Search PubMed⌕ Search

Biomedical subjects

G Ertl

Publications and source records attributed to G Ertl.

At least 109 records · Page 6Linked to original sources
PubMed1998

[Transition of myocardial ischemia to heart failure].

Myocardial ischemia results in myocardial dysfunction. Recovery may be delayed ("stunning"), or persistent if perfusion remains reduced ("hibernation") and ischemia may go on to necrosis, thus, contributing to chronic heart failure. In addition, myocardium not directly affected by ischemia may undergo adaptive processes like hypertrophy and dilatation, which may result in chronic left heart failure. This process is characterized by hemodynamic, neurohumoral, and progressive morphologic changes of the heart which are closely interrelated. Hemodynamic changes basically consist of an increase in left ventricular filling pressure and a decrease in global ejection fraction, and, in most cases years after myocardial infarction, in an increase in systemic vascular resistance and right atrial pressure. Neurohumoral changes consist of an increase in plasma catecholamines, atrial natriuretic factor and vasopressin, and in an activation of the renin-angiotensin-system. Plasma endothelin-1 was recently reported to be increased in patients with heart failure, and prognosis was related to endothelin levels. Diminished response of vessels to endothelium (EDRF/NO) dependent vasodilatation suggests impairment of vascular endothelium in heart failure. Local changes of cardiac neurohumoral systems could contribute to structural changes of the heart, e.g., systemic activation to hemodynamic changes. Structural changes of the heart are characterized by an increase in volume and thickness of surviving myocardium and an expansion of ischemic and necrotic myocardium. Molecular control of these processes which include various cell types, such as cardiomyocytes and cardiofibroblasts, are currently an issue of intense research and could result in specific therapeutic importance.

Chronic Disease↗
PubMed1998

Chronic effects of early started angiotensin converting enzyme inhibition and angiotensin AT1-receptor subtype blockade in rats with myocardial infarction: role of bradykinin.

OBJECTIVE: The long-term effects and mechanisms of early started angiotensin converting enzyme (ACE) inhibition post myocardial infarction (MI) are not well understood. Chronic effects of early ACE inhibition on hemodynamics, left ventricular diastolic wall stress and remodeling were, therefore, compared to that of angiotensin AT1-receptor subtype blockade in rats with experimental myocardial infarction. The contribution of bradykinin potentiation to both ACE inhibitor and angiotensin AT1-receptor subtype blockade was assessed by cotreatment of rats with a bradykinin B2-receptor antagonist. METHODS: MI was produced by coronary artery ligation in adult male Wistar rats. The ACE inhibitor, quinapril (6 mg/kg per day), or the angiotensin AT1-receptor subtype blocker, losartan (10 mg/kg per day), administered by gavage, and the bradykinin B2-receptor antagonist, Hoe-140 (500 micrograms/kg per day s.c.), administered either alone or in combination with quinapril or losartan, were started 30 min after MI and continued for eight weeks. RESULTS: Quinapril and losartan reduced left ventricular end-diastolic pressure and global left ventricular diastolic wall stress only in rats with large MI. Pressure volume curves showed a rightward shift in proportion to MI size that was not prevented by quinapril or losartan treatment. Only the ACE inhibitor reduced left ventricular weight and this effect was prevented by cotreatment with the bradykinin antagonist. Baseline and peak cardiac index and stroke volume index, as determined using an electromagnetic flowmeter before and after an acute intravenous volume load, were restored by quinapril, whereas losartan had no effects. CONCLUSION: Treatments starting 30 min after coronary artery ligation, with either quinapril or losartan, reduced preload only in rats with large MI. Despite this unloading of the heart, structural dilatation was not prevented by this early treatment. Only quinapril improved cardiac performance and reduced left ventricular weight and this effect was abolished by cotreatment with Hoe-140, suggesting an angiotensin II blockade-independent, but bradykinin potentiation-dependent, mechanism.

Adrenergic beta-Antagonists↗
PubMed1998

Aggravation of left ventricular remodeling by a novel specific endothelin ET(A) antagonist EMD94246 in rats with experimental myocardial infarction.

