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Biomedical subjects

F Ledda

Publications and source records attributed to F Ledda.

At least 55 records · Page 3Linked to original sources
PubMed1984

Inhibition of the cardiac response to sympathetic nerve stimulation by opioid peptides and its potentiation by morphine and methadone.

[D-Ala2,D-Leu5]enkephalin (1-10 microM) and [Met5]enkephalin-Arg-Phe (1-10 microM) produced concentration-dependent inhibition of the cardiac response to field stimulation of the adrenergic nerve terminals in preparations pretreated with peptidase inhibitors (captopril 10 microM, bestatin 10 microM, thiorphan 0.3 microM and L-leucyl-L-leucine 2 mM). The inhibitory response to the opioid agonists was evident in preparations superfused with solutions containing 1.8 mM calcium, but not in those containing 3.6 mM calcium. Moreover the inhibition was antagonized by naloxone 10 microM. [D-Ala2,Met5]enkephalinamide (1-3 microM) and beta-endorphin (1-3 microM) did not significantly affect the sympathetic response. The cardiac response to sympathetic stimulation was not inhibited but, on the contrary, was potentiated by morphine (3-10 microM) and methadone (3-10 microM). It is suggested that the depressant effect of the opioid peptides was due to stimulation of presynaptic inhibitory opiate receptors on adrenergic nerve terminals of the heart, and that the potentiation of the sympathetic response by morphine and methadone was probably attributable to an unspecific inhibitory effect on the neuronal uptake of noradrenaline.

Animals↗
PubMed1984

Alterations of drug toxicity in cardiovascular disease.

The past ten years have seen a rapid expansion in the field of cardiovascular pharmacology. New indications for old agents have appeared and new powerful drugs have been introduced, including entirely new classes of compounds. The availability of so many agents has considerably expanded the risk of life-threatening adverse reactions due to overdosage or to inappropriate drug associations. The liability to encounter severe side effects is often enhanced in patients with underlying cardiovascular diseases, which may change the usual drug action either by inducing modifications of the drug pharmacolinetic or by altering the receptor sensitivity. In most cases these kind of reactions are predictable on the ground of the knowledge of both the drug mechanism of action and the functional alterations induced by the disease. However entirely unexpected adverse reactions may also occur in cases in which unrecognized alterations exist, whose pathophysiology has not been fully elucidated. Recent demonstrations that some physiopathological influences, as well as prolonged drug treatment, can modulate the number of adrenergic receptors in the cardiovascular system has offered a clue to a better understanding of at least some episodes of altered responsiveness to cardiovascular drugs, previously considered of unknown origin. The possibility of obtaining some indications of the adrenoceptor status in man, by the assessment of the receptor density in circulating blood cells, seems to represent a promising diagnostic approach to the problem of disease induced adrenergic regulation and its possible consequences in terms of altered drug responsiveness.

Anti-Arrhythmia Agents↗
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↗
PubMed1984

Differences between the prejunctional effects of phenylephrine and clonidine in guinea-pig isolated atria.

The prejunctional effects of clonidine and phenylephrine were studied in guinea-pig isolated atria by means of field stimulation of the sympathetic nerve terminals during the cardiac refractory period, in the presence of 1 microM atropine. Clonidine (10-100 nM) produced a dose-dependent decrease in the stimulus-inotropic response curve; the IC50 for clonidine was increased about 70 times by the pretreatment of the preparations with 1 microM yohimbine. The effect of clonidine was not modified by 0.5 microM prazosin. Unlike clonidine, phenylephrine (1-10 microM) induced a statistically insignificant increase in the contractile force of preparations stimulated at 4 Hz. The inhibitory effect of phenylephrine (1-10 microM) was partially prevented by either 1 microM yohimbine or 0.5 microM prazosin. However, it was antagonized, to about the same degree as that observed with clonidine, by the pretreatment of the preparations with both 1 microM yohimbine and 0.5 microM prazosin. The results seem to indicate that one component of the prejunctional effects of phenylephrine may be mediated by presynaptic alpha-adrenoceptors belonging to the alpha 1-subtype.

