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Otmar Pachinger

Publications and source records attributed to Otmar Pachinger.

62 records · Page 4Linked to original sources

Short- and long-term changes of flow-mediated vasodilation in patients under statin therapy.

BACKGROUND: Flow-mediated vasodilation (FMD) of the brachial artery (BA) has been shown to improve in response to lipid-lowering therapy and other therapeutic interventions, usually within 1 to 2 months. Whether FMD remains improved under therapy in the longer term is unknown. HYPOTHESIS: The aim of this study was to examine the short- and long-term changes of FMD under statin therapy. METHODS: Flow-mediated vasodilation and nitroglycerin-mediated vasodilation (NMD) of the BA were measured with high-resolution ultrasound (13 MHz) at baseline and at 4 and 10 months in 18 consecutively recruited patients with coronary artery disease (CAD), in whom statin therapy was newly established. RESULTS: The decrease of total plasma cholesterol levels after 4 and 10 months of statin therapy (243 +/- 31 vs. 186 +/- 30 vs. 191 +/- 40 mg/dl; p < 0.001) was accompanied by an increase in FMD from 4.4 +/- 3.8% at baseline to 9.6 +/- 2.7% at 4 months and to 9.5 +/- 2.6% at 10 months (p < 0.001). Nitroglycerin-mediated vasodilation showed a trend toward improvement after 4 months (14.6 +/- 7.5 vs. 19.1 +/- 3.6 vs. 19.4 +/- 5.6%; NS). The FMD/NMD ratio also rose significantly after 4 months and remained improved after 10 months of statin therapy (0.31 +/- 0.25 vs. 0.52 +/- 0.16 vs. 0.50 +/- 0.14; p < 0.01). CONCLUSION: Statin therapy is associated with sustained improvement of endothelial function up to 10 months. These data support the utility of FMD for the assessment of vascular function in response to lipid-lowering therapy or other therapeutic interventions in long-term studies.

Adult↗

[3-D echocardiography: new developments and future prospects].

Due to limitations in transthoracic and occasionally transesophageal 2-D echocardiography with respect to volumetric analysis and morphologic and functional assessment in patients with congenital malformations and valvular heart disease, additional diagnostic tools have been established. In parallel with the rapid evolution in computer technology, 3-D echocardiography has grown into a well-developed technique, such as volume-rendered 3-D reconstruction, capable of displaying dynamic morphology depicting depth of the structures, their attachment, and spatial relation to the surrounding tissue. Nevertheless, the complexity of data acquisition and data processing required for adequate dynamic 3-D echocardiographic imaging and volumetric analysis does not allow to use this approach routinely. The commonly used dynamic 3-D echocardiography means off-line computer-assisted image reconstruction from a series of cross-sectional echocardiographic images using currently available transesophageal and transthoracic transducers. Alternatively, real-time 3-D echocardiography based on novel matrix, phased-array transducer technology has been introduced. Although this technique can be easily combined with any routine examination, its clinical use is limited because of a lower image quality in comparison with dynamic 3-D echocardiography. Up to now, there is no transesophageal approach available using real-time 3-D echocardiography. Recently, dynamic 3-D echocardiographic technique has matured noticeably. Beside the well-known sequential scanning, which is characterized by a fixed probe and patient in space and predetermined motion of the transducer, the freehand scanning using an electromagnetic location system has found its way to clinical environment. The main advantage of this technique is that the transducer can be freely moved by the examiner and, thus, the data set acquired within a routine examination. Also 3-D rendering and display have been developed further. In this respect, especially the "real-time rendering mode" allowing the reconstructed 3-D image to be animated and moved in space and to look at it from different perspectives has gained increasing acceptance. In valvular heart disease, reconstructive surgical treatment is aspired. 3-D echocardiographic imaging is the only technique providing "surgical views" prior to opening the heart. It is capable of distinguishing particular destructive substructures of the valves and the valvular apparatus. Especially in mitral valvular reconstruction, it is of clinical importance to achieve optimal surgical results. With respect to volumetric and mass analysis, 3-D echocardiography is more accurate and reproducible in comparison with conventional 2-D analysis. It provides data independent of geometric assumptions, what may considerably influence the results in the presence of wall motion abnormalities, especially in aneurysmatic ventricles. Volumetric analysis of the aneurysmal portion may also be helpful prior to surgical resection. 3-D echocardiography can also be recommended as a valuable additional approach to atrial septal defect (ASD), corrected transposition of the great arteries, cor triatriatum, and, within limits, to ventricular septal defect (VSD) as well. Especially with respect to ASD and VSD, the potential significance of 3-D echocardiography prior to device closure is emphasized. At present, its additional information in decision-making and the increasing number of clinical cases that can be addressed and answered already justify the clinical use of this technique.

