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E Fleck

Publications and source records attributed to E Fleck.

At least 19 recordsLinked to original sources
PubMed1992

Myocardial adenine nucleotide concentrations and myocardial norepinephrine content in patients with heart failure secondary to idiopathic dilated or ischemic cardiomyopathy.

It has been suggested that chronically reduced myocardial adenosine triphosphate (ATP) content causes contractile dysfunction in dilated cardiomyopathy. Because total adenine nucleotides (ATP, adenosine diphosphate and monophosphate) may reflect chronic changes in energy metabolism better than may ATP alone, myocardial ATP, and adenosine diphosphate and monophosphate were determined in endomyocardial biopsy specimens from 19 patients with dilated cardiomyopathy, and decreased left (30 +/- 2%) and right (34 +/- 3%) ventricular ejection fractions, and from 11 patients with ischemic cardiomyopathy (left ventricular ejection fraction 38 +/- 3%), and compared with those from 28 normal control subjects (ejection fraction greater than 55%) to assess myocardial energy metabolism in heart failure. Myocardial norepinephrine was measured simultaneously in the same biopsy specimens to assess if the myocardium studied for adenine nucleotide content was metabolically altered. Myocardial total adenine nucleotides as well as ATP levels in 19 patients with dilated cardiomyopathy (39 +/- 3 and 23 +/- 3 nmol/mg of noncollagen protein, respectively) were unchanged in comparison with those of control subjects (37 +/- 4 and 23 +/- 3, respectively); patients with ischemic cardiomyopathy were not significantly different (30 +/- 3 and 19 +/- 3, respectively). Myocardial norepinephrine in the same biopsy specimens from patients with dilated (5.8 +/- 1.1 pg/micrograms of noncollagen protein) or ischemic (5.7 +/- 1.3) cardiomyopathy was significantly decreased compared with that of normal control subjects (12 +/- 1.1).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenine Nucleotides↗
PubMed1992

Adenine nucleotide metabolism and contractile dysfunction in heart failure--biochemical aspects, animal experiments, and human studies.

In myocardial hypertrophy and heart failure a series of adaptational changes occur some multiplying contractile units, others slowing shortening velocity and increasing economy of contraction. The demonstration of energy-saving mechanisms in heart failure has prompted further investigations of energy providing and utilizing metabolic pathways. The use of myocardial ATP as a substrate occurs mainly at the myosin-ATPase and at the Ca-ATPase of the sarcoplasmic reticulum. As the Michaelis constant of both enzymes for ATP is in the micromolar (microM) range, whereas cellular ATP content is about 5000 microM, these enzymes are not controlled by the availability of ATP as a substrate. In experimental heart failure in large animals, normal or reduced creatine phosphate levels (in most cases together with normal adenine nucleotides) have been described. Reduced creatine phosphate is found in models with increased oxygen consumption, and creatine phosphate may buffer the ATP pool in these models. In human heart failure due to dilated cardiomyopathy, where resting oxygen consumption per unit mass and lactate extraction are normal in most patients, normal adenine nucleotides, creatine phosphate, and mitochondrial function have been described in the initial studies. These results have been challenged by one study showing decreased ATP levels in dilated cardiomyopathy, correlating with the decrease in ejection fraction. However, only ATP has been measured in this study, whereas total adenine nucleotides may be a more suitable parameter. Recently published results have again demonstrated normal ATP and total adenine nucleotides in human heart failure. In the same patients, significantly decreased myocardial norepinephrine was measured, indicating that metabolic changes had occurred in these hearts, but were independent of adenine nucleotides.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗
PubMed1992

Relaxation of human coronary artery and arteria mammaria by K(+)-channel openers.

Three agents with K(+)-channel-opening activity--nicorandil, bimakalim (EMD 52692), and EMD 56431--were tested for vasorelaxation abilities in human coronary artery and human arteria mammaria. The potency orders were bimakalim = EMD 56431 >> nicorandil for relaxation in human coronary artery and bimakalim = EMD 56431 >> nicorandil in human arteria mammaria. These data demonstrate that K(+)-channel openers are effective vasorelaxant agents in human coronary artery and human arteria mammaria. Bimakalim and EMD 56431 were more potent than nicorandil, a drug that also activates guanylate cyclase.

