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Biomedical subjects

E Erdmann

Publications and source records attributed to E Erdmann.

At least 235 records · Page 13Linked to original sources
PubMed1992

Effect of the phosphodiesterase inhibitor UK 61260 on human myocardial inotropy and diastolic relaxation.

The phosphodiesterase inhibitor UK 61260 exhibits positive inotropic activity in animal studies and is under clinical investigation for treatment of congestive heart failure (CHF). We examined the lusitropic and inotropic responses to UK 61260 in electrically driven (1 Hz, 37 degrees C) human auricular trabeculae (AUT, aortocoronary bypass operation, nonfailing hearts, n = 13) and in papillary muscle strips (PAP) from moderately (New York Heart Association, NYHA II-III, mitral valve replacement, n = 6) and terminally (NYHA IV, heart transplantation, n = 7) failing human hearts. For comparison, we studied the effects of UK 61260 after prestimulation with forskolin (FOR 0.03 microM) and isoprenaline (ISO 0.03 microM), as well as the effects of milrinone (MIL 1-1,000 microM), ISO (0.01-10 microM), ouabain (OUA, 0.1 microM), and Ca2+ (1.8-15 mM) in failing human myocardium alone. UK 61260 increased force of contraction (FOC), peak rate of tension increase (+T) and decay (-T) significantly (p less than 0.01) in AUT but not in PAP of NYHA II-III and NYHA IV. Only after prestimulation (FOR and ISO), was UK 61260 effective in stimulating FOC in NYHA II-III and NYHA IV. UK 61260 increased (p less than 0.01) +T and -T, resulting in a shortening of twitch time. As judged from the EC50 values, UK 61260 increased FOC more potently than MIL. The effectiveness of OUA and Ca2+ in increasing developed tension in human failing myocardium was significantly higher as compared with UK 61260. We conclude that during stimulation of the cardiac beta-adrenoceptor-adenylate-cyclase system, UK 61260 increases myocardial systolic and diastolic function in failing human myocardium.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Positive inotropic effects due to partial agonistic activity of the beta-adrenoceptor antagonist celiprolol following amplification of cAMP formation in failing human myocardium.

The present study investigated the effects of celiprolol a novel beta 1-antagonist with partial beta 2-agonist activity on the human failing heart. Experiments were performed on isolated electrically driven atrial and ventricular cardiac preparations and in membrane preparations from the left ventricles of nine patients (four with dilated cardiomyopathy; five with ischemic cardiomyopathy) undergoing cardiac transplantation for terminal heart failure. Celiprolol produced a negative inotropic effect in atrial and ventricular heart muscle. However, in the presence of forskolin--which activates the catalyst of the adenylate cyclase-or the cAMP phosphodiesterase inhibitor milrinone, celiprolol produced concentration-dependent positive inotropic effects and positive lusitropic effects. Experiments with the beta 1-and beta 2-selective antagonists CGP 207.12A and ICI 118.551, respectively, suggest that the positive inotropic response is mediated by beta 2-adrenoceptors. In radioligand binding experiments, a selectivity of 15.7 [-Gpp(NH)p] or 23.9 [+Gpp(NH)p] as judged from the Ki values--of binding to beta 2-adrenoceptors was measured in the failing human ventricular myocardium. Competition curves with celiprolol alone and in the presence of the guanine nucleotide Gpp(NH)p revealed no evidence for agonist activity at beta 1- or beta 2-adrenoceptors. It is concluded that amplification of the cAMP response is able to unmask partial agonist activity of celiprolol in the failing human heart at beta 2-adrenoceptors. The inotropic measurements are a more sensitive approach than radioligand binding studies. Whether the pharmacological profile of celiprolol will be useful in conditions like heart failure is questionable with respect to the potential downregulation of beta 2-adrenoceptors by its partial agonist activity.

Adrenergic beta-Agonists↗
PubMed1992

Antiadrenergic effect of M-cholinoceptor stimulation on human ventricular contractility in vivo.

