Biomedical subjects

E Kickenweiz

Publications and source records attributed to E Kickenweiz.

6 recordsLinked to original sources

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

The regulation of intracellular Mg2+ in guinea-pig heart, studied with Mg(2+)-selective microelectrodes and fluorochromes.

Because of the reported presence of a Na(+)-Mg2+ exchanger in guinea-pig but not in ferret myocardium, the Mg2+ extrusion mechanism in guinea-pig myocardium has been reinvestigated using Mg(2+)- and Na(+)- selective microelectrodes and the fluorochromes mag-fura-2 and -5. The mean [Mg2+]i measured with microelectrodes in trabeculae or papillary muscles was 0.72 mmol/l (n = 22, thirteen experiments; range 0.42-1.23 mmol/l). Increasing [Mg2+]o from 0.5 mmol/l to either 10.5 or 20 mmol/l caused small increases in [Mg2+]i. Decreasing [Na+]o by 50% had no effect on the [Mg2+]i and there was no change in [Na+]i on increasing [Mg2+]o from 0.5 to 10.5 mmol/l. Varying pHo or changing pHi with NH4Cl did not influence the [Mg2+]i. In vitro calibration of mag-fura-2 and -5 using the ratio method gave values for K'd (experimentally determined dissociation constant) of 22.2 +/- 2.7 (mean +/- S.D., n = 7) and 25.7 +/- 1.3 (n = 4) mmol/l respectively. Mag-fura-2 reacted to physiological concentrations of Ca2+ and mag-fura-5 to changes in pH. In isolated myocytes, Na+ removal gave an apparent increase of [Mg2+]i with mag-fura-2 but not with mag-fura-5. However, when the pHi was altered with NH4Cl mag-fura-5 showed an apparent decrease in [Mg2+]i on application and an apparent increase on removal, with a time course similar to the pHi changes. It is concluded that Mg2+ extrusion in guinea-pig myocardium is not via a Na(+)-Mg2+ exchanger. The use of mag-fura-2 and -5 are limited in their application because of Ca2+ and H+ sensitivity respectively.

Animals↗

PubMed1993

Vasodilative response to hypoxia and simulated ischemia is mediated by ATP-sensitive K+ channels in guinea pig thoracic aorta.

Local vasodilation in response to hypoxia or ischemia improves perfusion and O2 supply of the affected tissue. This local vasodilation thus constitutes the most important mechanism in the prevention of ischemic cell injury. The regulation of vascular tone has mainly been attributed to changes of cytoplasmatic Ca2+ ((Ca2+)i) concentrations in vascular smooth muscle cells. The mechanism underlying these changes has not, however, been elucidated so far. Using aortic strips of guinea pigs (transversally cut in spirals; normal Tyrode, in mM: NaCl 150, KCl 4.5, MgCl2 2, CaCl2 2.5, glucose 10; buffered with 10 mM HEPES at pH 7.4; equilibrated with 100% O2 at 31 degrees C) the authors could show that metabolic blockade (glucose replaced by 10 mM 2-deoxyglucose (DOG) led to a relaxation of the preparation. Thus, in four experiments, resting tension decreased from 0.75 g by 27% +/- 12% within two hours (% of maximal contractile force developed by each preparation when depolarized with 43 mM KCl and 101.5 mM NaCl). When the same experiment was carried out in the presence of 1 mM tolbutamide (a known blocker of ATP-dependent K+ channels) in vascular smooth muscle no such relaxation could be seen (n = 4). Furthermore, in the same type of preparation, similar results have been obtained upon hypoxic relaxation (100% O2 replaced by 100% N2), where 1 mM tolbutamide also prevented vasodilation. Thus, hypoxic/ischemic vasodilation in response to glycolytic inhibition (DOG) and hypoxia (N2) is based upon the opening of K+ ATP channels and hence can be prevented by sulfonylureas (the opening of K+ ATP channels would lead to hyperpolarization (increased K+ conductance, Goldmann equation), thus diminishing the open probability of voltage-gated Ca2+ channels with subsequent vasodilation). This inhibition by sulfonylureas of vasodilative response to ischemia may also constitute the so far unknown cause of the increased cardiovascular mortality seen under sulfonylurea treatment.

Adenosine Triphosphate↗