Benzopyrans↗
PubMed1992

In vivo measurement of endothelium-dependent vasodilation with substance P in man.

Endothelial cells synthesize and metabolize vasoactive substances which are involved in the regulation of vascular tone. Among these factors, the endothelium-derived nitric oxide (NO) appears to be of major importance. Many studies observed an impairment of the generation, release, or the diffusion of endothelial NO across the vascular intima in laboratory animals with various experimental diseases such as hypercholesterolemia, atherosclerosis and hypertension. In human coronary arteries obtained from explanted hearts impaired endothelium-dependent relaxations were measured in atherosclerotic segments. The hypothesis of a decreased NO mediated vasodilation in patients with coronary artery disease was further underscored by in vivo studies in man using intracoronary infusions of the endothelium-dependent vasodilator acetylcholine and quantitative coronary angiographic measurements of the diameter changes. From these observations it was assumed that endothelial dysfunction, in particular a profound inability of the coronary endothelium to relax via NO dependent mechanisms may play an important role in the pathogenesis of abnormal coronary vasomotion. However, further investigations in man reveal that the ability of the coronary endothelium of patients with coronary artery disease or vasospastic angina to produce endothelial NO is less affected as judged from the effects of acetylcholine. In recent investigations a largely preserved endothelial function could be measured in these patients when the endothelium-dependent vasodilator substance P was used as a tool for the measurement of NO dependent relaxation. Thus, endothelial dysfunction does not appear to serve as a major cause of abnormal vasoconstriction in coronary artery disease or vasospastic angina in man.

Acetylcholine↗
PubMed1992

Bradykinin degrading activity in cultured human endothelial cells.

The role of angiotensin-converting enzyme (ACE), neutral endopeptidase 24.11 (NEP), and other peptidases in the endothelial degradation of bradykinin was investigated in cultured human umbilical vein endothelial cells (HUVEC). The major part of the kininase II activity on intact cells was attributed to ACE activity, the minor part to NEP activity. Amastatin, as aminopeptidase inhibitor, and DL-2-mercaptomethyl-3-guanidinoethyl-thiopropionic acid (MGTA), an inhibitor of kininase I, did not affect endothelial kininase activity. The decline of the bradykinin concentrations in the supernatant of intact endothelial monolayer indicated a total kininase activity of 289 +/- 27 fmol/min/dish. The calculated activity of ACE was 223 fmol/min/dish and the neutral endopeptidase activity was 51 fmol/min/dish. Thus, ACE and neutral endopeptidase are the main kininases in the degradation of bradykinin by intact endothelial cells. In contrast to the intact endothelial monolayers, in homogenates additional kininase activity was found which was not affected by either ACE and NEP inhibitors nor by amastatin and MGTA.

3-Mercaptopropionic Acid↗
PubMed1992

Local potentiation of bradykinin-induced vasodilation by converting-enzyme inhibition in isolated coronary arteries.

The interaction of angiotensin-converting enzyme (ACE) inhibitors and bradykinin was investigated in isolated bovine and human coronary arteries. Rings with and without endothelium were mounted in organ chambers for measurement of isometric force. The effects of the ACE inhibitors lisinopril, enalaprilat, fosinoprilat, ramiprilat, and captopril were determined during submaximal stimulation with bradykinin or other vasodilators. Lisinopril and captopril alone did not affect vascular tone; however, in rings with endothelium partially relaxed with bradykinin (> or = 10(-10) M), all ACE inhibitors caused further relaxations. Lisinopril did not affect bradykinin concentrations in the incubation medium. Mechanical removal of the endothelium or incubation with nitro-L-arginine or the bradykinin2-receptor antagonist Hoe 140 prevented the relaxations to bradykinin and lisinopril. Other vasodilators including acetylcholine, adenosine diphosphate, substance P, or SIN-1 did not prime the rings to respond to ACE inhibitors. Endothelium-dependent relaxations to lisinopril were also observed in human coronary arteries treated with bradykinin (> or = 10(-7) M). Thus, ACE inhibitors potentiate endothelium-dependent relaxations to submaximal concentrations of bradykinin in bovine and human coronary arteries. This local mechanism occurs regardless of elevated bradykinin concentrations in the blood and reduced angiotensin II generation.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1992

Endothelium-dependent relaxations are augmented in rats chronically treated with the angiotensin-converting enzyme inhibitor enalapril.

