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Hugo A Katus

Publications and source records attributed to Hugo A Katus.

154 records · Page 9Linked to original sources
PubMed2002

Adrenergic activation of cardiac phospholipase D: role of alpha(1)-adrenoceptor subtypes.

OBJECTIVE: Adrenergic stimulation of the heart leads to activation of the phospholipase D signal transduction pathway with formation of the intracellular second messengers phosphatidic acid and diacylglycerol, which may play a role in the development of myocardial hypertrophy by activating mitogen-activated protein kinases and protein kinase C. So far, the adrenergic receptor subtypes mediating activation of cardiac phospholipase D are not known. METHODS: We developed an assay for determination of phospholipase D activity in the isolated perfused rat heart. Utilizing the phospholipase D specific transphosphatidylation reaction the stable product phosphatidylethanol (PEtOH) is formed in rat hearts perfused in the presence of 1% ethanol. Myocardial PEtOH formation was used as a marker of phospholipase D activity and was determined by HPLC and evaporative light-scattering detection (PEtOH microg/mg myocardial protein). RESULTS: Basal PEtOH formation in unstimulated hearts was 0.06+/-0.01 microg/mg. Stimulation of the hearts with norepinephrine resulted in a concentration-dependent phospholipase D activation with a maximum formation of PEtOH (0.17+/-0.01 microg/mg) at 100 micromol/l norepinephrine. The norepinephrine-induced increase in PLD activity was completely blocked by the alpha(1)-adrenoceptor antagonist prazosin and was unaffected by the beta-adrenoceptor antagonist propranolol. Further characterisation of alpha(1)-adrenoceptor subtypes with selective alpha(1)-adrenoceptor antagonists demonstrated a complete inhibition of the norepinephrine-induced phospholipase D activation by WB 4101 (alpha(1A)-selective: 0.06+/-0.01 microg/mg) and by BMY 7378 (alpha(1D)-selective: 0.07+/-0.01 microg/mg). In contrast, the alpha(1B)-adrenoceptor antagonist chloroethylclonidine had no inhibitory effect on norepinephrine-stimulated phospholipase D activity (0.14+/-0.01 microg/mg). CONCLUSION: Adrenergic activation of the cardiac phospholipase D signal transduction pathway is mediated by alpha(1)-adrenoceptors. Here, the alpha(1A)-adrenoceptor subtype, but not the alpha(1B)-adrenoceptor are coupled to activation of cardiac phospholipase D.

Adrenergic alpha-Antagonists↗
PubMed2002

TLR4-mediated inflammatory activation of human coronary artery endothelial cells by LPS.

OBJECTIVE: Blood levels of cytokines are commonly elevated in severe congestive heart failure (CHF) and in coronary artery disease (CAD). While the adverse effects of cytokines on contractile function and myocardial cell integrity are well studied, little is known on whether cardiac cells are only targets or active players in these inflammatory reactions. METHODS AND RESULTS: We tested if human coronary artery endothelial cells (HCAEC) may become a source of cytokine and adhesion molecule expression when stimulated with bacterial lipopolysaccharide (LPS). Analysis of HCAEC supernatants by ELISA identified enhanced secretion of IL-6, IL-8, and MCP-1 while endothelin-1 was not increased. IL-1beta, IL-10, or TNF-alpha were not detectable by ELISA while RT-PCR revealed enhanced mRNA expression of IL-1beta and TNF-alpha but not IL-10. FACS analysis showed an LPS-induced upregulation of ICAM-1, VCAM, and ELAM-1. LFA-1 could not be detected. We further characterized receptors involved in LPS-induced signaling. Our results indicate that activation of HCAEC by LPS requires Toll-like receptor (TLR) 4. Pretreating the cells with the 3-hydroxy-3-methylglutaryl CoA (HMG CoA) reductase inhibitor Cerivastatin reduced IL-6 release. CONCLUSIONS: Taken together, our results indicate that activated HCAEC may act as inflammatory cells and thus directly contribute to the progression of CHF and CAD.

Cell Adhesion Molecules↗
PubMed2002

Continuous Holter telemetry of atrial electrograms and marker annotations using a common Holter recording system: impact on Holter electrocardiogram interpretation in patients with dual chamber pacemakers.

The impact of continuous telemetry of atrial electrogram and marker annotations on Holter ECG interpretation was assessed in 98 patients with bipolar dual chamber pacemakers (VDD pacemakers n = 29, DDD(R) systems n = 69). Atrial electrogram and marker annotations were continuously sampled by a telemetry coil that was externally positioned on the pacemaker pocket, amplified, and transduced to a three-channel Holter ECG recorder in addition to an ECG recording. Holter tapes were analyzed by two experienced investigators for quality of P wave recognition and episodes suspicious of pacemaker dysfunction. Initially, only the ECG channel was analyzed. Thereafter, results were compared to those achieved on the basis of the complete recording including atrial electrogram and marker annotations. Recognition of atrial rhythm was markedly improved by Holter telemetry. During 99.3% of recording time telemetry showed a satisfying quality, whereas ECG alone allowed a reliable P wave recognition only during 84.4% of recording time (P < 0.001). One hundred twenty-nine episodes suspicious of pacemaker malfunction occurred in 17 of 98 patients. By analysis of ECG, only 78.3% of episodes were concordantly classified by the investigators. However, 98.4% of all episodes were properly identified when atrial electrogram and marker annotations were added to the analysis (P < 0.001). In particular, discrimination between atrial undersensing, sinus bradycardia, and atrial sensed events within the refractory periods was facilitated. Holter telemetry of atrial electrogram and marker annotations facilitates the analysis of Holter ECGs in pacemaker recipients and improves the detection of pacemaker dysfunctions.

