Biomedical subjects

G Ertl

Publications and source records attributed to G Ertl.

At least 55 records · Page 3Linked to original sources

PubMed2001

Serial magnetic resonance imaging of microvascular remodeling in the infarcted rat heart.

BACKGROUND: Alterations in the coronary circulation are important determinants of myocardial function. Few data are available, however, about microvascular changes in reactive hypertrophy. With MRI, serial determination of myocardial microcirculation after myocardial infarction (MI) is feasible. METHODS AND RESULTS: We quantitatively determined myocardial perfusion and relative intracapillary blood volume using an MRI technique. Infarct size, myocardial mass, and left ventricular volumes were determined with cine MRI. Rats were investigated at 8, 12, and 16 weeks after MI (mean MI size 24.1+/-2.0%) or sham operation. Vasodilation was induced by adenosine. In the infarcted group, maximum perfusion decreased significantly from 8 to 16 weeks (5.6+/-0.3 versus 3.5+/-0.2 mL. g(-1). min(-1), P<0.01) compared with sham animals (5.5+/-0.3 versus 5.0+/-0.2 mL. g(-1). min(-1), P=0.17). Myocardial mass increased significantly (559.1+/-20.8 mg at 8 weeks versus 690.9+/-42.7 mg at 16 weeks, P<0.05) compared with sham-operated animals (516.3+/-41.7 versus 549.2+/-32.3 mg). Basal relative intracapillary blood volume increased significantly to 15.7+/-0.5 vol% at 8 weeks after MI and remained elevated (16.8+/-0.6 vol%) at 16 weeks compared with 12.1+/-0.3 vol% (P<0.01) in sham-operated rats. CONCLUSIONS: Our results indicate that significant microvascular changes occur during cardiac remodeling. Hypoperfusion in the hypertrophied myocardium is related to an increase in vascular capacity, suggesting a compensatory vasodilatory response at the capillary level. These microvascular changes may therefore contribute to the development of heart failure.

Animals↗

PubMed2001

Turing-type patterns on electrode surfaces.

We report stationary, nonequilibrium potential and adsorbate patterns with an intrinsic wavelength that were observed in an electrochemical system with a specific type of current/electrode-potential (I-phi(DL)) characteristic. The patterns emerge owing to the interplay of a self-enhancing step in the reaction dynamics and a long-range inhibition by migration currents rather than by diffusion. Theoretical analysis revealed that this self-structuring of the electrode occurs in all electrochemical systems with an S-shaped I-phi(DL) characteristic in wide and well-accessible parameter ranges. This unusual pattern-forming instability in electrochemical systems has all the characteristics of the mechanism proposed by Turing in 1952 in the framework of an early theory of morphogenesis. Our finding might account for structure formation in certain biological systems that have gradients in the electric potential and may open new paths for fabricating patterned electrodes.

Journal Article↗

PubMed2001

Fast high-resolution magnetic resonance imaging demonstrates fractality of myocardial perfusion in microscopic dimensions.

The fractal nature of heterogeneity of myocardial blood flow and its implications for the healthy and diseased heart is not yet understood. The main hindrance for investigation of blood flow heterogeneity and its role in physiology and pathophysiology is that conventional methods for determination of myocardial perfusion have severe limitations concerning temporal and spatial resolution and invasiveness. In isolated rat hearts, we developed a nuclear magnetic resonance technique that does not depend on contrast agents and in which the apparent longitudinal relaxation time is made perfusion sensitive by selective preparation of the imaging slice. This perfusion-sensitive relaxation time is determined within 40 seconds as a map with a high spatial in-plane resolution of 140x140 microm(2) and a thickness of 1.5 mm. Perfusion imaging was validated with the established microsphere technique. Additionally, the congruence between perfusion-sensitive T:(1) maps and first-pass perfusion imaging was demonstrated. As an application of high-resolution perfusion imaging, fractal analysis of the spatial distribution of perfusion was performed. We were able to demonstrate that the fractality of this distribution exists even in microscopic dimensions. Vasodilation by nitroglycerin modulated the fractal pattern of perfusion, and the decrease of the fractal dimension indicated a shift toward homogeneity. This implies that parameters of the fractal distribution depend on the microvascular tone rather than on anatomic preformations; ie, fractality is a functional characteristic of perfusion.