Echocardiography, Three-Dimensional↗

Plasma cardiac troponin T closely correlates with infarct size in a mouse model of acute myocardial infarction.

BACKGROUND: Cardiac troponins replaced creatine kinase and lactate dehydrogenase isoenzymes as criterion standards for the laboratory diagnosis of myocardial damage. However, there are only few publications on correlations of cardiac troponin T (cTnT) with pathologically determined infarct size which are flawed by insufficient sample size. METHODS: In 38 anesthetized wildtype mice, the chest and pericardium were opened and the left descending artery was ligated. After sham operation, all mice recovered. Twenty-four hours after surgical induction of acute myocardial infarction heparinized blood samples were collected, the animals sacrificed and hearts harvested. Plasma cTnT was measured by a quantitative rapid assay using the Cardiac Reader (Roche Diagnostics). The hearts were cut into four transverse sections which were stained with 1.5% triphenyltetrazolium chloride for evaluation of necrosis by computerized planimetry. Pearson correlation coefficients were calculated between histological infarct size and cardiac markers. RESULTS: Infarct sizes ranged from 14% to 55% of left ventricle and cTnT concentrations from 3.9 to 14.1 microg/l. cTnT correlated closely with histological infarct size (r = 0.84, p < 0.001). CONCLUSIONS: This study for the first time demonstrates a close correlation of cTnT release with pathological infarct size in a suitable experimental model with a sufficient sample size.

Animals↗

Global P wave duration on the 65-lead ECG: single-site and dual-site pacing in the structurally normal human atrium.

INTRODUCTION: Pacing is believed to prevent atrial fibrillation by reducing atrial activation time. Exact correlation between P wave duration (PWD) on surface ECG and endocardial atrial activation time is still unexplored. METHODS AND RESULTS: In 15 patients without structural heart disease (9 women, age 45 +/- 14 years), single site [high right atrium (HRA), coronary sinus ostium (CSos), distal CS (CSd), high RA septum (Bachmann's bundle, BB)] and dual-site pacing (various combinations) was performed after ablation of supraventricular tachycardia. A 65-lead surface ECG was recorded simultaneously. Endocardial atrial activation time was measured off-line (stimulus - last bipolar recording), and the respective PWD was assessed using the root mean square and 65-channel summary plots. PWD during pacing from BB was significantly shorter (96 +/- 12 msec) than during HRA (121 +/- 15 msec), CSos (108 +/- 9 msec), and CSd pacing (126 +/- 14 msec; P < 0,01, respectively). PWD during dual-site pacing (HRA+BB, 91 +/- 14 msec; HRA+CSos, 96 +/- 7 msec; HRA+CSd, 90 +/- 7 msec; BB+CSd, 96 +/- 12 msec) was not significantly shorter than during pacing from BB. Correlation between endocardial atrial activation time and PWD was 0.83. CONCLUSION: PWD during single-site and dual-site atrial pacing represents endocardial atrial activation time and can be measured precisely using the 65-lead surface ECG. The fact that high septal pacing results in the shortest PWD may have implications for preventive pacing in patients with atrial fibrillation.

Adult↗

Linoleic acid-stimulated vascular adhesion molecule-1 expression in endothelial cells depends on nuclear factor-kappaB activation.

Endothelial activation is an important step in atherogenesis. In addition to established cardiovascular risk factors, such as hypercholesterolemia, hypertension, diabetes mellitus, and homocysteinemia, high plasma levels of triglyceride-rich lipoproteins may be an important cause of endothelial activation as well. Free fatty acids hydrolyzed from core triglycerides of these particles can exert both pro- and anti-inflammatory effects on the vascular wall. omega-3 fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have been shown to inhibit cytokine-induced endothelial activation. In contrast, we and others have previously shown that the omega-6 fatty acid linoleate activates transcription factor nuclear factor-kappaB (NF-kappaB) in endothelial cells. In this study, we show that linoleic acid stimulates vascular adhesion molecule-1 (VCAM-1) protein and mRNA expression in cultured human endothelial cells, as assessed by immunofluorescence and Northern blotting. Release of shedded soluble VCAM-1 from cultured human endothelial cells was also increased by the addition of linoleic acid, as determined by enzyme-linked immunosorbent assay (ELISA). By use of cultured rat aortic endothelial cells transfected with an IkappaB super-repressor (DeltaN2 cells), we provide evidence that NF-kappaB signalling is required in the linoleic acid-induced VCAM-1 expression in endothelial cells, whereas other transcription factors appear to be involved in the increased endothelial plasminogen activator inhibitor-1 (PAI-1) production in response to linoleic acid. These findings suggest that diets rich in linoleic acid may be proinflammatory and thus atherogenic by activating vascular endothelial cells.

