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Biomedical subjects

E Fleck

Publications and source records attributed to E Fleck.

At least 235 records · Page 13Linked to original sources
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↗
PubMed1989

Ciclosporin A inhibits endothelium-dependent vasodilatation and vascular prostacyclin production.

Aortic rings dissected from rats treated with ciclosporin A (30 mg/kg per day for five days) showed reduced relaxation induced by the endothelium-dependent vasodilator acetylcholine, but unchanged responses induced by glyceryl trinitrate. After eight weeks of ciclosporin A treatment, the relaxation induced by both acetylcholine and glyceryl trinitrate was inhibited. In addition, phenylephrine-induced contractions were slightly enhanced and vascular prostacyclin production was reduced by more than 80%. These effects may participate in the hypertensive and thrombo-embolic complications associated with the clinical use of ciclosporin A.

6-Ketoprostaglandin F1 alpha↗
PubMed1989

Characterization and localization of receptors for epidermal growth factor in ovine skin.

Specific receptor sites for murine epidermal growth factor (EGF) have been characterized and their distribution determined in ovine skin. Binding of 125I-labelled EGF to skin membrane particles was temperature- and time-dependent, with equilibrium being reached within 1 h at 23 degrees C. Analysis of skin biopsies collected from ten castrated Merino sheep demonstrated the presence of a single class of saturable, high-affinity binding sites with a dissociation constant of 64 +/- 4 (S.E.M.) pmol/l and a binding capacity of 33.8 +/- 4.5 fmol/mg protein. Skin particle binding of 125I-labelled EGF was inhibited equipotently by mouse salivary gland EGF, EGF produced by recombinant DNA procedures and urogastrone. The EGF peptides 1-48, 6-53 and 7-53, derived from the native molecule by enzymatic cleavage, were much less potent. The relative binding potency of these molecules was correlated with their ability to induce precocious eyelid opening in mice and to inhibit wool follicle activity. Synthetic fragments representing the major structural domains of the EGF molecule (EGF(29-44), EGF(33-42) and EGF(3-31] were inactive in both the receptor and bioassays. Autoradiography of skin sections incubated with 125I-labelled EGF in vitro or of sections from skin which was perfused with 125I-labelled EGF in vivo demonstrated that EGF receptors were localized in undifferentiated cells of the epidermis and sebaceous glands, the inner and outer root sheath and bulb of wool follicles and in dermal arterioles. Differences in receptor concentration were observed between follicles following in-vivo perfusion of 125I-labelled EGF but not when the in-vitro labelling technique was used. The presence of receptors in these regions is consistent with the morphological changes in sheep skin in response to EGF administration which have been reported previously.

Animals↗
PubMed1989

[Use of a noninvasive parameter of early diastolic ventricle function for the detection of graft rejection following heart transplantation].

Since changes in left ventricular early diastolic time intervals can be expected as one of the first detectable functional alterations indicating acute rejection in cardiac transplant patients, time-constant Te, a parameter derived from digitized M-mode echocardiogram, was proved as a marker of acute rejection. Echo results of 30 transplant patients (5-63 yrs) were correlated with myocardial biopsy results (48 rejection negative, 16 rejection positive) of the same day. In transplant patients the M-mode echo parameter Te is prolonged even in phases without rejection (79.0 +/- 12.5 ms vs 64.0 +/- 7.9 ms of healthy controls; p less than 0.0001). Te of transplant patients during rejection were significantly longer than Te of patients without rejection (97.8 +/- 17.9 ms vs 79.0 +/- 12.5 ms; p less than 0.0001). Individual courses demonstrate that rejection is associated with further prolongation of Te and that Te returns to individual basic value in response to treatment. So, Te may prove as a useful noninvasive marker of acute cardiac rejection.

Adolescent↗
PubMed1989

[Myocardial catecholamine content in heart failure--I: Regional distribution in explanted hearts. Comparison between dilated cardiomyopathy and coronary heart disease].

