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Biomedical subjects

A Mugelli

Publications and source records attributed to A Mugelli.

At least 73 records · Page 4Linked to original sources
PubMed1984

A low-cost microcomputer system for automated analysis of intracellular cardiac action potentials.

A microcomputer system for automated analysis of action potentials recorded from cardiac Purkinje fibers is described. The system is based upon a DMD 800 microcomputer built around a Z80 microprocessor. Two different sampling intervals are used for analog-to-digital conversion of action potential recorded from driven fibers. The following parameters can be obtained on-line: action potential amplitude; overshoot; maximum diastolic potential; action potential duration measured both at -60 mV and at 90% of complete repolarization; and maximum rate of rise of the upstroke. The digitized form of five consecutive action potentials can be stored on a floppy disk. The automated system eliminates hand measurements; the on-line analysis of the action potentials during pharmacological interventions allows a rapid appreciation of drug effects.

Action Potentials↗
PubMed1984

Alpha-adrenoceptor stimulation enhances automaticity in barium-treated cardiac Purkinje fibers.

We used intracellular microelectrodes to study the effect of alpha-adrenoceptor stimulation on automaticity of sheep cardiac Purkinje fibers exposed to low (10(-5) - 4 X 10(-5) M) barium concentrations. Concentrations of norepinephrine (NE) (3 X 10(-8) - 3 X 10(-7) M), which did not induce spontaneous activity in the absence of barium, consistently induced or enhanced it (if already present) in the presence of barium. Similar results were obtained in the presence of practolol (10(-6) M), which in 13 out of 17 experiments did not counteract the effect of NE. However, phentolamine (3 X 10(-7) M) caused a slowing or blocking of the spontaneous activity induced by NE in barium-treated preparations either in the presence or in the absence of practolol. We conclude that alpha-adrenergic responsiveness is enhanced in barium-treated Purkinje fibers and that under these experimental conditions, alpha-adrenoceptor stimulation may influence automaticity. The possible mechanisms underlying such effects are discussed.

Action Potentials↗
PubMed1983

Barium-induced spontaneous activity in sheep cardiac Purkinje cells.

We used intracellular microelectrodes to study the electrophysiological effects of low barium concentrations (1--4 x 10(-5) M) on sheep cardiac Purkinje fibers. The main effect of barium was an increase in action potential duration (APD) both at -60 mV (APD-60) and at 100% repolarization (APD100). The prolongation of APD was greater at a lower (30/min) than at a higher driving rate (120/min). Barium significantly modified the normal linear relationship between driving rate and APD. The effects of barium on APD were enhanced by lowering [K+]0 and antagonized by increasing [Ca2+]0. Barium caused a slowing of phase 3 repolarization, a steepening of diastolic depolarization and induced spontaneous activity in the resting potential range during the interruption of the drive. The first spontaneous action potential was usually preceded by an oscillatory potential. By means of several procedures (lowering [K+]0, increasing [Ca2+]0, increasing the driving rate) it was possible to identify two separate mechanism underlying the initiation of spontaneous activity: (1) enhancement of normal diastolic depolarization and (2) induction of oscillatory afterpotentials. Finally, barium induced repetitive activity through early afterdepolarizations. We conclude that in Purkinje fibers low barium concentrations cause a lengthening of APD and can induce spontaneous activity by means of at least three different mechanisms. The main factor underlying the barium effects seems to be a reduction in potassium conductance.

Action Potentials↗
PubMed1982

Some characteristics of the inotropic effects of histamine H1- and H2-receptor agonists in comparison with those of alpha- and beta-adrenoceptor agonists.

The positive inotropic effects of 2-pyridyl-ethylamine (PEA) and of 4-methylhistamine (4MeH) were studied in isolated guinea-pig ventricular strips electrically stimulated at a rate of 60 and 150/min. The increase in contractile tension induced by PEA (10(-7)-3 X 10(-4) M) in the presence of cimetidine (10(-5) M) was associated with a slight increase in time to peak tension and with a lengthening of the relaxation phase; the positive inotropic effect of PEA was significantly higher at a frequency of 60/min than at 150/min. Conversely, the inotropic response to 4MeH (10(-8)-3 X 10(-6) M) was not frequency dependent, and was associated with an evident decrease in relaxation time. Moreover, 4MeH consistently antagonized, in dose-dependent manner, the negative inotropic effects induced by the calcium antagonistic drug D600 and by lowering calcium concentration in the medium, and was able to restore the contractility abolished by treatment of preparations with a high K+ medium. On the other hand PEA, in the presence of cimetidine, scarcely antagonized the negative inotropic effects induced either by D600 or by low calcium solution, and was unable to restore the contractility of K+-depolarized preparations. The characteristics of the inotropic response of the H1-receptor agonist were very similar to those of the alpha-adrenoceptor agonist phenylephrine. This observation suggests that a common mechanism is probably involved in the inotropic effects mediated by H1 and by alpha receptors, and that this mechanism does not include a stimulation of the calcium transmembrane influx.

