Biomedical subjects

Gert Baumann

Publications and source records attributed to Gert Baumann.

64 records · Page 4Linked to original sources

PubMed2002

Inhibition of the ubiquitin-proteasome pathway induces differential heat-shock protein response in cardiomyocytes and renders early cardiac protection.

The effects of proteasome inhibition (PI) on heat-shock protein (HSP) expression in cardiomyocytes were investigated. Neonatal rat cardiomyocytes were incubated with MG132 (0.1-10 microM) for 1 h. Induction of various HSPs was determined by real-time PCR and Western blotting. PI induced a 2- to 3-fold increase in HSP27, HSP60, and HSP90, and a 18-fold increase in HSP70 mRNA expression, whereas HSP40 levels were unaffected. Western blotting revealed increased protein expression for HSP70 after PI. Similar results were obtained with MG262. HSP induction correlated with enhanced survival of neonatal cardiomyocytes after sublethal heat stress in XTT testing. In papillary muscles, pretreatment with MG132 (10 microM, 90 min) was associated with enhanced recovery of the contractile parameters after a 40-min hypoxia. In these proof-of-principle experiments, we show that PI induces differential heat-shock response in cardiomyocytes, accompanied by enhanced cell survival and functional recovery after various forms of stress.

Animal Population Groups↗

PubMed2002

Removal of cardiodepressant antibodies in dilated cardiomyopathy by immunoadsorption.

OBJECTIVES: The objective of this study was to investigate whether immunoadsorption (IA) removes cardiodepressant antibodies from the plasma of patients with dilated cardiomyopathy (DCM), as well as to describe their effects on isolated rat cardiomyocytes. BACKGROUND: Immunoadsorption induces early hemodynamic improvement in patients with DCM. The mechanisms for this improvement remain to be elucidated. METHODS: Patients with DCM (n = 11; left ventricular ejection fraction < 30%, cardiac index [CI] < 2.5 l/min per m(2)) were treated with IA on three consecutive days, with one IA session daily, by application of specific antibody columns directed against human immunoglobulin (Ig). Immunoadsorption was also conducted on 500 ml of blood taken from nine healthy donors (control subjects). After passage of plasma, the IA columns were regenerated. Column eluent (CE) was collected and dialyzed (100 kD). Confocal laser scanning microscopy was used to analyze the effects of CE on cell contraction and on Ca(2+)-dependent fluorescence in isolated, field-stimulated adult rat cardiomyocytes loaded with cell-permeable Fluo-3. Immunoprecipitation with different preparations of myocardial protein fractions was used for characterization of cardiotropic antibodies. RESULTS: During IA, the IgG plasma level decreased from 10.7 +/- 0.6 to 2.4 +/- 0.1 g/l (mean +/- SEM), and the CI increased from 2.2 +/- 0.1 to 2.7 +/- 0.2 l/min per m(2) (p < 0.01). The CE obtained from control subjects did not influence Ca(2+) transients or cell shortening of cardiomyocytes. In contrast, in patients with DCM, the CE collected during the first regeneration cycle of the first IA session caused an immediate and dose-related decrease of Ca(2+) transients (dilution 1:5; -22.7 +/- 5.5%; p < 0.01) and cell shortening (dilution 1:5; -29.9 +/- 6.0%, p < 0.01). Early hemodynamic improvement among the patients correlated with the cardiodepressant effect of CE on the isolated cardiomyocytes. Purification of CE by protein A adsorption indicated that the cardiodepressant substances are antibodies. Immunoprecipitation revealed that the eliminated antibodies are capable of binding to various myocardial proteins. CONCLUSIONS: Cardiac autoantibodies play a functional role in DCM, and their removal may induce early hemodynamic improvement.

Animals↗

PubMed2002

Ubiquitin-proteasome pathway as a new target for the prevention of restenosis.

BACKGROUND: The ubiquitin-proteasome system is the major intracellular protein degradation pathway in eucaryotic cells. It regulates central mediators of proliferation, inflammation, and apoptosis that are fundamental pathomechanisms in the development of vascular restenosis. METHODS AND RESULTS: Effects of proteasome inhibition on neointima formation were studied in a balloon injury model in the rat carotid artery. Local application of the proteasome inhibitor MG132 (1 mmol/L) resulted in significant inhibition of intimal hyperplasia, that is, by 74% (P=0.008). This effect was accompanied by decreased proliferation, reduced infiltration of macrophages, and prolonged apoptosis, as determined by immunohistochemical and TUNEL analyses. Functional effects of proteasome inhibition on proliferation, activation of nuclear factor kappa B, and apoptosis were further characterized in rat primary vascular smooth muscle cells. MG132 dose-dependently inhibited vascular smooth muscle cell proliferation with 50% inhibition at 10 micromol/L. TNFalpha-induced degradation of IkappaBalpha and beta was blocked, and activation of nuclear factor kappa B was suppressed in a concentration-dependent manner in bandshift assays. Moreover, proteasome inhibition (1 to 50 micromol/L MG132) induced apoptotic cell death up to 80%, as confirmed by DNA/Histone-ELISA and TUNEL-FACS analysis. Specificity of proteasome inhibition was shown by accumulation of multiubiquitinylated proteins and accumulation of specific proteasomal substrates. CONCLUSIONS: These proof-of-principle experiments demonstrate that inhibition of the ubiquitin-proteasome system effectively reduces neointima formation in vivo, which corresponds to strong antiproliferative, anti-inflammatory, and proapoptotic effects in vitro and in vivo. Our data suggest the ubiquitin-proteasome system as a new target in the prevention of vascular restenosis.