An endothelin (ET(A)) antagonist reduced mortality and an ET(A) + ET(B) antagonist prevented left ventricular dilatation in rats with large myocardial infarction. This study tested the hypothesis that long-term blockade of the ET(A) receptor would have beneficial effects on left ventricular function and remodeling. Three hours after coronary artery ligation or sham operation in rats, EMD94246 (100 mg/kg/day, n=62) or placebo (n=62) was given by gavage. Eight weeks later, left ventricular hemodynamic measurements were performed and left ventricular volume determined with a double-lumen catheter after KCl-induced cardiac arrest. EMD94246 treatment had no effects on mortality or hemodynamic parameters. In rats with large infarcts, EMD94246 significantly increased left ventricular volume (2.5+/-0.1 vs. 2.2+/-0.1 ml/kg; p < 0.05). The nonpeptide ET(A)-selective antagonist EMD94246 promoted chronic left ventricular dilatation in rats with large myocardial infarction.

Animals↗
PubMed1997

Atomic and macroscopic reaction rates of a surface-catalyzed reaction

The catalytic oxidation of carbon monoxide (CO) on a platinum (111) surface was studied by scanning tunneling microscopy. The adsorbed oxygen atoms and CO molecules were imaged with atomic resolution, and their reactions to carbon dioxide (CO2) were monitored as functions of time. The results allowed the formulation of a rate law that takes the distribution of the reactants in separate domains into account. From temperature-dependent measurements, the kinetic parameters were obtained. Their values agree well with data from macroscopic measurements. In this way, a kinetic description of a chemical reaction was achieved that is based solely on the statistics of the underlying atomic processes.

Journal Article↗
PubMed1997

Chronic endothelin receptor blockade attenuates progressive ventricular dilation and improves cardiac function in rats with myocardial infarction: possible involvement of myocardial endothelin system in ventricular remodeling.

BACKGROUND: Left ventricular dilatation after myocardial infarction is associated with impaired ventricular function and heart failure and has important implications for survival. The purpose of this study was to investigate the role of endothelin-1 (ET-1) in ventricular dilatation and the effects of chronic endothelin receptor blockade by a mixed ET(A) and ET(B) receptor blocker (bosentan) on the circulating and cardiac endothelin systems. METHODS AND RESULTS: Three hours after coronary ligation or sham operation, bosentan (100 mg x kg body wt(-1) x d(-1)) or placebo was given by gavage. Seven days and 8 weeks after surgery, hemodynamic and left ventricular volume studies were performed. Acute bosentan treatment (7 days) had no effects on hemodynamic parameters and early left ventricular dilatation. In the rats with large infarcts, chronic bosentan treatment (8 weeks) versus placebo reduced left ventricular systolic pressure (116+/-2 versus 125+/-3 mm Hg, P<.05) and arterial pressure (93+/-2 versus 103+/-3 mm Hg, P<.05), improved stroke volume index (0.69+/-0.06 versus 0.52+/-0.04 mL/kg, P<.05), and prevented in part the rightward shift of the pressure-volume curve. Chronic bosentan treatment also decreased ET-1 levels (390+/-33 versus 475+/-22 pg/g tissue, P<.05) and density of ET-1 receptors (262+/-24 versus 346+/-31 fmol/mg protein, P<.05) in left ventricular myocardium. CONCLUSIONS: In the present study, a mixed ET(A) and ET(B) receptor antagonist (bosentan) partially prevented left ventricular dilatation and improved hemodynamics, suggesting that endothelin plays a role in left ventricular remodeling after myocardial infarction. Supporting this hypothesis, we show inhibitory effects of bosentan on the peripheral and myocardial endothelin system.

Animals↗
PubMed1997

Myocardial phosphocreatine-to-ATP ratio is a predictor of mortality in patients with dilated cardiomyopathy.

