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Biomedical subjects

I Maragno

Publications and source records attributed to I Maragno.

9 recordsLinked to original sources
PubMed1991

An analysis of the mechanism of the inotropic action of some milrinone analogues in guinea-pig isolated atria.

1. It has been reported previously that the milrinone analogues, ethyl 5-cyano-1,6-dihydro-2-methyl-6-oxo-3 pyridine carboxylate (I) and ethyl 5-cyano-1,6-dihydro-2-ethyl-6-oxo-3 pyridine carboxylate (II) exert a positive inotropic effect (EC50 = 15.6 +/- 0.2 microM and 40.3 +/- 0.1 microM) both on spontaneously beating and on electrically driven atria from reserpine-treated guinea-pigs. In the present study the mechanism of the inotropic action of these two agents was investigated. 2. In electrically driven left atrium from reserpine-treated guinea-pigs the EC50 values for inotropic activity for compounds (I) and (II) corresponded to that of milrinone (EC50 = 25 +/- 0.1 microM) but compound (I) induced a greater maximum effect. This corresponded to a percentage increase in developed tension over control of 63 +/- 0.3 whereas the maximum inotropic effect of milrinone was 48 +/- 0.3 and that of compound (II) was 47 +/- 0.2. 3. The inotropic activity of compounds (I) and (II) (10-100 microM) was resistant to propranolol (0.1 microM), thus excluding the involvement of beta-adrenoceptors. 4. Since the inotropism induced by compounds (I) and (II) was not reduced by carbachol (1 nM-0.5 microM), an action involving changes in adenosine 3':5'-cyclic monophosphate (cyclic AMP) can be excluded. 5. The inotropic action of compounds (I) and (II) was blocked selectively by 8-phenyltheophyline (10 microM) or adenosine deaminase (2 u ml-1). 6. Both (I) and (II) inhibited, in an apparently competitive manner, the negative inotropic effect induced by N6-(L-phenylisopropyl) adenosine (L-PIA), a stable adenosine agonist. The pA2 values for (I) and (II) were 4.79 and 4.36, respectively.7. In rat brain compounds (I) and (II) inhibited the specific binding of N6-cyclohexyl[3H]-adenosine- ([3H]-CHA) with an IC50 of 0.18 + 0.01 mM and 0.25 + 0.02 mm, respectively, which were similar to their IC50 values for blocking the PIA-induced negative inotropic effect and which are also in the range of concentrations that are effective in inducing positive inotropism in guinea-pig atria.8. The results from the present study suggest that antagonism of endogenous purines causes positive inotropism without affecting intracellular cyclic AMP levels.

Adenosine↗
PubMed1990

Comparison between the cardiac effects induced by muzolimine and furosemide in guinea-pig atria.

Muzolimine (10-500 microM) induced a concentration-dependent reduction of both the contractile force and frequency in spontaneously beating atria and in electrically driven left atrium from reserpine-treated guinea pigs. This negative inotropic response was unaffected by the addition of atropine to the perfusion fluid, and it was highly sensitive to changes in external Ca2+ concentration. Both in spontaneously beating and in electrically driven atrium, muzolimine (50-400 microM) antagonized, in an apparently competitive manner, the increase in contractile force induced by cumulative addition of CaCl2 (0.68-9.59 mM) to the bathing fluid. Muzolimine (50-100 microM) reduced the inotropic response to low (5-30 nM), but not high (50-100 nM) concentrations of Bay K 8644, a calcium-channel agonist. The inotropic effects of 8-phenyltheophylline and of ouabain were antagonized by muzolimine (10-100 microM) in a noncompetitive manner, while the response to noradrenaline was not altered. Similar to muzolimine, verapamil at a concentration suitable to block calcium channels inhibited, in a noncompetitive way, the inotropic effect induced by 8-phenyltheophylline and by ouabain without altering the contractile response to noradrenaline. Furosemide (10 and 100 microM) did not influence the contractile force or the frequency of spontaneously beating atria, nor the inotropic effect induced by CaCl2, 8-phenyltheophylline, ouabain, or noradrenaline. These results indicate that the influence of muzolimine on guinea-pig atria originates from an inhibition of Ca2+ influx into cardiac cells and that furosemide does not mimic the effect of muzolimine at this level.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1978

Plasma renin activity in coarctation of the aorta before and after surgical correction.

