Biomedical subjects

S Dhein

Publications and source records attributed to S Dhein.

76 records · Page 5Linked to original sources

PubMedDate not supplied

Sodium channel blockade enhances dispersion of the cardiac action potential duration. A computer simulation study.

The goal of this study was to elucidate the causes why the proarrhythmic activity of sodium channel blocking drugs is enhanced during the post-infarction period. Therefore, we studied the effects of a reduction in sodium conductance on the action potential duration and its dispersion in a simulated array of 1600 ventricular myocytes. Cardiac tissue is known to possess anisotropic properties with regard to the intercellular electrical resistances (R). Infarction as well as aging causes deposition of collagen in the cardiac tissue, thereby inducing zones of high electrical resistance leading to a non-uniform anisotropy (Spach et al., Circ Res 62:811, 1988). For our study an array of 40*40 ventricular myocytes was simulated using Beeler-Reuter-algorithms. Physical tissue properties were assumed to be either a) uniform anisotropic (i.e., all longitudinal R = 5000 omega cm, all transversal R = 20,000 omega cm; UA) or b) non-uniform anisotropic (i.e., transversal R for the inner 10*10 cells was set to 10(10) omega cm; NUA). Mean action potential duration (APD) was increased under UA (287 ms. dispersion: 0.8 ms) when compared to NUA (285 ms, disp.: 3.2 ms). Assuming a 25% decrease in sodium conductance, we found the total activation time (TAT) to be increased (from 99 to 139 ms), indicating slowing of conduction, APD to be shortened (from 287 to 259 ms), and the APD-dispersion to be increased (from 0.8 to 29 ms) in UA. These changes were more pronounced in the case of NUA: increase in TAT from 103 to 150 ms, APD-shortening from 285 to 214 ms and a marked increase in APD-Dispersion from 3.2 to 53 ms). From these results it is concluded that a) the effects of a reduced sodium conductance are more pronounced in NUA tissue, and b) that the resulting increase in dispersion may provoke arrhythmia by local differences in APD. This may be one of the mechanisms underlying the increased proarrhythmic risk of class I antiarrhythmic drugs in the postinfarction period.

Action Potentials↗

PubMedDate not supplied

Nitric oxide (EDRF) enhances the vasorelaxing effect of nitrendipine in various isolated arteries.

Recent studies suggest endothelium to be involved in the vasorelaxation of calcium antagonists of the 1,4-dihydropyridine type, which may at least in part be mediated by endothelium-derived relaxing factor (EDRF = NO). To study this effect further, the influence of L-NG-nitro arginine (L-NNA), a specific inhibitor of EDRF-synthesis, on nitrendipine-induced vasorelaxation was examined in different isolated porcine arteries. Coronary, basilary, and tail arteries were bathed in Krebs-Henseleit solution and endothelial function was verified by means of substance P, an EDRF releasing neuropeptide. Vasorelaxation of nitrendipine in PGF2 alpha-precontracted arteries was studied in the presence and absence of L-NNA. Nitrendipine-induced vasorelaxation was markedly reduced by the addition of L-NNA in all vessels studied. Tachyphylactic effects of nitrendipine could be excluded. The obtained results may be explained by an enhancement of nitrendipine action by basally released EDRF, alternatively, by an increased EDRF-release induced by this calcium antagonist. Therefore, in a second series of experiments the release of EDRF was studied in isolated coronary arteries under cumulative application of nitrendipine. Using the nitric oxide scavenging properties of oxyhemoglobin, EDRF release was measured spectrophotometrically by means of methemoglobin formation. The application of nitrendipine resulted in a concentration-dependent increase in the extinction rate, indicating an increased release of NO which could be inhibited by preincubation with L-NNA. It may be concluded that, in functionally intact vessels, vasorelaxation induced by nitrendipine may additionally be mediated by an increased release of EDRF.

Animals↗

PubMedDate not supplied

Prearrhythmia: changes preceding arrhythmia, new aspects by epicardial mapping.

