[Ion channels and arrhythmias].

Changes in ionic currents through ion channels of the myocardial cell membrane have to be regarded as main cause of cardiac arrhythmias. Three basic arrhythmogenic mechanisms are responsible for the initiation of tachyarrhythmias: 1. The disturbance of normal automaticity in cardiac pacemaker cells dependent on the currents If, ICa-L, ICa-T or IK-ACh,Ado and the occurrence of abnormal automaticity in atrial and ventricular working myocardium based on the currents ICa-L, INa, IK, IK1 or IK-ACh,Ado.

Different inhibition patterns of tedisamil for fast and slowly inactivating transient outward current in rat ventricular myocytes.

Tedisamil has been described as a selective inhibitor of a fast inactivating transient outward current (i(to,f)) in rat ventricular myocytes. Because recent reports demonstrated the existence of a second slowly inactivating transient component (i(to,s)) we investigated i(to,s) and differentiated the effects of tedisamil on both transient outward current components and their influence on action potential duration. Standard electrophysiological techniques were used for whole cell recordings at 24-26 degrees C from enzymatically isolated myocytes.

Effects of 17beta-estradiol on action potentials and ionic currents in male rat ventricular myocytes.

This study describes electrophysiological effects of estrogens in isolated male rat ventricular myocytes. According to the literature these cells do not express the nuclear estrogen receptor. Action potentials or membrane currents were recorded in the whole-cell configuration with standard techniques.

[Electrophysiologic effects of K+ and Mg2+ in the hypoxia model].

The influence of Mg2+ and K+ on reoxygenation arrhythmias following 18 min of hypoxia (pO2 about 1 mm Hg, no glucose, 10 mmol/l2-desoxyglucose) has been investigated in isolated guinea-pig left atria (stimulation rate 1 Hz). Duration of reoxygenation arrhythmias was slightly reduced by increase in Mg2+ (0.6 to 4.

Modulation of pacemaker activity in sheep cardiac Purkinje fibers by stimulation of beta-adrenoceptor subtypes.

The electrophysiological effects mediated by beta 1- and beta 2-adrenoceptors in spontaneously active sheep cardiac Purkinje fibers were investigated using the non-selective agonist (-)-isoproterenol (IPN) and the selective agonists (-)-noradrenaline (beta 1) and procaterol (beta 2) in the absence and presence of the selective antagonists bisoprolol (beta 1) and ICI 118,551 (beta 2). IPN (0.01 mumol/l) increased the spontaneous rate by 54% and the slope of diastolic depolarization by 68% of the respective control values.

Characterization of histamine receptors in the ureter of the dog.

We investigated the effects of histamine on the motility of isolated segments from canine ureters and characterized pharmacologically the histamine receptors involved. We also evaluated the effects of various autacoids (5-HT, carbachol, noradrenaline, thromboxane, prostaglandin F2alpha) on the motility of canine ureters. Histamine as well as the H1 receptor agonist 2-(2-pyridyl)ethylamine elicited a concentration-dependent contraction.

Inhibition of pacemaker current by the bradycardic agent ZD 7288 is lost use-dependently in sheep cardiac Purkinje fibres.

The inhibition of the pacemaker current (if) in sheep cardiac Purkinje fibers by ZD 7288 [4-(N-ethyl-N-phenylamino)-1,2-dimethyl-6-(methylamino)pyrimidinium++ + chloride] is lost use-dependently. This disinhibition of if was investigated by using the two-microelectrode voltage-clamp technique. The pulse protocol consisted of a rest period (holding potential of about -50 mV, 1-10 micromol/l ZD 7288) followed by a train of test pulses (potential negative to -100 mV, stimulation frequency 0.

Phorbol ester-stimulated adherence of neutrophils to endothelial cells is reduced by adenosine A2 receptor agonists.