BACKGROUND: In patients with heart failure due to dilated cardiomyopathy, cardiac energy metabolism is impaired, as indicated by a reduction of the myocardial phosphocreatine-to-ATP ratio, measured noninvasively by 31P-MR spectroscopy. The purpose of this study was to test whether the phosphocreatine-to-ATP ratio also offers prognostic information in terms of mortality prediction as well as how this index compares with well-known mortality predictors such as left ventricular ejection fraction (LVEF) or New York Heart Association (NYHA) class. METHODS AND RESULTS: Thirty-nine patients with dilated cardiomyopathy were followed up for 928+/-85 days (2.5 years). At study entry, LVEF and NYHA class were determined, and the cardiac phosphocreatine-to-ATP ratio was measured by localized 31P-MR spectroscopy of the anterior myocardium. During the study period, total mortality was 26%. Patients were divided into two groups, one with a normal phosphocreatine-to-ATP ratio (>1.60; mean+/-SE, 1.98+/-0.07; n=19; healthy volunteers: 1.94+/-0.11, n=30) and one with a reduced phosphocreatine-to-ATP ratio (<1.60; 1.30+/-0.05; n=20). At re-evaluation (mean, 2.5 years), 8 of 20 patients with reduced phosphocreatine-to-ATP ratios had died, all of cardiovascular causes (total and cardiovascular mortality, 40%). Of the 19 patients with normal phosphocreatine-to-ATP ratios, 2 had died (total mortality, 11%), one of cardiovascular causes (cardiovascular mortality, 5%). Kaplan-Meier analysis showed significantly reduced total (P=.036) and cardiovascular (P=.016) mortality for patients with normal versus patients with low phosphocreatine-to-ATP ratios. A Cox model for multivariate analysis showed that the phosphocreatine-to-ATP ratio and NYHA class offered significant independent prognostic information on cardiovascular mortality. CONCLUSIONS: The myocardial phosphocreatine-to-ATP ratio, measured noninvasively with 31P-MR spectroscopy, is a predictor of both total and cardiovascular mortality in patients with dilated cardiomyopathy.

Adenosine Triphosphate↗
PubMed1997

The effect of perfusion on T1 after slice-selective spin inversion in the isolated cardioplegic rat heart: measurement of a lower bound of intracapillary-extravascular water proton exchange rate.

Many NMR measurements of cardiac microcirculation (perfusion, intramyocardial blood volume) depend on some kind of assumption of intracapillary-extravascular water exchange rate, e.g., fast exchange. The magnitude of this water exchange rate, however, is still unknown. The intention of this study was to determine a lower limit for this exchange rate by investigating the effect of perfusion on relaxation time. Studies were performed in the isolated perfused cardioplegic rat heart. After slice-selective inversion, the spin lattice relaxation rate of myocardium within the slice was studied as a function of perfusion and compared with a mathematical model which predicts relaxation rate as a function of perfusion and intracapillary-extravascular exchange rate. A linear relationship was found between relaxation rate T(-1) and perfusion P normalized by perfusate/tissue partition coefficient of water, lambda: deltaT(-1) = m x deltaP/lambda with 0.82 < or = m < or = 1.06. Insertion of experimental data in the model revealed that a lower bound of the exchange rate from intra- to extravascular space is 6.6 s(-1) (4.5 s(-1), P < 0.05), i.e., the intracapillary lifetime of a water molecule is less than 150 ms (222 ms, P < 0.05). Based on this finding, the T1 mapping after slice-selective inversion could become a valuable noncontrast NMR method to measure variations of perfusion.

Animals↗
PubMed1997

Study of microcirculation by coloured microspheres and NMR-microscopy in isolated rat heart: effect of ischaemia, endothelin-1 and endothelin-1 antagonist BQ 610.