The aim of our studies was to examine the electrophysiological conditions prior to the onset of arrhythmia in order to analyze in more detail whether arrhythmia is a sudden event or whether there are early signs preceding arrhythmia. For this purpose a computer-assisted mapping system equipped with 256 AgCl-electrodes for unipolar epicardial multichannel-recording was constructed that provided high temporal and spatial resolution (4 kHz/channel; 1 mm interelectrode distance). The electrodes were fixed to the surface of an isolated rabbit heart (prepared according to the Langendorff-technique; constant perfusion pressure 70 cm H2O; Tyrode solution equilibrated with 95% O2 and 5% CO2 at 37 degrees C) covering nearly the whole heart's surface. The activation times at each electrode were determined as the timepoints of the fastest negative deflection of the epicardial potentials. From these data the origins of epicardial activation were determined ("breakthrough points", BTP), and for each electrode a vector was constructed giving direction and velocity of the epicardial activation. This analysis was carried out for single heart beats under control conditions, under arrhythmogenic conditions (induced either by lowering the K+ concentration from initially 5.4 to finally 2.0 mmol/l or by application of ouabain 0.1, 0.2 or 0.3 mumol/l) or during manifest arrhythmia. By comparison of heart beats under these various conditions with control conditions we determined the percentage of identical BTP (deviating less than 1 mm) and of similar vectors (deviating less than 5 degrees). Under control conditions 80% BTP remained unchanged over a period of 60 min and about 30% of the vectors were similar. Reduction of the extracellular K(+)-concentration or treatment with ouabain resulted in a progressive, concentration-dependent decline in BTP- or vector-similarity (in still rhythmically beating hearts). In some cases these treatments finally lead to variant forms of arrhythmia. Critical values for the onset of arrhythmia were a reduction to 45% BTP-similarity and 18% vector-field-similarity. From these results it is concluded that arrhythmia is preceded by a state characterized by a derangement of the typical activation pattern which may be called prearrhythmia.

Animals↗

PubMedDate not supplied

Vasoconstrictions mediated by an endothelium-derived vasoconstricting factor (EDCF).

To enlighten the role of endothelium in the generation of vasospasms we examined vascular tone after reduction of oxygen supply in dependence on endothelial function in isolated vessels (rabbit aorta abdominalis, pig coronary, and pulmonary artery). Therefore, after ligation of all side branches, vessel segments, prepared either with or without endothelium, were cannulated and arranged in two systems (with two segments each) in a serial manner (system I: endothelium-denuded vessel followed by an endothelium-denuded segment) and perfused with Tyrode's solution (constant flow 20 ml/min). Pressure gradient over each segment was continuously measured. Endothelial function was checked by perfusion with 1 mumol/l actetylholine after precontraction with 0.1 mumol/l norepinephrine, thereby inducing an EDRF mediated vasodilation (greater than 70%) indicating normal endothelial function. After 2 h equilibration with Tyrode's solution the preparations of rabbit aorta abdominalis were perfused for 30 min with oxygen-deprived medium (reduction from 95% O2 and 5% CO2 to 95% N2 and 5% CO2) and a marked long lasting (60 min) increase in pressure gradient (indicating vasoconstriction) was observed in those endothelium-denuded vessel segments which were mounted distal to a normal vessel with an intact endothelium. This contraction could be inhibited by pretreatment with either 1 mumol/l dexamethasone. 1 mumol/l indomethacine or 10 mumol/l methylene blue or attenuated by the TXA2-antagonist BM 17133 (5 mumol/l) but not by radical scavengers as superoxid dismutase or by inhibition of the lipoxygenase by nordihydroguaretic acid. From these results it is concluded that endothelium releases a vasoconstricting factor (EDCF) at pO2 values beneath 550 mm Hg. This EDCF seems to depend on phospholipase A2 and cyclooxygenase, but because of the long-lasting effect it is probably no prostanoid itself, especially not TXA2.

Animals↗