The study was designed to evaluate the effects of chronic inhibition of angiotensin-converting enzyme (ACE) on the reactivity of the endothelium and the smooth muscle to vasoconstrictor and vasodilator stimuli in normal rats. Male rats were treated orally for 6 weeks with enalapril (10 mg/kg/day, n = 10) or with placebo (n = 10). Endothelium-dependent relaxations to acetylcholine and adenosine diphosphate were augmented in aortic rings from rats treated with enalapril compared with controls, whereas the response to the endothelium-independent vasodilator SIN-1 were similar. Contractions induced by phenylephrine and angiotensin II remained unchanged. Thus, the results suggest that chronic ACE inhibition enhances the release of relaxing factors from the endothelium in normotensive rats.

Acetylcholine↗
PubMed1992

Effects of converting enzyme inhibition on endothelial bradykinin metabolism and endothelium-dependent vascular relaxation.

The effects of ACE-inhibitors on bradykinin metabolism and bradykinin-induced endothelium-dependent relaxation were studied in isolated coronary arteries and endothelial cells in culture. The results suggest that ACE-inhibitors affect coronary vascular tone by at least two endothelium-dependent and bradykinin-mediated mechanisms: First, ACE-inhibitors decrease endothelial bradykinin degredation which is accompanied by an augmented bradykinin mediated endothelium-dependent relaxation. Second, ACE-inhibitors evoke endothelium-dependent relaxations in coronary arteries stimulated with threshold concentrations of bradykinin, which cannot be attributed to an inhibition of bradykinin degradation. The effect appears to represent a new mechanism which may be based on an interaction of the bradykinin receptor and the angiotensin converting enzyme on the cellular level.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1991

Myocardial catecholamine concentrations in dilated cardiomyopathy and heart failure of different origins.

Myocardial catecholamine concentrations were determined in endomyocardial biopsies from patients with heart failure to assess if tissue catecholamine levels relate to the severity of myocardial damage or the aetiology of the underlying disease. Methodological studies revealed a good reproducibility of catecholamine determinations in biopsies; the variance between paired biopsies was below 17% when myocardial catecholamines were related to non-collagen protein (NCP). Myocardial norepinephrine (in pg micrograms-1 NCP) levels were comparable in patients with dilated cardiomyopathy (DCM, 5.3 +/- 3.4, n = 22) and in patients with coronary or valvular heart disease (5.6 +/- 4.7, n = 14). In both groups, a significant reduction of myocardial norepinephrine was found (controls 12.0 +/- 3.4, P less than 0.0006). In a subgroup of patients with heart failure and a LVEF less than 30% (3.9 +/- 3.5, n = 17) myocardial norepinephrine content was lower than in patients with heart failure and LVEF of 31-55% (6.6 +/- 3.4, n = 19) (both P less than 0.05 against controls: 12.0 +/- 3.4, n = 16). A correlation between myocardial norepinephrine and LVEF was found in DCM (P less than 0.001, r = 0.70). The loss of myocardial norepinephrine is a characteristic feature of heart failure. It is independent of the origin of failure, but correlates with the impairment of LV function.

Cardiomyopathy, Dilated↗
PubMed1991

[Endothelial protection].

Explore the source record for details and available documents.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1991

Coronary angiography and interventional cardiology.

The purpose of coronary arteriography is to image the pathoanatomic morphology fundamental to diagnosis and therapy. Interventional cardiology aims to eliminate the pathologic substrate as completely as possible. The interventional techniques and the assessment of their success are based on an exact geometric and, in particular, functional analysis of coronary artery stenoses. Recent progress in coronary arteriography has involved, firstly, quantification of structural and functional aspects. Secondly, the direct application of the information provided, which permits immediate diagnosis and treatment, demands real-time availability and maximum quality, especially for imaging difficult geometric conditions.

Angioplasty, Balloon, Coronary↗
PubMed1991

[Coronary fistulas--high prevalence in patients with heart transplantation].

