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Biomedical subjects

E Erdmann

Publications and source records attributed to E Erdmann.

At least 361 records · Page 20Linked to original sources
PubMed1985

Concentration-response curves of positive inotropic agents before and after ouabain pretreatment.

Current therapy for congestive heart failure (diuretics, digitalis, vasodilators) may be insufficient. Addition of a second positive inotropic substance to digitalised patients has been previously shown to increase cardiac index and decrease vascular resistance. To test the hypothesis that the positive inotropy of ouabain can be increased by other inotropic agents, the following studies were performed. Firstly, concentration-response curves of positive inotropic agents (ouabain, dobutamine, dopamine, orciprenaline, phenylephrine, theophylline, amrinone, sulmazole and histamine) were measured in contracting left atria and papillary muscles from cat and guinea pig hearts. The maximal increase in force of contraction was similar for all compounds except histamine and phenylephrine which gave decreased effects in guinea pig heart muscle. Secondly, these positive inotropic agents were added to the contracting heart muscles after maximal inotropy without toxicity of a ouabain concentration which gave more than 90% of the maximal increase in force of contraction. In guinea pig left atria, dobutamine was the only compound to give a significant, although transient, increase in force of contraction above the maximal ouabain response. Theophylline (2 X 10(-4) mol X litre-1, EC25) produced significant decreases in force of contraction. In papillary muscles, low concentrations of all positive inotropic compounds, except amrinone, significantly increased force of contraction after a submaximal ouabain concentration. However, the maximal increase in force of contraction after combined addition of ouabain and a second inotropic agent was not different from the maximal increase with ouabain, dobutamine or dopamine alone. Addition of higher concentrations of the second inotropic agents after ouabain pretreatment led to a markedly increased incidence of toxicity with only transient positive inotropic effects. These results indicate that any haemodynamic improvement observed in adequately digitalised patients after combined positive inotropic therapy is unlikely to result from directly additive inotropic effects but is probably a result of other cardiovascular effects such as vasodilatation.

Aminopyridines↗
PubMed1985

[Age-dependent regulation of cardiac glycoside receptors].

Specific binding of cardiac glycosides to their receptors precedes their actions on the myocardium. Thus changes in the number and affinity of these membrane bound receptors will vary the response to cardiac glycoside therapy and the incidence of side-effects. Several studies have reported an age-dependent decrease in the number of cardiac glycoside receptors in animals as well as in human erythrocytes. These results may explain the increase in cardiac glycoside sensitivity with age which is not accounted for by the reduction in kidney function. Furthermore, changes in both binding affinity and capacity are known to occur in several diseases which are more common in older patients. Therefore, we have measured the number and affinity of cardiac glycoside receptors in atrial samples from 209 patients and in papillary muscle samples from 59 patients taken during coronary bypass graft surgery or mitral valve replacement. Further, the maximal increase in force of contraction was measured using papillary muscle strips from some of these patients. Our results show no significant age-dependent alteration in the characteristics of the cardiac glycoside receptors but a reduced myocardial receptor density in males (3.47 +/- 0.14 X 10(14)/g protein) compared with females (4.44 +/- 0.21 X 10(14)/g protein) (p less than 0.001) which is more pronounced in older patients. About 30% fewer cardiac receptors either per g protein or per g wet weight are present in patients with coronary heart disease or dilative cardiomyopathy. The maximal inotropic effect of ouabain in human papillary muscle strips is correlated with the number of cardiac glycoside receptors present.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1985

Progression of coronary and valvular heart disease in patients on dialysis.

Coronary heart disease and end-stage renal disease: Coronary heart disease is frequent in patients with end-stage renal disease. Without invasive procedures coronary heart disease is often not diagnosed in patients with end-stage renal disease. We have no evidence for accelerated progression of coronary heart disease under conditions of dialysis. Valvular heart disease and end-stage renal disease: Valvular heart disease shows an increasing frequency depending on the period of dialysis. Valvular heart disease is often unnoticed and constantly underestimated without invasive investigation. Valvular heart disease often indicates a bad prognosis in our patients with end-stage renal disease.

Adult↗
PubMed1985

[Changes of affinity and capacity of cardiac glycoside receptors].

The receptor for cardiac glycosides probably is identical with the (Na+ + K+)-ATPase (approximately 250 000 Daltons). Its affinity for the therapeutically used glycosides is extremely different in different species (KD approximately 10(-9)M (human heart) - approximately 10(-7)M (rat heart]. In the latter, two distinct receptor types have been demonstrated (high- and low-affinity receptors) with different effects. In the human heart, there may be two cardiac glycoside receptors as well, although this has not been proved as yet. The number of cardiac glycoside receptors and their affinity is regulated in certain states and diseases. An increased receptor density is found in hyperthyroid states, in chronic hypokalaemia and in chronic digitalis treatment. A decreased number is measured in ischemic heart disease, in dilated cardiomyopathy and in hypothyroidism. Parallel to the decreased receptor density the maximal cardiac glycoside induced positive inotropy is reduced. Pronounced toxicity occurs, if the digitalis dose is increased in spite of missing effects.

Aging↗
PubMed1984

[Percutaneous transluminal extraction of an embolized central venous catheter].

Despite all precautions in two cases a large fragment of a transvenously placed central-venous catheter broke off and became lodged in the right atrium. In both the fragments were removed successfully and without complication with the Dotter intravascular retriever catheter, percutaneously introduced into the femoral vein. Staphylococci were grown from both catheter fragments after removal. These cases illustrate once again the value of radio-opaque venous catheters.