Animals↗
PubMed1984

[Electrophysiologic and anti-arrhythmia properties of propafenone deducible from experimental studies in vitro].

The aim of our study was to analyze which of the basic "in vitro" properties of Propafenon could be relevant to the antiarrhythmic action, as well as to contribute to its classification among the antiarrhythmic drugs. Propafenon belongs to class 1 of Singh and Hauswirth's classification and its characteristics are similar to those of lidocaine; Propafenon may act mainly on ventricular arrhythmias caused by a reentry circuit or by increased automaticity including those which occur in the post-ischemic state and those due to digitalis toxicity. A peculiar aspect of Propafenon seems, however, to be the beta-receptor blocking activity (especially beta-2) shown at therapeutical doses. Such property can induce a depression of heart rate and contractility mainly in patients with a compensatory increase of the sympathetic tone. On the contrary, the calcium-antagonist action of Propafenon is very weak, as it is detected only at doses 80-100 times higher than those that exert an electrophysiologic action. It is also possible that the pharmacological activity of the drug "in vivo" can assume aspects different from those expected from "in vitro" experiments, because of the various metabolites of Propafenon demonstrated in human beings.

Anti-Arrhythmia Agents↗
PubMed1984

Differences between the effects of phenylephrine and other inotropic interventions on post-rest contraction in guinea-pig ventricular strips.

The influence of several inotropic interventions on the strength of the post-rest contraction (PCR) was studied in isolated guinea-pig ventricular strips. In preparations stimulated at 1 Hz and incubated in 3.6 mM Ca++, the PRC-maximum potentiation was obtained after a rest interval of 2 sec (optimum resting time: ORT); a post-rest potentiation was present until 15 sec of rest. An increase in stimulation rate and in Ca++ concentration induced a shift in the ORT towards 15-20 sec, and an increase in the potentiation of PRC. At a low stimulation rate (0.33 Hz) the PRC was lower than steady-state contraction (SSC) at all rest intervals tested. Phenylephrine (5 X 10(-6) M) did not modify the ORT either at 1 or 2.5 Hz, and reduced the height of PRC at 0.33, 1 and 2.5 Hz. These results are discussed in terms of the different effects induced by the various inotropic interventions on cellular calcium availability.

Animals↗
PubMed1983

Reoxygenation dysrhythmias in the isolated guinea-pig heart: sensitivity to prazosin, atenolol and practolol.

Isolated guinea-pig hearts were perfused aerobically for 60 min, then made anoxic for 30 min and finally reoxygenated for 30 min. The effects of prazosin, atenolol and practolol on contractility, coronary pressure, ECG and LDH release were examined. Prazosin and atenolol were able to reduce significantly the incidence of ventricular fibrillation and LDH release. The same two drugs increased the recovery of normal electrical activity after 30 min of reoxygenation. Practolol, on the other hand, was ineffective in reducing the incidence of ventricular arrhythmias and LDH release.

Animals↗
PubMed1983

Overall evaluation of treatment modalities for heroin addiction in a toxicology unit.

A survey of treatment results is presented, using a variety of guidelines for the therapy of different features of heroin addiction in a toxicology unit. Data on 3,211 inpatients under treatment from 1972 are analyzed separately, as well as the follow-up status of 1,262 outpatients who were enrolled in a methadone treatment program. The results are discussed in terms of reliability of the programs and their risk-benefit ratios for the community.

Clonidine↗
PubMed1982

Possible presynaptic inhibitory effect of etorphine on sympathetic nerve terminals of guinea-pig heart.

Etorphine (1-4 microM) dose dependently reduced the sympathetic response induced by trains of field pulses in guinea-pig isolated atria stimulated at 4 Hz; this effect was antagonized by 10 microM naloxone. Since etorphine did not modify the dose-inotropic effect curve of exogenous noradrenaline in the same preparation, it is suggested that the depressant effect of the opioid agonist was due to stimulation of presynaptic inhibitory opiate receptors on adrenergic nerve terminals of the heart.

Animals↗
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↗
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↗