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Biomedical subjects

W von Scheidt

Publications and source records attributed to W von Scheidt.

At least 19 recordsLinked to original sources
PubMed2001

Expression of endomyocardial nitric oxide synthase and coronary endothelial function in human cardiac allografts.

BACKGROUND: Inducible nitric oxide synthase (iNOS) is expressed and is functionally active in the presence of transplant arteriosclerosis. However, the early involvement of iNOS in alterations of microvascular endothelial function in the absence of preexisting lesions remains unclear; this information would be of prognostic value. We studied the course of iNOS mRNA expression, transcardiac nitric oxide production, and their potential association with microvascular coronary endothelial dysfunction in human cardiac allografts. METHODS AND RESULTS: A total of 42 patients were studied at 1, 6, and 12 months after heart transplantation. Microvascular coronary flow velocity reserve (CFVR) was tested in an endothelium-dependent (acetylcholine) and -independent manner (adenosine) using a Doppler flow wire. Endomyocardial iNOS expression was determined by reverse transcription polymerase chain reaction. iNOS protein and nitrotyrosine levels were detected by immunohistochemistry. Transcardiac plasma nitrite/nitrate (NOx) levels were measured by the Griess reaction. CFVR was impaired in 26.1% of patients (n=11) at 1 month and in 31% of patients (n=13) at 12 months after heart transplantation. Patients who developed impaired CFVR in the first year showed a significant increase in iNOS gene expression. Patients with impairment of CFVR 1 month after heart transplantation had higher levels of iNOS mRNA than patients with a normal CFVR. Patients with an initial impairment of CFVR who did not improve over time presented with significantly higher iNOS mRNA levels. iNOS protein and nitrotyrosine were expressed in the endomyocardial vessels of patients with impaired CFVR. Transcardiac NOx release was higher in patients with impaired CFVR. CONCLUSIONS: In human cardiac allografts, microvascular endothelial dysfunction is associated with an enhanced endomyocardial iNOS mRNA expression and higher transcardiac NOx production and is accompanied by the expression of nitrotyrosine protein, suggesting peroxynitrite plays a role in the disease process. The data from the present study suggest an important role for the iNOS/nitric oxide pathway in the regulation of microvascular function in the absence of preexisting atherosclerotic lesions.

Acetylcholine↗
PubMed2001

Simvastatin treatment is associated with improvement in coronary endothelial function and decreased cytokine activation in patients after heart transplantation.

OBJECTIVES: This study was designed to assess the association between 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibition, coronary endothelial function and cytokine activation in heart transplant recipients without angiographically detectable disease. BACKGROUND: Coronary endothelial dysfunction contributes to cardiac allograft vasculopathy. The vasoprotective effects of statins in heart transplant recipients may include restoration of endothelial function and suppression of allograft inflammatory activity. METHODS: Heart transplant recipients (one to three years after heart transplant) were divided into three groups based on the total cholesterol levels: group 1 (n = 21), patients with a history of hypercholesterolemia adequately controlled with simvastatin; group 2 (n = 19), patients with hypercholesterolemia not adequately treated with simvastatin; and group 3 (n = 40), patients without hypercholesterolemia. Coronary vasomotor function and intimal thickness as well as coronary sinus and aortic cytokine concentrations (tumor necrosis factor [TNF]-alpha, interleukin [IL]-6 and soluble IL-2 receptor) were investigated. In a prospective one-year follow-up study, changes in coronary endothelial function and cytokine levels were compared between 11 hypercholesterolemic patients treated with simvastatin and 9 controls. RESULTS: Epicardial and microvascular endothelial functions were better in groups 1 and 3 than they were in group 2 (p < 0.01 and p < 0.05). Transcardiac IL-6 and TNF-alpha gradients were significantly increased in groups 2 and 3 compared with group 1 (IL-6: p < 0.05; TNF-alpha: p < 0.01). Plaque areas were significantly increased in groups 1 and 2 (p < 0.05 vs. group 3), whereas lumen area was increased in group 2 compared with group 1 (p < 0.05), demonstrating adaptive vascular remodeling. In patients treated with simvastatin, coronary endothelial function and cardiac cytokine activity significantly improved during the one-year follow-up. CONCLUSIONS: Inhibition of allograft inflammatory activity and attenuation of the coronary endothelial dysfunction observed in cardiac transplant recipients during treatment with simvastatin may represent an important mechanism by which HMG-CoA reductase inhibitors protect against the development of cardiac allograft vasculopathy.

Coronary Angiography↗
PubMed2001

Coronary flow reserve and nitric oxide synthases after cardiac transplantation in humans.