Aged↗
PubMed1984

Cardiac glycoside receptors in cultured heart cells--II. Characterization of a high affinity and a low affinity binding site in heart muscle cells from neonatal rats.

The binding of [3H]ouabain has been studied in (Na+ + K+)-ATPase enriched cardiac cell membranes, as well as in cardiac muscle and non-muscle cells in culture--all obtained from hearts of neonatal rats. The binding has been correlated with ouabain-induced inhibition of (Na+ + K+)-ATPase (cardiac cell membranes) and the inhibition of active (86Rb+ + K+)-influx (cardiac muscle and non-muscle cells in culture). Furthermore, the effect of ouabain on the amplitude of cell-wall motion and contraction velocity has been studied in electrically driven cardiac muscle cells. In muscle and non-muscle cells, two classes of ouabain binding sites have been identified. In rat heart muscle cells, the high affinity binding site has a dissociation constant (KD) of 3.2 X 10(-8) M and a binding capacity (B) of 0.2 pmole/mg protein (80,000 sites/cell); the values for the low affinity binding site are: KD = 7.1 X 10(-6) M; B = 2.6 pmole/mg protein (10(6) sites/cell). The binding to both types of binding sites is depressed by K+ and abolished after heat denaturation of the cells. The kinetics of [3H]ouabain binding to rat heart muscle cells (association and dissociation rate constants, K+- and temperature-dependence of association and dissociation processes) have been characterized. In rat heart muscle and non-muscle cells, the binding of [3H]ouabain to the low affinity site results in inhibition of the (86Rb+ + K+)-influx (EC50 = 1.3 and 1.5 X 10(-5) M ouabain), a decrease in cell-K+ (EC50 = 1.9 and 1.4 X 10(-5) M) and an increase in cell-Na+ (10(-5)-10(-4) M). The ouabain-induced positive inotropic effect (increase in amplitude of cell-wall motion, increase in contraction velocity) in cardiac muscle cells is observed only at ouabain concentrations greater than or equal to 5 X 10(-6) M, and it is therefore probably attributed to occupation of the low affinity binding site. Coupling of occupation of the low affinity site by ouabain with drug-induced inhibition of the sodium pump and with drug-induced positive inotropic action is further substantiated by kinetic measurements. In contrast, occupation of the high affinity binding site does not produce any measurable inhibition of the sodium pump activity or positive inotropy.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1984

Non-additive positive inotropic effects of amrinone and ouabain on cat papillary muscles.

Amrinone has been shown to produce haemodynamic benefits in digitalis-treated patients. Since amrinone is a positive inotropic agent on isolated heart muscle, these benefits may mean that amrinone increases the maximal ouabain-induced increase in force of contraction, without causing toxicity. We have therefore measured, in cat right ventricular papillary muscles, the inotropic effects of ouabain, amrinone alone and amrinone with a maximally effective, non-toxic ouabain concentration (2 X 10(-7) M). Ouabain is much more potent than amrinone (EC50-values: ouabain, 8 X 10(-8) M, amrinone, 1-2.8 X 10(-3) M). The highest amrinone concentration used (6 X 10(-3) M) produced a significantly lower increase in force of contraction than ouabain (2 X 10(-7) M) in the same muscles. After ouabain (2 X 10(-7) M) produced a stable effect, no further increase in force of contraction was observed with any amrinone concentration. Sustained arrhythmias were observed in five of six muscles at 3 X 10(-3) M amrinone with ouabain (2 X 10(-7) M), but in only one of these muscles with amrinone 3 X 10(-3) M alone. Since the positive inotropic effects of amrinone are not additive with those from a maximally effective ouabain concentration, the haemodynamic benefits seen in patients are probably due to non-cardiac effects of amrinone such as vasodilatation.

Aminopyridines↗
PubMed1984

Influence of digitalis and diuretics on ouabain binding sites on human erythrocytes.

It has been reported that during chronic treatment with digitalis, the number of digitalis binding sites is increased in human erythrocytes [22]. From this finding a tachyphylaxis for cardiac glycosides has been postulated. We reinvestigated this problem in several groups of patients. The number of 3H-ouabain binding sites per erythrocyte in control persons (group I) was 214 +/- 60, n = 43 (means +/- SD). The dissociation constant (KD) was 1.8 +/- 0.5 nM. Thirteen patients (group II) taking cardiac glycosides only, for at least 6 months, had 281 +/- 99 (p less than 0.05) ouabain binding sites per single red cell, KD = 1.8 +/- 0.7 nM. Group III (34 patients) took digitalis for more than 6 months and diuretics for at least 3 months (352 +/- 126 (p less than 0.001), KD = 1.6 +/- 0.6). Twenty-three of these (group IV) were taking a combination with "K+-saving" diuretics (336 +/- 194 (p less than 0.01), KD = 1.6 +/- 0.5) and (group V, 11 patients) a combination with "K+-losing" diuretics (462 +/- 133 (p less than 0.001), KD = 1.4 +/- 0.4). Nine patients (group VI) had a chronic hypokalemia, mainly due to taking furosemide (437 +/- 98 (p less than 0.001), KD = 1.5 +/- 0.4). Four control persons took 50 mg hydrochlorothiazide daily for more than 4 months without measurable K+-losses and without changes in ouabain binding sites. It is concluded from these findings that diuretic treatment with chronic hypokalemia in addition to digitalis is accompanied by a significant increase in ouabain binding sites in human red cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