To quantify the myocardial catecholamine content in heart failure patients and to assess the regional distribution of catecholamines, we investigated norepinephrine and dopamine concentrations in explanted hearts from 34 patients in end-stage heart failure. 28 patients with cardiomyopathy were compared with six patients with coronary artery disease. In comparison with the right atria of a control group without heart failure, reduced myocardial norepinephrine contents (in pg/micrograms non-collagen protein (NCP] were found in all areas of the explanted hearts: controls: right atrium 17.6 +/- 6.6; cardiomyopathy: right atrium 7.1 +/- 7.9, right ventricle 4.4 +/- 2.7, septum 3.8 +/- 1.5, left ventricle 3.5 +/- 1.4. Coronary artery disease: right atrium 7.0 +/- 6.9, right ventricle 4.2 +/- 2.6, septum 3.6 +/- 1.4, left ventricle 3.4 +/- 1.4. Highest norepinephrine levels were measured in the right atrium. Right ventricle, septum, base and midventricular portion of the left ventricle had lower concentrations and were not different from each other. In contrast to reduced norepinephrine (NE) levels in all patients, dopamine (Dop) was inhomogenously elevated (only in a subgroup of 44%). Catecholamine contents in any two arbitrarily selected areas correlated significantly (NA: r = 0.53-0.77; Dop: r = 0.81-0.93, p less than 0.05 in all cases). The patients with heart failure due to dilated cardiomyopathy and to coronary artery disease did not differ in myocardial catecholamine levels or distribution. In end-stage heart failure a significant loss of myocardial norepinephrine independent from the underlying disease is found. It affects all areas of the hearts but does not equalize catecholamine content in ventricles and atria.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

[Myocardial catecholamine content in heart failure--II: Measurement in endomyocardial biopsies, reference systems, normal values].

To enable the assessment of a possible gradual loss of myocardial catecholamines in heart failure, we determined control values in endomyocardial biopsies from normal human right ventricular myocardium. The reproducibility of the determinations and its dependence on the reference system, wet weight (wwt) or non-collagen-protein (NCP), was investigated in explanted hearts. Parallel determinations of norepinephrine in several samples from 1-2 mg in the same heart yielded a variability of about 20%. To obtain reproducible values, catecholamine concentrations had to be related to non-collagen-protein. Non-collagen-protein content was higher in the ventricles (138 +/- 16 micrograms/mg wwt) than in the atria (102 +/- 15 micrograms/mg wwt). Norepinephrine levels in normal human myocardium, measured in right ventricular endomyocardial biopsies were 10.3 +/- 3 pg/micrograms NCP. If they were compared with norepinephrine levels in right atrial samples from 11 patients without heart failure, obtained at open heart surgery (17.6 +/- 6 pg/micrograms NCP), an atrioventricular gradient, with ventricular norepinephrine content being 58% of right atrial levels was calculated for healthy human hearts. This gradient was almost identical with that found in heart failure, patients, where right ventricular norepinephrine amounted to 60% of right atrial levels. This implicates a percentually homogeneous loss of norepinephrine in heart failure, which, however, does not equalize ventricular and atrial levels. Thus, to interpret myocardial catecholamine content in cardiac diseases, normal values in corresponding areas are mandatory.

Adult↗
PubMed1989

[Heart transplantation in childhood].

In nine patients between the ages of 3 months and 18 years with endstage heart failure, orthotopic heart transplantation was performed. Seven of these patients suffered from dilative cardiomyopathy. Additional diagnoses were tricuspid atresia in one case, and hypoplastic left-heart syndrome in another case. Seven of these children (77.7%) were catecholamine-dependent before the operation. The postoperative immunosuppressive treatment consisted of a combination therapy of cyclosporine A, azathioprine, and prednisolone, similar to the treatment in adults. Diagnosis of rejection was based on both invasive (endomyocardial biopsy) as well as noninvasive methods (intramyocardial electrogram, echocardiography, cytoimmunological monitoring). Out of nine transplanted children and adolescents, seven are presently alive and well after a mean follow-up period of 29 months. Two patients died of graft failure. One case with irreversible renal failure, secondary to chronic cyclosporine A toxicity required kidney transplantation 2 1/2 years following heart transplantation, this being the only significant late complication up to now. Our results indicate that heart transplantation allows for survival of seriously ill children and adolescents at a similar rate as that of older patient groups. Physical and social rehabilitation has been quite favorable and has been encouraging for further pursuit of this concept.

