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Biomedical subjects

A Mugelli

Publications and source records attributed to A Mugelli.

At least 55 records · Page 3Linked to original sources
PubMed1990

Histamine and abnormal automaticity in barium- and strophanthidin-treated sheep Purkinje fibers.

We used intracellular microelectrodes to study the effects of histamine on both normal and abnormal automaticity in sheep Purkinje fibers. Histamine, dimaprit and 4-methylhistamine caused a similar reduction of the action potential duration in driven Purkinje fibers. Histamine (10-6 M) induced spontaneous activity in p previously quiescent preparations more often than did equimolar concentrations of dimaprit and 4-methylhistamine. The effects of histamine on automaticity were enhanced in the presence of barium In fact histamine, at concentrations which were unable to induce automaticity in normal preparations, induced it in the presence of barium. In Purkinje fibers manifesting barium-induced automatic activity, histamine (10-7--10-6M) significantly increased the average number of spontaneous action potentials and shortened the time of their appearance. In the same range of concentrations, histamine dose-dependently increased the iological manifestation of calcium overload. Histamine (10-6--10-4M) increased the OAP amplitude of strophanthidin -treated Purkinje fibers, eventually inducing triggered extrabeats. All these previously described effects were selectively blocked by cimetidine (10-5 M). It is concluded that histamine may induce cardiac arrhythmias under conditions of calcium overload and that this effect may be due to induction or enhancement of oscillatory afterpotentials.

Animals↗
PubMed1990

Electrophysiological characterization of cardiac beta 2-adrenoceptors in sheep Purkinje fibers.

The electrophysiological effects mediated by beta 2-adrenoceptor stimulation were studied in sheep cardiac Purkinje fibers. beta 2-Adrenoceptor stimulation was achieved by using isoproterenol (ISO) in the presence of the highly selective beta 1-antagonist CGP 20712A. ICI 118,551 was used as a selective beta 2-antagonist. In driven preparations, ISO (0.1 to 1 microM) caused a positive inotropic effect which was associated with the shortening of action potential duration and was completely abolished only by the simultaneous presence of CGP 20712A (0.3 microM) and ICI 118,551 (50 nM). In previously quiescent preparations, ISO (0.1 to 1 microM) induced spontaneous activity in 15 out of 24 preparations. In the presence of CGP 20712A (0.3 microM) only five preparations out of 24 became automatic when exposed to ISO, and their rate of firing was significantly reduced (13 +/- 4 vs. 43 +/- 6 beats/min, P less than 0.05) with respect to ISO alone. CGP 20712A completely abolished the steepening of diastolic depolarization and the increase of the pacemaker current caused by ISO (0.1 to 1 microM). The beta 2-antagonist ICI 118,551 (50 nM) completely failed to modify the effect of ISO on the rate of spontaneous firing, the slope of diastolic depolarization and the pacemaker current. On the other hand, the increase of oscillatory afterpotential (OAP) amplitude caused by ISO in strophanthidin-treated preparations was significantly reduced only by the beta 1-antagonist CGP 20712A, but not by the beta 2-antagonist ICI 118,551. These results demonstrate that beta 2-adrenoceptors are functionally present in sheep Purkinje fibers where their stimulation consistently causes a positive inotropic effect. However, beta 2-adrenoceptors do not appear to affect the processes of normal automaticity, and do not greatly contribute to triggered activity due to OAPs.

Action Potentials↗
PubMed1990

Cardiac electrophysiologic effects of a new calcium antagonist, lacidipine.

Lacidipine is a new 1,4-dihydropyridine derivative with potent and long-lasting antihypertensive activity. We used intracellular microelectrodes to characterize the electrophysiologic properties of lacidipine on different cardiac preparations. Lacidipine (10(-8) -10(-6) M) dose-dependently decreased contractility of driven sheep Purkinje fibers. For concentrations less than or equal to 10(-7) M, this effect was associated with a selective decrease of the plateau height. Higher concentrations (3 X 10(-7) and 10(-6) M), however, affected action potential amplitude, overshoot, and maximum rate of depolarization. In the same range of concentrations, lacidipine did not affect normal automaticity of guinea-pig sinus node and sheep Purkinje fibers. Lacidipine (10(-6) M) consistently blocked barium-induced abnormal automaticity in Purkinje fibers and reduced the amplitude and Vmax of the slow action potentials induced by histamine (10(-5) M) in guinea pig papillary muscle depolarized by potassium (22 mM). The effect of lacidipine on the slow inward current (Isi) was studied in shortened Purkinje fibers under voltage-clamp conditions. Lacidipine (10(-7)-10(-6) M) reduced the Isi without affecting the I-V relationship. None of the effects of lacidipine was reversed by 2-h washout. The results indicate that lacidipine has calcium-antagonistic properties in cardiac tissues. Its cardiac effects occur at concentrations 100 times higher than those active in the vascular smooth muscle. The lack of recovery of the lacidipine effects suggests that its interaction with the calcium channel may occur at an inner site of the cell membrane.

