[Imaging procedures in diagnosis of aortic dissection].
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Aortic Dissection↗
Biomedical subjects
E Erdmann
Publications and source records attributed to E Erdmann.
[Indications for ACE inhibitors in chronic heart failure].
Chronic systolic heart failure after coronary heart disease or dilated cardiomyopathy is characterized by an increasing dilatation of the left ventricle and raised intracardial pressures. The higher the NYHA class, the higher are usually preload and afterload of the left ventricle. Concomitantly, the renin-angiotensin-aldosterone-system is stimulated, leading to neurohormonal activation of vasoconstrictive hormones. This will reduce the already depressed myocardial function even more. The addition of ACE-inhibitors to diuretics and digitalis has improved the prognosis of patients with severe and moderate heart failure. Thus, there is no question today that ACE-inhibitors are needed in chronic heart failure, irrespective of the origin. New investigations indicate that diuretics and digitalis are also needed in severe or moderate heart failure. They certainly lead to a decrease of symptoms. The significance of the local ACE-system seems to be greater than that of the circulating ACE-system, when chronic heart failure after myocardial infarction has to be treated. The prophylactic use of ACE-inhibitors after myocardial infarction with decreased ejection fraction will reduce the necessity of admittance to hospital and will also improve the prognosis.
Angiotensin-Converting Enzyme Inhibitors↗
[Digitalis therapy 1994].
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Angiotensin-Converting Enzyme Inhibitors↗
Sensitization of adenylate cyclase by halothane in human myocardium and S49 lymphoma wild-type and cyc- cells: evidence for inactivation of the inhibitory G protein Gi alpha.
Halothane has been reported to sensitize the myocardium towards the effects of exogenous catecholamines in patients and laboratory animals. This study was aimed at investigating the catecholamine-sensitizing effects of halothane as well as the underlying subcellular mechanisms in human myocardium. Halothane augmented the positive inotropic effect of isoprenaline but not of Ca2+. The increase of the effect of isoprenaline by halothane was more pronounced in failing myocardium, with increased Gi, than in nonfailing donor hearts. Halothane (1%) increased basal as well as isoprenaline-, NaF-, cholera toxin-, and guanylylimidodiphosphate [Gpp(NH)p]-stimulated adenylate cyclase in human myocardial membranes (p < 0.05). Treatment of membranes with pertussis toxin increased adenylate cyclase by 40% and abolished the effect of halothane. Halothane had no effect on forskolin-stimulated adenylate cyclase. The same results, i.e., a pertussis toxin-sensitive increase of adenylate cyclase stimulation by halothane, were obtained in S49 cyc-, wild-type, or recombinant Gs alpha-reconstituted cyc- cell membranes. Carbachol-stimulated guanosine-5'-O-(3-[35S]thio)triphosphate binding was not influenced by halothane, but halothane attenuated the inhibition of adenylate cyclase by Gpp(NH)p in S49 cyc- cells. These data show that halothane stimulates adenylate cyclase and sensitizes adenylate cyclase after stimulation by beta-adrenoceptor agonists and guanine nucleotides due to an impairment of Gi alpha function. This mechanism may play a role in the halothane sensitization of myocardial adenylate cyclase towards catecholamines.
Adenylyl Cyclases↗
[Molecular biology in cardiology. Changes in the phenotype in heart failure and myocardial hypertrophy].
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Calcium↗
Inotropic effect of the cardioprotective agent 2,3-butanedione monoxime in failing and nonfailing human myocardium.