Adolescent↗
PubMed1989

Endothelium-derived relaxing factor in human coronary artery.

Over the last few years it has become apparent that endothelial cells release many vasoactive substances, including prostacyclin, endothelium-derived relaxing factor (EDRF), endothelium-derived contracting factor(s), and endothelium-derived hyperpolarizing factor. The picture that is rapidly emerging from research in this field is that abnormalities in the production and release of these substances may occur and contribute to many pathophysiologic states. For example, an impaired release of EDRF, the endogenous prototype of the nitrovasodilator drugs and a powerful vasodilator, appears to be involved in abnormal vasomotor function in diseases, such as atherosclerosis and hypertension. This view is supported by recent pharmacological experiments with isolated human coronary arteries freshly obtained from patients at heart transplantation, and clinical studies using quantitative coronary angiography. However, even in atherosclerotic arteries, EDRF-mediated vasodilation may contribute considerably to the actual vascular tone, since the release of EDRF upon appropriate stimulation in patients with moderate coronary artery disease appears to result in a vasodilation which is similar to that induced by an intracoronary infusion of nitroglycerin.

Coronary Artery Disease↗
PubMed1989

Extended donor age in cardiac transplantation.

Approximately one third of brain-dead organ donors are above the age of 35 years. These donors have been used routinely for heart transplantation because the risks of compromised early graft function and potentially accelerated graft atherosclerosis remained nuclear. The increasing length of the waiting list and a 30% death rate of those on the waiting list for donor organs in our heart transplant program led to acceptance of donor hearts up to 54 years of age. Of a total number of 233 donor hearts, 74 were between 36 and 54 years old (group 2). These hearts were compared for early and chronic graft function with a group of 159 patients who received hearts from donors aged 1-35 years (group 1). All but three group 2 hearts were accepted without coronary angiography. Early postoperative graft function was sufficient in all 72 group 2 patients, whereas in group 1, early graft failure in nine (5.7%) patients led to death or required retransplantation. Forty-one patients in group 2 and 79 patients in group 1 were restudied at annual intervals between 1 and 4 years postoperatively by complete cardiac angiography. Mean late postoperative left and right ventricular ejection fractions were normal in both groups. Graft atherosclerosis was found in seven (8.9%) patients in group 1 and in four (9.8%) patients in group 2.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Different effects of growth hormone on growth and function of isolated adult and fetal rat pancreatic islets.

We simultaneously determined 3H-thymidine incorporation, DNA content, and insulin biosynthesis in adult and fetal rat pancreatic islets. 3H-thymidine incorporation was measured after tissue solubilization. DNA was measured fluorometrically. Insulin biosynthesis was determined through 3H-leucine incorporation after immunoprecipitation and binding to protein A-sepharose. Addition of growth hormone caused a significant increase in 3H-thymidine incorporation into both the adult and the fetal islets, but only the adult islets experienced an increase in DNA content. The increase in 3H-leucine incorporation was also significant only in the adult islets. The dynamics of 3H-thymidine incorporation after growth hormone administration were different in the adult and the fetal pancreas. Fetal islets have the potential to increase their incorporation of 3H-thymidine, but very limited potential for insulin biosynthesis.

Animals↗
PubMed1988

Restenosis after balloon dilatation of coronary stenosis, multivariate analysis of potential risk factors.