Action Potentials↗
PubMed1989

Antiarrhythmic properties of naloxone: an electrophysiological study on sheep cardiac Purkinje fibers.

Recent data suggest that the opioid antagonist naloxone may exert an antiarrhythmic action on arrhythmias caused by coronary artery occlusion and reperfusion in experimental animals. We used intracellular microelectrodes to study the direct electrophysiological properties of naloxone. Experiments were carried out on sheep cardiac Purkinje fibers, the electrical and mechanical activity of which were recorded simultaneously. Naloxone (10(-7)-10(-4) M) caused a prolongation of the action potential duration, a decrease in the maximum rate of depolarization, a flattening of the slope of diastolic depolarization and a decrease in contractility. Naloxone at 10(-6) M significantly reduced the rate of spontaneously beating Purkinje fibers and at 10(-5) M completely blocked normal automaticity. Naloxone had, however, intriguing effect on the oscillatory afterpotentials, which is a relevant arrhythmogenic mechanism. While naloxone (10(-7)-10(-4) M) did not affect the digitalis-induced oscillatory afterpotentials, it increased the amplitude of the barium-induced oscillatory afterpotentials at lower concentrations (10(-7) M) and decreased the amplitude of these potentials at high concentrations (10(-6)-10(-4) M). It is concluded that naloxone exerts a direct electrophysiological effect on cardiac cells and that this effect is probably important for explaining the antiarrhythmic action of naloxone.

Action Potentials↗
PubMed1988

Electrophysiological mechanism for the antiarrhythmic action of propafenone: a comparison with mexiletine.

1. The antiarrhythmic potency of propafenone was evaluated in the guinea-pig isolated heart; arrhythmias were induced with (a) digitalis intoxication and (b) hypoxia followed by reoxygenation. 2. Propafenone, 0.5 microM, was found to be the minimal but effective antiarrhythmic concentration. The antiarrhythmic activity of propafenone developed slower than that of 10 microM mexiletine, which was the lowest effective concentration under the same experimental conditions. 3. The electrophysiological effects of propafenone were then studied on sheep cardiac Purkinje fibres (manifesting oscillatory afterpotentials and triggered automaticity induced by barium or strophanthidin) and compared with those of 10 microM mexiletine. 4. Both 0.5 microM propafenone and 10 microM mexiletine consistently blocked triggered activity in sheep Purkinje fibres. The onset of the effect of propafenone was slower than that of mexiletine. 5. Unlike mexiletine, propafenone did not reduce the amplitude of oscillatory afterpotentials. 6. In contrast, propafenone significantly reduced Vmax in barium- and strophanthidin-treated preparations. 7. It is concluded that the antiarrhythmic action of propafenone on digitalis- and reoxygenation-induced arrhythmias is probably due to an electrophysiological mechanism different from that of mexiletine. Mexiletine, by reducing the amplitude of oscillatory afterpotentials, prevents the attainment of the threshold; propafenone, by reducing the excitability of the cell, increases the threshold and consequently an oscillatory afterpotential of the same amplitude will not generate arrhythmias.

Animals↗
PubMed1987

Electrophysiological effects mediated by the stimulation of cardiac beta 2-adrenoceptors with tulobuterol.

We studied the electrophysiological effects of the specific beta 2-agonist tulobuterol in the guinea-pig sinus node and in sheep cardiac Purkinje fibers. Stimulation of beta 2-adrenoceptors by tulobuterol resulted in a slight increase in the rate of firing of the sinus node. In Purkinje fibers, however, automaticity was not affected up to concentrations of 10(-6) M. Consistently, tulobuterol (10(-8)-10(-6) M) did not affect the pacemaker current studied under voltage-clamp conditions. In the same range of concentrations (10(-8)-10(-6)M) tulobuterol dose-dependently increased the contractile force of driven Purkinje fibers. Tulobuterol, at a very high concentration (10(-5) M), had membrane depressant effects as demonstrated by the block of automaticity induced in the spontaneously beating Purkinje fibers and by the reduction of the maximum rate of depolarization in driven preparations. Our results suggest that stimulation of beta 2-adrenoceptors with tulobuterol in sheep Purkinje fibers is associated with an inotropic rather than a chronotropic effect. On the whole, the data confirm the lack of cardiac side effects of tulobuterol.

