatation. High mRNA signal intensity was associated with significantly reduced coronary flow response to acetylcholine compared to patients with low myocardial gene expression (coronary flow reserve 2.4+/-0.9 vs 3.4+/-0.8, respectively; P < 0.005). Morphological coronary changes early after transplantation were not correlated to endothelin plasma levels or myocardial gene expression. CONCLUSION: Coronary endothelial vasomotor dysfunction after cardiac transplantation is associated with an increased myocardial endothelin mRNA expression and decreased endothelin-uptake by the heart. We postulate that early activation in the endothelin system may have a pivotal role in the acceleration of the atherosclerotic process in transplant patients.

Adult↗
PubMed1999

Lung function and cardiopulmonary exercise performance after heart transplantation: influence of cardiac allograft vasculopathy.

STUDY OBJECTIVE: The reduced exercise capacity observed in most patients after heart transplantation may be due to treatment with immunosuppressive drugs, deconditioning, cardiac denervation, and graft rejection. Cardiac allograft vasculopathy (CAV) is presently the major factor limiting long-term survival after transplantation. Little information is available with regard to the relationship between CAV and functional impairment in these patients. DESIGN: Prospective. SETTING: A university hospital and a large transplant center. PATIENTS: About 37+/-5 months (range, 2 to 137 months) after orthotopic heart transplantation, 120 patients underwent lung function testing, cardiopulmonary exercise testing, and right and left heart catheterization. Significant CAV was defined as a stenosis > or =70% or severe diffuse obliteration in any of the three main vessels. Group I (n = 28) had a significant CAV; group II (n = 92), without a remarkable CAV, was the control group. MEASUREMENTS AND RESULTS: Overall, the maximum heart rate was 86+/-2% of what was predicted, and the peak oxygen consumption was 18.8+/-0.7 mL/kg/min (64% of that predicted). Groups I and II did not show significant differences with regard to anthropometric data, hemodynamic measurements, or number of rejection episodes. Group I exhibited significant differences in maximum heart rate (120+/-5 vs. 134+/-3 beats/min; p<0.01), work capacity (47+/-5% vs. 59+/-3%; p<0.05), peak oxygen uptake (16+/-1 vs. 20+/-1 mL/min/kg; p<0.01), and functional dead space ventilation (31+/-2 vs. 26+/-1; p<0.01). Pretransplant status, etiology of heart failure, ischemic time, and the number of rejection episodes did not correlate with any exercise parameter. CONCLUSIONS: Following heart transplantation, patients with significant CAV show a diminished exercise capacity, a reduced oxygen uptake, and a ventilation-perfusion mismatch. Thus, CAV may be a major factor limiting exercise capacity in heart-transplant patients.

Adult↗
PubMed1998

[The role of echocardiography in preoperative diagnosis of cardiac risk in patients before non-cardiac surgical interventions].

Echocardiography is a noninvasive method for cardiac evaluation. A review of the current literature shows that the routine use of echocardiography for assessing perioperative cardiac risk in patients undergoing noncardiac surgery can not be supported. Only patients with suspected relevant heart valve diseases, acute heart failure, cardiomyopathy or condition after heart or heart-lung transplantation may benefit from preoperative echocardiography. In patients with suspected or proven coronary artery disease stress echocardiography offers the most relevant additional information for the anaesthesiologist. However, because of the high financial and personal implications it should be reserved to those patients who are not able to perform a normal stress test. Besides in patients in whom transthoracic echocardiography doesn't offer sufficient information or is not possible transesophageal echocardiography plays only a minor role in preoperative cardiac evaluation.

Echocardiography↗
PubMed1998

Endothelium-dependent microvascular vasomotion and its correlation with vasoactive mediators early after cardiac transplantation in humans.

Endothelial dysfunction precedes and predicts transplant vasculopathy. We investigated the relationship between endothelial dysfunction and the vasoactive mediators nitric oxide and endothelin, 33.7 +/- 2.0 days after heart transplantation. Coronary flow was measured in 18 patients to determine the endothelial microvascular vasomotor response to acetylcholine. Endomyocardial biopsies were taken to determine the levels of gene expression of isozymes of endothelin and nitric oxide synthases (NOS). Blood samples from the coronary sinus and aorta were withdrawn for measurement of endothelin, nitrite and cytokines. Five patients (30%) showed an impaired coronary flow reserve response to acetylcholine, significantly higher inducible NOS gene expression and significant transcardiac nitrite production. Plasma nitrite correlated with tumour necrosis factor-alpha levels in coronary sinus and a transcardiac net extraction of endothelin was noted in all patients. In conclusion, 30% of patients develop endothelial dysfunction early after heart transplantation; this correlates with the expression and activation of vasoactive and immunomodulatory mediators, which may predict the development of transplant vasculopathy.