OBJECTIVE: Coronary endothelial dysfunction may precede morphological changes in both the epicardial conduit and microvascular resistance vessels in heart transplant recipients. Since the development of transplant atherosclerosis is the major limiting factor for long-term survival, the identification of early mediators of vasomotor dysfunction may be of therapeutic interest. We therefore investigated the potential relationship between the expression of nitric oxide synthases (NOS) and coronary endothelial function in human cardiac transplant recipients over time. METHODS: Forty-two human cardiac transplant recipients were studied at 1 and 12 months after heart transplantation (HTx). The microvascular coronary flow velocity reserve (CFVR) was tested for endothelium-dependent (acetylcholine) and -independent (adenosine) stimuli by intravascular Doppler flow-wire. Epicardial diameter changes were evaluated by quantitative coronary angiography. Endomyocardial inducible (iNOS) and endothelial constitutive nitric oxide synthase were determined by RT-PCR. Nitric oxide production (nitrite and nitrate (NOx)) and TNF-alpha were measured in plasma samples from the aorta and coronary sinus. RESULTS: CFVR was impaired in 26.1% (n=11) of patients at 1 month and in 31% (n=13) 12 months after HTx. iNOS-mRNA levels were significantly higher in patients with impaired endothelium-dependent CFVR. In addition, only in these patients were TNF-alpha levels higher and these correlated with plasma NOx levels at 1 and 12 months post-HTx (1 month: r=0.81, P=0.001; 12 months: r=0.62, P=0.04). CONCLUSIONS: Coronary microcirculatory dysfunction in response to acetylcholine is present in nearly 30% of patients during the first year following transplantation. These patients present with higher iNOS-mRNA expression and TNF-alpha plasma levels. Selective modulation of the TNF-alpha/iNOS-pathway may be of therapeutic value to improve coronary endothelial dysfunction in cardiac transplant recipients.

Adult↗
PubMed2001

Reappearance of cardiac presynaptic sympathetic nerve terminals in the transplanted heart: correlation between PET using (11)C-hydroxyephedrine and invasively measured norepinephrine release.

UNLABELLED: Previously, sympathetic reinnervation of the transplanted heart has been described using invasive catheterization techniques and noninvasive radionuclide imaging techniques. However, little is known about the agreement between these 2 methods. Thus, correlation between (11)C-hydroxyephedrine (HED) PET and invasively measured norepinephrine (NE) release was investigated in transplant recipients in this study. METHODS: Using PET and the catecholamine analog HED, 17 patients were studied between 2 mo and 13.6 y after transplantation. Based on results in completely denervated hearts, areas with HED retention >7%/min were defined as reinnervated. Additionally, transcardiac NE release induced by intravenous tyramine (55 microg/kg) was measured by coronary sinus and aortic catheterization within 1 wk of the PET study. NE levels between coronary sinus and aortic root, DeltaNE(CS-AO), were calculated at baseline and after tyramine administration. Differences of more than 3 SD of baseline (>163 pg/mL) were interpreted as reinnervation. RESULTS: HED retention indicated reinnervation in 10 patients. Maximal HED retention ranged from 4.3%/min to 16.4%/min. DeltaNE(CS-AO) 1 min after tyramine administration ranged between -10 pg/mL and 1157 pg/mL, and 8 patients were above the reinnervation threshold. Fisher's exact test demonstrated good agreement between results of PET and DeltaNE(CS-AO) measurements (P = 0.002). Maximal HED retention was also significantly correlated with NE release (r = 0.69; P = 0.001). CONCLUSION: Results of invasively measured NE release and noninvasive (11)C-HED PET are well correlated. This study further supports the usefulness of PET as a noninvasive approach for detection of reappearance of catecholamine uptake sites after heart transplantation.

Adrenergic Fibers↗
PubMed2000

Effects of Celsior and University of Wisconsin preservation solutions on hemodynamics and endothelial function after cardiac transplantation in humans: a single-center, prospective, randomized trial.

Optimal preservation of the myocardium remains a major concern in clinical and experimental heart transplantation. The present study compared the efficacy of University of Wisconsin (UW) and Celsior preservation solution with respect to myocardial performance, epicardial and microvascular endothelial vasomotor function and myocardial expression of endothelin and nitric oxide synthases in humans. Forty-one cardiac transplant recipients received either UW (n = 20) or Celsior (n = 21) preserved hearts. Catecholamine and vasodilator requirements were assessed within the first 5 postoperative days. Left ventricular performance and endothelial function was assessed 1 month after transplantation. Endothelin and nitric oxide synthase gene expression were detected in myocardial biopsy samples. Celsior preserved hearts required significantly more catecholamines and vasodilators within the first 5 postoperative days. Myocardial performance and endothelial function were comparable 1 month after transplantation. Total ischemic time correlated with impaired endothelial function in the Celsior but not in the UW group. Endothelin and inducible nitric oxide synthase gene expression were significantly higher in the Celsior group. The results of the study show that both solutions provide myocardial protection with regard to left ventricular performance and endothelial function 1 month after cardiac transplantation. The necessity for higher vasodilator and catecholamine therapy in Celsior preserved hearts suggests post-ischemic myocardial stunning within the first 5 postoperative days. The positive correlation between impaired endothelial function and total ischemic time in the Celsior group requires longitudinal investigation in particular with regard to the development of allograft vasculopathy.