Although the investigation of coronary microcirculation is of great importance, available methods have severe restrictions. They do not allow the study of vasodynamics of resistance vessels and microscopic conductance vessels simultaneously in the isolated beating rat heart. We now demonstrate that the combined measurement of perfusion which reflects the state of resistance vessels and cross-sections of microscopic conductance vessels is feasible in the model of the isolated constant flow perfused rat heart. Perfusion measurement was based on injection of coloured microspheres. Cross-sections of microscopic conductance vessels (diameter >140 micron) were determined by NMR-microscopy by flow weighted imaging. Both methods were established recently by our group. The combined measurement was applied to hearts which were subjected to ischaemia and reperfusion (group 1: n=5, 15 min ischaemia/group 2: n=7, 30 min ischaemia/measurements before ischaemia and 15/30 min after reperfusion), 200 pmol endothelin-1 bolus application (group 3: n=6/measurements before and 5 min after drug application), continuous infusion of the endothelin-1 antagonist BQ 610 (group 4: n=6/measurements before and 20 min after onset of infusion), and 200 pmol endothelin-1 application superimposed on 20 min of continuous BQ 610 infusion (group 5: n=7/combined measurement before BQ 610 infusion and 5 min after endothelin-1 application). In group 1, 15 min reperfusion restored the pre-ischaemic perfusion state, whereas conductance vessels were dilated (80.8+/-2.6%), after 30 min reperfusion pre-ischaemic conditions were also restored for conductance vessels. In group 2, a redistribution of perfusion from left ventricular endocardium to the right ventricular wall was observed. Post-ischaemic rhythm disturbances made NMR-imaging in this group impossible. In group 3, a shift of perfusion from the left ventricular myocardium to the right ventricular wall was observed. Similarly, the cross-section of left ventricular conductance vessels decreased (-32.6+/-2.1%), whereas size of right ventricular vessels increased. In group 4, BQ 610 had no effect on perfusion nor on vessel size and antagonized the effect of endothelin-1 on perfusion and vessel size in group 5.

Animals↗
PubMed1997

Cardiac high-energy phosphate metabolism in patients with aortic valve disease assessed by 31P-magnetic resonance spectroscopy.

BACKGROUND: The purpose of this work was to determine the clinical and hemodynamic correlates of alterations in cardiac high-energy phosphate metabolism in patients with aortic stenosis and with aortic incompetence. METHODS: Fourteen volunteers, 13 patients with aortic stenosis, and 9 patients with aortic incompetence were included. Patients underwent echocardiography and left and right heart catheterization. 31P-MR spectra from the anterior myocardium were obtained with a 1.5 Tesla clinical MR system. RESULTS: Aortic stenosis and aortic incompetence patients had similar New York Heart Association (NYHA) classes (2.77 +/- 0.12 vs 2.44 +/- 0.18), ejection fractions (normal), left ventricular (LV) end-diastolic pressures, and LV wall thickness. In volunteers, phosphocreatine/adenosine triphosphate (ATP) ratios were 2.02 +/- 0.11. For all patients, phosphocreatine/ATP was significantly reduced (1.64 +/- 0.09; *p = 0.011 vs volunteers). Phosphocreatine/ATP decreased to 1.55 +/- 0.12 (*p = 0.008) in aortic stenosis, while in aortic incompetence, phosphocreatine/ATP only showed a trend for a reduction (1.77 +/- 0.12; p = 0.148). For all patients, phosphocreatine/ATP decreased significantly only with NYHA class III (1.51 +/- 0.09; *p = 0.001), but not with NYHA classes I and II (phosphocreatine/ATP 1.86 +/- 0.18). In aortic stenosis, phosphocreatine/ATP ratios decreased (1.13 +/- 0.03; *p = 0.019) only when LV end-diastolic pressures were > 15 mm Hg or when LV diastolic wall stress was > 20 kdyne cm-2 (1.13 +/- 0.03; *p = 0.024). CONCLUSIONS: For a similar clinical degree of heart failure in human myocardium, volume overload hypertrophy does not, but pressure overload does, induce significant impairment of cardiac high-energy phosphate metabolism. In aortic valve disease, alterations of high-energy phosphate metabolism are related to the degree of heart failure.

Adenosine Triphosphate↗
PubMed1996

Chemiluminescence in the Agglomeration of Metal Clusters

The agglomeration of copper or silver atoms in a matrix of noble gas atoms to form small clusters may be accompanied by the emission of visible light. Spectral analysis reveals the intermediate formation of electronically excited atoms and dimers as the source of the chemiluminescence. A mechanism is proposed, according to which the gain in binding energy upon cluster formation may even lead to the ejection of excited fragments as a result of unstable intermediate configurations. A similar concept was introduced in the field of nuclear reactions by Niels Bohr 60 years ago.

Journal Article↗