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Biomedical subjects

U Borchard

Publications and source records attributed to U Borchard.

At least 55 records · Page 3Linked to original sources
PubMed1985

Electrophysiological and antiarrhythmic actions of tocainide in isolated heart preparations of the guinea pig.

Comparison of the action of tocainide in guinea pig atrial and ventricular myocardium has led to the following results: Tocainide effects a similar increase in threshold of alternating current induced arrhythmias in spontaneously beating right atria as well as stimulated left atria and papillary muscles. APD30 and APD90 (action potential duration at 30 and 90% repolarization) are decreased by tocainide in papillary muscles, especially at a low stimulation rate, but increased in left atria. On the other hand, maximum upstroke velocity of the action potential (Vmax) is decreased at a high stimulation rate (use-dependence) in both tissues. These effects are completely reversed by washing with drug-free solution within 15 min in papillary muscles and 60 min in left atria, respectively. Resting state block of Na-channels by tocainide occurs in left atria to a small degree (10-20%), but is negligible in ventricular myocardium. Recovery of Vmax following stimulus-induced inactivation is delayed by tocainide in papillary muscles and left atria. Functional refractory period is increased in left atria and in papillary muscles by tocainide. In the concentration range above 75 mumol/l the concentration response curve reaches a plateau in papillary muscles but shows a further steep increase in left atria. Quantitative analysis of the dynamic Na-channel blockade by tocainide in atrial myocardium using the modulated receptor hypothesis suggests that the drug shows a high affinity to activated and a low affinity to inactivated Na-channels.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1984

Influence of arrhythmogenic and antiarrhythmic agents on alternating current-induced arrhythmias in guinea-pig heart preparations.

The method for inducing arrhythmias or asystole by the application of a 50 Hz alternating current (ac) has been applied to isolated guinea-pig left atria and papillary muscles in order to characterize arrhythmogenic and antiarrhythmic substances. Aconitine, BaCl2 (less than 2 mmol/l) and hypoxia decrease threshold of ac-arrhythmia and ac-asystole, in both tissues to a similar extent, whereas carbachol and BaCl2 (greater than 2 mmol/l) increase threshold. The calcium antagonists nifedipine and diltiazem lower threshold of ac-asystole but differ with respect to threshold of ac-arrhythmia, which is increased by 10(-6) mol/l diltiazem in left atria and papillary muscles by about 30% and remains nearly unaffected with nifedipine. The Na+-inhibitory substance flecainide reverses the decrease in threshold of ac-arrhythmia and ac-asystole brought about by aconitine. Threshold of ac-arrhythmia lowered by hypoxia is increased by diltiazem in a concentration-dependent manner, whereas decrease of threshold of ac-asystole is even augmented. Therefore, the method offers an opportunity of quantifying the action of arrhythmogenic agents at concentrations which are too low to induce arrhythmia, as well as to characterize the activity of antiarrhythmic drugs in the presence of arrhythmogenic substances.

Aconitine↗
PubMed1984

[Animal experimental studies on the pharmacology of a new anti-arrhythmic of the imino-cycloheptane series, stirocainide].

The action of 2- benzal -1-(2'-diisopropyl-amino-ethoxy-imino)- cycloheptane hydrogenfumarate ( Stirocainide , Th 494) has been investigated on isolated guinea-pig atria and papillary muscles and on the circulation of the anaesthetized and conscious cat. Th 494 is characterized as a Na+-inhibitory antiarrhythmic agent in isolated atria and papillary muscles. 1-10 mumol/l Th 494 induces only a small increase in action potential duration in both preparations, whereas no change in resting potential or amplitude of the action potential is observed. The action on the maximal rate of rise of the action potential (Vmax) depends on the rate of stimulation ("use-dependence"), this effect being somewhat smaller in atria as compared to papillary muscles. The increase in threshold of alternating current induced arrhythmias and in functional refractory period is also smaller in atria. Isometric force of contraction is reduced by Th 494 in guinea-pig atria and papillary muscles to a greater extent than in rabbit and cat. In the anaesthetized cat 2 mg/kg Th 494 i.v. induces a transient decrease in heart rate and a decrease in the maximal rise of left ventricular pressure. In addition, 4 mg/kg i.v. induces a transient decrease in systolic and diastolic blood pressure as well as a broadening of the QRS complex in the ECG. High doses of 4 and 8 mg/kg, respectively, lead to arrhythmias and apnoea, 8 mg/kg to exitus. Atropine does not influence the action of Th 494. 2 and 4 mg/kg Th 494 do not alter the action of norepinephrine on heart and circulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1983