Adenosine↗
PubMed2000

An association between microvascular endothelial dysfunction, transcardiac nitric oxide production and pro-inflammatory cytokines after heart transplantation in humans.

Endothelial dysfunction anticipates the development of transplant coronary artery disease (TxCAD) observed more than 1 year after transplantation (HTx). We investigated whether in patients early after HTx myocardial inducible and constitutive nitric oxide synthases (iNOS; cNOS) are expressed and cardiac nitric oxide production occurs. Moreover, a possible relationship to alterations in endothelium dependent and independent vasomotor function was assessed. Forty-two transplant recipients were studied 37 +/- 5 days after HTx. Microvascular coronary flow velocity reserve (CFVR) was tested endothelium dependent (acetylcholine; 30 microg/min x 5 min/i.c.) and independent (adenosine; 160 microg/min x 5 min/i.c.) by Doppler flow wire. Flow velocity increase by a factor greater than 2 was considered normal. Quantitative coronary angiography was used to assess epicardial vasomotor function in response to the same stimuli. Myocardial iNOS and cNOS gene expression were detected by semiquantitative reversed transcriptase polymerase chain reaction. Plasma nitrite levels (microM) were measured by spectrophotometry. Cytokines (TNF-alpha, IL-6; pg/ml) were measured by enzyme linked immunosorbent assay. In 26.1% of patients (n = 11; group A) an impaired endothelium dependent CFVR (1.65 +/- 0.23 increase) was observed; in 73.9% (n = 31, group B) a normal endothelium dependent CFVR (3.0 +/- 0.7 increase; P = 0.003) was observed. Myocardial iNOS and cNOS gene expression did not differ between the two groups. Transcardiac cytokine production was noted in 58.8% of patients for IL-6 and in 53.3% for TNF-alpha. Coronary sinus (CS) levels of TNF-alpha, IL-6 and nitrite were higher in group A. A significant increase in nitrite production was found only in patients with impaired endothelium dependent CFVR (aorta: 43.9 +/- 3.7 vs CS: 52.8 +/- 5.6, P = 0.05), suggesting transcardiac nitric oxide production. In addition, CS nitrite levels correlated with CS TNF-alpha levels in patients with impaired CFVR (r = 0.44, P = 0.003). Microvascular endothelium dependent CFVR is impaired in 26% of patients early after HTx. Activation of cytokines and the NO pathway seem to be involved in this vasomotor dysfunction The association between cardiac nitric oxide production and TNF-alpha in this group indicates a chronic high immunologic process, which may represent an early and important target for therapy and prevention of TxCAD.

Adenosine↗
PubMed2000

Cardiac allograft vasculopathy--problem and model.

Cardiac allograft vasculopathy (CAV) is an accelerated form of atherosclerosis induced by immunological endothelial injury with subsequent inflammatory repair responses in a milieu of additional nonimmunological risk factors. It is the leading cause of death beyond the first year after transplantation. The clinical situation is characterized by a poorly controlled complexity of pathogenetic and protective mechanisms and the heterogeneous nature concerning functional and structural manifestations, disease progression and prognosis. An early risk prediction algorithm for CAV is required in order to establish optimized preventive and therapeutical strategies. Experimental animals serve as model systems to selectively investigate different steps of the injury cascade providing specific insights into key mechanisms operating in CAV. Beyond its importance in transplantation medicine, human CAV can be taken as an unique model of atherosclerosis allowing evaluation and correlation of vascular function and morphology with the humoral and intracardiac activity/expression of mediators of the disease. Thus, CAV, beyond being a cumbersome clinical problem, represents an unique and attractive model of atherosclerosis in humans offering perspectives beyond the usual.

Algorithms↗
PubMed2000

The clinical dilemma of cardiac allograft vasculopathy--an introduction to the clinical session.