This study was undertaken to analyze change in stenosis caliber up to six months after PTCA with respect to regression or progression as well as to detect factors which possibly influencing the restenosis rate. A computer assisted system with high accuracy was used for two-dimensional quantitation of stenosis. A linear multivariate analysis was applied to quantitative and qualitative angiographic data as well as to clinical findings obtained before, immediately after and six months post-PTCA in 95 consecutive patients in whom 101 stenoses were dilatated. All patients were on a standard medical regimen of aspirin or coumadin and nifedipine. After six months, 56 patients showed a change in minimal stenosis area (mSA) of less than 1 mm2 (no progression), 33 patients showed a decrease in mSA of greater than 1 mm2 which rendered the stenosis with greater than 70% luminal reduction, and 12 patients showed a decrease in mSA of greater than 1 mm2 which did not, however, result in high-grade luminal narrowing. With regard to factors capable of affecting restenosis rate, there was no relationship between extent of dilatation achieved, local dissection, stenosis configuration or localization, calcification, patient age, sex, duration of symptoms, overweight, cholesterol, triglycerides, HDL, LDL, smoking, hypertension or diabetes. However, a relationship was found between the discontinuation of aspirin or coumadin as a result of GI side effects or bleeding (2% no progression; 20% progression). Thus, antiplatelet therapy appears to be important with respect to long-term results after PTCA.

Angina Pectoris↗
PubMed1987

[Carnitine metabolism--changes in the end stage of dilated cardiomyopathy and ischemic heart muscle disease].

Biochemical analyses from endomyocardial biopsies indicate that cardiac energy metabolism is altered in patients with end-stage cardiac failure. Myocardial energy production is predominantly based on fatty acid oxidation. Carnitine, a naturally occurring compound, plays an essential role in fatty acid oxidation by carrying long-chain fatty acids into the mitochondrial matrix where they undergo beta-oxidation. In experimental animals, myocardial carnitine deficiency may cause cardiomyopathies which are reversible with carnitine substitution. Rare human diseases, as systemic carnitine deficiency, are associated with impaired cardiac function. We therefore investigated carnitine metabolism in patients with cardiac failure. Plasma and myocardial carnitine levels were measured in 55 patients undergoing cardiac transplantation because of end-stage cardiac failure based on dilated cardiomyopathy (DC, n = 30) or coronary artery disease (CAD, n = 22). Elevated plasma carnitine levels (controls: 49 +/- 12 microM; DC: 82 +/- 38 microM; p less than 0.001, CAD: 86.9 +/- 21.6 microM; p less than 0.05) were found in both patient groups (Fig. 1). Plasma carnitine did not correlate with creatinine (Fig. 2). Compared to controls, myocardial carnitine levels were significantly reduced: DC: 5.9 +/- 1.45 nmol/mg NCP; CAD: 5.84 +/- 1.84 nmol/mg NCP; controls: 15.6 +/- 5.4 nmol/mg NCP (Fig. 3). No correlation between myocardial and plasma levels was found (Fig. 5).(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiomyopathy, Dilated↗
PubMed1987

Protection of the ischemic myocardium by propionylcarnitine taurine amide. Comparison with other carnitine derivatives.

The cardioprotective effect of the two synthetic carnitine derivatives, propionylcarnitine taurine amide (PCTA) and butyrylcarnitine taurine amide (BCTA), were studied in isolated perfused rat hearts. The protective effects of PCTA and BCTA were compared with those of chemically similar compounds, which have already been investigated in part and reported on; i.e. propionylcarnitine, carnitine, taurine and the combination of propionylcarnitine and taurine. The addition of either PCTA or BCTA significantly improved the recovery of cardiac function of ischemic reperfused hearts. PCTA (0.5 mM) treated hearts regained 75%, 91% and 89% of their preischemic values for cardiac output, left ventricular pressure and dp/dt after 90 min ischemia and 15 min reperfusion. These parameters of cardiac function remained impaired in control hearts which recovered only 38% of the initial preischemic cardiac output, 73% of initial intraventricular developed pressure and 64% of initial positive dp/dt. The cardioprotective effects of PCTA, BCTA and propionylcarnitine were in the same range. However, PCTA and BCTA acted in 20-fold lower molar concentrations compared to propionylcarnitine. Carnitine (11 mM), taurine (11 mM) as well as the combination of propionylcarnitine and taurine at low concentrations had no cardioprotective effect in these experiments. Myocardial adenosine triphosphate (ATP) and creatine phosphate (CP) concentrations were significantly higher in the PCTA or BCTA treated hearts than in controls, and lactate levels were reduced.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