The relevance of an indirect negative inotropic effect of pharmacological or vagally mediated M-cholinoceptor stimulation in the human ventricle in vivo is unknown. The inotropic response induced by isoproterenol (isoprenaline, 20 ng.kg-1 x min-1), measured by m-mode echocardiography as the increase of fractional shortening in seven healthy subjects, was reduced from 17.1 +/- 4.3 to 9.1 +/- 3.9% (P < 0.01) by M-cholinoceptor stimulation using intravenous injection of 3.6 micrograms/kg carbachol. However, the inotropic response of increasing doses of isoprenaline (5-20 ng.kg-1 x min-1) did not differ in 13 healthy subjects without and after M-cholinoceptor blockade (atropine, 0.015 mg/kg i.v.); the increase of fractional shortening amounted to 17.4 +/- 4.0 vs. 19.5 +/- 4.8% (NS) in response to 20 ng.kg-1 x min-1 isoprenaline. It is concluded that pharmacological M-cholinoceptor stimulation of the human ventricle significantly reduces the inotropic response of beta-adrenoceptor stimulation. This may offer a new therapeutic approach to attenuate an increased cardiac sympathetic tone. However, M-cholinoceptor blockade, i.e., interruption of parasympathetic influences, does not augment the inotropic response to beta-adrenoceptor stimulation. Therefore, in healthy resting humans a physiological role of the parasympathetic nervous system in mediating an indirect negative inotropic effect on ventricular contractility seems to be absent.

Adult↗
PubMed1992

Intracellular calcium handling in isolated ventricular myocytes from patients with terminal heart failure.

BACKGROUND: Experiments were performed in human ventricular myocytes to investigate properties of excitation-contraction coupling in patients with terminal heart failure. Myocytes were isolated from left ventricular myocardium of patients with cardiac failure caused by dilated or ischemic cardiomyopathy undergoing transplantation. These results were compared with those obtained from cells of healthy donor hearts that for technical reasons were not suitable for transplantation. METHODS AND RESULTS: [Ca2+]i transients and Ca2+ currents were recorded from isolated cells under voltage clamp perfused internally with the Ca2+ indicator fura 2. In cells that were stimulated externally, the cell-permeant form of the indicator, fura 2-AM, was used. When action potentials were to be recorded, cells were stimulated in current clamp mode. Unstimulated Ca2+ current densities were not significantly different in myopathic and control cells. In diseased myocytes, resting [Ca2+]i levels were 165 +/- 61 nmol/l, compared with 95 +/- 47 nmol/l in normal cells. With 5 mmol/l Na+ in the pipette, peak [Ca2+]i transients were 367 +/- 109 and 746 +/- 249 nmol/l, respectively. The decline of [Ca2+]i during diastole was significantly slower in myopathic cells than in control cells. This was a result of a prolongation of the action potential and of a reduced Ca2+ sequestration by the sarcoplasmic reticulum. CONCLUSIONS: These results may partly explain the alterations of contractility in vivo in patients with heart failure.

Action Potentials↗
PubMed1992

Isolated presynaptic inotropic beta-adrenergic supersensitivity of the transplanted denervated human heart in vivo.

BACKGROUND: The regulation of contractility of the transplanted heart depends on circulating catecholamines resulting from cardiac denervation. Supersensitivity to circulating catecholamines may result from loss of presynaptic neuronal uptake or upregulation of postsynaptic beta-adrenergic receptors. METHODS AND RESULTS: Dose-response curves using the beta-adrenergic receptor agonists isoprenaline (no neuronal uptake) and epinephrine (neuronal uptake) were performed in vivo. The inotropic response was measured echocardiographically as the increase of fractional shortening (delta FS) and the increase of the systolic pressure/dimension ratio (delta P/D). The inotropic response to increasing doses of isoprenaline (5-20 ng/kg.min) was identical in 36 heart transplant recipients compared with 13 control subjects: delta FS during 20 ng/kg.min isoprenaline amounted to 18.2 +/- 6.2% versus 17.4 +/- 4.0% (NS) and delta P/D to 2.3 +/- 1.2 mm Hg/mm versus 2.2 +/- 0.5 mm Hg/mm (NS), respectively. A vagally mediated indirect negative inotropic effect in the innervated hearts was excluded by identical inotropic responses to isoprenaline in control subjects without and after atropine pretreatment. The inotropic response to increasing doses of epinephrine (10-40 ng/kg.min) was significantly augmented in 13 heart transplant recipients compared with 11 control subjects: delta FS during 40 ng/kg.min epinephrine amounted to 19.9 +/- 2.6% versus 8.6 +/- 2.0% (p less than 0.001) and delta P/D to 2.3 +/- 0.9 mm Hg/mm versus 0.6 +/- 0.3 mm Hg/mm (p less than 0.001), respectively. Pretreatment with desipramine (blockade of neuronal uptake) in control subjects resulted in a significantly increased inotropic response: delta FS during 40 ng/kg.min epinephrine amounted to 17.6 +/- 3.6% (p less than 0.001 versus untreated controls, NS versus heart transplant recipients) and delta P/D to 1.7 +/- 0.8 mm Hg/mm (p less than 0.001 versus untreated controls, NS versus heart transplant recipients). CONCLUSIONS: These findings provide evidence against a postsynaptic inotropic supersensitivity or subsensitivity of the beta-adrenergic receptor-effector system of the transplanted denervated human heart in vivo. However, a marked presynaptic inotropic supersensitivity is present because of denervation-associated loss of neuronal catecholamine uptake.