Animals↗

PubMed2001

Heterogeneous catalysis on the atomic scale.

Information about the elementary processes underlying heterogeneous catalysis may be obtained by investigating well-defined single crystal surfaces. The success of this "surface science" approach for "'real" catalysis can be demonstrated, for example, with ammonia synthesis. The progress of catalytic reactions can be observed on an atomic scale by applying scanning tunneling microscopy and other surface physical techniques, as is shown with different examples in this paper: CO oxidation on a Pt(111) surface proceeds preferentially along the boundaries between adsorbed O and CO patches. Ru is practically inactive for the same reaction under lower pressure conditions but is transformed into RuO2 under atmospheric pressure conditions, where part of the surface Ru atoms function as coordinatively unsaturated sites (cus). In contrast, in the hydrogen oxidation reaction on Pt(111), an autocatalytic reaction step comes into prominence, and is responsible for the formation of propagating concentration patterns on the surface as a characteristic of nonlinear dynamics. Additionally, the limits of the concept of thermal equilibrium in surface rate processes are explored by applying ultrafast (femtosecond) laser techniques.

Journal Article↗

PubMed2001

Angiotensin II type 1 receptor regulation and differential trophic effects on rat cardiac myofibroblasts after acute myocardial infarction.

Fibroblast growth in the scar and surviving tissue is a key element of the remodeling post myocardial infarction. The regulation of fibroblast growth after acute myocardial infarction remains to be determined. Recently, Angiotensin II has been demonstrated to be a mitogen for neonatal cardiac fibroblasts. In this study adult rat cardiac fibroblasts were isolated from different regions of the infarcted rat heart and Angiotensin II effects examined. Adult Wistar-rats were sham operated or left coronary artery ligated. After 4 days, hearts were removed and fibroblasts from sham operated, infarct- and non-infarct regions of the left ventricle isolated. Radioligand binding studies were performed and cell number, cell area, total protein, and AT(1) receptor mRNA after stimulation determined. Radioligand binding studies demonstrated that myofibroblasts expressed a single class of high affinity Angiotensin II AT(1) receptors. Myofibroblasts from the infarct area revealed a lower maximal binding capacity, compared to sham operated myocardium. Conversely, myofibroblasts from the non-infarct area had a higher expression of Angiotensin II AT(1) receptor mRNA compared to sham operated myofibroblasts. Angiotensin II (1 microM, 48 h) increased cell-number in sham operated and non-infarct, but not in infarct myofibroblasts. Angiotensin II elevated total protein in sham operated, non-infarct, and infarct myofibroblasts. In addition, Angiotensin II increased cell area in sham operated and infarct myofibroblasts. These data demonstrate that Angiotensin II acted as a mitogen in sham operated and non-infarct myofibroblasts and stimulated hypertrophy in infarct myofibroblasts. These regional different effects of Angiotensin II might participate in the remodeling post myocardial infarction.

Angiotensin II↗

PubMed2001

Serial cine-magnetic resonance imaging of left ventricular remodeling after myocardial infarction in rats.