The drug 2,3-butanedione monoxime (BDM) was suggested to be a potent cardioprotective agent useful for cardiopreservation. The present study investigated the activity of BDM and its mechanism of action in human myocardium. In electrically driven left ventricular papillary muscle strips and right atrial trabeculae from failing (heart transplants) and nonfailing (donor hearts) human myocardium, isometric force development and the force-frequency relationship were examined. To study the sarcolemmal actions of BDM, competition experiments with 125I-iodocyanopindolol, 3H-ouabain and 3H(+)PN 200-110 were performed. The effect of BDM on the contractile apparatus was tested by investigating its effects on Ca++ sensitivity and on the relaxation parameters of skinned fiber preparations. In papillary muscle strips and in atrial trabeculae, BDM (0.001-30 mM) depressed the isometric force of contraction in a concentration-dependent manner. BDM was more potent in atrial than in ventricular tissue and it shifted the Ca++ concentration-response curve in atrial and ventricular tissue to the right. The potency of BDM to depress force development was significantly lower compared with the L type of Ca++ channel antagonist nifedipine in both atrial and ventricular myocardium. In the presence of 10 mM BDM, the force-frequency relationship becomes positive in failing myocardium but not in the presence of 1 mM BDM, which did not affect the specific binding of 125I-iodocyanopindolol, 3H-ouabain or 3H(+)PN 200-110. This indicated there was no action on beta adrenoceptors, cardiac glycoside receptors and dihydropyridine-type Ca++ channels.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
C-terminal modifications of pertussis toxin-sensitive G-protein alpha-subunits differentially affect immunoreactivity. Evidence against endogenous ADP-ribosylation in human heart, lung, thrombocytes and adipose tissue.
Immunochemical detection of pertussis toxin-sensitive guanine-nucleotide binding proteins has been suggested to represent the most direct approach to quantitate the protein than pertussis toxin-catalysed [32P]ADP-ribosylation. The latter technique is potentially hampered by pre-existing covalent modification of the C-terminus. However, limited data exist as to whether and in what way modifications of the C-terminus affect immunoreactivity of Gi alpha (alpha-subunit of the inhibitory G-protein of adenylyl cyclase). Membranes from human myocardium, thrombocytes, adipose tissue and lung were treated with pertussis toxin or N-ethylmaleimide. Both, conditions prevented high affinity agonist binding to m-cholinoceptors and inhibited [32P]ADP-ribosylation by pertussis toxin consistent with the notion that the modifications took place at the C-terminus. Pertussis toxin treatment increased immunoreactivity to different antisera raised against the C-terminal decapeptide of transducin alpha (KENLKDCGLF, DS 1-4, AS). N-Ethylmaleimide reduced immunoreactivity towards all antisera studied. Pertussis toxin reduced the mobility of Gi alpha on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) depending on the presence of the toxin and sensitivity to inhibition of ADP-ribosylation by nicotinamide. In native membranes from none of the tissues studied, immunoreactive material comigrating with pertussis toxin-modified form of Gi alpha was detected. It is concluded that modification of the C-terminus by pertussis toxin or N-ethylmaleimide resulting in the same functional consequence, i.e. prevention of high affinity agonist receptor binding, is capable of producing opposite changes of immunoreactivity. Pertussis toxin treatment reduces the electrophoretic mobility on SDS-PAGE. Separation of the native and pertussis toxin-modified form of Gi alpha on SDS-PAGE demonstrates that endogenously ADP-ribosylated Gi alpha is lacking in membranes from human myocardium, thrombocytes, lung and adipose tissue.
Adenosine Diphosphate Ribose↗
Force-frequency-relation in human atrial and ventricular myocardium.
In human heart failure, an increase in frequency of stimulation is followed by a reduced force of contraction in vivo and in vitro. The present study aimed to investigate whether a different origin of the myocardial sample or pretreatment with the cardioprotective agent 2,3-butanedione-monoxime (BDM) influences the force-frequency-relationship in electrically driven muscle strips taken from failing and nonfailing human myocardium. With as well as without pretreatment with BDM, the altered force-frequency-relationship in failing compared to nonfailing human ventricular myocardium can be observed. The effectiveness and the potency to increase force of contraction following an increase in frequency of stimulation was significantly higher in atrial than in ventricular myocardium in nonfailing and failing tissue. The different observations in atrial and ventricular myocardium provide evidence for functionally relevant differences in the electromechanical coupling between the human atrial and ventricular myocardium.
Adult↗
Correlation of myosin heavy chain expression in the rat with cAMP in different models of hypertension-induced cardiac hypertrophy.