Cardiac allograft vasculopathy is the major long-term problem after heart transplantation. However, the assumption, mostly based on experimental animal data, that human CAV is an immune-mediated diffuse concentric intimal proliferation with progressive, homogenous vessel narrowing, involving equally epicardial arteries and the microcirculation, leading inevitably to ischemic organ failure and death, does not adequately reflect the complexity of the clinical setting. CAV in humans is much more characterized by a very heterogeneous pattern concerning pathogenetic mechanisms (e.g., immune activation, ischemia-reperfusion injury, CMV infection, hyperlipoproteinemia), protective mechanisms (e.g., remodeling, endothelium-derived vasodilators), endothelial dysfunction, morphological manifestations, involvement of the microcirculation, temporal appearance, disease progression and prognosis. Thus, clinicians have to deal with several clinical dilemmas of the disease, which can be summarized in three simple questions: how can CAV be detected/diagnosed, how can CAV and related events be predicted, and finally how can CAV be prevented and treated. Initial and promising answers to these pivotal questions have been found in recent years, and continuing progress is under way.

Algorithms↗
PubMed2000

Heart allograft endothelial cell dysfunction. Cause, course, and consequences.

Allograft coronary endothelial cells can serve as potent stimulators (antigen-presenting cells) as well as targets of allogeneic lymphocyte reactivity. Independent of the cause leading to endothelial cell injury after transplantation, endothelial cell activation and dysfunction occurs, associated with modification in endothelial cell-dependent molecule expression. The prevalence of coronary endothelial vasomotor dysfunction is approximately 20-30% during the first year, and 30-40% in the long-term follow-up. Importantly, no association is detectable between endothelial dysfunction and intimal thickness, suggesting two distinct entities of allograft vasculopathy. Early predictors of vasomotor dysfunction are proinflammatory cytokines and endothelin expression. Repetitive subendocardial ischemia during myocardial stress (due to microvascular dysfunction) may result in an impairment of left ventricular function. In non-transplant patients coronary endothelial dysfunction predicts cardiac events during long-term follow-up. It is reasonable that early administration of endothelial-protective compounds is necessary for protection of allograft endothelial dysfunction and vasculopathy during follow-up. The explanted donor heart may offer a potential for gene therapy techniques including modification of allograft phenotype and modulation of the host alloimmune response. Other protective strategies may include improvement of cardioplegic solutions and reperfusion strategies, recovery of the imbalance between vasoactive mediators, and treatment with HMG-CoA-reductase inhibitors and/or ACE inhibitors.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2000

Coronary vasomotor dysfunction in the cardiac allograft: impact of different immunosuppressive regimens.

Immunosuppression may have an important impact on early graft coronary endothelial injury. We investigated functional and morphologic coronary alterations, myocardial expression, and cardiac release of possible mediators of allograft vasculopathy within 6 months after cardiac transplantation with respect to different immunosuppressive regimens. Epicardial and microvascular endothelium-dependent and endothelium-independent vasomotor function and epicardial intimal thickening were measured in 8 transplant recipients treated with cyclosporin A (CyA), azathioprine, and prednisone (group 1), 9 transplant recipients treated with tacrolimus (TKL), azathioprine, and prednisone (group 2), and 14 patients treated with TKL, mycophenolate mofetil (MMF), and prednisone (group 3). The gene expressions of inducible and endothelial nitric oxide synthase (iNOS and eNOS), endothelin-1, prostacyclinsynthase, and thromboxansynthase were analyzed in endomyocardial biopsy specimens using semiquantitative reverse transcription polymerase chain reaction. Transcardiac cytokine release, endothelin-1, and nitrate-release were determined from plasma samples. Epicardial endothelial dysfunction (vasoconstriction to acetylcholine > 10%) and microvascular smooth muscle cell dysfunction (flow velocity increase to adenosine and nifedipine < 2.0) were enhanced in heart transplant recipients immunosuppressed with TKL, azathioprine, and prednisone. The prevalence of epicardial dysfunction was 78% in group 2 versus 44% and 46% in group 1 and 3 (p < 0.05), respectively. The prevalence of microvascular dysfunction was 56% in group 2 versus 13% and 7% in group 1 and 3 (p < 0.02), respectively. Coronary vasomotor dysfunction was associated with increased myocardial iNOS expression (p < 0.05), decreased eNOS expression (p < 0.05), and enhanced cardiac immunoreactive interleukin-6 (p < 0.01). Coronary intimal thickening was not different between the groups. The combination of TKL and MMF appears to be superior to TKL and azathioprine (and comparable to CyA and azathioprine) concerning preservation of early coronary vasomotor function, eNOS expression, iNOS suppression as well as cardiac interleukin-6 release. This may have an important impact on subsequent development of transplant coronary atherosclerosis.

Adult↗
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↗