J.Gy. Papp

Role of slow delayed rectifier K+-current in QT prolongation in the alloxan-induced diabetic rabbit heart

Aim:  In diabetes mellitus, several cardiac electrophysiological parameters are known to be affected. In rodent experimental diabetes models, changes in these parameters were reported, but only limited relevant information is available in other species, having cardiac electrophysiological properties more resembling the human, including the rabbit. The present study was designed to analyse the effects of experimental type 1 diabetes on ventricular repolarization and the underlying transmembrane potassium currents in rabbit hearts.

ORM‐10103, a novel specific inhibitor of the Na+/Ca2+ exchanger, decreases early and delayed afterdepolarizations in the canine heart

At present there are no small molecule inhibitors that show strong selectivity for the Na+/Ca2+ exchanger (NCX). Hence, we studied the electrophysiological effects of acute administration of ORM‐10103, a new NCX inhibitor, on the NCX and L‐type Ca2+ currents and on the formation of early and delayed afterdepolarizations.

Blockade by cimetidine of the effects of histamine on adenylate cyclase activity, spontaneous rate and contractility in the developing praenatal heart

ConclusionsThe results support the view that in man cardiac responsiveness to histamine appears at a very early stage of development. It might also be suggested that in human embryonic and foetal hearts the adenylate cyclase activating, positive chronotropic and ventricular inotropic effects of histamine are mediated via H2-type histaminergic receptors.

Cardiac adenylate cyclase activity in relation to beta-adrenergic responses

Abstract The effect of beta-adrenergic receptor agonists (isoproterenol, hexoprenaline, salbutamol) on the adenylate cyclase activity and some functional parameters of the atrial and ventricular myocardium of the rabbit was investigated. The influence of isoproterenol was studied also in the presence of beta-adrenergic receptor antagonists (practolol, pindolol). The beta-adrenergic stimulants had a similar decreasing order of relative potency (isoproterenol > hexoprenaline > salbutamol) in stimulating atrial or ventricular adenylate cyclase, in increasing atrial or ventricular contractility, spontaneous atrial rate, the maximum driving frequency of the ventricular myocardium and in reducing ventricular electrical threshold. Isoproterenol proved to be the most potent adrenergic agonist also in decreasing atrial electrical threshold, but in this respect salbutamol was slightly more active than hexoprenaline. Practolol and pindolol inhibited the effects of isoproterenol on adenylate cyclase activity and also on the functional parameters. Some statistical correlation was also found between the adrenergically-induced rise in cyclic AMP levels and the corresponding changes in the physiological functions of the myocardium. However, concentrations of the studied adrenergic agonists required to equally activate adenylate cyclase produced significantly different effects on the functional parameters, and analysis of the results has shown that the observed correlations reflect, at least in part, parallel processes rather than an exclusive cause and effect relationship.

Potassium channels sensitive to combination of charybdotoxin and apamin regulate the tone of diabetic isolated canine coronary arteries.

Aims:  Functional roles of calcium‐activated potassium channels on the mechanical activity of epicardial coronary arteries obtained from a canine model of diabetes were investigated.

An exploratory conformational analysis of 3-mercapto-propanamide and 2-methyl-3-mercapto-propanamide as well as their S-deprotonated conjugate basis: an ab initio study

Abstract Ab initio conformational analysis has been carried out on 3-mercapto-propanamide, ( R )- and ( S )-2-methyl-3-mercapto-propanamide as well as their S -deprotonated conjugate basis. They were carried out at the HF/3-21G level of theory. The topology of the conformational potential energy surfaces and hypersurfaces have been analysed.

Antiarrhythmic Action of Calcium Antagonists

The marked coronary dilating and negative inotropic effect of prenylamine /1/ as well as that of verapamil /2/ was described in the early sixties, however Fleckenstein et al. /3/ were the first to show that these agents are capable of depressing cardiac contractility in concentrations not yet affecting the action potential. Thus they inhibit the electromechanical coupling. The authors attributed this effect to a drug induced depression of the transmembrane inward Ca2+ current hence the name: calcium antagonists /Ca-s/. Later Grun and Fleckenstein /4/ have shown electromechanical uncoupling effect of CA-s in the smooth muscle too. The steadily growing interest has initiated a number of experimental and clinical studies showing that in addition to its scientific importance introduction of this new group of drugs into clinical therapy represents a major breakthrough.