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Biomedical subjects

E Erdmann

Publications and source records attributed to E Erdmann.

At least 289 records · Page 16Linked to original sources
PubMed1989

Coupling of adenosine receptors to a pertussis toxin-sensitive G protein in the human heart.

The adenosine receptors in myocardial membranes of human explanted hearts were labeled with the radiolabeled ligand [3H]DPCPX (1,3-dipropyl-8-cyclopentylxanthine). Agonist competition curves revealed high- and low-affinity states. The addition of guanylyl imidodiphosphate (Gpp (NH)p) converted all receptors to a low-affinity state. The portion of high-affinity states and the influence of guanine nucleotides were most pronounced at 22 degrees C. Only low-affinity states could be detected in pertussis toxin-treated membranes. It is concluded that adenosine receptors in the human ventricle couple via a G protein sensitive to pertussis-toxin. Alterations of the coupling of adenosine receptors might have a pathophysiological role in dilated cardiomyopathy in which pertussis toxin substrates are increased.

Adult↗
PubMed1989

Digitalis intoxication and treatment with digoxin antibody fragments in renal failure.

Severe digitalis intoxication today is preferentially treated by intravenous infusion of Fab fragments of digoxin antibodies (Digitalis Antidot BM). The kinetics of Fab fragments in the circulation are well known when kidney function is normal or slightly impaired. There are no data available, however, in complete renal failure. We observed a patient with life-threatening digitalis intoxication (serum digoxin, 3.7 ng/ml) and anuria, who was treated successfully by 160 mg Fab fragments i.v. Serum digoxin and Fab fragment concentrations could be followed for 229 h. The extrarenal clearance of Fab fragments was lower (5.6 ml/min) than in patients with normal kidney function (10.9 ml/min). This finding suggests that lower doses than usual might be sufficient for treating patients with severe digitalis intoxication and renal failure.

Acute Kidney Injury↗
PubMed1989

Positive inotropic stimulation in the normal and insufficient human myocardium.

Cardiac alpha- and beta-adrenoceptors and the positive inotropic effects of several adenylate cyclase dependent and independent agents have been measured in papillary muscle strips from patients without, as well as with moderate and severe heart failure. The number of beta-adrenoceptors was found to be decreased depending on the degree of heart failure. This does not apply to alpha-adrenoceptors, which remain unchanged. The antagonist affinity of adrenoceptors for the different ligands did not change in heart failure. Maximal increases in force of contraction were measured after raising Ca++ up to 15 mM in the muscle strips. In healthy human myocardium, isoprenaline, dobutamine, IBMX or cardiac glycosides increase force of contraction to the same maximal values as Ca++ does. However, in cardiac tissue from heart failure patients, positive inotropic agents which increase intracellular cAMP or are cAMP-dependent are less effective than Ca++. Furthermore, the results seem to indicate a homologous (agonist specific) downregulation of receptors in moderate heart failure and a heterologous downregulation in severe heart failure. Thus, many well known positive inotropic drugs lose their effectiveness just when they are needed most: in severe heart failure.

Cardiac Output, Low↗
PubMed1989

Screening of positive inotropic agents in isolated cardiac preparations from different sources.

The present study was designed to elucidate whether or not the positive inotropic effects of isoprenaline, milrinone, and DPI 201-106 in myocardial tissue from various sources reveal reliable results for the failing human heart. Therefore, in vitro positive inotropic responses were studied in human papillary muscle strips from patients with moderate heart failure (NNYHA II-III), human atrial trabeculae (HAT), isolated papillary muscles from Wistar-Kyoto rats (WK), and from spontaneously hypertensive rats (SHR). Results were compared with the effects of the compounds in papillary muscle strips from patients with severe heart failure (NYHA IV). In NYHA IV, positive inotropic responses were smaller for isoprenaline and milrinone than in NYHA II-III. The response to DPI 201-106 was more pronounced. In HAT, the effects of isoprenaline and milrinone were greater than in NYHA IV. The positive inotropic effect of DPI 201-106 was similar. In SHR, only the positive inotropic effect of isoprenaline was smaller than in WK. The effects of DPI 201-106 and milrinone did not differ. These data show that inotropic responses in NYHA II-III, HAT, WK, and SHR differ from the severely failing myocardium. It is concluded that new positive inotropic agents should be screened in human myocardial tissue from patients with heart failure, as experimental results from other sources may be irrelevant in this respect.