The purpose of the present study was the serial investigation of morphological and functional changes after left coronary artery ligation in the intact rat using cine-magnetic resonance imaging (MRI). MRI studies were performed 4, 8, 12, and 16 weeks after myocardial infarction (MI) with an echocardiogram (ECG)-triggered cine-fast low-angle shot (FLASH)-sequence in a 7-Tesla magnet. MI-size, left ventricular (LV) mass and volumes, cardiac index, ejection fraction (EF), and remote wall and scar thickness of 11 Wistar rats were compared to four sham-operated rats. Stress MRI with dobutamine (10 microl/kg x minute) was performed at 16 weeks. In MI groups (small MI < 30%, N = 5, large MI > 30%, N = 6), there was significant increase of LV mass (small MI + 47.8% increase, large MI + 74.1%) and wall thickness (large MI 1.21 +/- 0.03 to 1.84 +/- 0.07 mm). Scar thickness declined from four to 16 weeks (large MI 0.92 +/- 0.06 to 0.38 +/- 0.02 mm, P < 0.05). End-diastolic volume of both MI groups was significantly elevated but increased further only in animals with large MI from four to 16 weeks (657.1 +/- 38.6 to 869.7 +/- 60.7 microL, P < 0.05). Compared to sham, EF was significantly depressed in MI (large MI 31.5 +/- 2.0%). Wall thickening declined from four to 16 weeks post-MI (large MI 50.9 +/- 9.9 to 28.9 +/- 4.4%, P < 0.05). During stress, sham and MI rats increased wall thickening from 66.5 +/- 8.2 to 111.2 +/- 6.7% and from 30.8 +/- 4.3 to 47.5 +/- 5.8%, respectively (P < 0.05). Hypertrophy was found in all animals with MI throughout the entire period of observation, whereas dilatation after four weeks was only detected in animals with large MI. These morphologic changes were accompanied by an early decline of EF; myocardial function characterized by wall thickening deteriorated later.

Animals↗

PubMed2001

Combined high-speed NMR imaging of perfusion and microscopic coronary conductance vessels in the isolated rat heart.

Noninvasive characterization of microcirculation at the level of both coronary conductance and resistance vessels is of major importance for the understanding of microvascular adaptive processes in the heart. The objective of this study was to determine simultaneously myocardial perfusion and microvessel diameters in the myocardium by magnetic resonance (MR) imaging within the same heart. A MR imaging method is presented which combines high-resolution perfusion measurement (140 x 140 microm2) by spin labeling with flow-weighted MR microscopy of coronary microvessels (phi > 140 microm). We determined changes in myocardial perfusion and vessel diameters of isolated beating rat hearts (n = 10) at rest and during administration of nitroglycerin (0.5 mg/min). Alterations in perfusion were validated by microsphere measurements. Under the influence of nitroglycerin an increase in perfusion (+2.51 +/- 0.4 ml x min(-1) x g(-1), mean +/- SEM) and vessel diameters (+14.22 +/- 1.92%) could be observed. Endocardial perfusion revealed a modest enhanced susceptibility to nitroglycerin in comparison to epicardial perfusion. Analysis of vessels according to their diameters showed no significant differences. MR imaging allows the noninvasive and simultaneous determination of conducting arteries and smaller resistance vessels in one and the same beating rat heart. Due to an excellent spatial resolution of these methods, transmural characterization of both parameters at rest and during vasodilation is feasible.

Animals↗

PubMed2001

Temporal fluctuations of myocardia high-energy phosphate metabolite with the cardiac cycle.

This review describes the temporal changes of high-energy phosphate metabolites during the cardiac cycle. Under baseline condition, the extent of cyclical changes ("cycling") of ATP, phosphocreatine and inorganic phosphate varies between 10-15%. Such energy oscillations are not augmented under various forms of metabolic stress including 1) inotropic stimulation, 2) acute hypoxia and 3) failing, chronically infarcted hearts. Thus, the concentrations of high-energy phosphates over the cardiac cycle are a tightly regulated entity, even when energetic needs are substantially augmented.

Adenosine Triphosphate↗

PubMed2001

Time course of cardiac structural, functional and electrical changes in asymptomatic patients after myocardial infarction: their inter-relation and prognostic impact.