In this study we investigated the effect of adenosine receptor agonists on the adherence of PMA-stimulated human neutrophils to cultured porcine aortic endothelial cells. Additionally, we studied the influence of adenosine analogues on the second messenger cAMP in neutrophils and cultured endothelial cells. In the presence of 10 ng/ml PMA, there was a rapid and stable increase on adherence of neutrophils to the endothelial layer.

Intracoronary magnesium is not protective against acute reperfusion injury in the regional ischaemic-reperfused dog heart.

Intravenous magnesium lowers mortality in patients with suspected myocardial infarction. We tested the hypothesis that the protective effect may be due to a direct, local influence of magnesium on myocardial reperfusion injury in a dog model of ischaemia/reperfusion. Ten anaesthetized open chest dogs underwent 1 h of left anterior descending artery (LAD) occlusion and 6 h of reperfusion.

Modulation of action potential duration by inhibition of the transient outward current in sheep cardiac Purkinje fibers.

In sheep cardiac Purkinje fibers concentration-dependent inhibition of transient outward current (ito) by 4-aminopyridine (4-AP, 3-1000 mumol/l) was recorded with the two-microelectrode voltage-clamp technique, and correlated effects on action potential duration measured at -70 mV (APD-70) were investigated. Half-maximal inhibition of ito-amplitude occurred at 15 mumol/l 4-AP. The drug exhibited no major effect on voltage-dependent control of inactivation but reduced the maximally available ito-current.

Effects of the bradycardic agent ZD 7288 on membrane voltage and pacemaker current in sheep cardiac Purkinje fibres.

The bradycardic mechanism of ZD 7288 (4-(N-ethyl-N-phenylamino)-1,2-dimethyl-6-(methylamino)pyrimidinium++ + chloride) was investigated in sheep cardiac Purkinje fibres. The pacemaker i(f)-current measured with the two-microelectrode voltage-clamp technique, as well as the diastolic depolarization rate and the frequency of spontaneously active fibres were evaluated. ZD 7288 did inhibit i(f)-current.

Adenosine A1 and A2 receptor agonists alter cardiac functions and prostacyclin release in the isolated guinea-pig heart.

The actions of the adenosine A1 receptor agonist CCPA (2-chloro-N6-cyclopentyladenosine) and the adenosine A2 receptor agonist CGS 21680 (2-[p-(2-carboxyethyl(phenethylamino]-5'-N- ethylcarboxamidoadenosine) on myocardial functions and prostacyclin release were studied in Langendorff-perfused guinea-pig hearts. In spontaneously beating hearts, perfused at constant pressure, CCPA reduced heart rate and left ventricular actively developed pressure with EC50 values of 54.4 +/- 8.

Activation of a potassium outward current by zymosan and opsonized zymosan in mouse peritoneal macrophages.

The effects of zymosan and human serum opsonized zymosan on membrane currents of adherent mouse peritoneal macrophages which had been cultured for 5 to 20 days were investigated with the whole-cell voltage-clamp technique. Both stimuli activated an outward current. The outward current activation was transient and lasted about 5 min.

Calcium antagonists in comparison: view of the pharmacologist.

A great number of calcium antagonists are available for the treatment of cardiovascular diseases. Differences in pharmacodynamic and/or pharmacokinetic properties can be used to optimize therapy in patients and to minimize side effects. In contrast to all dihydropyridine (DHP) derivatives, drugs of the verapamil type slow atrioventricular conduction and are widely used for treatment of supraventricular tachycardia.

A slowly inactivating transient outward current in rat ventricular myocytes.

In rat ventricular myocytes we found two components of transient outward current, which could be discriminated time- and voltage- dependently. Besides the well known fastly inactivating transient outward current (ito,f, tau = 35 +/- 8 ms, n = 4) we investigated properties of a slowly inactivating transient outward current (ito,s, tau = 1.7 +/- 0.

Activation of membrane outward currents by human low density lipoprotein in mouse peritoneal macrophages.