Adrenergic beta-Agonists↗
PubMed1986

The role of temperature on the development of oscillatory afterpotentials and triggered activity.

Increasing evidence suggests that calcium dependent oscillatory afterpotentials (OAP) may play a pivotal role in the genesis of reperfusion-induced arrhythmias. Many factors may influence the vulnerability of the heart to reperfusion arrhythmias, some of which may possibly affect the development of OAP. Since intramyocardial temperature changes during ischemia and reperfusion, it may be speculated that the rapid rewarming of the ischemic area during reperfusion favors the development of associated arrhythmias. We thought it important to examine the effects of sudden changes in temperature on OAP and subsequent triggered activity. Evidence is presented that raising the bath temperature from 34 degrees C to 37 degrees C causes a transient increase above the control level of the OAP amplitude, and that if the OAP is large enough to reach the threshold a triggered rhythm ensues. These results suggest that sudden rewarming of calcium overloaded cell (as it happens during reperfusion of the ischemic myocardium) may favor the development of abnormal automaticity due to OAP.

Animals↗
PubMed1986

Enhancement by norepinephrine of automaticity in sheep cardiac Purkinje fibers exposed to hypoxic glucose-free Tyrode's solution: a role for alpha-adrenoceptors?

A period of drive in the presence of norepinephrine (NE) may be followed by the induction or acceleration of spontaneous activity. Experiments were carried out in sheep cardiac Purkinje fibers to determine whether the effects of NE on automaticity were modified during superfusion with hypoxic glucose-free Tyrode's solution and to assess the possible contribution of alpha-adrenergic influences on automaticity under these conditions. The following results were obtained: Low concentrations of NE (10(-7) and 3 X 10(-7)M) were able to induce automaticity after a period of drive in normal oxygenated (97% O2, 3% CO2) Tyrode's solution. Superfusion with hypoxic (97% N2, 3% CO2) glucose-free Tyrode's solution enhanced NE-induced automaticity. Practolol, in concentrations able to block the effects of NE in normal oxygenated solution, did not counteract the effects of NE in hypoxic glucose-free solution. Yohimbine, but not prazosin, antagonized the effects of NE in hypoxic glucose-free solution. At the same concentration, yohimbine did not affect transmembrane potentials or automaticity induced by isoproterenol. It is concluded that alpha-adrenergic responsiveness appears to be enhanced during superfusion in vitro with hypoxic glucose-free solution, and that alpha-adrenoceptors belonging to the alpha 2-subtype in sheep cardiac Purkinje fibers might influence abnormal automaticity, possibly through an effect on oscillatory potentials.

Animals↗
PubMed1986

In vitro evaluation of the beta-blocking and electrophysiological properties of mepindolol.

The electrophysiological and beta-blocking effects of mepindolol have been examined in isolated guinea-pig preparations and sheep cardiac Purkinje fibers. Mepindolol did not show selectivity for blocking the chronotropic and inotropic responses to isoprenaline on isolated guinea-pig preparations, and was practically equally potent in blocking the effect of isoprenaline on isolated guinea-pig trachea. Mepindolol 10(-7) M fully antagonized the positive chronotropic effect of isoprenaline (10(-7) M) in Purkinje fibers. However, normal automaticity, action potential characteristics, effective refractory period, membrane responsiveness of Purkinje fibers were unaffected by mepindolol up to 10(-6) M. On the whole, mepindolol appears to be a potent beta-blocker with no cardioselectivity, exerting membrane depressant effect only at concentrations 100-1000 times higher than those exerting effective beta-blockade.

Adrenergic alpha-Antagonists↗
PubMed1985

Role of the oscillatory afterpotentials in the arrhythmogenic action of histamine.

We used intracellular microelectrodes to study the effect of histamine on oscillatory afterpotentials (OAPs). OAPs were induced by exposing cardiac Purkinje fibers to barium (10(-5) M) and to strophanthidin (3 X 10(-7) M). Histamine consistently increased the amplitude of the barium-induced OAPs. Similar results were obtained in strophanthidin-treated preparations: histamine, in fact, was able to increase the OAPs amplitude and eventually to induce triggered activity. The effect of histamine was antagonized by cimetidine (10(-5) M). The possible role of the OAPs in the arrhythmogenic action of histamine is discussed.

