PubMed Health⌕ Search

Biomedical subjects

A Schmeisser

Publications and source records attributed to A Schmeisser.

18 recordsLinked to original sources
PubMed2006

Evaluation of pulmonary vascular response to inhaled iloprost in heart transplant candidates with pulmonary venous hypertension.

OBJECTIVE: Chronic left-heart failure is often associated with the development of pulmonary venous hypertension. In heart transplant candidates this is of great significance because the healthy donor heart has to compensate the increased right-ventricular afterload. Right-ventricular dysfunction is still responsible for 19% of all early deaths after orthotopic heart transplantation. Careful preoperative assessment of pulmonary vascular resistance by right-heart catheterization is essential. Reversibility testing is generally carried out to clarify therapeutic options for the post-transplant period. The objective of this case series is to report our institutional experience with inhaled iloprost compared to the common used oxygen/nitroglycerin method for reversibility testing. METHODS: Right-heart catheterization was performed in 23 patients with severely impaired left-ventricular function (EF < or = 25%, pVO2 < or = 14 ml/kg/min, NYHA III or IV) with combined pulmonary venous hypertension (TPG > 12 mm Hg and or PVR > 250 dyn x s x cm(-5)). An intraindividual comparison was performed between of the hemodynamic effect with oxygen/nitroglycerin s.l. and inhaled iloprost. RESULTS: The transpulmonary gradient fell significantly from an initial 16 mm Hg to 13 mm Hg on oxygen/nitroglycerin s.l. compared to 10 mm Hg on inhaled iloprost. Pulmonary vascular resistance fell significantly from an initial 344 dyn x s x cm(-5) to 270 dyn x s x cm(-5) on oxygen/nitroglycerin s.l. compared to 209 dyn x s x cm(-5) on inhaled iloprost. On inhaled iloprost a moderate systemic effect was noticed. CONCLUSION: In heart transplant candidates with pulmonary venous hypertension reversibility testing with inhalation of iloprost is a save method and significantly more effective than the combination of inhaled oxygen plus nitroglycerin s.l.

Administration, Inhalation↗
PubMed2006

Apoptosis of human macrophages by Flt-4 signaling: implications for atherosclerotic plaque pathology.

BACKGROUND: Neointimal inflammation and angiogenesis are important contributors of progression and destabilization of the atherosclerotic plaque. While the role of vascular endothelial growth factor (VEGF) and its receptors VEGF-R1 (Flt-1) and VEGF-R2 (Flk-1) in this process has clearly been defined, expression of the VEGF-R3 (Flt-4) has only been documented on lymphatic and tumor endothelium. This study examined Flt-4 expression in human atherosclerotic plaque and explored its implications for atherosclerotic disease. METHODS AND RESULTS: Carotid artery thrombendartherectomy specimens from 10 patients with unstable plaque were stained for Flt-4 and its specific growth factors VEGF-C and VEGF-D. Microvascular endothelial cells (MVEC) stained positive for VEGF-C and -D, but not for Flt-4. Interestingly, macrophages within inflammatory perivascular regions coexpressed Flt-4, VEGF-C and VEGF-D. In vitro studies confirmed the expression of Flt-4, VEGF-C and VEGF-D in human monocytes and cultured macrophages. Treatment of macrophages with VEGF-D induced apoptosis as determined by annexin V staining, by immunoblotting of activated caspase 3, and by the ratio of Bcl-2/Bax as well as by DNA fragmentation. Immunohistochemical studies of advanced human carotid atherosclerotic plaque confirmed the coexpression of Flt-4 with activated caspase 3 and TUNEL staining in macrophages, indicating an ongoing apoptotic process. CONCLUSION: Human monocytes/macrophages express VEGF-C and -D and their receptor Flt-4 in vitro and in vivo within advanced atherosclerotic lesions. Flt-4, in turn, mediates monocyte/macrophage apoptosis and may this way alter plaque stability.

Aged↗
PubMed2006

High diagnostic accuracy of NT-proBNP for cardiac origin of pleural effusions.

