Biomedical subjects

M Bachernegg

Publications and source records attributed to M Bachernegg.

7 recordsLinked to original sources

PubMed1996

Involvement of the L-arginine-nitric oxide pathway in hyperglycaemia-induced coronary artery dysfunction of isolated guinea pig hearts.

The effects of hyperglycaemia and L-arginine on flow-induced reduction of coronary artery resistance were investigated in isolated guinea pig hearts. In the presence of indomethacin, hyperglycaemia caused an increase in flow-induced vasodilatation (P < 0.05). Hyperosmotic controls failed to mimic this effect. Addition of L-arginine strongly enhanced this effect. Addition of D-arginine failed to mimic the effects of L-arginine. The effect of L-arginine was abolished by co-administration of NG-nitro-L-arginine. In the absence of indomethacin and L-arginine, the effect of hyperglycaemia was blunted, suggesting the formation of vasoconstrictive prostanoids. Addition of L-arginine again resulted in a significant increase in flow-induced vasodilatation. In conclusion our results suggest that increased flow-induced vasodilatation under hyperglycaemic conditions depends on an adequate supply of L-arginine to maintain sufficient formation of nitric oxide.

Animals↗

PubMed1995

Elevation of D-glucose impairs coronary artery autoregulation after slight reduction of coronary flow.

Diabetes mellitus is thought to increase the susceptibility of tissue to hypoxic injury through D-glucose-induced alterations of intracellular metabolism. Therefore the effects of hyperglycaemia on coronary artery autoregulation under slight reduction of coronary flow were investigated in isolated perfused guinea-pig hearts. Under normal (10 mM) D-glucose concentrations coronary autoregulation was intact in response to a slight reduction of coronary flow (from 6 to 4.5 mL min-1) when L-arginine as a precursor of the endothelium-derived relaxing factor (EDRF/NO) was available and formation of prostaglandines was intact. Under high (44 mM) D-glucose concentrations on the other hand, a sustained vasodilatation dependent on the availability of L-arginine was observed, when formation of prostaglandins was blocked. This effect was partially reduced in the presence of prostaglandin synthesis. Furthermore, the effect of L-arginine under both conditions could be antagonized by the L-arginine-analogue NG-nitro-L-arginine-methyl-ester (100 microM). Our results suggest that hyperglycaemia impairs coronary artery autoregulation by reducing the threshold for hypoxic vasodilatation in an EDRF/NO-dependent manner. Concomitantly a shift from the formation of vasodilatatory to vasoconstrictive prostaglandines was observed. These results might be of particular interest in patients with diabetes mellitus and ischaemic heart disease.

Animals↗

PubMed1994

Frequency-dependent effects of propafenone decrease with duration of ventricular tachycardia in isolated guinea pig hearts.

Na+ channel blockers terminate tachyarrhythmias primarily by rate-dependent effects. The purpose of this study was to investigate the use-dependent effects of propafenone in isolated guinea pig and rabbit hearts perfused by the method of Langendorff. In the presence of propafenone (0.3 microM) during ventricular pacing, an abrupt decrease of the pacing cycle length (220 ms to 120 ms) slowed the intraventricular conduction with a transient peak QRS prolongation of 33.8 +/- 2.0% after 5.7 +/- 0.5 s (P < 0.01) which subsequently decreased to a steady state of 14.0 +/- 2.5% after 38.0 +/- 5.5 s (mean +/- S.E.M.; n = 10; P < 0.01). The ventricular effective refractory period was significantly prolonged if evaluated by a train of 10 basic stimuli (S1) (interstimulus interval: 120 ms) followed by a premature stimulus (S2). However, when the train of basic stimuli was increased the effective refractory period diminished progressively. An initial increase in total activation time vanished with continued rapid ventricular stimulation. These effects may be explained by a shortening of the action potential during high rates resulting in a decreased binding of propafenone to Na+ channels.

Action Potentials↗

PubMed1994

Action of ATP on ventricular automaticity.

ATP is an effective treatment of supraventricular tachycardia when the atrioventricular (AV) node is part of the reentrant circuit. However, the lower a pace-maker in the pacemaker hierarchy, the more sensitive it is to adenosine. Therefore, we investigated the effects of ATP on ventricular automaticity in in vivo and in vitro conditions. Wide and narrow QRS complex tachycardia in 46 patients was treated with 6, 12, and 18 mg ATP as sequential intravenous (i.v.) bolus. ATP terminated tachycardias in 67%. Bolus infusion ATP caused < or = 6.4-s asystole that was self-limited. Perfusion of isolated spontaneously beating guinea pig heart with 100 microM ATP completely suppressed ventricular automaticity. After ATP-infusion was discontinued, the first ventricular beat was evident after 3.1 +/- 0.9 s and sinus node activity recovered with a time constant of 3.0 +/- 1.1 s. Because sinus node and ventricular automaticity recovered within seconds after ATP infusion was discontinued in vitro, recovery in vivo is also likely to be determined by the short half-life (+1/2) of ATP.