Both genetically determined and artificially-induced hypertension lead to cardiac hypertrophy and shift the myosin heavy chain (MHC) expression to the beta-MHC form. The cause of this change in gene expression is unknown. To contribute to the understanding of this phenomenon, we correlated the MHC expression in the left ventricle with basal, Forskolin- and isoprenaline-stimulated adenylate cyclase activity (cAMP production of membrane fractions). We used two control rat strains [Wistar-Hagemann (WH), Wistar-Kyoto (WKY)] and several rat models of hypertension: one clip-one kidney (1C-1K), desoxycorticosterone-treated rats (DOCA), rats with reduced renal mass (RRM) and spontaneously hypertensive rats (SHR). The level of hypertension correlated positively with the degree of cardiac hypertrophy (P < 0.01) and negatively (P < 0.05) with cAMP production, e.g. the higher the degree of hypertension, the lower both basal and stimulated cAMP levels. In addition we found that the lower the basal, isoprenaline- and Forskolin-stimulated cAMP production the lower was the expression of the alpha-MHC isoenzyme (P < 0.05). Thus, our data suggest that the decreased alpha-MHC expression upon hypertension-induced cardiac hypertrophy could be mediated via decreased adenylate cyclase activity and thus decreased intracellular cAMP production.
Adenylyl Cyclases↗
Effect of olsalazine and mesalazine on human ileal and colonic (Na+ + K+)-ATPase. A possible diarrhogenic factor?
Olsalazine (azodisalicylate) and mesalazine (5-aminosalicylic acid) have recently been developed as new treatment modalities for inflammatory bowel disease to avoid sulfasalazine-related side effects. However, there are reports regarding new and hitherto unexpected side effects in some patients receiving olsalazine or mesalazine, such as watery diarrhea. Since sodium pump activities play an important role in the pathogenesis of water and electrolyte disturbances, we investigated the influence of olsalazine and mesalazine on human ileal and colonic (Na+ + K+)-ATPase and its specific [3H]-ouabain binding. We found a concentration-dependent inhibition of ileal and colonic (Na+ + K+)-ATPase by olsalazine with an IC50 of 4.1 mM and 4.8 mM, respectively. Mesalazine inhibited this enzyme in the ileum with an IC50 of 4.0 mM and in the sigmoid colon with an IC50 3.5 mM. In addition, [3H]-ouabain binding was inhibited by mesalazine with an IC50 of 3.6 mM. The maximal inhibition, however, did not exceed 80% under any conditions (up to 10 mM drug concentration). Olsalazine and mesalazine induce inhibition of the ileal and colonic sodium pump activities that may (in addition to other possible mechanisms) mediate impaired water and electrolyte absorption. This is possibly of clinical relevance in patients with severely damaged mucosa. In patients with milder forms of mucosal inflammation, this inhibition most likely is of minor importance because of the great capacity of the (Na+ + K+)-ATPase and the incomplete inhibition leaving at least 20% of the enzyme activity intact.
Aminosalicylic Acids↗
Percutaneous transluminal coronary angioplasty of focal coronary lesions after cardiac transplantation.
Transplant coronary artery disease is the greatest impediment to long-term survival beyond the first year after cardiac transplantation. Transplant coronary artery disease shows a heterogeneous angiographic appearance, but focal stenoses can occur alone or at least predominate. Based on an angiographic indication 35 critical focal lesions causing narrowing by 75% or more were treated by PTCA during 23 procedures in seven patients 18-84 months after cardiac transplantation. Three patients each underwent only one procedure and four underwent repeated procedures [2, 3, 4 and 11, respectively). Primary success was achieved without any complication in 35 of 35 lesions (100%). The mean degree of stenosis was reduced from 86 +/- 9% to 28 +/- 17% (P < 0.001). The rate of restenosis was 18/29 (62%) at a mean of 4 months after angioplasty. Four patients are alive and free of adverse effects (symptoms, myocardial infarction, repeated percutaneous transluminal coronary angioplasty, retransplantation) 16 +/- 10 months after their last angioplasty. One patient underwent a successful second heart transplantation 26 months after the first angioplasty. Two patients died, 1 and 31 months after the last angioplasty. In conclusion, percutaneous transluminal coronary angioplasty can be performed safely with an excellent primary success rate in critical focal transplant coronary artery disease. The rate of restenosis is higher than in native coronary artery disease. Long-term follow-up depends on the individually variable accelerated nature of graft atherosclerosis.