Coronary artery fistulas have recently been reported to occur frequently in patients after heart transplantation due to repeated endomyocardial biopsies. To investigate if there is a relationship between development of coronary artery fistulas and the number of biopsies performed in transplanted patients, we studied the prevalence and localization of coronary artery fistulas in 168 patients after heart transplantation and in 100 control subjects. In addition to biplane ventriculography of the left ventricle, and in two-thirds of the patients the right ventricle as well, coronary angiography in multiple projections was performed at yearly intervals. The angiographic criterion for a coronary fistula was specified as visualization of a direct confluence from the arterial vascular lumen into a cardiac chamber, independent of size, which occurred prior to the venous phase, documented by opacification of the coronary sinus or great cardiac vein. The size of the fistula was assessed semi-quantitatively into one of three categories as small, barely detectable flow from a small arterial vessel with opacification of less than 10% of the involved chamber, large with direct flow from a large branch with opacification of more than one-third of the involved chamber (Figures 1a to 1c). Endomyocardial biopsies were performed weekly for the first three months after transplantation, thereafter, the interval was increased one week every three months. The prevalence of coronary fistulas in patients after heart transplantation was higher at 135/168 than in control subjects at 43/100. There were also more fistulas per patient (1.8 vs 0.67) in those transplanted than in control subjects (Figures 2a and 2b).(ABSTRACT TRUNCATED AT 250 WORDS)

Arteriovenous Fistula↗
PubMed1990

[Cytomegalovirus infection and coronary sclerosis after heart transplantation].

Serological tests for cytomegalovirus (CMV) after cardiac transplantation were performed at six to eight-week intervals on 26 patients (3 females and 23 males; mean age 46 [15-62] years) with angiographic or ultimately autopsy evidence of coronary atherosclerosis (group 1) and 24 patients (5 females and 19 males; mean age 45 [25-56] years) without coronary disease in the transplanted heart. A positive result meant an at least fourfold increase in CMV IgG titre, demonstration of CMV IgM or direct viral isolation from blood or other body fluid. In 20 patients of group 1 (77%) a CMV infection had occurred after the transplantation, but in only six patients (25%) in the group 2 (P less than 0.0001). These results are interpreted as demonstrating a relationship between CMV infection and rapidly progressive coronary atherosclerosis after cardiac transplantation.

Adolescent↗
PubMed1990

Defective myocardial carnitine metabolism in congestive heart failure secondary to dilated cardiomyopathy and to coronary, hypertensive and valvular heart diseases.

Reduced myocardial carnitine concentrations in the explanted heart and elevated plasma levels have been found in patients undergoing heart transplant for end-stage congestive heart failure (CHF). To evaluate a possible loss of myocardial carnitine in less severe stages of CHF, total myocardial carnitine levels were compared in right ventricular endomyocardial biopsies from 28 patients with mild, moderate and severe dilated cardiomyopathy, 8 patients with CHF of different origin and 13 normal control subjects. If possible, free myocardial carnitine and free and total plasma carnitine were also determined. For the first time, myocardial carnitine levels have been measured in endomyocardial biopsies from 13 normal human hearts (control values: 9.9 +/- 0.8 nmol/mg noncollagen protein). In comparison with these control values, total myocardial carnitine was significantly reduced in patients with dilated cardiomyopathy (6.1 +/- 0.5 nmol/mg noncollagen protein, p less than 0.0001), and CHF of other origins (6.6 +/- 1.1 nmol/mg noncollagen protein, p less than 0.02). Free myocardial carnitine concentrations in dilated cardiomyopathy (4.6 +/- 0.4 nmol/mg noncollagen protein) and CHF of different origin (4.4 +/- 0.5 nmol/mg noncollagen protein) were also significantly different from control values (control values: 9.7 +/- 0.7 nmol/mg noncollagen protein, p less than 0.0001 and p less than 0.005 for both groups). The loss of free and total myocardial carnitine was comparable in dilated cardiomyopathy and CHF due to other diseases. In contrast, plasma free and total carnitine levels in the CHF patients were significantly elevated (67 +/- 5.5 mumol/liter, control values 41 +/- 3.7 mumol/liter, p less than 0.005). Alterations in myocardial carnitine metabolism represent nonspecific biochemical markers in CHF with yet unknown consequences for myocardial function.

