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Biomedical subjects

A Mugelli

Publications and source records attributed to A Mugelli.

83 records · Page 5Linked to original sources
PubMed1975

Studies on the positive inotropic effect of phenylephrine: a comparison with isoprenaline.

1. The effects of phenylephrine and isoprenaline on the isometric contraction of guinea-pig ventricle were compared over the whole range of their respective dose-response curves. 2. In preparations driven at 2.5 Hz the increase in contractile force induced by either isoprenaline of phenylephrine was linearly correlated to an increase in maximum velocity of force development. The relaxation time was shortened by isoprenaline but not by phenylephrine. 3. The negative inotropic effect induced by delta [N-(3,4-dimethoxyphenethyl)-N-methyl-amino]-alpha-(3,4,5-trimethoxyphenyl)alpha-isopropylvaleronitrile hydrochloride (D(600)) was reversed by isoprenaline, but little influenced by phenylephrine. 4. The study of the interval-force relationship shows that the increase in contractile force induced by phenylephrine (3 X 10(-5) M) was relatively greater at low frequencies of stimulation, and that the maximum effect was reached at the frequency of 1 Hz. 5. The positive inotropic effect of phenylephrine (10-4 M) was significantly higher at a frequency of 1 Hz than at 2.5 Hz; the effect of isoprenaline (3 x 10-8 M) was not significantly different at the two driving frequencies. 6. In preparations driven at 1 Hz the inotropic effect of the lower concentrations of phenylephrine was due to an increase in the time to peak tension without any change of the maximum velocity of force development; however an increase of this parameter became evident only after higher concentrations of the amine (10-5 M or more), associated with a progressive shortening of the time to peak. 7. A correlation between mechanical and electrophysiological effects of phenylephrine is attempted; the suggestion is advanced that the prolongation of the action potential and of the active state duration may be an important factor in the inotropic effect of phenylephrine.

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Cellular electrophysiological aspects of myocardial protection.

Oxygen radicals (OR) generated at the time of reflow of the ischaemic myocardium may cause 'reperfusion injury'. To protect myocardium from this injury, it is important to understand how OR cause their deleterious effects on myocytes. Here we describe the basic electrophysiological alterations caused by OR in patch-clamped ventricular myocytes isolated from the rat heart. Oxygen radicals generated by dihydroxyfumarate (DHF) caused a lengthening of action potential duration (APD) and the appearance of arrhythmogenic alterations such as early and delayed afterdepolarizations. Prolongation of APD was accompanied by a reduction in calcium and potassium currents. When intracellular calcium levels were kept constantly low by 500 microM EGTA in the pipette solution, the effects of DHF on action potential duration and the occurrence of early afterdepolarizations were largely prevented. It is concluded that exposure to OR may induce electrophysiological alterations in isolated myocytes. They are related to changes in specific ionic currents and in levels of intracellular calcium.

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PubMedDate not supplied

Induction by histamine of oscillatory activity in sheep Purkinje fibers and suppression by verapamil or lidocaine.

Histamine (1--2 x 10(-5) M) induced or enhanced oscillatory activity in four of five sheep Purkinje fibers depolarized by a low-potassium medium. These effects of histamine were readily antagonized by 2 x 10(-5) M burimamide but were unaffected by 10(-5) M practolol. Oscillatory activity was consistently induced or enhanced by 5 x 10(-6) M adrenaline in five preparations. Oscillatory activity, whether induced by histamine or adrenaline, was always abolished by verapamil (0.22--2.2 x 10(-6 M) but in only one of five experiments by lidocaine (4.2 x 10(-5) M). We conclude that induction of oscillatory responses may be added to the other arrhythmogenic mechanisms produced by histamine through the stimulation of H2 receptors. We confirmed that oscillatory activity is very effectively suppressed by verapamil.

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PubMedDate not supplied

Electrophysiological and antiarrhythmic properties of propafenon in isolated cardiac preparations.

Propafenon, a new antiarrhythmic drug, caused a 30% decrease in maximal driving frequency and a 65 ms net increase in functional refractory period of isolated guinea pig atria at a concentration as low as 0.5 microgram/ml. The spontaneous rate of isolated atria and the contractility of electrically driven ventricular strips were reduced after treatment with propafenon 1 microgram/ml. Propafenon 0.5 microgram/ml also altered action potentials of sheep Purkinje fiber. It reduced the action potential and overshoot amplitudes, decreased the maximum rate of depolarization of the action potential upstroke in a frequency-dependent fashion, shortened the action potential and effective refractory period, and depressed the membrane responsiveness. Moreover, propafenon antagonized the chronotropic and inotropic effects of isoprenaline in isolated guinea pig heart preparations; the pA2 value was about 6.4. Finally, propafenon possessed very weak calcium antagonist properties, being about 100 times less potent than verapamil in this respect. We conclude that propafenon is an antiarrhythmic drug with beta-adrenoceptor blocking and "membrane stabilizing" activities in the same range of concentrations and that it has a calcium antagonistic activity only at much higher concentrations.

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PubMedDate not supplied

In vitro cardiac electrophysiological effects of prenylamine.

In order to get information on some of the effects of prenylamine (bradycardic effect, negative inotropic effect, triggering of "torsade de pointes"), we studied with intracellular microelectrodes its electrophysiological actions on guinea-pig sinus node and papillary muscle, on sheep Purkinje fibers and rabbit sino-atrial node isolated myocytes. Prenylamine (10(-6)-10(-5) M) reduced the firing rate of sinus node preparations. This effect was associated with a slowing of the rates of diastolic depolarization, of depolarization and of repolarization, and with a slight depolarization of the maximum diastolic potential. A dose-dependent decrease of the slope of the first 100 msec of the diastolic depolarization was observed. Prenylamine (10(-6) M) also reduced the amplitude of the pacemaker current (If) recorded using the patch-clamp technique from rabbit sino-atrial node cells. Prenylamine (3 x 10(-7)-3 x 10(-6) M) dose-dependently reduced contractility of Purkinje fibers; the effect was associated with a lowering of the plateau, a decrease of the maximum rate of depolarization and a shortening of the action potential duration. Prenylamine was also able to abolish early and delayed after-depolarizations which are two kinds of calcium-dependent electrical activities relevant for the genesis of triggered arrhythmias, such as "torsade de pointes". It is concluded that prenylamine, a nonselective calcium antagonist, presents an intriguing in vitro electrophysiological profile which makes any extrapolation to its in vivo pharmacology extremely complex.

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PubMedDate not supplied

Electrophysiological evaluation of the beta-blocking properties and direct membrane effects of l-moprolol and its enantiomer d-moprolol.

The electrophysiological and beta-blocking properties of l- and d-moprolol have been studied in sheep cardiac Purkinje fibers. l-Moprolol (0.3-100 nM) dose-dependently antagonized the inotropic (ED50 = 1.2 +/- 0.4 nM) and chronotropic (ED50 = 5.8 +/- 0.6 nM) effects of isoprenaline. d-Moprolol (0.3-100 nM) was fully devoid of beta-blocking properties under the same experimental conditions. Both isomers had the same electrophysiological profile: they did not influence action potential characteristics, contractility and normal automaticity up to 1 microM. On the whole, l-moprolol appears to be a potent beta-blocker, exerting membrane depressant effects only at a concentration 2000 times higher than those exerting effective beta-blockade.

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