Adult↗
Magnesium restores the altered force-frequency relationship in failing human myocardium.
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Adult↗
Long-term myocardial function after heart transplantation.
With an increasing number of heart transplantations and an improved survival rate a characterization of the long-term hemodynamic profile of the transplanted heart is necessary. 222 cardiac catheterizations were performed in 71 heart recipients under cyclosporine A immunosuppression during a 7-year follow-up after transplantation. Hemodynamic evaluation revealed a non-progressive arterial hypertension due to an increased systemic vascular resistance, leading to a mild increase of left-ventricular chamber stiffness. Parameters of systolic myocardial function were found to be normal and did not deteriorate during the 7 year period. The prevalence of allograft coronary angiopathy increased from 13% one year to 54% five years after transplantation. Myocardial function was neither adversely influenced by the presence of coronary angiopathy nor by the number or severity of former rejection episodes. Unchanged annual pressure-volume loops excluded the development of a dilated or restrictive posttransplantation cardiomyopathy. Thus, not the myocardial function, but the coronary angiopathy represents the most critical cardiac long-term problem after transplantation.
Adolescent↗
Evidence for an interaction of halothane with the L-type Ca2+ channel in human myocardium.
BACKGROUND: The present study was aimed at investigating the underlying mechanisms for the cardiac depressant effect of halothane. To test the hypothesis, whether there is an interaction of halothane with the L-type Ca2+ channels in human myocardium and whether this interaction has functional consequences for force generation in the human myocardium, effects of halothane were studied in human myocardial membranes and isolated cardiac preparations. METHODS: The experiments were performed on isolated, electrically driven ventricular preparations (1 Hz, 37 degrees C) and cardiac membranes with radioligand binding experiments using 3H-PN 200-110. Myocardium from human failing and non-failing hearts was obtained at cardiac surgery. RESULTS: Halothane produced a negative inotropic effect, which was similar in nonfailing and failing myocardium. Halothane shifted the concentration-response curve for the positive inotropic effect of the L-type Ca2+ channel agonist BayK 8644 to the right. The density of dihydropyridine receptors as judged from 3H-PN 200-110 radioligand binding experiments was similar in nonfailing and failing myocardium, whereas the density of beta-adrenoceptors was reduced. Halothane concentration dependently reduced the binding of 3H-PN 200-110, an antagonist at the 1,4 dihydropyridine receptor site of the Ca2+ channel, to myocardial membranes. Furthermore, halothane produced a rightward shift of the competition curve of BayK 8644 for binding of 3H-PN 200-110 to cardiac membranes. CONCLUSIONS: In human ventricular myocardium, halothane exhibits an interaction with the L-type Ca2+ channel by interfering with its dihydropyridine binding sites. This may explain, at least in part, the observed negative inotropic effect of this agent and could hypothetically play a general role in its anesthetic effects.
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
Effects of halothane on beta-adrenoceptors and M-cholinoceptors in human myocardium: radioligand binding and functional studies.