OBJECTIVES: We prospectively studied the relationship between left ventricular (LV) dilation, dysfunction, electrical instability and death in patients after a first myocardial infarction (MI) without symptoms of heart failure and ischemia. BACKGROUND: Mechanisms linking LV dysfunction and sudden death in patients after MI remained controversial. METHODS: Left ventricular volumes, hemodynamics, electrocardiogram and 24-h Holter recordings were sequentially obtained between two days and seven years after MI. Left ventricular catheterization and coronary angiography were performed, and revascularization was performed if appropriate. RESULTS: Death occurred in 16 (12%) of the 134 patients included; it was of cardiac origin in 14 (88%) and sudden in origin in 12 (75%) patients. Of 37 (28%) patients with LV dilation, 12 died (32%); four patients (5.8%) died in the group without dilation. Left ventricular dilation was closely related to signs of electrical instability, as indicated by a significant correlation between end-diastolic LV volume index, Lown score (r = 0.98, p < 0.0001) and QTc prolongation (r = 0.998, p < 0.01), respectively. CONCLUSIONS: Patients with progressive remodeling are at increased risk of sudden death in chronic MI. Cardiac electrical instability is closely related to progressive LV dilation. Parameters of electrical instability and remodeling are predictors of sudden death. The findings suggest that remodeling might serve as a link between dysfunction, electrical instability of the heart and sudden death after MI.

Cardiac Output↗

PubMed2001

Endogenous cannabinoids mediate hypotension after experimental myocardial infarction.

OBJECTIVES: We sought to determine whether endocannabinoids influence hemodynamic variables in experimental models of acute myocardial infarction (MI). BACKGROUND: Hypotension and cardiogenic shock are common complications in acute MI. Cannabinoids are strong vasodilators, and endocannabinoids are involved in hypotension in hemorrhagic and septic shock. METHODS: The early effect of left coronary artery ligation on hemodynamic variables was measured in rats pretreated with the selective cannabinoid(1) receptor (CB(1)) antagonist SR141716A (herein referred to as SR, 6.45 micromol/kg body weight intravenously) or vehicle. Endocannabinoids produced in monocytes and platelets were quantified by liquid chromatography/mass spectrometry (LC/MS), and their effects on blood pressure and vascular reactivity were determined. RESULTS: After MI, mean arterial pressure (MAP) dropped from 126 +/- 2 mm Hg to 76 +/- 3 mm Hg in control rats, whereas the decline in blood pressure was smaller (from 121 +/- 3 mm Hg to 108 +/- 7 mm Hg, p < 0.01) in rats pretreated with SR. SR increased the tachycardia that follows MI (change [Delta] in heart rate [HR] = 107 +/- 21 beats/min vs. 49 +/- 9 beats/min in control rats, p < 0.05). The MI sizes were the same in control rats and SR-treated rats. Circulating monocytes and platelets isolated 30 min after MI only decreased MAP when injected into untreated rats (DeltaMAP = -20 +/- 5 mm Hg), but not in SR-pretreated rats. The endocannabinoids anandamide and 2-arachidonyl glycerol were detected in monocytes and platelets isolated after MI, but not in cells from sham rats. Survival rates at 2 h after MI were 70% for control rats and 36% for SR-treated rats (p < 0.05). Endothelium-dependent arterial relaxation was attenuated in SR-treated rats (maximal relaxation: 44 +/- 3% [p < 0.01] vs. 70 +/- 3% in control rats) and further depressed by SR treatment (24 +/- 5%, p < 0.01 vs. MI placebo). CONCLUSIONS: Cannabinoids generated in monocytes and platelets contribute to hypotension in acute MI. Cannabinoid(1) receptor blockade restores MAP but increases 2-h mortality, possibly by impairing endothelial function.

Animals↗

PubMed2001

Myocardial perfusion imaging using a non-contrast agent MR imaging technique.

INTRODUCTION: A MR imaging (MRI) method has been developed to determine quantitatively myocardial perfusion (P) in the rat heart in vivo. This method has the potential to non-invasively measure cardiac perfusion without the use of a contrast agent by exploiting the endogenous contrast from flowing blood itself. METHOD AND RESULTS: Principle of the technique is the arterial spin labeling of endogenous water protons within the short axis imaging slice. Arterial spin labeling techniques are based on a model that uses inflow effects to relate intrinsic changes in longitudinal relaxation (T1) to tissue perfusion. Perfusion is determined from the difference between a slice selective and a global inversion recovery experiment. Perfusion was determined at rest and during hyperemia induced by intravenous adenosine (3 mg/(kg min)). The MR perfusion values were compared with perfusion data obtained in the same animal using the colored microspheres (MS) technique as the gold standard. The MR perfusion (mean +/- SEM) was 3.3 +/- 0.2 ml/min/g at rest and 4.6 +/- 0.6 ml/min/g during adenosine. Perfusion values obtained by colored MS were 3.4 +/- 0.2 and 4.7 +/- 0.8 ml/min/g at rest and during vasodilation, respectively. Adenosine decreased mean arterial pressure (MAP) from 120 to 65 mmHg which implies a reduction of coronary resistance (CR) to about 50% of baseline. CONCLUSION: Our study shows that quantitative mapping of perfusion may be performed non-invasively by MRI. The MR perfusion data are in excellent correlation with data obtained by the well-established colored MS technique. Determination of perfusion reserve confirms that coronary perfusion is highly dependent on blood pressure due to changes in CR.

