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Biomedical subjects

F Ledda

Publications and source records attributed to F Ledda.

At least 109 records · Page 6Linked 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.

Action Potentials↗
PubMed1973

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↗
PubMedDate not supplied

Enhancement of the vasoconstrictor response to KCL by nitric oxide synthesis inhibition: a comparison with noradrenaline.

The role of the vascular endothelium in the response to a vasoconstrictor agent acting through a non-receptorial mechanism, such as KCl, was tested in the isolated mesenteric vascular bed of the rat. It was confirmed that the vasoconstrictor response evoked by stimulation of sympathetic terminals was unaffected by 100 microM NG-nitro-D-arginine methyl ester (D-NAME), but was significantly potentiated by 100 microM NG-nitro-L-arginine methyl ester (L-NAME) and by removal of endothelium. Responses to exogenous noradrenaline (1-100 microM) were also enhanced by treatment with 100 microM NG-monomethyl-L-arginine (L-NMMA) and with L-NAME, but not with D-NAME. The potentiating effect of NO synthesis inhibitors was reversed by 1 mM L-arginine. Moreover, the noradrenaline-induced vasoconstriction was significantly increased by endothelium-deprivation. Potassium chloride (80 mM) induced a vasoconstrictor response which was not modified by pretreatment with prazosin (0.1 microM) and yohimbine (0.1 microM). The response to KCl was unaffected by D-NAME (100 microM) but the L-stereoisomer induced a significant increase in the perfusion pressure. In endothelium-denuded preparations the vasoconstrictor response to KCl was greater than in control conditions and was quantitatively similar to that observed in L-NAME-treated preparations. The responses to electrical field stimulation, noradrenaline and KCl in endothelium-denuded preparations were not modified by L-NAME. The results suggest that an increase in vascular tone, per se, may represent a trigger for the release of endothelium-derived relaxing factor from endothelial cells.

Amino Acid Oxidoreductases↗
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.

Action Potentials↗