Effects of the calcium antagonist diltiazem on action potentials, slow response and force of contraction in different cardiac tissues.

Action potential duration in human and guinea-pig ventricular myocardium is reduced by diltiazem greater than or equal to 10 mumol/l. A reduction of action potential amplitude and maximum upstroke velocity is observed only at high concentrations of diltiazem (30 mumol/l). In depolarized myocardium (rabbit SA- and AV-node, guinea-pig papillary muscle depolarized by (K+)0 = 27 mmol/l) diltiazem greater than or equal to 0.3 mumol/l reduces amplitude and maximum upstroke velocity of the calcium-dependent action potentials. The decrease in maximum upstroke velocity of the slow response in depolarized guinea-pig papillary muscle is enhanced by elevation of the stimulation frequency, as are the negative inotropic effects (use-dependence). In contrast to nifedipine diltiazem also delays the recovery of the maximum upstroke velocity of the slow response after stimulus-induced inactivation. The reduction of maximum upstroke velocity induced by nifedipine is independent of the rate of activation whereas the blockade induced by diltiazem consists of a small blockade during rest and a profound use-dependent blockade.

Action Potentials↗
PubMed1982

Characterization of antiarrhythmic drugs by alternating current induced arrhythmias in isolated heart tissues.

A new method for inducing arrhythmias or asystolia by the application of a 50 HZ alternating current (ac) to electrically driven heart preparations has been developed and applied to isolated left atria and right ventricular papillary muscles of the guinea-pig. An increase in driving frequency from 1 to 3 HZ effects a significant reduction of the threshold of ac-arrhythmia in guinea-pig papillary muscles but no change in atria. A decrease in temperature from 31 degrees C to 25 degrees C and an increase in [Ca2+]0 from 1.25 to 5 mmol/l elevates threshold for ac-arrhythmia and -asystolia. The fast sodium channel inhibitors quinidine, carticaine and benzylamino-5,6-dihydro-8,9-dimethoxy-imidazo-5,1-a-isoquinoline hydrochloride (HE-36) increase threshold of ac-arrhythmia in left atria and papillary muscles, whereas the slow channel inhibitor verapamil is ineffective in concentrations up to 6 mumol/l. Threshold of ac-arrhythmia is elevated by quinidine predominantly in papillary muscles. Carticaine and HE-36 are effective in left atria and papillary muscles to almost the same extent. Threshold of ac-asystolia is increased mainly in papillary muscles by quinidine and HE-36; carticaine produces a similar increase in left atria and papillary muscles. Verapamil even leads to a decrease in threshold predominantly in papillary muscles. It is concluded that model arrhythmias induced by alternating current are brought about mainly by an increase in Na+-conductance of cardiac cell membranes. The negative chronotropic potency in right atria occurs in the sequence verapamil greater than quinidine greater than carticane approximately HE-36. The negative inotropic potency in papillary muscle occurs in the same sequence but HE-36 increases force of contraction.

Adrenergic beta-Antagonists↗
PubMed1981

The positive inotropic action of triamterene in isolated heart tissues. Its interaction with beta-adrenergic agonists and electrophysiological investigations.