Aged↗
PubMed2002

Prognostic significance of admission cardiac troponin T in patients treated successfully with direct percutaneous interventions for acute ST-segment elevation myocardial infarction.

BACKGROUND: Cardiac troponin T (cTnT) elevations at admission indicate a high-risk subgroup of patients with acute ST-segment elevation myocardial infarction, possibly due to a higher failure rate of reperfusion therapies. OBJECTIVE: We sought to determine the predictive role of admission cTnT in patients with ST-segment elevation myocardial infarction undergoing successful direct percutaneous coronary intervention. METHODS: A total of 218 consecutive patients with ST-segment elevation myocardial infarction were enrolled. Patients were stratified according to admission cTnT and infarct location. They were followed prospectively for short-term and long-term outcomes. RESULTS A positive cTnT (47.7%) was associated with higher mortality rates at 30 days (14.4% vs. 3.5%, p = .003) and 12 months (17.3% vs. 4.4%, p =.007). cTnT allowed discrimination of patients at high and low risk for cardiac death at 30 days and 12 months among anterior (19.2% vs. 7.9%, p = .19, and 25% vs. 13.2%, p = .22, respectively) and, more impressively, among nonanterior acute myocardial infarction (9.6% vs. 1.3%, p = .04, and 11.5% vs. 1.3%, p = .017, respectively). In multivariate analysis, older age, anterior infarct location, and depressed left ventricular function were the most potent independent predictors of future risk. Among clinical variables available at admission, cTnT indicated independently a higher risk of cardiac death (odds ratio, 3.1 [1.07-9.01], p =.038). This increased risk associated with a positive cTnT was almost independent of time delays from onset of symptoms to admission (3.8 vs. 2.3 hrs in cTnT-positive vs. cTnT-negative patients, p <.001). CONCLUSIONS: Admission cTnT is a strong predictor of future cardiac risk in patients with ST-segment elevation myocardial infarction, despite successful restoration of Thrombolysis in Myocardial Infarction grade 3 coronary flow by direct percutaneous coronary intervention.

Aged↗
PubMed2002

[Beta blockers in heart failure therapy with special reference to the COPERNICUS Study].

During the past 15 years, the pathophysiological concept of heart failure as a neurohormonal disease has influenced heart failure therapy substantially. ACE-inhibitors have become the mainstay of heart failure therapy. In addition, beta blocker evolved to be effective in improving survival in this disease. Recently, the COPERNICUS study established the efficacy of carvedilol in severe heart failure and extended the benefits of this drug first observed in patients with mild and moderate symptoms to those with advanced disease. In this study, carvedilol resulted in a significant reduction of all-cause mortality and combined mortality and hospitalization, the frequency of hospitalizations, the risk of repeated hospitalizations, the number of days in hospital, the average duration of each admission and the utilization of treatments and procedures for heart failure. Carvedilol was well tolerated, improved the sense of well-being, was associated with a lower risk of a serious adverse event, particularly one related to the progression of heart failure and fewer patients requiring withdrawal of treatment for an adverse event. These favourable results were equally seen in all subgroups. Carvedilol treatment was even cost-effective in severe disease. Therefore, this new therapeutic option should be available to all patients with symptomatic systolic heart failure.

Adrenergic beta-Antagonists↗
PubMed2002

Intracoronary beta radiation for in-stent restenosis in a patient with percutaneously treated hypertrophic cardiomyopathy and coronary artery disease.

Atherosclerotic coronary artery disease is not uncommon in elderly patients with hypertrophic cardiomyopathy. These disease entities are increasingly being treated with catheter-based techniques. We report an elderly symptomatic woman treated simultaneously with coronary angioplasty, stenting and transcoronary ablation of septal hypertrophy who developed in-stent restenosis 7 months later, and was then treated with brachytherapy. Six-month and 1-year post-brachytherapy follow-up revealed a good angiographic result and adequate symptomatic relief. This is the first report describing the feasibility and efficacy of intracoronary beta radiation in a patient with hypertrophic cardiomyopathy.

Aged↗
PubMedDate not supplied

Penetrating atherosclerotic ulcer of the ascending aorta: a delayed complication of coronary artery bypass surgery--a case report.

A 71-year-old woman, undergoing coronary angiography during preoperative evaluation for a major noncardiac surgery, was fortuitously detected as having penetrating atherosclerotic ulcer of the ascending aorta 5 years after coronary artery bypass surgery. While acute aortic dissections have been described after coronary bypass grafting, penetrating atherosclerotic ulcer of the ascending aorta as a delayed complication of bypass surgery has never been reported. The patient was treated conservatively and closely observed. A brief review of literature is also presented.

Aged↗