Animals↗
PubMed1989

Reduced effects of dopexamine on force of contraction in the failing human heart despite preserved beta 2-adrenoceptor subpopulation.

The results of the present study show that the reduction of the total number of beta adrenoceptors affected the beta 1-adrenoceptor subpopulation, whereas the beta 2 adrenoceptors were not detectably altered in the failing heart. Dopexamine had a 9.8-fold greater affinity to beta 2 adrenoceptors than to beta 1 adrenoceptors. In nonfailing myocardium, dopexamine increased force of contraction concentration-dependently. However, dopexamine alone had no effect in papillary muscle strips from moderately (NYHA II-III) and severely (NYHA IV) failing myocardium. However, in the presence of milrinone, it concentration-dependently increased force of contraction. Under this condition, the effectiveness was slightly less pronounced in NYHA IV than in NYHA II-III. Dopexamine concentration-dependently stimulated adenylate cyclase activity. Experiments with the beta 1-selective antagonist CGP 207.12 A and the beta 2-selective antagonist ICI 118.551 showed that both stimulation of adenylate cyclase and the increase of force of contraction are mediated by beta 2 adrenoceptors. It is concluded that although the number of beta 2 adrenoceptors is preserved in the failing myocardium, dopexamine alone does not increase force of contraction. However, the positive inotropic effect of dopexamine, which is observed in the presence of milrinone and the stimulation of adenylate cyclase activity by dopexamine are mediated by beta 2 adrenoceptors. Therefore, beta 2 adrenoceptors exist in the human myocardium, are coupled to adenylate cyclase, and are capable of increasing force of contraction. These results provide evidence for an impaired coupling of beta 2 adrenoceptors to mechanisms beyond receptor occupation in terminal heart failure.

Adenylyl Cyclases↗
PubMed1989

The value of positive inotropy in acute and chronic heart failure.

The different pathophysiological causes of acute and chronic heart failure prohibit a simple therapeutic approach with only one type of drug. Recent investigations have shown that the judicious use of positive inotropic agents, diuretics, and vasodilators in addition to dietary and exercise therapy can relieve the symptoms of heart failure and improve the quality of life as well as the prognosis. Apparently, the major breakthrough of modern treatment has not been the use of new or old positive inotropic drugs but rather the careful use of preload and afterload reducing agents. The proper place for beta-blocker therapy in chronic systolic or diastolic heart failure has not been established yet.

Acute Disease↗
PubMed1989

Inotropic response to DPI 201-106 in the failing human heart.

1. The present study was designed to characterize the positive inotropic response to DPI 201-106 in isolated papillary muscle strips obtained from heart failure patients undergoing surgery. 2. The positive inotropic responses to isoprenaline and milrinone and cardiac beta-adrenoceptor density were also determined. 3. DPI 201-106 increased the force of contraction in papillary muscle strips from patients with moderate (NYHA II-III) and severe (NYHA IV) heart failure, in a concentration-dependent manner. This positive inotropic effect was more pronounced in tissues from NYHA IV patients. Furthermore, these responses were greater than those produced by milrinone or isoprenaline. The positive inotropic effects of isoprenaline and milrinone were reduced in NYHA IV compared to NYHA II-III. Consistently, there was also a smaller density of beta-adrenoceptors in myocardium from NYHA IV than in NYHA II-III. The positive inotropic effect of Ca2+ was similar in tissues from both groups of patients. 4. The positive inotropic effect of DPI 201-106 was not antagonized by adenosine or carbachol, whereas both compounds reduced the positive inotropic effect of isoprenaline. 5. DPI 201-106 did not increase the Ca2+ -sensitivity of chemically skinned ventricular fibres, whereas a significant increase of the Ca2+ -sensitivity was obtained with trifluoperazine. 6. It is concluded that DPI 201-106 produces significant positive inotropic effects in tissue excised from the failing human heart. The lack of inhibition by adenosine and carbachol might contribute to its greater effectiveness in NYHA IV than NYHA II-III and indicates that its mechanism of action is cyclic AMP-independent. A sensitization of the contractile proteins to Ca2+ does not appear to be important for the positive inotropic action of DPI 201-106 in the failing human heart.

Adenosine↗
PubMed1989

Characterization of A1 adenosine receptors in atrial and ventricular myocardium from diseased human hearts.