Adrenergic alpha-Agonists↗
PubMed1982

H1- and H2-receptors in the guinea-pig heart: an electrophysiological study.

The mechanical and electrophysiological effects of 2-pyridylethylamine (PEA) and 4-methylhistamine (4MeH) in different sections of guinea-pig heart were examined. 4MeH produced a dose-dependent increase in contractility in the right ventricle and the right atrium, and a decrease in functional refractory period (FRP) in all the sections studied; the action potential duration was decreased and the plateau phase was usually heightened in both atria and the ventricle. These effects were consistently antagonized by cimetidine. PEA-induced changes in contractility, FRP and the action potential profile were studied in the presence of cimetidine. Triprolidine antagonized PEA effects on FRP and the action potential profile only in the left atrium. The results obtained are discussed in terms of the functional role of both H1 and H2 receptors in the various guinea-pig heart sections.

Action Potentials↗
PubMed1982

Separation of the oscillatory current from other currents in cardiac Purkinje fibres.

An oscillatory current (Ios) can be recorded after depolarising clamps of a given amplitude and duration. To determine whether Ios depends on other currents activated during the clamp, the Ios was investigated in the absence and in the presence of 4-aminopyridine (4-AP) and cesium (Cs). The following results were obtained. 4-AP, as expected, markedly reduced the early outward current Iqr, and this effect was fully reversible. The Ios persisted when Iqr was suppressed by 4-AP and in fact became greater. Also, several procedures (progressive increase in clamp duration, two step repolarisation, repetitive clamps) affected Ios similarly whether Iqr was present or not. Ios does not depend on the plateau current Ix1 since with 4-APIos increased while the tail of Ix1 were unaffected. Cesium abolished the pacemaker current but not Ios, demonstrating that Ios does not result from an oscillatory behaviour of the pacemaker current. Often Cs reduced the amplitude of Ios: prolonging the depolarising clamp increased Ios but did not restore the pacemaker current. It is concluded that the oscillatory current is independent of either the early outward current Iqr or the pacemaker current. Also, while the action of 4-AP and Cs on Iqr and the pacemaker current are confirmed, it appears doubtful that these two agents act specifically on these two currents alone.

4-Aminopyridine↗
PubMed1981

An oscillatory current in sheep cardiac Purkinje fibers.

The inward current ("oscillatory current") which may be present after the end of a depolarizing clamp was studied in sheep cardiac Purkinje fibers by means of a voltage-clamp method. The following results were obtained. In order to appear, the oscillatory current (Ios) requires a previous depolarization to approximately or equal to -20 mV or beyond and a repolarization to approximately or equal to -40 mV or to more negative potentials. The Ios requires a minimum duration of the depolarizing clamp and becomes larger with longer clamps. With repolarization to more negative potentials (approximately or equal to 90 mV), Ios becomes smaller and may disappear. Also Ios can be triggered twice if the potential is clamped to two different levels in succession. By several procedures which modify the other known currents (fast Na+ current, slow inward current, early outward current, plateau current Ix1 and pacemaker current), it can be demonstrated that Ios is not due to their oscillatory behavior and can occur in the absence of any one of them. Interventions which increase the contractile force presumably by increasing intracellular calcium stores enhance the Ios or may make it appear. In fact, these interventions may extend the voltage range over which Ios appears. These interventions include lowering potassium, increasing calcium, trains of depolarizing clamps, and administration of norepinephrine and of strophanthidin. It is concluded that Ios is a physiological event which is enhanced by certain procedures, and it appears to be of much importance in drive-induced arrhythmias under different conditions.

Action Potentials↗
PubMed1981

The influence of some cardiodepressant drugs on the histamine-induced restoration of contractility in potassium-depolarized heart preparations.

The ability of some drugs to affect calcium movements in cardiac fibers was tested using a simple method. Guinea-pig ventricular strips were depolarized by 22 mM K+ and their mechanical activity was restored by histamine (10(-5) M); in in these conditions, the effects on contractility of the classic calcium antagonistic drugs nifedipine, verapamil and D600, of the antiarrhythmic drugs lidocaine, quinidine and propafenon, and of a barbiturate, thiopental, were assessed. These drugs were chosen because all of them have been reported as affecting cardiac contractility. It was observed that the ED50 values obtained for the calcium antagonists were in good agreement with those calculated by other authors using different techniques. Moreover, it was found that at high concentrations either the antiarrhythmic drugs or thiopental showed a cardiodepressant activity; the likely explanation of their effects is discussed.

