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Biomedical subjects

F Ledda

Publications and source records attributed to F Ledda.

At least 91 records · Page 5Linked to original sources

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

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

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.

Action Potentials

Effects of noradrenaline and isoprenaline, in combination with - and -receptor blocking substances, on the action potential of cardiac Purkinje fibres.

1. The effects of noradrenaline and isoprenaline on the repolarization phase of the action potential have been studied in the Purkinje fibres of sheep heart, electrically driven at constant rates.2. Isoprenaline (2, 5 and 8 x 10(-8) g/ml.) increases the slope of phase 2 of repolarization and decreases the plateau length; the resulting decrease in action potential duration is concentration dependent, but not rate dependent.3. The effect of isoprenaline on the action potential duration is entirely blocked by propranolol (10(-7) g/ml.) and unaffected by phentolamine (5 x 10(-7) g/ml.).4. In phentolamine (5 x 10(-7) g/ml.) pretreated preparations the response induced by noradrenaline (5 x 10(-8), 1 and 5 x 10(-7) g/ml.) is very similar to that induced by isoprenaline.5. In propranolol (2.5 x 10(-7) g/ml.) pretreated preparations noradrenaline causes a lengthening of the plateau phase and an increase in action potential duration.6. The relationship of these results to the presence of both alpha- and beta-receptors in cardiac Purkinje fibres is discussed.

Action Potentials