We investigated whether a postsynaptic sensitization by halothane for beta-adrenoceptor-mediated effects occurs in diseased human myocardium. In addition, we hoped to achieve further insights into the cellular mechanism and, in particular, the role of M-cholinoceptors and beta-adrenoceptors. The experiments were performed on isolated, electrically driven atrial and ventricular preparations and membranes isolated from human hearts obtained at cardiac surgery. Halothane concentration-dependently reduced binding of [3H]quinuclidinylbenzilate ([3H]QNB) to M-cholinoceptors but had no effect on equilibrium saturation binding of 125-iodocyanopindolol (125I]Cyp) to beta-adrenoceptors. High-and low-affinity states of agonist binding of carbachol to M-cholinoceptors were not affected, but halothane inhibited high-affinity binding of isoprenaline to beta-adrenoceptors. In contrast, halothane augmented the potency and efficacy of the positive inotropic effect of isoprenaline in atrial and ventricular myocardium. The "direct" negative inotropic effect in atrial and the "indirect" negative inotropic effect in ventricular myocardium by M-cholinoceptor stimulation with carbachol was unchanged by halothane. We conclude that in human atrial and ventricular myocardium a sensitization to catecholamines is induced by halothane, the mechanism of which is likely to be located at the postsynaptic level of the sympathetic neuroeffector junction. Facilitated coupling of beta-adrenoceptors or an uncoupling of M-cholinoceptors with reduced negative inotropic effects of agonist does not play a role. We showed that sensitization of this system apparently is due to direct actions of halothane on the G-protein-coupled adenylate cyclase complex.
Catecholamines↗
CT and MR evaluation of pericardial constriction: a new diagnostic and therapeutic concept.
Eighty patients with pericardial constriction confirmed by catheter data were studied by CT (n = 79), MR imaging (n = 24), or both. To determine the validity of these imaging methods for subsequent treatment, 30 patients' studies were evaluated retrospectively (1980-1984) and 50 (1985-1991) prospectively. Twenty patients from the first group and 30 patients from the second group underwent pericardiectomy. By systematic analysis of CT scans and MR images it was possible to characterize the morphology of pericardial constriction (n = 80); to identify global (n = 27), right-sided (n = 46), left-sided (n = 2), annular (n = 2), effusive (n = 2), and epicardial (n = 1) forms of pericardial constriction; and to define parameters of myocardial atrophy and fibrosis (n = 17). Seventeen patients had myocardial atrophy, fibrosis, or both. Seven of them underwent pericardiectomy; all died of acute myocardial failure (100%). Four (9.3%) of 43 patients without myocardial atrophy or fibrosis died as a consequence of other complications. The method of thoracotomy and periepicardiectomy was continuously adjusted to the preoperative CT and MR findings. Thus, the clinical use of CT and MR imaging in patients with known or suspected pericardial constriction is based on (a) exclusion of patients with restrictive hemodynamics from diagnostic thoracotomy, (b) preoperative determination of the method of thoracotomy and extent of pericardiectomy, and (c) exclusion of patients with myocardial atrophy or fibrosis from pericardiectomy.
Adult↗
Effects of exercise on myocardial adenylate cyclase and Gi alpha expression in senescence.
The present study investigated the influence of physical training on alterations leading to reduced adenosine 3',5'-cyclic monophosphate (cAMP) formation in aged myocardium. Senescent (28-mo-old) rats underwent a moderate treadmill exercise program and were compared with sedentary controls. In myocardial membranes from aged rats, isoprenaline-stimulated adenylate cyclase activity (AC) was reduced compared with that in young animals and was accompanied by an increase of pertussis toxin substrates (17.5%) and an increased amount of immunodetectable inhibitory guanine nucleotide-binding proteins (Gi alpha; 72%). Physical training reduced the amount of Gi alpha proteins (30-35%) in young and old animals and enhanced only isoprenaline-stimulated AC in the aged rats, and basal and 5'-guanylylimidodiphosphate [Gpp(NH)p]- as well as isoprenaline-stimulated AC in young rats. Physical training or aging had no effect on the number of beta-adrenoceptors or m-cholinoceptors or on forskolin-stimulated AC in either group. The amount of immunodetectable stimulatory guanine nucleotide-binding proteins (Gs alpha) using an antiserum raised against the COOH-terminal peptide of Gs alpha (RMHLRQYELL) was unchanged in either condition. It is concluded that enhanced Gi alpha expression might be one mechanism leading to depressed cAMP formation in aged myocardium. Depressed AC and increased Gi alpha can be partially reversed by physical training, especially in young myocardium. Gi alpha might serve as a regulator of cardiac AC in a variety of physiological and pathophysiological situations in the absence of beta-adrenoceptor changes.
Adenylate Cyclase Toxin↗