Adult↗
PubMed1992

Desensitization of adenylate cyclase and increase of Gi alpha in cardiac hypertrophy due to acquired hypertension.

The present study investigated whether reduced adenylate cyclase activity and an increase in inhibitory guanine nucleotide binding proteins (Gi alpha), which have been observed in the failing human heart, already occur in myocardial hypertrophy before the stage of heart failure. In membranes of hypertrophic hearts from rats with different forms of experimentally induced hypertension without heart failure (one-kidney, one clip rats, deoxycorticosterone-treated rats, and rats with reduced renal mass), basal as well as isoprenaline-, 5'-guanylylimidodiphosphate-, and forskolin-stimulated adenylate cyclase activity was reduced. The activity of the catalyst was depressed in deoxycorticosterone but unchanged in one-kidney, one clip and reduced renal mass compared with controls. The number of beta-adrenergic receptors was similar in all groups. Radioimmunological quantification of Gi alpha proteins revealed an increase by 73% in one-kidney, one clip, 67% in reduced renal mass, but only 20% in deoxycorticosterone compared with sham-operated, age-matched control rats. The increase of Gi alpha was accompanied by smaller changes of pertussis toxin-induced [32P]ADP-ribosylation of a 40-kd membrane protein. It is concluded that Gi alpha contributes to the reduced adenylate cyclase activity in cardiac hypertrophy in one-kidney, one clip and reduced renal mass and to a smaller extent in deoxycorticosterone. It is suggested that an enhanced expression of Gi alpha could occur not only in severe heart failure but also in cardiac hypertrophy and could, therefore, contribute to myocardial depression and progression of disease in heart failure. In addition, Gi alpha might represent an important regulatory mechanism for cardiac adenylate cyclase activity and thus, might play an important role in various cardiac diseases.

Adenylyl Cyclases↗
PubMed1992

[Clinical aspects of differential drug therapy of chronic heart failure].

Treatment of chronic heart failure with ACE-inhibitors has greatly improved the prognosis. In addition to ACE-inhibitors, diuretics seem to be necessary to decrease mortality, whereas the importance of cardiac glycosides has not been demonstrated unequivocally. Nevertheless, modern treatment of chronic heart failure in all stages should be a combination of diuretics, digitalis, and ACE-inhibitors rather than a stepwise addition of drugs depending on the severity of the disease. An increased heart rate leads to increased myocardial O2-consumption, decreased O2-supply, ischemia, and reduced contractility. Betablocker-induced reduction of heart rate does, however, not necessarily improve symptoms or hemodynamic conditions. The optimal heart rate in large failing hearts is not known yet. Probably, it is dependent on the type and severity of myocardial disease or impairment. In this respect, the sarcoplasmatic release and uptake of Ca2+ plays the most important role in the disordered force-frequency-relation in chronic heart failure.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1992

Radiation-induced heart disease: morphology, changes in catecholamine synthesis and content, beta-adrenoceptor density, and hemodynamic function in an experimental model.