Adult↗
PubMed1990

Myocardial catecholamine content after heart transplantation.

Myocardial catecholamine levels have not yet been determined in the transplanted human heart. We measured norepinephrine, epinephrine, and dopamine in endomyocardial biopsies from 19 short-term (organ age, 6.6 +/- 6 months) and five long-term (organ age, 62 +/- 2 months) heart transplant patients. Results were compared with those from 10 normal control subjects. In 17 of 19 short-term heart transplant patients, myocardial catecholamines were undetectable, indicating values below 0.1 pg/micrograms noncollagen protein, which was the detection threshold of our assay. In the remaining two patients, myocardial catecholamines (pg/microgram noncollagen protein) were norepinephrine (1.4 and 3.2), epinephrine (0.8 and 1.9), and dopamine (0.9 and 2.3), respectively. In the five long-term heart transplant patients, myocardial catecholamines were not detected. Catecholamine concentrations in 10 healthy control subjects were norepinephrine (10.3 +/- 2.9), epinephrine (0.36 +/- 0.51), and dopamine (0.52 +/- 0.40). Low myocardial norepinephrine levels (less than 20% of control values) with unexplained high levels of epinephrine and dopamine were found in single transplant patients. In most heart transplant patients, however, myocardial catecholamines were undetectable up to five years after transplantation, indicating that the adrenergic response of these hearts probably depends on variations in plasma catecholamines or cardiac beta-receptor density.

Biopsy↗
PubMed1990

Metabolic alterations in end-stage and less severe heart failure--myocardial carnitine decrease.

Severe tissue carnitine deficiency impairs fatty acid oxidation. In explanted hearts from patients with end stage heart failure a 57% carnitine decrease was found in comparison with healthy donor hearts (p less than 0.05). The reduction of myocardial carnitine levels affected all areas of the explanted hearts to a comparable extent. Carnitine decreases in patients with dilated cardiomyopathy or coronary artery disease were similar. Endomyocardial biopsies from patients with less severe heart failure due to cardiomyopathy (n = 28) or other myocardial diseases (n = 8) showed a 42% decrease of total myocardial carnitine (in nmol/mg non-collagen protein) in comparison with biopsies from patients with normal cardiac function (controls) (heart failure: 5.7, confidence interval 4.2-7.0; controls 9.3, confidence interval 7.6-12.0, p less than 0.005). Free myocardial carnitine in heart failure was also different from controls (heart failure: 4.2, confidence interval 3.7-5.3; controls 10.3, confidence interval 7.5-12.2, p less than 0.001). The decrease of free and total myocardial carnitine was comparable in dilated cardiomyopathy and heart failure due to other diseases. Alterations in myocardial carnitine content represent therefore non-specific biochemical markers in heart failure with yet unknown consequences for myocardial function.

Adult↗
PubMed1990

[Directional atherectomy--current status].

To deal with the problem of restenosis after PTCA, several new methods and devices for treating atheromatous lesions have been developed. Among the promising techniques, is the opportunity to remove atheromatous material with the directional coronary atherectomy catheter designed by J.B. Simpson. The atherectomy catheter consists of a housing at the catheter tip with a concave cutting device which is rotated at a speed of 2000 r.p.m. The housing is positioned at the stenosis by means of a central guidewire; the material to be removed protrudes into the housing. With an inflatable balloon on the opposite side, the position of the housing is fixed in the coronary artery, the plaque is pressed further into the orifice and severed by the rotating blade. The material removed remains in the tip of the housing and can be used for morphologic examination as well as for functional studies with individual cell cultures. Experience published to date encompasses the results of 1032 treated stenoses. The majority of the treated lesions, 53%, were localized in the left anterior descending coronary artery; in 22% the lesion were located in the right coronary artery, in 17% in an aorto-coronary venous bypass graft. Due to the difficulty in positioning the relatively rigid atherectomy catheter, the method has only been employed in the circumflex artery in 6%. In a substantial number of patients, the stenoses had already been subjected to PTCA; in 57% of 963 patients treated with atherectomy, angioplasty had been performed previously, in 25% bypass grafting had been carried out. The primary success rate was 93%.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