The purpose of the present study was to characterize adenosine receptors in human atrial and ventricular myocardium. In isolated electrically driven preparations, adenosine produced "direct" negative inotropic effects in atrial myocardium (AT). In ventricular myocardium (VE), it only had negative inotropic properties when force of contraction had been stimulated with isoprenaline ("indirect" effect), but it has no inotropic effect alone. The adenosine receptor antagonist 8-phenyltheophylline antagonized the "direct" and "indirect" effects; these findings indicated that both effects were mediated by adenosine receptors. In cardiac membranes from human AT and VE, adenosine receptors were characterized with [3H]-8-cyclopentyl-1,3-dipropylxanthine (DPCPX) binding. The effects of agonists R-(-)-N6-phenylisopropyladenosine (R-PIA), S-(+)-N6-phenylisopropyladenosine (S-PIA), and 5'-(N-ethylcarboxamido) adenosine (NECA) and the effects of guanine nucleotides [Gpp(NH)p] were studied also. The antagonist affinities as judged from the apparent affinity, Kd, of [3H]DPCPX were similar in AT (2.2 nmol/l; 95% confidence limits, 1.4-3.7) and VE (1.8 nmol/l; 95% confidence limits, 1.0-3.0). The number of adenosine receptors was 1.7 times greater in AT (26.9 +/- 2.33 fmol/mg protein; n = 5) than in VE (16.2 +/- 2.3 fmol/mg protein; n = 5). High and low affinity states of adenosine receptors evaluated with the influence of Gpp(NH)p on agonist competition with R-PIA were similar in AT or VE. The rank orders of potency for agonists (R-PIA greater than S-PIA greater than NECA) and antagonists (DPCPX greater than 8-phenyltheophylline greater than theophylline) were characteristic for the A1 receptor subtype. It is concluded that A1 adenosine receptors exist in the human myocardium. Since binding properties were similar in AT and VE, the same A1 adenosine receptor probably couples to different effectors in a similar guanine nucleotide-dependent way. [3H]DPCPX is the first radiolabeled antagonist ligand that allows detection of A1 adenosine receptors and their coupling in the human myocardium.

GTP-Binding Proteins↗
PubMed1989

Increased number of cardiac adrenergic receptors following local heart irradiation.

The effect of local X irradiation on cardiac alpha and beta receptors was studied in Wistar rats. Animals were given local heart irradiation with single doses of 15 or 20 Gy and were examined after a range of latency times of 7 to 400 days. Using the radioactive ligands [3H]CGP-12177 and [3H]prazosin, the maximal binding capacity was determined from saturation experiments. At 7 days after 20 Gy the maximal binding capacity of both alpha and beta receptors was reduced to below the level of untreated control animals. Subsequently it rose continually to a maximum of 160% of the control level for beta receptors and 130% for alpha receptors at 400 days postirradiation. The antagonist affinity as judged from the dissociation constant for [3H]CGP 12177 and [3H]prazosin did not change significantly. A similar effect was observed after 15 Gy. An increase in adrenergic receptors may represent an important pathogenetic link between early morphological and late functional changes in the pathogenesis of radiation-induced heart disease.

Adrenergic alpha-Antagonists↗
PubMed1989

Comparison of sodium-meglumine ioxaglate and iopromide in coronary angiography.

A clinical study was carried out in 20 patients in coronary angiography to compare two low-osmolar contrast media, sodium-meglumine ioxaglate and iopromide. Ten patients presented a stage III coronary disease and the other ten had a stage IV coronary disease. In the latter group, 70% of the patients received sodium-meglumine ioxaglate and 30% were given iopromide. None of the patients given iopromide had a previous history of allergic-like reactions to contrast media as opposed to the sodium-meglumine ioxaglate group where two patients had a previous hypersensitivity reaction to contrast agents. In spite of these adverse conditions in the sodium-meglumine ioxaglate group, no significant difference was found between both preparations as to overall tolerability. The following side effects were observed: slight nausea and wheezing in a patient given sodium-meglumine ioxaglate; medium intense nausea, vomiting and headache in a patient administered iopromide; one case of angina pectoris occurring 8 minutes post-injection of iopromide. Similarly, no significant difference in overall cardiac tolerability could be found between the two contrast media, although sodium-meglumine ioxaglate would tend to be better tolerated in terms of heart rate and contractility. Radiographic efficacy was considered to be equivalent for both contrast agents though the test solutions had different iodine concentrations. In summary, the two low osmolar contrast media proved well tolerated and showed satisfactory diagnostic efficacy in this population at high cardiovascular risk.

Angiography↗