To study further the pathophysiology of radiation-induced cardiomyopathy, we investigated resting hemodynamics, myocardial catecholamine synthesis and storage, and beta-adrenoceptor density after local heart irradiation. In Wistar rats, a radiation dose of 20 Gy eventually leads to compromised myocardial function which is characterized by a reduction in cardiac output to 43 +/- 11% and in the left ventricular ejection fraction to 66 +/- 7.5%, and an increase in the left ventricular end-diastolic volume to 187 +/- 17% of control values. This reduction in function is correlated with focal degeneration of 23 +/- 4% of the myocardium. Measurement of tyrosine hydroxylase activity and catecholamine content revealed that catecholamine biosynthesis is unchanged in the adrenals but is significantly reduced in the hearts of irradiated animals, while cardiac beta-adrenoceptor density is increased to about 140% of that in age-matched controls. This is in contrast to findings in dilated or ischemic cardiomyopathy. Time-course studies showed that the development of myocardial degeneration starts simultaneously with the decrease in cardiac output and ejection fraction and the increase in beta-adrenoceptors at 50-80 days postirradiation. Myocardial degeneration is maximal in extent and severity at 100 days and does not progress thereafter. Cardiac output decreases at 80-100 days postirradiation to 60 +/- 7% of control values. A significant further decrease is seen only when congestive heart failure becomes manifest at 249 +/- 21 days after 20 Gy. Thus there is a delay between structural myocardial injury and hemodynamic deterioration which could be due to a compensatory increase in beta-adrenoceptor density during the initial stages of the cardiomyopathy.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

[Adrenergic beta receptors and guanine nucleotide binding proteins (G-proteins) of the failing human heart].

In heart failure, the sympathetic nervous system is activated. The increased release of norepinephrine from the heart and the elevated levels of circulating catecholamines produce a downregulation of myocardial beta 1-adrenoceptors. In ischemic cardiomyopathy and mitral valve disease, a downregulation of beta 2-adrenoceptors has been observed also. The beta-adrenoceptor downregulation closely correlates to the reduced positive inotropic effects of beta-adrenoceptor agonists. In addition, an increase of the inhibitory guanine-nucleotide binding protein (Gi alpha) has been observed, while the levels of the stimulatory guanine-nucleotide binding protein (Gs alpha), the activity of the catalyst and the anti-adrenergic effects of A1-adenosine receptor- or m-cholinoceptor stimulation remain unchanged in the failing human heart. The increase of Gi alpha correlated closely to the reduced positive inotropic responses to the cAMP-phosphodiesterase inhibitor milrinone. In the failing human heart, the beta-adrenoceptor downregulation and the increased expression of Gi alpha represent pathobiochemical alterations which are involved in the reduced effects of cAMP-dependent positive inotropic agents. The therapeutic reversal of these pathobiochemical alterations is a future promise in the treatment of heart failure.

GTP-Binding Proteins↗
PubMed1992

Increase of the extracellular magnesium concentration reduces cardiac glycoside toxicity in the human myocardium.

We studied the influence of magnesium on contractility and on force-frequency-relationship as well as on the positive inotropic and toxic effects of ouabain (OUA) on electrically driven human right auricular trabeculae. Radioligand binding experiments were performed with myocardial tissue from nonfailing and from terminally failing patients. Magnesium produced a concentration-dependent negative inotropic effect (P < .05). In contrast, OUA (0.03-0.1 mumol/l) concentration-dependently increased isometric force of contraction. The maximal positive inotropic effect of OUA (5.9 +/- 0.9 mN; 1 mmol/l of magnesium) was unchanged after increasing magnesium from 1 to 2 mmol/l (5.8 +/- 0.9 mN). OUA was as effective as Ca++ (15 mmol/l; 6.7 +/- 0.5 mN). OUA (0.05 and 0.03 mumol/l) exerted toxic effects after 2 hr and 0.08 or 0.1 mumol/l of OUA after 30 min, respectively. Time until toxic effects occurred after OUA (0.1 mumol/l) was significantly longer with 2 mmol/l of magnesium compared to 1 mmol/l of magnesium. In right auricular trabeculae, the force of contraction increased with increasing frequency (0.5-1 .5 Hz) of stimulation. The force-frequency-relationship becomes negative after elevation of extracellular Ca++ (2.4 mmol/l of Ca++) (2 Hz: 92 +/- 5.5% basal). Magnesium restored the force-frequency-relationship in the presence of enhanced Ca++ concentration (2.4 mmol/l of Ca++; 2 mmol/l of Mg++; 2 Hz: 145 +/- 16.9% basal). The receptor-density and affinity measured by [3H]OUA binding was not different in nonfailing and failing myocardium. Magnesium increased concentration-dependently the affinity of [3H]OUA to its receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Heart failure and electrolyte disturbances.