Animals↗

Clinical ECG mapping and imaging of cardiac electrical excitation.

Combining electrocardiographic mapping and 3D+time anatomical data enables noninvasively the imaging of the electrical excitation sequence in the human heart. A bidomain-theory based surface heart model activation time imaging approach was employed to image single beat data of atrial and ventricular depolarisation. Activation time maps were reconstructed for three patients who underwent an electrophysiologic study. The sinus rhythm and a rhythm according to a pacing protocol were reconstructed for two patients. For the third patient the accessory pathway of the WPW syndrome was localized. For focal arrhythmias, this model-based imaging approach might allow the guidance and evaluation of antiarrhythmic interventions, for instance, in case of catheter ablation or drug therapy.

Adult↗

Decreased high-energy phosphate ratios in the myocardium of men with diabetes mellitus type I.

AIMS/HYPOTHESIS: To investigate whether alterations in high-energy phosphates occur in the myocardium of persons with diabetes mellitus type I. Microvascular abnormalities and dysfunction via thickening of the basement membrane are known to occur in diabetic patients. Myocardial high-energy phosphates have been shown to be reduced by ischemia, and alterations of the cardiac metabolism are the primary consequence of myocardial ischemia. METHODS: The present study involved 34 male patients (mean age 35.5 +/- 10.1) with diabetes mellitus type I and 35 healthy male volunteers (mean age 36 +/- 8.6) as age-matched controls. Phosphorus-31 magnetic resonance spectroscopic imaging of the heart was performed in all subjects using a 1.5-T whole-body magnetic resonance scanner. The ratios of phosphocreatine (PCr) to beta-adenosinetriphosphate (beta-ATP) were calculated. Moreover, echocardiographic evaluation and stress tests were performed in all individuals. RESULTS: The myocardium of patients with diabetes mellitus type I showed significantly decreased ratios of PCr to beta-ATP compared with healthy controls in the left ventricle (1.90 +/- 0.4 vs. 2.15 +/- 0.3, p < 0.05). We found a moderate negative correlation between the ratio of PCr to beta-ATP in the left ventricle and both, the diastolic left ventricular function (E/A; r = -0.41) and the glycohemoglobin A1c (GHbA1c; r = -0.42). CONCLUSION: This study demonstrates for the first time a decreased ratio of PCr to beta-ATP in the myocardium of persons with diabetes mellitus type I without a known history of coronary heart disease.

Adenosine Triphosphate↗

Heme oxygenase activity modulates vascular endothelial growth factor synthesis in vascular smooth muscle cells.

Hypoxia, cytokines, and nitric oxide (NO) stimulate the generation of vascular endothelial growth factor (VEGF) and induce heme oxygenase-1 (HO-1) expression in vascular tissue. HO-1 degrades heme to carbon monoxide (CO), iron, and biliverdin, the latter being reduced to bilirubin by biliverdin reductase. In the present study, we investigated the role of HO-1 in the modulation of VEGF synthesis in rat vascular smooth muscle cells (VSMC). In VSMC stimulated with cytokines, inhibition of NO production significantly, but not completely, reduced VEGF release. In contrast, inhibition of HO activity by tin protoporphyrin IX (SnPPIX) totally prevented cytokine-induced increase in VEGF, despite an augmented synthesis of intracellular NO. Stimulation of HO-1 activity by hemin enhanced VEGF production; this effect was abrogated by blockade of the HO pathway. Similarly, VEGF synthesis induced by hypoxia was down-regulated by SnPPIX, but not by inhibitors of NO synthase. To elucidate further a direct involvement of HO-1 in the observed effects, we generated transfected cells that overexpressed the HO-1 gene. Notably, these cells synthesized significantly more VEGF protein than cells transfected with a control gene. Among the products of HO-1, biliverdin and bilirubin showed no effect, whereas iron ions inhibited VEGF synthesis. Exposure of cells to 1% CO resulted in a marked accumulation of VEGF (20-fold increase) over the basal level. Our data indicate that HO-1 activity influences the generation of VEGF in VSMC in both normoxic and hypoxic conditions. As CO and iron, respectively the inducer and the inhibitor of VEGF synthesis, are concomitantly produced during the degradation of heme, these data indicate that HO by-products may differentially modulate VEGF production.

Animals↗