A prospective study was performed to evaluate the diagnostic accuracy of N-terminal-pro-B-type natriuretic peptide (NT-proBNP) levels, measured simultaneously in serum and pleural fluid, in identifying pleural effusions due to heart failure. Pleural fluid and serum samples from all patients presenting for thoracentesis between April 2004 and May 2005 were simultaneously collected. The discriminative properties of NT-proBNP levels in identifying pleural effusions due to heart failure were determined by receiver operating characteristic curve analysis and compared to the diagnostic value of finding a transudate by Light's criteria. Ninety-three patients were evaluated, 27% with cardiac effusion and 73% with exudative effusions of various cause. Levels of NT-proBNP in pleural fluid and serum correlated closely. Serum and pleural fluid NT-proBNP levels were significantly elevated in patients with cardiac effusion. With a cut-off value of 4,000 ng.L(-1), NT-proBNP levels in pleural fluid and serum displayed comparably high diagnostic accuracies of 92 and 91%, respectively. All patients misclassified by Light's criteria were correctly identified by measuring NT-proBNP levels. N-terminal-pro-B-type natriuretic peptide levels in either pleural fluid or serum showed a high diagnostic accuracy compared to traditional criteria. Thus measuring N-terminal-pro-B-type natriuretic peptide is a valuable additional diagnostic tool for the detection or exclusion of cardiac origin of pleural effusions.

Aged↗
PubMed2005

Transcatheter closure of atrial septal defects improves right ventricular volume, mass, function, pulmonary pressure, and functional class: a magnetic resonance imaging study.

OBJECTIVE: To characterise prospectively by magnetic resonance imaging (MRI) changes in right ventricular (RV) volume, function, and mass after transcatheter closure of atrial septal defects (ASDs) and to evaluate the course of pulmonary pressure and functional class criteria. METHODS: In 20 patients with secundum-type ASD and dilated RV diameter, MRI was performed to quantify RV end diastolic (RVEDV) and end systolic volumes (RVESV), RV mass, tricuspid annular diameter, and RV ejection fraction before and 6 and 12 months after transcatheter closure of the ASD. RV systolic pressure was measured during follow up by transthoracic echocardiography. RESULTS: Functional class improved in the majority of patients after ASD closure. RVESV (from 81 (18) ml/m2 to 53 (15) ml/m2, p < 0.001), RVEDV (from 127 (17) ml/m2 to 99 (18) ml/m2, p < 0.001), and RV mass (from 79 (10) g to 63 (8) g, p < 0.01) decreased significantly during follow up, although tricuspid annular diameter did not. RV ejection fraction improved (by 9% compared with baseline, p < 0.05) and RV systolic pressure decreased significantly (from 33 (8) mm Hg to 24 (6) mm Hg, p < 0.001) after closure. CONCLUSION: MRI studies showed significant improvement of RV volumes, mass, and function after transcatheter closure of ASDs. Restoration of the RV leads to decreased pulmonary pressure resulting in a better functional class in the majority of patients.

Adult↗
PubMed2005

[Bacterial pericarditis].

HISTORY AND CLINICAL FINDINGS: A 65-year-old previously healthy man was referred because of high fever, progressive dyspnea and retrosternal pain for 2 days. On admission, the patient was already in a reduced general condition, blood pressure was 120/70 mmHg, heart rate irregular at 75/min and temperature at 39.7 degrees C. Auscultation of the heart revealed distant heart sounds, murmurs were not present, but mild rales were heard over both lung bases. Jugular veins were congested. INVESTIGATIONS: ECG showed a generalized ST-segment elevation with preserved R-waves, slightly depressed PR-segment and atrial bigemini. Chest X-ray revealed an enlarged cardiac silhouette with signs of a pneumopericardium. Transthoracic echocardiography showed a circular pericardial effusion and haemodynamic impairment. Percutaneous pericardiocentesis revealed a purulent effusion with microbiological proof of pneumococci. The primary infectious focus was a maxillary sinusitis caused by pneumococci. DIAGNOSIS: Bacterial pericarditis due to by haematogenous spread of pneumococci. TREATMENT AND COURSE: Antibiotic therapy consisted of intravenous ceftriaxon and gentamicin. To rinse the pericardial space and drain the thick, purulent effusion subxiphoidal, pericardiocentesis and insertion of a drainage tube were done. Physiological saline was put into the pericardial space several times a day, drained and analysed microbiologically. In the meantime rinsing of the infected maxillary sinus was performed. Transthoracic echocardiography was done repeatedly to rule out complications of bacterial pericarditis, especially constrictive pericarditis. The pericardial tube was removed after proof of a sterile drainage 9 days after insertion. The patient was discharged after 4 weeks of hospitalization without clinical or echocardiographic signs of diastolic dysfunction. CONCLUSION: Suspected bacterial pericarditis must be treated as an emergency and confirmed or ruled out by percutaneous pericardiocentesis.