Electrolyte abnormalities are a frequent and potentially hazardous complication in patients with heart failure. This may be due to the pathophysiological alterations seen in the heart failure state leading to neurohumoral activation (stimulation of the renin-angiotensin-aldosterone system, sympathoadrenergic stimulation), and due to the complications of therapy with diuretics, cardiac glycosides or ACE inhibitors. Patients with heart failure may exhibit hyponatremia due to a decrease in water excretion, which may be related to the enhanced release of both angiotensin and vasopressin and can be exaggerated by diuretic therapy. Along with potassium and calcium, magnesium influences cardiovascular function. Magnesium and potassium deficiencies play an important role in the development of cardiac arrhythmias. Magnesium is essential for the maintenance of intracellular potassium concentration. Although there are conflicting data regarding the prevalence of hypomagnesemia in patients with chronic heart failure (the values range from 7-37%), multiple studies have documented lower magnesium concentrations in patients with heart failure than in normal controls. As magnesium and potassium are mainly intracellular ions, measurements in serum or plasma are of limited value to assess magnesium status. There was no correlation between the intracellular electrolyte content and the electrolyte levels in plasma, either for mononuclear cells or erythrocytes or for myocardial and skeletal muscle. Loop diuretics (e.g. furosemide) are supposed to cause a substantial loss of both magnesium and potassium in the plasma and intracellular space. The potassium-sparing diuretics amiloride and triamterene are reported to also exert magnesium-sparing effects. Recently, ACE inhibitors have been documented to have important magnesium-conserving actions, possibly via their effect on glomerular filtration. Hyperkalemia, secondary to the use of ACE inhibitors in patients with heart failure, is well documented. Digoxin directly limits the renal tubular reabsorption of magnesium, therefore increasing magnesium excretion. Low magnesium and potassium concentrations increase cardiac glycoside toxicity. In contrast, elevated levels of magnesium decrease the sensitivity of human myocardium to antiarrhythmogenic actions of cardiac glycosides, without affecting maximally developed tension. Moreover, magnesium increases binding affinity of cardiac glycosides to the receptor. The antiarrhythmic action of magnesium is suspected to be mediated by a reduced sensitivity to electrophysiological changes induced by Ca2+, thus indicating Ca2+ antagonistic properties of magnesium. Magnesium deficiency has also been implicated in sudden death, notably in patients with congestive heart failure. Therefore, when treating congestive heart failure, one must consider how to prevent depletion of electrolytes or how to replete potassium and magnesium in deficiency states.

Arrhythmias, Cardiac↗
PubMed1991

[Heart arrhythmias in advanced age].

Holter monitoring has revealed that bradycardiac and tachycardic arrhythmias are frequent in apparently healthy subjects aged over 75. Even in elderly patients with known cardiovascular disease, however, such arrhythmias usually do not correlate with the clinical symptoms giddiness, palpitations or syncope. For this reason, prior to possible therapeutic measures, an accurate investigation of the underlying cause and the demonstration of a causal relationship between documented arrhythmias and symptomatology is necessary. Account must be taken of the particular pharmacotherapeutic situation in old age, in which the pharmacokinetics and pharmacodynamic properties of almost all drugs are modified.

Aged↗
PubMed1991

Failure of [32P]ADP-ribosylation by pertussis toxin to determine Gi alpha content in membranes from various human tissues. Improved radioimmunological quantification using the 125I-labelled C-terminal decapeptide of retinal transducin.