Angioplasty, Balloon↗

PubMed2002

[Standards in interventional therapy of coronary artery disease].

This review provides an overview of current percutaneous coronary interventional techniques (PCI) in patients with acute and chronic coronary artery disease. The indications for PCI have expanded during the past two decades, and no absolute contraindications remain. The chief limitations to event free survival following balloon angioplasty have been abrupt vessel closure in the short term and restenosis in the long term. The therapeutic effect of arterial vessel enlargement through PCI is accompanied by various degrees of arterial injury with exposure of thrombogenic components. Depending on the degree of activation of the coagulation cascade, as well as platelet adhesion and aggregation, this may result in intracoronary thrombus formation and subsequent ischemic sequelae. Therefore, inhibition of platelets and the coagulation system has always been central to interventional investigations. Restenosis has been the most important long-term limitation of PCI. Coronary artery stents have become an important adjunct to conventional balloon angioplasty owing to their dual function of reducing acute complications and the long term risk of restenosis. Although coronary artery stents serve as antirestenosis devices and reduce target vessel revascularisation requirements compared with balloon angioplasty, they themselves become a source of restenosis. In-stent restenosis is a major challenge for the interventionalist. None of the available interventional modalities provides optimal acute results, and long-term results are even poorer. This is especially true for diffuse in-stent restenosis lesions which have high recurrence rates. Thus, mechanical treatment modalities for evolved in-stent restenosis can only be one step in a comprehensive strategy for prevention and treatment. Brachytherapy as an adjunct seems to be especially promising, but late thrombosis, delayed restenosis and the potential for very late fibrosis are matters of concern. As attention has turned towards the prevention of in-stent restenosis new techniques such as drug delivering stents and gene therapy to inhibit the biological reaction of the vessel wall are likely to obtain greater importance.

Angioplasty, Balloon, Coronary↗

PubMed2002

Negative inotropic mediators released from the heart after myocardial ischaemia-reperfusion.

The heart responds to ischaemic stimuli with release of negative inotropic mediators such as cytokines, platelet-activating factor, oxygen free radicals, arachidonic acids, nitric oxide, adenosine, and still unidentified "cardiodepressant factors" that modulate myocardial performance via autocrine and paracrine coupling. This review summarises experimental and clinical data on the role of negative inotropic mediators that are released from cardiac cells (including cardiomyocytes, endothelial cells, and resident mast cells) after myocardial ischaemia-reperfusion.

Adenosine↗

PubMed2002

Myocardial contrast echocardiography for predicting functional recovery after acute myocardial infarction.

UNLABELLED: Myocardial contrast echocardiography (MCE) is a promising diagnostic tool for detecting microvascular integrity. The aim of the study was to investigate the comparative specificity and sensitivity of intravenous MCE, technetium-99m Sestamibi single-photon emission computed tomography (SPECT) and dipyridamole-dobutamine (DIDO) stress echocardiography for predicting functional recovery after coronary revascularization in patients with acute myocardial infarction (AMI). METHODS: In a prospective, observational study, 17 consecutive patients short after AMI who received successful treatment with primary percutaneous coronary angioplasty (PTCA) plus stent-implantation were examined with DIDO (dipyridamole with 0.28 mg/kg over 4 min plus dobutamine up to 10 mcg/kg/min), MCE (10 ml 4 g, 400 mg/ml Levovist intravenously; second harmonic power imaging) within 12-24 h and resting perfusion SPECT within 48-72 h after PTCA. Functional recovery of regional contractile function after 6-month follow-up was the gold standard to assess viability. RESULTS: The rate of agreement between SPECT and MCE was 69% and between SPECT and a positive response to stress echo was 76% for combined DIDO. MCE showed a higher sensitivity (96%) in the identification of viability than SPECT (77%) and combined DIDO alone (79%). Specificity was lower for viability recognition with MCE (58%) compared with SPECT (93%) and DIDO (87%). CONCLUSIONS: The wall motion response during DIDO echocardiography is useful in the prediction of recovery of regional and global ventricular function after revascularization in patients after AMI. Combined intravenous MCE and DIDO is more accurate in the diagnosis of stunned myocardium than Tc-99m-MIBI SPECT alone.

Echocardiography↗

PubMed2002

Comparison of electrocardiogram and intrathoracic electrogram signals for detection of ischemic ST segment changes during normal sinus and ventricular paced rhythms.