Animals↗
PubMed1980

alpha-Sympathomimetic amines and calcium-mediated action potentials in guinea-pig ventricular muscle.

1 The ability of amines, having alpha- or alpha- and beta-adrenoceptor stimulating activity, to restore excitability and contractility in heart preparations partially depolarized by potassium, was investigated in guinea-pig ventricular muscle in order to elucidate the mechanism of the positive inotropic effect mediated via alpha-adrenoceptors. 2 In preparations in which fast sodium channels were inactivated by K+-rich medium (22 mM) slow electrical responses as well as contractions were consistently induced by high concentrations of phenylephrine (10(-4) to 3 X 10(-4) M) and synephrine (3 X 10(-4) M). 3 The restorative effective effects of both phenylephrine and synephrine were unaffected by phentolamine (10(-5) M) but were readily abolished by practolol (10(-5) M) or sotalol (10(-5) M). 4 Methoxamine induced a dose-dependent positive inotropic effect in ventricular strips paced at 0.5 Hz in normal Tyrode solution; the maximum increase in contractile tension was obtained with methoxamine 10(-4) M. However, at the same concentration, the amine did not induce slow electrical responses in potassium-depolarized preparations. 5 It is concluded that the induction of slow responses by phenylephrine and synephrine is due to beta-adrenoceptor stimulation, and that the increase in cardiac contractility caused by alpha-adrenoceptor stimulation does not involve an increase in slow inward calcium current.

Action Potentials↗
PubMed1977

Studies on the positive inotropic effect of dopamine in the guinea-pig heart.

The positive inotropic effect of dopamine has been studied in isolated ventricular strips of guinea-pig heart. The concentration-inotropic response curve for dopamine was significantly shifted to the right by pretreatment with reserpine. In preparations obtained from animals pretreated with reserpine (2.5 mg/kg, 24 h prior to the experiment) the dose-response curve was not significantly affected by haloperidol, a dopamine vascular receptor antagonist (10(-6)-3X10(-6) M). The inotropic effect of dopamine was antagonized by practolol (3X10(-7)-10(-6) M), but not by phentolamine (3X10(-6)-10(-5) M); moreover the alpha-adrenoceptor blocking drug (10(-5) M) did not affect the curve for dopamine in the presence of practolol (3X10(-7) M). In preparations in which fast sodium channels were blocked by K+ -rich medium, slow electrical responses (calcium-mediated action potentials) as well as contractions were induced by high concentrations of dopamine (10(-4)-3X10(-4) M); again these responses were unaffected by phentolamine or haloperidol, but were blocked by practolol. It was concluded that in the guinea-pig ventricular muscle dopamine induced a positive inotropic effect through both indirect and direct action, and that the latter is due to the activation of beta-adrenoceptors.

Animals↗
PubMed1977

A histamine-induced decrease of action potential duration in cardiac muscle mediated by the H2 receptors.

The effects of histamine (10(-7)--10(-5) M) on the cardiac action potential have been studied in ventricular strips of guinea pig heart, electrically driven at a constant rate. A decrease of action potential was constantly observed at histamine concentrations above 10(-6) M. No significant variations of the other electrophysiological parameters were induced by the amine. The decrease in the duration of the action potential was blocked by burimamide at a concentration (10(-4) M) which induced only a slight changes in action potential outline. It is suggested that the shortening of the repolarization phase induced by histamine is due to the H2 receptor-mediated activation of the calcium inward current, which can increase the intracellular calcium concentration influencing the potassium permeability.

Action Potentials↗
PubMed1976

Frequency dependence of the alpha-adrenoceptor-mediated positive inotropic effect in guinea pig heart.

Evidence for the role of alpha-adrenoceptors in the production of a positive inotropic effect has been obtained chiefly in heart preparations stimulated at a low rate (1 or 1.4 Hz). However, our previous results suggested that the alpha-receptor-mediated positive inotropic effect could be frequency dependent. In the present study cumulative concentration-inotropic effect curves were obtained in guinea pig ventricle strips treated with adrenaline and stimulated at 1 and at 2.5 Hz. Phentolamine (3 X 10(-6) M) and practolol (10(-6) M) were employed as antagonists. Phentolamine antagonized the effect of low concentrations of adrenaline (10(-9)-10(-8) M) in preparations driven at 1 Hz, but did not modify the curve of the agonist at the higher stimulation rate. In preparations driven at 1 Hz, practolol antagonized the effect of adrenaline at concentration above 3 X 10(-8) M without affecting the curve at lower concentrations, the beta-blocker competitively anatagonized the effect of the agonist at 2.5 Hz. It was concluded that a shortening of the interval between beats abolishes the alpha-mediated positive inotropic effect.

Animals↗