Aged↗
PubMed2004

Delay of neutrophil apoptosis in acute coronary syndromes.

Apoptosis of polymorphonuclear neutrophils (PMN) is currently discussed as a key event in the control of inflammation. This study determined PMN apoptosis and its underlying mechanisms in controls (C), patients with stable (SAP) or unstable angina (UAP), and with acute myocardial infarction (AMI). Blood was drawn from 15 subjects of each C, SAP, UAP, and AMI. Apoptosis was measured by flow cytometry in isolated PMN (propidium iodide staining) and PMN from whole blood (CD16, FcgammaRIII). Serum cytokines were determined by enzyme-linked immunosorbent assay. Apoptosis of isolated PMN was delayed significantly in acute coronary syndromes (ACS) as compared with SAP or C (C, 51.2+/-12.6%; SAP, 44.9+/-13.6%; UAP, 28.4+/-10.1%; AMI, 20.3+/-8.5%; AMI or UAP vs. SAP or C, P<0.001). These results were confirmed by measurement of PMN apoptosis in cultured whole blood from patients and controls. Moreover, serum of patients with ACS markedly reduced apoptosis of PMN from healthy donors. Analysis of patients' sera revealed significantly elevated concentrations of tumor necrosis factor alpha, interferon-gamma (IFN-gamma), granulocyte macrophage-colony stimulating factor (GM-CSF), and interleukin (IL)-1beta in ACS (vs. C and SAP). IFN-gamma, GM-CSF, and IL-1beta significantly delayed PMN apoptosis in vitro. Furthermore, coincubation of PMN with adenosine 5'-diphosphate-activated platelets significantly inhibited PMN apoptosis as compared with coculture with unstimulated platelets. This study demonstrates a pronounced delay of PMN apoptosis in UAP and AMI, which may result from increased serum levels of IFN-gamma, GM-CSF, and IL-1beta and from enhanced platelet activation. Therapeutical modulation of these determinants of PMN lifespan may provide a new concept for the control of inflammation in ACS.

Acute Disease↗
PubMed2003

Upregulation of CD40-CD40 ligand (CD154) in patients with acute cerebral ischemia.

BACKGROUND AND PURPOSE: Inflammation and hypercoagulability contribute to the development of acute cerebral ischemia. Both can be mediated by the CD40 system. This study investigated whether the CD40 system and related mediators are upregulated in patients with transient ischemic attack (TIA) or stroke. METHODS: Seventeen patients with TIA, 60 patients with complete stroke, and 15 control subjects were investigated. CD154 and P-selectin were analyzed on platelets and CD40 on monocytes during and 3 months after acute cerebral ischemia by double-label flow cytometry. Blood concentrations of soluble CD154 and monocyte chemoattractant protein-1 (MCP-1) were evaluated. RESULTS: Our main findings are as follows: (1) patients with acute cerebral ischemia showed a significant increase of CD154 on platelets and CD40 on monocytes compared with controls; (2) plasma levels of soluble CD154 were significantly higher in these patients; (3) these patients had significantly higher numbers of prothrombotic platelet-monocyte aggregates; (4) the chemoattractant MCP-1 was significantly elevated in cerebral ischemia; and (5) at 3 months' follow-up, upregulation of CD154 still persisted in patients with previous acute cerebral ischemia. CONCLUSIONS: Patients with acute cerebral ischemia show upregulation of the CD40 system, which might contribute to the known proinflammatory, proatherogenic, and prothrombotic milieu found in these patients.

Acute Disease↗
PubMed2001

Upregulation of CD40 and CD40 ligand (CD154) in patients with moderate hypercholesterolemia.