Action Potentials↗
PubMed1985

Effect of verapamil and diltiazem on calcium-dependent electrical activity in cardiac Purkinje fibres.

The effects of verapamil and diltiazem on normal action potentials, abnormal automaticity at depolarized membrane potential and oscillatory afterpotentials were compared in sheep cardiac Purkinje fibres. Concentrations of verapamil and diltiazem exerting the same action on abnormal automaticity due to slow action potentials, caused different effects on action potential characteristics and on oscillatory afterpotentials. Diltiazem significantly shortened action potential duration whereas verapamil slightly lengthened it (NS). Diltiazem appeared to be more effective than verapamil in preventing the development of oscillatory afterpotentials induced by barium or by strophanthidin. In 50% of barium-treated preparations, verapamil caused the appearance of spontaneous activity due to enhanced normal diastolic depolarization, while diltiazem had no such effect. The observed differences were explained in terms of the different effects of the two drugs on currents other than the slow inward current, since diltiazem was more potent than verapamil in depressing Vmax.

Action Potentials↗
PubMed1985

Electrophysiological mechanisms for the antiarrhythmic action of mexiletine on digitalis-, reperfusion- and reoxygenation-induced arrhythmias.

The antiarrhythmic potency of mexiletine was evaluated on three groups of guinea-pig isolated hearts. Arrhythmias were induced (a) with digitalis intoxication, (b) with hypoxia followed by reoxygenation and (c) with ischaemia followed by reperfusion. Mexiletine 10 microM was found to be very effective against all three types of arrhythmias in all three groups. The electrophysiological effects of mexiletine were then studied on sheep cardiac Purkinje fibres manifesting oscillatory afterpotentials and triggered automaticity induced by barium or strophanthidin. Mexiletine 10 microM consistently decreased the amplitude of oscillatory afterpotentials and blocked subsequent triggered activity in sheep Purkinje fibres. In contrast, mexiletine 10 microM had no significant effect on Vmax in normal, barium- and strophanthidin-treated preparations. The results are discussed in relation to the mechanisms of antiarrhythmic action of mexiletine.

Action Potentials↗
PubMed1985

Comparative evaluation of the effects of lidocaine (lignocaine) hydrochloride and salicylate on nervous and Purkinje fibres.

Lidocaine hydrochloride and lidocaine salicylate (lisacaine) have been tested on the frog node of Ranvier, on the sheep cardiac Purkinje fibres and rat phrenic nerve-diaphragm. On the node of Ranvier both drugs produced the same degree of reduction of peak INa and steady-state potassium current and the same degree of shift of the steady-state inactivation curve for INa to more negative potential. Lisacaine took less time to reach the steady-state effect. On the cardiac Purkinje fibres both drugs decreased the action potential duration without any detectable difference; but their effects on V max (i.e. the maximum rate of depolarization) were different that of lisacaine being faster. On the rat phrenic nerve-diaphragm both drugs produced the same percentage of reduction of the contractile response of diaphragm but, the action of lisacaine was faster. Therefore the lidocaine molecule with the salicylate anion while displaying the same anaesthetic effectiveness has a faster action than the hydrochloride.

Action Potentials↗
PubMed1985

Influences of age on the positive inotropic effect mediated by alpha- and beta-adrenoceptors in rat ventricular strips.

The positive inotropic effect of phenylephrine (in the presence of atenolol) and isoprenaline was studied in isolated right ventricular strips obtained from Wistar rats aged 2 weeks, 3 months, and 26 months. The positive inotropic effects induced by phenylephrine and isoprenaline were higher in the 2-week-old than in the 3- or 26-month-old rats. The typical 'alpha-type' or 'beta-type' responses were induced by phenylephrine (plus atenolol) or isoprenaline, in all the age groups. The EC50 values for the alpha-mediated positive inotropic effect decreased with age, while the EC50 value for the positive inotropic effect of isoprenaline increased in the senescent heart. These results suggest an enhanced alpha-adrenergic sensitivity in the senescent heart.

Aging↗
PubMed1984

On the presence of H1-receptors in various sections of guinea-pig heart: a correlation between binding and functional studies.

The binding of 3H-mepyramine in different sections of guinea-pig heart was examined. 3H-mepyramine binds to a single class of binding sites to guinea-pig ventricular membranes and to right atrial suspension with an apparent dissociation constant (Kd) of 4.35 nM and 14.90 nM respectively. When treated as those obtained from the right atrium, the left atrial suspensions do not seem to bind 3H-mepyramine specifically.

Aminopyridines↗