Triamterene (20--80 mumol/l) inhibits the positive inotropic action of orciprenaline in guinea-pig left atria. 200 mumol/l triamterene completely suppress the effect of orciprenaline (10(-8)--10(-4) mol/l). But if orciprenaline is applied first and triamterene afterwards no antagonism can be seen; triamterene shows an additional positive inotropic effect. A mathematical model is presented which allows a quantitative description of the interaction if two different sites of action are accepted for triamterene: a stimulating effect mediated via inhibition of phosphodiesterase and leading to an increase in slow inward current and an inhibition of the orciprenaline-adenylcyclase complex. The additional increase in contractile force by triamterene after pretreatment with orciprenaline can be explained by the model if the blocking site of triamterene is not considered. Triamterene increases force of isometric contraction and broadens action potential in all repolarization phases in guinea-pig left atria to a greater extent than in papillary muscles. 100 mumol/l triamterene increases action potential duration at 30% repolarization in atria by 109 +/- 13% (n = 4) and in papillary muscles by 28 +/- 4% (n = 4). These effects also occur to a similar degree when the animals have been pretreated with reserpine 2 mg/kg on 2 days prior to the experiment. Maximum upstroke velocity of atrial and ventricular action potentials is not changed up to 100 mumol/l triamterene, indicating its lack of influence on cardiac fast sodium channels.

Action Potentials↗
PubMed1980

Carticaine: action of the local anesthetic on myelinated nerve fibres.

Unlike other clinically used local anesthetics, carticaine contains a thiophene ring. Current voltage relations of peak sodium current INa and steady state potassium current IK were measured in voltage clamp experiments on the node of Ranvier of Rana esculenta. The dependence of the maximum sodium conductance on external concnetration of carticaine is described by an apparent dissociation constant KNa = 0.065 mM at pH = 7.3. An apparent dissociation constant KK = 0.147 mM at pH = 7.3 was calculated on the basis of the action of carticaine on the maximum potassium conductance. Similar to other amine local anesthetics, carticaine blocks sodium channels at a lower concentration than potassium channels, but lower concentrations of the thiophene derivative than of the benzene derivatives are needed to block the ionic channels. The partition coefficients in-octanol/Soerensen buffer at pH = 7.35 follow the sequence lidocaine (46) more than carticaine (17) more than procaine (2). Therefore, the action of these local anesthetics on sodium channels and potassium channels seems not to follow mere lipid solubility properties of the neutral drug. Increasing the pH from 6.3 to 8.3 favoured the neutral drug form and enhanced the block of both ionic channels but the relative reduction of the ionic currents was larger for potassium currents.

Animals↗
PubMed1978

Effects of the antituberculous agent ethambutol on myelinated nerve.

The action of the antituberculous agent ethambutol on the myelinated nerve was studied in two ways: (1) Resting and compound action potentials of the desheathed sciatic nerve were measured; (2) Na+ and K+ currents through the node of Ranvier were investigated by means of the voltage clamp. Reversible dose-dependent decreases of the compound action potential and of the conduction velocity were observed when ethambutol was applied in concentrations of 1--7 mM for 15 min; prolongation up to 60 min caused irreversible changes in membrane function and a decrease in Ca content. Ethambutol induced a hyperpolarizing change of the resting potential. When the nerve was depolarized in Ca2+-free solutions, ethambutol repolarized the nerve membrane. Ethambutol instantly reduced sodium and potassium currents through the nodal membrane. Presumably ethambutol acts primarily as a Ca2+ chelating cation on negative charges at the nerve membrane.

Action Potentials↗
PubMed1977

Monomeric methylmethacrylate (MMA) acts on the desheathed myelinated nerve and on the node of Ranvier.

The influence of monomeric methylmethacrylate (MMA) on resting and compound action potential of the isolated desheathed sciatic nerve of the frog (sucrose gap method) was determined. Above 10 mM there was a dose-dependent decrease of the compound action potential and a hyperpolarization of the membrane which was augmented with increasing MMA concentrations (4.1 mV +/- 0.2 S.E.M. after 50 mM MMA). The depolarization in low [Ca2+]0 solutions or with veratrine was reversed by MMA. The homologous ethyl, allyl and n-butyl esters were more effective than MMA, and the isobutyl ester less effective, whereas Na-methacrylate and methacrylamide showed no influence. Voltage clamp experiments on the node of Ranvier indicated that 50 mM MMA led to a decrease of the Na+ and K+ currents.

Action Potentials↗