BACKGROUND: Hypercholesterolemia, a risk factor for cardiovascular disease, is associated with inflammation and hypercoagulability. Both can be mediated by the CD40 system. This study investigated whether the CD40 system is upregulated in patients with moderate hypercholesterolemia and whether it is influenced by therapy with a hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitor. METHODS AND RESULTS: Fifteen patients with moderate hypercholesterolemia and 15 healthy control subjects were investigated. CD154 and P-selectin were analyzed on platelets and CD40 was analyzed on monocytes before and under therapy with the statin cerivastatin by double-label flow cytometry. Blood concentrations of soluble CD154 and monocyte chemoattractant protein-1 (MCP-1) were evaluated. Our main findings were as follows. Patients with moderate hypercholesterolemia showed a significant increase of CD154 and P-selectin on platelets and CD40 on monocytes compared with healthy subjects. Soluble CD154 showed a nonsignificant trend for higher plasma levels in patients. A positive correlation was found for total or LDL cholesterol and CD154, but not for CD40 on monocytes. The latter was upregulated in vitro by C-reactive protein, which was found to be significantly elevated in patients with moderate hypercholesterolemia. CD154 on platelets proved to be biologically active because it enhanced the release of MCP-1, which was markedly elevated in an in vitro platelet-endothelial cell coculture model and in the serum of patients. Short-term therapy with a HMG-CoA reductase inhibitor significantly downregulated CD40 on monocytes and serum levels of MCP-1. CONCLUSION: Patients with moderate hypercholesterolemia show upregulation of the CD40 system, which may contribute to the known proinflammatory, proatherogenic, and prothrombotic milieu found in these patients.

Adult↗
PubMed2001

Monocytes coexpress endothelial and macrophagocytic lineage markers and form cord-like structures in Matrigel under angiogenic conditions.

OBJECTIVES: It has been shown that circulating human non-adherent CD34+ cells coexpressing vascular endothelial growth factor (VEGF)-R2 and AC133 have the capacity to differentiate into adherent mature endothelial cells. However, prior studies have demonstrated that a much bigger subset of primary adherent mononuclear cells can also form endothelial progenitor cells (EPC). To determine the origin of the latter cell population we tested the hypothesis: do monocytes as a firmly adherent and plastic cell type have the potential to differentiate into an endothelial phenotype. METHODS: CD34-/CD14+ monocytes were isolated from human peripheral blood by adherence separation and magnetic bead selection (purity >90%) and cultured on fibronectin-coated plastic dishes (medium containing VEGF 10 ng/ml, basic fibroblast growth factor (bFGF) 2 ng/ml, insulin like growth factor (IGF-1) 1 ng/ml, 20% fetal calf serum). RESULTS: After 2 weeks of culture, using fluorescence activated cell analysis we observed a new expression of the endothelial markers von Willebrand factor (vWf), VE-cadherin (VE) and ec-NOS in 45.2, 12.4 and 9.8% of the cells, respectively. The proportion of cells expressing these markers further increased after 4 weeks (94.2, 89.7 and 58.8% of these cells, respectively). The proportion of CD45 expressing cells remained unchanged during this period. However, after 14 days the specific macrophage antigen CD68 was newly expressed in 62% of the analysed cells with a further increase to 90% after 28 days of culture. In three-dimensional gel (Matrigel the formation of cord- and tubular-like structures was observed. CONCLUSION: The present data indicate that under angiogenic stimulation macrophages develop an endothelial phenotype with expression of specific surface markers and even form cord- and tubular-like structures in vitro suggesting that this cell population may be recruited for vasculogenesis.

Antigens, CD↗
PubMed2001

Patients with acute coronary syndromes express enhanced CD40 ligand/CD154 on platelets.