Adenosine Triphosphate↗

PubMed1993

A comparison of the effects of adenosine and verapamil on the conduction and pacemaker system of isolated guinea pig hearts.

Adenosine and verapamil are effective in the treatment of supraventricular arrhythmias. Also, both substances can provoke sinus node arrest or a third-degree atrioventricular (AV) block with a ventricular escape rhythm. The aim of this study was to compare the effects of adenosine and verapamil on sinus rate and on the rate of the ventricular escape rhythm while a third-degree AV block was induced by both drugs. Experiments were performed on isolated spontaneously beating guinea pig hearts perfused by the method of Langendorff. A third-degree AV block was induced by adenosine at a concentration of 30 microns and by verapamil at a concentration of 1 micron. Adenosine (30 microns) reduced sinus rate only moderately whereas it nearly halved the rate of the ventricular escape rhythm compared with that produced by cutting the AV node. In contrast, verapamil left the rate of the ventricular escape rhythm unchanged but nearly halved the spontaneous sinus rate compared with control conditions. In conclusion, adenosine and verapamil given at dosages with comparable effect on the AV node have markedly different effects on different pacemakers in the same heart. In the treatment of supraventricular arrhythmias, adenosine probably should be used with great caution since it can cause a very slow ventricular escape rhythm.

Adenosine↗

PubMed1993

Frequency-dependent effects of adenosine and verapamil on atrioventricular conduction of isolated guinea pig hearts.

Frequency-dependent depressant effects of a drug on slow channels in the atrioventricular (AV) node are important in its efficacy against supraventricular tachycardias. Verapamil terminates reentrant supraventricular arrhythmias by depressing conduction through the AV node. Similar effects have been described for adenosine. We compared the use-dependent effects of both drugs on AV nodal conduction in isolated guinea pig hearts perfused by the method of Langendorff. Adenosine 3 microM and verapamil 0.01 microM caused a comparable prolongation of AV conduction time (AVCT) and reduction in sinus rate (SR). The time dependence of drug-induced changes in AV conduction was characterized after the atrial pacing rate was changed abruptly. The basic cycle length was shortened abruptly from 240 to 180 ms. The resulting time constant for adenosine (tau = 467 +/- 187 beats, mean +/- SD) was significantly (p < 0.05) longer than that for verapamil (tau = 264 +/- 121 beats). At a pacing cycle length of 180 ms, the rate-dependent conduction slowing tended to be more pronounced in the presence of adenosine than of verapamil. Adenosine had more pronounced frequency-dependent effects on AV conduction than did the calcium channel blocker verapamil. This may explain the higher clinical efficacy of adenosine in supraventricular tachycardias in which the AV node forms a part of the reentrant circuit.

Adenosine↗

PubMedDate not supplied

Effects of adenosine on electrical activity of isolated guinea pig hearts.

Negative chronotropic and dromotropic effects of adenosine seem to be responsible for its antiarrhythmic action on supraventricular tachyarrhythmias. To further characterize the effects of adenosine on supraventricular arrhythmias heart rate, conduction, refractoriness, the time to steady-state of AV-nodal conduction slowing and of sinus rate reduction were evaluated. Changes of heart rate, conduction intervals and effective refractory periods were determined by the use of a high-resolution ECG recording technique in isolated guinea pig hearts perfused by the method of Langendorff. Adenosine in concentrations of 3 and 10 microM reduced sinus rate and prolonged AV-nodal conduction significantly, while intraventricular and His bundle conduction were not altered. The maximal effect of adenosine on the sinus node and AV nodal conduction occurred after 636 +/- 109 and 111 +/- 35 (mean +/- SE) beats, respectively. During programmed stimulation at a cycle length of 250 ms, adenosine reduced atrial ERP in a dose-dependent manner. At cycle lengths of 170 and 200 ms, adenosine increased the atrial ERP at 3 microM, and then progressively shortened the ERP at higher doses. At all adenosine concentrations used, the usual rate-dependent adaption in ERP was suppressed. These observations explain the efficacy of adenosine against supraventricular tachyarrhythmias where the AV-node forms a part of a reentrant circuit. Adenosine shortened the atrial ERP, but at high pacing rates also led to a relative prolongation of the atrial ERP as the rate-dependent adaption was suppressed. These opposite effects of adenosine may explain earlier contradictory findings of its action on atrial arrhythmias.

Adenosine↗