Animals↗

PubMed2001

Postpericardiotomy syndrome and cardiac tamponade as a late complication after pacemaker implantation.

In a 78-year old woman, pacemaker implantation was complicated by a transient perforation of the endocardial lead. The patient was in stable condition for up to 7 weeks after implantation, after which pericardial effusion and subacute cardiac tamponade developed and pericardiocentesis became necessary. This case illustrates that even after initially uneventful pacemaker lead perforation, careful, long-term follow-up is necessary to recognize the potential development of late postpericardiotomy syndrome.

Aged↗

PubMed2001

Cardiac metabolism and function in patients with multiple sclerosis: a combined 31P-MR-spectroscopy and MRI study.

OBJECTIVE: Involvement of the autonomic system in multiple sclerosis (MS) may concur with dysfunction of the cardiovascular system. The introduction of potentially cardiotoxic immunosuppressive drugs like Mitoxantrone into the treatment of MS warrants proper assessment of preexisting heart disease. However, systematic analyses of functional and metabolic derangements in MS are missing. Using quantitative 31P-MR-spectroscopy (MRS) and MR-imaging (MRI) metabolic and functional parameters were analyzed in patients with MS in comparison to healthy volunteers. SUBJECTS/METHODS: 14/15 patients with MS could be included in the study, as the MRS examination of one patient had to be excluded from analysis due to movement during the examination. Using chemical shift imaging (CSI) and AMARES, phosphocreatine (PCr) to adenosine triphosphate (ATP) ratios, characterizing myocardial high-energy phosphate metabolism, were determined. Additionally, absolute concentrations of PCr and ATP were calculated by SLOOP (Spatial Localization with Optimal Pointspread Function). Analysis of functional changes was performed by Cine-MRI. 14 healthy volunteers matched for age and gender served as control. RESULTS: A significant decrease of absolute PCr concentration was observed in patients with MS compared to matched volunteers (p < 0.05), whereas ATP concentrations showed no significant changes (p = 0.27). Metabolite ratios calculated by SLOOP or AMARES showed a tendency to be reduced in patients, however, did not reach significance (p = 0.08, SLOOP; p = 0.47, AMARES). Using volunteers' mean values +/- 2 x SD as cut off value revealed PCr changes in 5 of 14 patients, whereas only 2 also had pathologic PCr/ATP ratios. Functional analysis by MRI depicted depressed left ventricular ejection fraction in 4 patients. CONCLUSIONS: The reduction in cardiac high-energy phosphates in some patients with MS points to a subclinical involvement of the heart. This may be important for treatment with potentially cardiotoxic drugs. Longitudinal studies are need to understand the clinical relevance of our findings.

Adenosine Triphosphate↗

PubMed2001

Mechanisms of the effects of nicorandil in the isolated rat heart during ischemia and reperfusion: a 31P-nuclear magnetic resonance study.