OBJECTIVE: To investigate whether CD40L/CD154 on platelets and soluble CD40L/CD154 may play a role in the inflammatory process of acute coronary syndromes. DESIGN AND SETTING: Observational study in a university hospital. PATIENTS: 15 patients with acute myocardial infarction, 25 patients with unstable angina, 15 patients with stable angina, and 12 controls. MAIN OUTCOME MEASURES: CD40L/CD154 on platelets, P-selectin/CD62P on platelets, soluble CD40L/CD154 serum concentrations. RESULTS: Mean (SD) CD40L/CD154 expression on platelets was 6.2 (2.8) MFI (mean fluorescence intensity) in the infarct group, 11 (3.3) MFI in the unstable angina group (p < 0.001 v infarction), 3.6 (0.9) MFI in the stable angina group (p < 0.01 v infarction; p < 0.001 v unstable angina), and 3.2 (1.0) MFI in the controls (p < 0.01 v infarction; p < 0.001 v unstable angina; NS v stable angina). Soluble CD40L/CD154 concentration was 5.2 (1.1) ng/ml in the infarct group, 4.2 (0.7) ng/ml in the unstable angina group (p < 0.001 v infarction), 2.9 (1.0) ng/ml in stable angina group (p < 0.001 v infarction and unstable angina), and 3.0 (0.5) ng/ml in the controls (p < 0.001 v infarction and unstable angina; NS v stable angina). At a six months follow up, there was lower expression of CD40L/CD154 on platelets in patients with unstable angina (12.3 (3.6) v 3.8 (1.2) MFI, p < 0.0001) and acute myocardial infarction (6.2 (2.8) v 3.5 (0.8) MFI, p < 0.01) compared with their admission values six months earlier. Patients with unstable angina who needed redo coronary angioplasty (PTCA) or who had recurrence of angina were characterised by increased CD40L/CD154 expression on platelets compared with the remainder of the study group (recurrence of angina: 12.7 (3.2) v 9.7 (1.6) MFI, p < 0.05; re-do PTCA: 14.3 (4.2) v 10.3 (2.1) MFI, p < 0.05). CONCLUSIONS: Both CD40L/CD154 on platelets and soluble CD40L/CD154 are raised in patients with unstable angina and myocardial infarction. These findings suggest that CD40-CD40L/CD154 interactions may play a pathogenic role in triggering and propagation of acute coronary syndromes.

Aged↗
PubMed2000

[Mitral valve prolapse].

Mitral valve prolapse has previously been found to be associated with severe cardiovascular complications such as embolic insults, infectious endocarditis, and sudden cardiac death. However, at the same time, in particular after adopting M-mode and 2D echo for diagnosis, prevalence of the disease was found to be very high, especially in the young. The dilemma of a disease which is frequent and mostly asymptomatic, but in some cases has catastrophic complications, has been solved by implementation of more restrictive diagnostic criteria based on an appreciation of the spatial morphology of the mitral annulus. These criteria call for diagnosis exclusively based on long axis views and a prolapse of > 2 mm beyond a line connecting the leaflet insertion points. "Classic prolapse" additionally requires diastolic thickness of the mitral leaflets of at least 5 mm. Two recent studies, a population-based study of mitral valve prolapse prevalence, and a case-control study of juvenile stroke patients compared to a group of young patients without a history of stroke, shed further light on this disease. The authors found that prevalence of mitral valve prolapse in an average population is 2-3% (1.3% for classic prolapse), without age or sex preponderance; the rate of cerebrovascular insults, congestive heart failure, and atrial fibrillation of patients with prolapse does not exceed that of the rest of the population; however, mitral insufficiency is more frequent; young patients with a history of cerebrovascular insult do not have higher mitral valve prolapse rates than young patients without previous insult.

Cross-Sectional Studies↗
PubMed2000

Decreased plasma concentrations of L-hydroxy-arginine as a marker of reduced NO formation in patients with combined cardiovascular risk factors.