The aim of the present study was to search for electrophysiological effects of human lipoproteins on membrane currents in mouse peritoneal macrophages which had been cultured for 5 to 20 days. Whole-cell currents were recorded by using a voltage-clamp technique. Low density lipoprotein (LDL, 100 micrograms/ml) increased a slowly activating nonspecific cation current (iso) in the positive potential range to 244 +/- 23% of the reference (test potential + 55 mV, n = 13, P < 0.

Adenosine A2-receptor activation at reperfusion reduces infarct size and improves myocardial wall function in dog heart.

Reestablishment of blood supply to ischemic myocardium leads to biochemical and cellular changes which are believed to reduce the amount of potentially salvageable myocardium (reperfusion injury). In this situation, adenosine is known to have myocardial protective properties. Activation of adenosine A2-receptors may account for most of the beneficial effects of adenosine in reperfusion injury because A2-receptor activation mediates vasodilation, inhibits neutrophil adhesion to vascular endothelium and diminishes generation of free radicals by neutrophils, thus acting on some of the key mechanisms of reperfusion injury such as postischemic vascular dysfunction and neutrophil-mediated damage.

Electrophysiological characterization of class III activity of a verapamil derivative in guinea-pig cardiac tissues.

In isolated guinea-pig papillary muscle ([K+]o: 4.7 mmol/l, stimulation rate: 1 Hz) the verapamil derivative NN-bis-(3,4-dimethoxyphenethyl)-N-methylamine)-HCl (YS035; 0.3-100 mumol/l) increased the action potential duration measured at 90% repolarization level (APD90) up to 132% of control and enhanced the force of contraction (Fc) up to 125% of control while resting potential (RP) and the maximum upstroke velocity (Vmax) remained nearly unchanged.

Electrophysiological characterization of histamine receptor subtypes in sheep cardiac Purkinje fibers.

The histamine-receptor-subtype-mediated effects on action potentials of electrically driven and spontaneously active isolated sheep cardiac Purkinje fibers were investigated using H1- and H2-selective agonists and antagonists. In electrically stimulated Purkinje fibers, histamine (3 mumol/l) increased the action potential plateau height, decreased the action potential duration measured at a repolarization level of -60 mV and enhanced the pacemaker activity. These effects were abolished by the H2-selective antagonist cimetidine (30 mumol/l), but were not impaired by the H1-selective antagonist dimetindene (0.

Inhibition of potassium outward currents and pacemaker current in sheep cardiac Purkinje fibres by the verapamil derivative YS 035.

The electrophysiologic mode of action and potency of the verapamil derivative YS 035 (N,N-bis-(3,4-dimethoxyphenethyl)-N-methyl amine) were investigated in sheep cardiac Purkinje fibres. Action potential duration measured at a repolarization level of -60 mV (APD-60) and membrane currents recorded with the two-microelectrode voltage-clamp technique were evaluated. At 10 mumols/l YS 035 APD-60 was increased to about 115% of reference.

Positive and negative contractile effects of neuropeptide Y on ventricular cardiomyocytes.

The potency of neuropeptide Y (NPY) to cause negative and positive contractile responses in rat ventricular cardiomyocytes was investigated. In these cells, NPY was found to activate the transient outward K+ current (Ito) and the slow inward Ca2+ current (Isi). As reported before (H.

[Adverse drug effects and their clinical importance within the scope of intensive care and emergency medicine].

Patients in intensive care often receive various drugs. Many of these patients have received previous treatment for chronic diseases. When different drugs are administered the possibility of unwanted drug interactions has to be considered.

[Ibopamine--pharmacologic principles].

Ibopamine is the 3,4-diisobutyrylester of N-methyl-dopamine (epinine). Oral ibopamine is transferred during and after resorption (first-pass effect) to the active metabolite epinine by blood and tissue esterases. 200 mg ibopamine lead to maximal plasma concentrations of 60 to 100 nmol/l.