INTRODUCTION: The aim of this study was to compare surface ECGs with electrograms (EGM) that are available from implanted devices for the ability to detect ischemic ST segment changes during normal sinus (NS) and ventricular paced (VP) rhythms. METHODS AND RESULTS: ECG leads I, II, and V2, right atrial ring to left pectoral patch (representing the can of the device), right ventricular ring to left pectoral patch, and right atrial ring to right ventricular ring EGM were recorded continuously during percutaneous transluminal coronary angioplasty. One balloon inflation (> or = 60 sec) was analyzed from each of 22 NS and 22 VP subjects. The parameter AST was defined as the maximum absolute ST segment deviation (from isoelectric) during the first 60 seconds of inflation, measured relative to the baseline (preinflation) ST segment deviation. For EGM, a normalized deltaST was defined as the AST divided by the ratio of QRS amplitudes of EGM to ECG. During NS, the deltaST for EGM (0.43 mV) was significantly larger than that of ECG (0.09 mV, P = 0.0001) but the normalized deltaST for EGM (0.11 mV) was comparable to that of ECG (0.09 mV, P = 0.45). During VP, the AST for EGM (1.08 mV) was significantly larger than that of ECG (0.17 mV, P = 0.0001), but the normalized AST for EGM (0.11 mV) was significantly smaller than that of ECG (0.17 mV, P = 0.02). CONCLUSION: During both NS and VP, ischemic ST segment changes were significantly larger in EGM than in ECG. Much of this difference appears to be related to larger amplitudes of EGM signals. (J

Aged↗

PubMed2002

Does contrast echocardiography with Optison induce myocardial necrosis in humans?

Myocardial contrast echocardiography is a promising diagnostic tool for detecting microvascular integrity. Multiple experimental laboratories have shown that diagnostic combined microbubble contrast and ultrasound exposure can cause vessel rupture and myocardial damage in laboratory animals. This study investigated the phenomenon of contrast ultrasonically induced myocardial damage in human beings. Twenty consecutive patients (mean age of 60 +/- 12 years, 14 men) underwent contrast echocardiography with intravenous Optison using a mechanical index of at least 1.4 (Vivid Five System (GE, Vingmed Ultrasound, Horton, Norway). Creatine kinase (CK), creatine kinase-isoenzyme MB (CK-MB); CK-MB mass, myoglobin, and troponin I were measured before and 2, 4, 8, and 24 hours after contrast echocardiography. There was no significant correlation concerning the response to contrast echocardiography for any pair of parameters at any time after the intervention. Only in 2 patients were there higher values for troponin I before and after contrast echocardiography without an increase of myoglobin, CK, or CK-MB mass and activity. These values were therefore interpreted as false positive because of renal failure and severe heart failure. The use of contrast echocardiography is without demonstrated risk of myocardial damage even in patients with different cardiologic entities.

Aged↗

PubMed2002

Cardiac troponin I sense-antisense RNA duplexes in the myocardium.

Natural antisense RNA is now thought to regulate, at least in part, a growing number of eukaryotic genes. It is becoming increasingly apparent that such endogenous antisense RNA molecules may modulate gene expression in a manner analogous to synthetic oligomers. Here, we report the detection of antisense-orientated RNA transcripts of cardiac specific troponin I in rat and human myocardium. Interestingly, the different sizes of the rat and human antisense cTNI transcripts suggest species-specific reverse transcription initiation sites. Moreover, for the first time in cardiomyocytes, we could demonstrate in vivo duplex formation between sense and antisense transcripts. The existence of antisense-sense duplexes represents compelling evidence and a potential mechanism for endogenous antisense transcript-mediated modulation of mRNA translation. The potential effect of attenuating translation was illustrated by in vitro and in vivo model systems. Testing several oligonucleotides based on the natural antisense sequences, the optimal region for inhibition of translation was identified as being close to the translational start codon.

Adult↗

PubMedDate not supplied

Electron beam tomography of interpulmonary saddle embolism: extent and vascular distribution.

PURPOSE: The purpose of this work was to assess morphology and secondary signs of interpulmonary emboli extending across the bifurcation of the main pulmonary artery (PA). METHOD: Retrospective evaluation of 780 electron beam tomographic studies of the chest yielded 17 cases of interpulmonary saddle embolism. Length, diameter, vascular distribution of the emboli, and secondary findings were prospectively assessed by two blinded reviewers. Follow-up studies were carried out in 12 of 17 patients (71%). RESULT: Mean total length of the emboli was 46.6 cm (range 20.9-81.5 cm). The mean diameter of the saddle embolus was significantly smaller at the level of the bifurcation than in the left or right PA (4.5, 7.7, and 7.4 mm, respectively; p < 0.01). Dilatation of the right heart was found in 10 of 17 cases (59%). At follow-up, the saddle state was no longer present in 8 of 12 patients (67%). CONCLUSION: Interpulmonary saddle emboli appear to be a transient form of acute pulmonary embolism, the site of predilection for rupture of the embolus being the level of the bifurcation. Their frequency may therefore be underestimated.

Acute Disease↗