Nicorandil (SG75) is a potent K+-channel activator with an additional nitro moiety. In the present study we investigated the potential mechanisms (K+-channel activation and nitric oxide [NO] release) for the effects of nicorandil on isolated perfused rat hearts during total global ischemia using 31P-nuclear magnetic resonance. After a 10-min control perfusion, hearts were subjected to treatment with nicorandil-containing (100, 300, or 1000 microM) buffer for 10 min, 15 min of total global ischemia, and 30 min of reperfusion. At high dose (10(-3) M), nicorandil reduced ATP depletion during ischemia by 26% compared with untreated hearts. Blockade of K+ channels by glibenclamide prevented this protective effect. At all doses (10(-4) to 10(-3) M), nicorandil reduced the accumulation of protons during ischemia compared with untreated hearts (pH 6.22 +/- 0.03 vs. 6.02 +/- 0.05 in untreated hearts at the end of ischemia). This effect was preserved after blockade of K+ channels by glibenclamide. Hearts treated with nitroglycerine before ischemia also showed reduced proton accumulation. Therefore, NO release accompanied by increased coronary flow before ischemia, which is caused by the nitro moiety of nicorandil and nitroglycerine treatment, results in reduced proton accumulation. During reperfusion, a pro-arrhythmic effect was observed in hearts treated with the nonpharmacologically high dose of nicorandil (1000 microM). Thus, we conclude that the effects of nicorandil are caused by the simultaneous action of both mechanisms K+-channel activation and NO release. The activation of K+ channels prevents deterioration of ATP during ischemia, whereas NO release and increased coronary flow reduce the accumulation of protons--and thus the decrease in pH--during ischemia.

Animals↗

PubMed2001

Anti-ischemic potential of drugs related to the renin-angiotensin system.

Actions mediated by the renin-angiotensin system may be inhibited at various levels: renin itself may be inhibited, angiotensin-I (A-1) conversion to angiotensin-II (A-II), or binding of A-II at the A-II type 1 (A-II1) receptor. The angiotensin-converting enzyme (ACE) inhibitors and the A-II1 receptor antagonists are now clinically established. Because ACE is a relatively unspecific peptidase which catalyses the breakdown of A-I, bradykinin and neuropeptides like substance P and neurotensin, the effects of ACE inhibitors go far beyond the prevention of A-II production. On the other hand, in certain tissues like vascular and cardiac tissue, A-II is produced by other enzymes, for instance chymase, and ACE inhibitors do not consistently prevent A-II production. The action of A-II1 receptor antagonists may also not be confined to prevention of binding of A-II at the A-II1 receptor, as by rebound more A-II may bind at the A-II type 2 (A-II2) receptor and thus mediate until now not well defined effects. Thus, anti-ischemic actions of these drugs may be related to multiple mechanisms. Inhibition of A-II effects at the A-II1 receptor may prevent systemic and coronary vasoconstriction and growth effects of A-II on various cell types. In addition, A-II may potentiate, by pre- and postsynaptic mechanisms, activation of the sympathetic nervous system. Prevention of breakdown of bradykinin, substance P and neurotensin may result in direct vasodilation or release of nitrous oxide from the endothelium. Thus, growth-inhibiting effects may also be mediated. All these mechanisms seem to direct to a reduction of cardiac load by vasodilation and to a limitation of cardiovascular cell growth. While the systemic circulating renin-angiotensin system is probably responsible for control of cardiac load, local systems seem to control cell growth. Systemic effects seem to depend on activation of the renin-angiotensin system which has been shown in various ischemic syndromes. Activation of various components of the renin-angiotensin system has been demonstrated in myocardial ischemia, acute myocardial infarction and coronary occlusion and reperfusion models as well as in chronic left ventricular dysfunction post-myocardial infarction. While animal models of stress-induced myocardial ischemia have revealed predominantly positive results, clinical studies, which mostly were small and not well controlled, were equivocal. Large clinical trials with ACE inhibitors in acute myocardial infarction showed small benefits over placebo. Hypotension seems to be a critical side-effect in this situation. Experimental models show protective effects of both ACE inhibitors and A-II1 receptor antagonists in the situation of ischemia and reperfusion. New data on large clinical trials in patients at risk of cardiovascular events but normal left ventricular function demonstrate clear benefits of an ACE inhibitor. Large clinical trials in patients with chronic left ventricular dysfunction post-myocardial infarction show reduction of ischemic events.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2000

Striking increase of natriuresis by low-dose spironolactone in congestive heart failure only in combination with ACE inhibition: mechanistic evidence to support RALES.