Patients with metabolic syndrome represent a group with extensive cardiovascular risk factors for the development of atherosclerosis, which may be preceded by an impairment of endothelial function. Endothelial dysfunction is characterized by a reduced availability of bioactive nitric oxide, the principal mediator of endothelium-dependent vasodilation. In the present study we assessed NO synthesis in vivo by measuring the NO-related amino acids L-arginine and L-citrulline and in particular the stable intermediate compound N(omega)-hydroxy-L-arginine (L-NHA) in patients with metabolic syndrome by using high-performance liquid chromatography (HPLC) analysis. As a prerequisite to our study, we measured the amino acid concentrations in 31 healthy volunteers to investigate gender and age differences. To prove whether blood drawn from peripheral veins reflects plasma concentrations of the whole vessel system, several blood samples from different regions were obtained from patients undergoing elective left and right heart catheterization. In the latter group, no significant differences were noted among the plasma concentrations between the different sample sites. In healthy volunteers, there were no significant differences in plasma concentrations of any one specific amino acid between males and females or age groups. The main finding of the study is that the intermediate product of NO synthesis, L-NHA, is significantly reduced in the plasma samples of patients with a metabolic syndrome as compared with samples from healthy control subjects. The plasma concentrations of the NO precursor L-arginine and the end product of NO synthesis, L-citrulline, were unchanged. In conclusion, our results suggest that plasma levels of L-NHA are independent of age and gender and are not different at various locations within the vascular system. In a group of patients at high risk for the development of atherosclerosis, we found reduced plasma concentrations of L-NHA, either caused by a decreased endothelial NO synthase activity or caused by an increased breakdown of L-NHA by pathways independent of NO synthase, resulting in a reduced availability of L-NHA for NO synthesis.

Adult↗
PubMed1999

Angiotensin II-induced superoxide anion generation in human vascular endothelial cells: role of membrane-bound NADH-/NADPH-oxidases.

BACKGROUND: Angiotensin II (ANG II) mediated hypertension accelerates atherosclerosis (AS) and thereby increases the incidence of myocardial infarction (MI). On the other hand, superoxide anion (O2-) is involved in the modification of low density lipoproteins, inhibition of prostacyclin (PGI2) formation and breakdown of nitric oxide. These events finally lead to rapid progression of AS and MI. In the present study, we investigate whether ANG II can induce O2- release from human vascular endothelial cells (HVECs) and the possible mechanisms involved. METHODS AND RESULTS: The expression of ANG receptors subtype-1 (AT-1) and subtype-2 (AT-2) were identified by using reverse transcription polymerase chain reaction and sequence analysis. The O2- production was dose-dependently increased in HVECs treated with ANG II (10(-7)-10(-9) M) and with a maximum rate after 1 h of incubation. This event was significantly inhibited by pretreatment of cells with the specific AT-1 blocker losartan (10(-7) M) and to a lesser extent by the specific AT-2 receptor blocker PD123319 (10(-7) M). The combined incubation of both receptor blockers was even more effective. In addition, our lucigenin-enhanced chemiluminescence assay showed that the activity of plasma membrane-bound NADH-/NADPH-oxidases derived from ANG II-treated cells was also significantly increased, this effect was reduced in cells pretreated with losartan or to lesser extent by PD123319. However, the activity of xanthine oxidase remained unchanged in response to ANG II. Furthermore, the basal O2- release from HVECs was inhibited in cells treated with angiotensin-converting enzyme (ACE) inhibitor, Lisinopril (10(-6) M), and this event could be reversed by ANG II. CONCLUSION: ANG II induces O2- release in HVECs via activation of membrane-bound NADH-/NADPH-oxidase, an effect, that is mediated by both AT-1 and AT-2 receptors. This suggests that acceleration of AS and MI in ANG II-mediated hypertension may at least be due to ANG II-induced O2- generation from vascular endothelial cells. In this case, the ACE inhibitors and the ANG receptor antagonists may act as causative "antioxidants".

Angiotensin II↗
PubMed1999

Priming of superoxide anion in polymorphonuclear neutrophils by brain natriuretic peptide.

In acute coronary syndromes such as unstable angina and myocardial infarction, serum concentration of brain natriuretic peptide, a cardiac hormone with potent vasodilatatory, natriuretic and diuretic activities, is elevated. Little is known about the effect of elevated BNP plasma concentration on free radical-mediated tissue damage in these states. We investigated the influence of human BNP 32 and its fragment BNP 7-32 on the production of superoxide anion by PMN, a major cause for myocardial damage. Although BNP showed itself no stimulatory potential on superoxide anion release in PMN, it enhanced significantly the stimulatory potential of cell stimuli such as fMLP or phorbol 12-myristate 13-acetate (PMA) in PMN. Thus our data show that the cardiac-derived hormone BNP influences an important function of PMN. This 'priming' effect of BNP on PMN may contribute to the tissue damage occuring during acute coronary syndromes.

Animals↗