The quantitative determination of pertussis-toxin-sensitive guanine-nucleotide-binding proteins (G-proteins) in cell membranes is still a problem. Pertussis-toxin-catalysed [32P]ADP-ribosylation strongly relies on the substrate quality of the alpha-subunits and is influenced by the concentration of nucleotides, beta gamma-subunits, the physicochemical properties of the membranes influencing the availability of Gi alpha for pertussis toxin, and covalent modification of Gi alpha. Quantification of immunoreactive material on Western blots can be only imprecisely performed by two-dimensional densitometry. In order to generate a method for quantification of pertussis-toxin-sensitive G-proteins in membranes we have developed a fast and sensitive radioimmunoassay. The C-terminal decapeptide of retinal transducin alpha (KENLKDCGLF) was 125I-labelled and used as tracer. Polyclonal antiserum (DS 4) was raised against this peptide. Gi alpha proteins were determined by competition of solubilized membranes for 125I-KENLKDCGLF binding to DS 4 using dilutions of retinal transducin alpha as standard. The interassay variation was less than 10%, with a sensitivity of 2.5 micrograms/ml. The density of Gi alpha was highest in human adipose tissue, followed by HL60 cells, lung, mononuclear leucocytes, thrombocytes and left ventricular myocardium. A striking difference was observed between the density of Gi alpha and the amount of incorporation of [32P]ADP-ribose into the 40 kDa membrane proteins by pertussis toxin in the same samples. This is also demonstrated by comparison of the weak [32P]ATP-ribosylation of pertussis toxin substrates with the density of immunoreactive Gi alpha on Western blots in tissues such as lung. This study shows that the Gi alpha content can be exactly determined by a sensitive and fast radioimmunoassay using iodinated synthetic peptide homologues of Gi alpha proteins. Radioimmunological quantification of Gi alpha might be able to detect the 'true' Gi alpha content of membranes without being hampered by influences on the [32P]ADP-ribosylation reaction. It is concluded that this newly developed method may become an important tool for studying expression of Gi alpha proteins in a variety of tissues or cell types, and for precisely quantifying the changes caused by pathological conditions.

Adenosine Diphosphate Ribose↗
PubMed1991

Contractility of the transplanted, denervated human heart.

The purpose of the study was to characterize the contractility of the transplanted human heart and to evaluate possible adverse effects of denervation or structural changes of the myocardium or coronary vessels. As an index of contractility, the linear slope k of the end-systolic pressure/dimension relationship during afterload increase with angiotensin II was determined by M-mode echocardiography in 34 heart transplant recipients and 20 healthy control subjects. Baseline findings for end-systolic diameter and systolic blood pressure were normal and similar in both groups, but the transplanted hearts performed at a significantly lower end-systolic wall stress (40.4 +/- 12 gm/cm2 vs 49.9 +/- 11 gm/cm2, p less than 0.001). Comparable increase of afterload was achieved in heart transplant recipients with significantly (p less than 0.001) less angiotensin II, which indicates increased vasoconstrictor sensitivity. Contractility index k did not differ between heart transplant recipients (12.95 +/- 4.9 mm/100 mm Hg) and control subjects (12.78 +/- 2.8 mm/100 mm Hg). This finding is consistent with a normal contractility of the transplanted, denervated human heart. Normal baseline contractility therefore is an intrinsic property of the intact heart, which is independent of autonomic neural control. Contractility was not compromised by increasing interval from transplantation or the presence of mild acute rejection or mild interstitial fibrosis. Mildly impaired contractility (k greater than 2 SD of k in control subjects) in four heart transplant recipients (12%) was neither associated with structural myocardial or coronary changes nor with rejection episodes or graft ischemic time. One may speculate that impaired contractility, which is present in a minority of heart transplant recipients, results from pretransplantation damage.

Adult↗
PubMed1991

Characteristics of calcium-current in isolated human ventricular myocytes from patients with terminal heart failure.

The Ca(2+)-current plays a prominent role in triggering excitation-contraction coupling in the mammalian heart. It is also a target of clinically important drugs such as catecholamines or Ca(2+)-channel blockers. Until now studies of Ca(2+)-channels in human ventricular myocardium have been hampered by the fact that adequate voltage control cannot be obtained in multicellular preparations. To characterize the properties of human myocardial Ca(2+)-currents, ventricular myocytes were isolated from explanted hearts of patients with end-stage heart failure undergoing cardiac transplantation. The current-voltage relation and voltage-dependent inactivation of L-type currents were similar to those in non-diseased guinea-pig myocardium. Currents could be stimulated with isoprenaline in a dose-dependent manner. When cells were superfused with a Na(+)-free solution in the presence of Tetrodotoxin, Cs+ and Tetraethylammonium to block interfering Na+ and K(+)-currents, depolarization from a holding potential of -90 mV to -80-(-)50 mV did not elicit any time-dependent inward-current. Changing the holding potential from -90 to -45 mV did not alter the current-voltage relation. We conclude that T-type Ca(2+)-currents do not seem to make a detectable contribution to the transmembrane Ca(2+)-influx and that L-type currents in human ventricular myocytes of patients with severe heart failure have characteristics that are similar to those in other mammalian species.

Action Potentials↗