BACKGROUND: A marked reduction of overall mortality in patients with severe congestive heart failure (CHF) has been demonstrated by addition of the mineralocorticoid receptor antagonist spironolactone to ACE inhibition. The aim of the present study was to examine a hypothesized interaction of spironolactone and ACE inhibitors in renal electrolyte and volume regulation. METHODS AND RESULTS: Wistar rats with extensive myocardial infarction or sham operation were treated with either placebo, the ACE inhibitor trandolapril, low-dose spironolactone, or a combination of the 2. Twelve weeks after infarction, rats were housed in metabolic cages. Urinary volume and sodium excretion were significantly increased in CHF rats on a combined treatment with spironolactone and trandolapril (21.2+/-2.6 mL/d, 2489+/-320 mmol/d, mean+/-SD; P<0.05 versus other experimental groups) versus placebo-treated rats (16.7+/-5.6 mL/d, 1431+/-458 mmol/d),whereas these parameters were not affected in rats on either spironolactone (16.1+/-6.6 mL/d, 1153+/-273 mmol/d) or trandolapril alone (15.9+/-4.2 mL/d, 1392+/-294 mmol/d). The effects on natriuresis coincided with a significant reduction of left ventricular end-diastolic pressure (LVEDP) in rats on trandolapril and spironolactone (10.8+/-8.2 mm Hg; P:<0.05 versus CHF placebo: 23.3+/-7.2 mm Hg; sham-operated rats: 5.1+/-0.9 mm Hg), whereas LVEDP remained elevated in rats treated with either compound alone. CONCLUSIONS: In the present study, we found an unexpected interaction of low-dose spironolactone and the ACE inhibitor trandolapril in experimental CHF leading to marked effects on renal electrolyte and volume regulation that were not apparent by treatment with either drug alone. These findings may explain the beneficial effects of spironolactone in CHF patients.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2000

Effect of quinapril initiated during progressive remodeling in asymptomatic patients with healed myocardial infarction.

Approximately 20% of patients with healed myocardial infarction develop asymptomatic progressive left ventricular (LV) dilation and remodeling and are at increased risk for progression to symptomatic congestive heart failure and premature death. It was the goal of this study to test whether quinapril may interrupt this process and to analyze potential mechanisms. Of 138 patients with an average infarct age of 56 months, 25 had asymptomatic progressive LV dilation and were randomized in a prospective, double-blind study to placebo or quinapril. At baseline (mean +/- SEM) ejection fraction was reduced (35 +/- 3% and 39 +/- 3%) and end-diastolic volume (gated single-photon emission computed tomography) increased (104 +/- 9 and 117 +/- 12 ml/m(2)) with placebo (n = 13) and quinapril (n = 12), respectively. Progressive dilation continued in patients taking placebo (6 months: 9.4 +/- 5.2 ml/m(2), 12 months 24.6 +/- 5. 4 ml/m(2); change from baseline: p <0.05 vs baseline; p <0.05 vs 6 months), but not with quinapril (6 months: -0.9 +/- 4.0 ml/m(2); 12 months: 4.1 +/- 5.2 ml/m(2) [p <0.05] vs placebo). Wedge pressure during bicycle exercise was similar at baseline, but at 12 months tended to be lower with quinapril (17 +/- 1 mm Hg) than with placebo (24 +/- 4 mm Hg, p = 0.1673). Thus, quinapril prevented further progression of asymptomatic LV dilation and remodeling after remote myocardial infarction, possibly due to attenuation of an exercise-induced increase in LV filling pressure.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2000

Electrochemical micromachining

The application of ultrashort voltage pulses between a tool electrode and a workpiece in an electrochemical environment allows the three-dimensional machining of conducting materials with submicrometer precision. The principle is based on the finite time constant for double-layer charging, which varies linearly with the local separation between the electrodes. During nanosecond pulses, the electrochemical reactions are confined to electrode regions in close proximity. This technique was used for local etching of copper and silicon as well as for local copper deposition.

Journal Article↗