Endothelin-1↗
PubMed1998

Conservative treatment of a paracardial abscess following post-infarct patch grafting.

A patient with previous patch grafts at the site of a ventricular aneurysm and over an ischaemic septal defect presented with an oval hypodense mediastinal mass consistent with a mediastinal abscess with blood cultures positive for Staphylococcus aureus. Surgical re-operation in this region was considered to be too risky and conservative treatment was pursued. Antibiotics were continued for a total of nearly 5 months of treatment. A computed tomographic scan prior to discharge indicated that the abscess was completely resolved.

Abscess↗
PubMed1998

The continuing challenge of cardiac transplant arteriosclerosis.

Coronary arteriosclerosis of the graft, a manifestation of CAV, continues to limit the long-term success of cardiac transplantation. It is characterized by vascular injury induced by a variety of noxious stimuli, including the humoral and cellular immune system response to the allograft, ischemia-reperfusion injury, viral infection, immunosuppressive drugs, and classical risk factors. The proliferative and obstructive vascular lesions are thought to develop through repetitive endothelial injury followed by repair response. T lymphocytes, macrophages and neutrophils migrate to the subendothelial area via the activity of endothelial adhesion molecules, and, in turn, produce various cytokines and growth factors which cause progression of the process. Development of anti-endothelial antibodies may progress CAV in specific settings. Intravascular ultrasound studies reveal a dual morphology with donor-transmitted or de novo focal, noncircumferential plaques in proximal segments and/or a diffuse, concentric pattern of intimal proliferation observed in distal segments. In addition to the morphological alterations, functional endothelial and smooth muscle cell alterations may occur independently and transiently. The use of cyclosporine A levels > 3 mg/kg/day, HMG-CoA-reductase inhibitors and calcium antagonists has been shown to decrease the progression of CAV. Strategies for blocking T-cell costimulation and expression of adhesion molecules, cytokines and antiendothelial antibodies, as well as, antiproliferative drugs, methods to augment endogenous nitric oxide bioavailability and newer immunosuppressive regimens may be protective to endothelial injury and subsequent development of CAV. Revascularization procedures have an established, but very limited role in the setting of significant focal lesions. The ethical dilemma surrounding retransplantation, however, is considerable because of the scarcity of donor hearts.

Animals↗
PubMed1997

Aggressive lowering of fibrinogen and cholesterol in the prevention of graft vessel disease after heart transplantation.

BACKGROUND: A combined treatment of statins and extracorporeal H.E.L.P.-apheresis (Heparin-mediated Extracorporeal LDL/fibrinogen Precipitation) has already been shown to be beneficial for coronary artery disease (CAD). Presumably high levels of LDL cholesterol, Lp(a), and fibrinogen also increase the risk for graft vessel disease (GVD). Therefore, we studied whether this concept can be applied in GVD, based on the hypothesis that GVD is an accelerated form of CAD. METHODS AND RESULTS: For comparison of statin treatment alone with the combined treatment, two matched groups of 10 cardiac transplant recipients were studied during a mean period of 3.6+/-1.0 years. Both groups were comparable in clinical characteristics, immunosuppressive medication, baseline plasma Lp(a), and high fibrinogen levels. Group I had normal LDL-C levels (3.36+/-0.60 mmol/L). Simvastatin alone was administered in this group to counteract the LDL-increasing effect of the immunosuppressive medication. Group II had marked hypercholesterolemia (LDL-C, 6.07+/-1.89 mmol/L), which was treated, in addition to simvastatin, with H.E.L.P.-apheresis weekly. GVD was assessed by coronary angiography. Simvastatin alone kept LDL-C levels within baseline limits but could not prevent GVD in 7 of 10 patients. In contrast, the combined treatment prevented GVD in 9 of 10 patients (P=.006) by simultaneous and drastic reduction of 48% LDL-C (P=.006), 35% fibrinogen (P=.002), and 47% Lp(a) (P=.006) below baseline. Both treatments were well tolerated and did not affect prevention of graft rejection and infections. CONCLUSIONS: A strategy of early, drastic lowering of fibrinogen, LDL-C, and Lp(a) helps to prevent GVD.

Adult↗