In 37 patients with coarctation of the aorta, arterial blood pressure and ambulant plasma renin activity (PRA) were determined before and, in 15 patients, after surgical correction. The systolic blood pressure was raised in all the cases and the diastolic pressure was raised in 30 patients. Ambulant PRA was increased in 11 patients when compared with normal subjects of similar age. Twelve of the 15 operated patients had a significant decrease of systolic pressure after operation. Eight had raised PRA, and in 7 of these PRA fell to normal after operation and the blood pressure also fell; in 1 patient the decrease of PRA was unaccompanied by a fall in blood pressure. Though there was no significant correlation between the changes in blood pressure and PRA after operation it seems possible from our results that the renin-angiotensin system may be activated and contribute to the raised arterial pressure which occurs in patients with aortic coarctation.

Adolescent↗
PubMed1978

[The experience with permanent cardiac pacing at the Surgical Clinic of the University of Padua Medical School (author's transl)].

A computer analysis is reported of the most significant data concerning 1624 pacemaker implantations and 1386 battery replacements. The patients were treated by endocardial stimulation with transvenous electrodes in 91% of the cases; the remainder: 9% received epicardial electrodes. The mode of stimulation was 2189 times "demand", 138 "synchronized" and 683 "asyncronous". Pacers of 13 different brands were used. At the beginning of our experience, the catheter was introduced through the superficial or profunda giugular vein: since 1969 the cephalic vein has been preferred. Epicardial electrodes were implanted via a left thoracotomy but in the most recent years the extrapleural phrenico-pericardial approach has been adopted. In a number of cases external pacemakers have been employed for permanent stimulation. The most common post-operative complications were infection (3.9%), skin erosion (2.2%), catheter rupture (3.5%), electrode dislodgement (1.7%). Such complications are becoming less frequent since 1969, due to technical improvements.

Adolescent↗
PubMed1977

[Reliability of premature atrial stimulation in the study of sinoatrial conduction time (author's transl)].

Premature atrial stimulation was carried out in 32 patients, and for each stimulus the basic cycle (A1A1), test cycle (A1A2), and the return cycle (A2A3) were analyzed. When A2A3 was plotted as the function of A1A2, a biphasic pattern, characterized by a slope phase followed by a "plateau", was observed in 25 subjects. Sinoatrial conduction time (SACT) was calculated using the Strauss method, which assumes that in the plateau A2A3 = A1A1 + SACT. Sinus arrhythmia was also determined in order to evaluate its importance in altering the results of premature atrial stimulation: it should be pointed out that when arrhythmia was marked it was impossible to calculate sinoatrial conduction time. An inverse correlation between A1A1 and the calculated SACT and between A1A1 and A2A3/A1A1 in the plateau was also demonstrated. The reliability of SACT obtained by premature atrial stimulation is discussed in relation to the results obtained and the data found in the literature.

Adolescent↗
PubMedDate not supplied

Vasodilatory activity of etozoline in rat and guinea-pig isolated aorta: study of the mechanism of action.

In isolated rings of guinea-pig aorta not responding to acetylcholine, the diuretic etozoline did not influence basal vascular tone but inhibited noradrenaline- and histamine-induced contractions. The inhibition was evident at concentrations of the diuretic (10 microM-1 mM) suitable to inhibit, in a competitive manner, the contractions evoked by a K+ channel blocker, tetraethylammonium, in the same preparation (Dorigo et al., 1989, 1990). In isolated rings of guinea-pig aorta, etozoline, at very low concentrations (1 nM-0.1 microM), inhibited also serotinin-induced contractions. The contractile effect of serotonin was abolished by nifedipine associated with 2-nitro-4-carboxyphenyl N,N-diphenyl-carbamate (an inhibitor of phospholipase C) or with etozoline, thus suggesting that the diuretic, besides inhibiting extracellular Ca++ uptake, also prevents intracellular Ca++ mobilization mediated by inositol triphosphate. In isolated rings of rat aorta responding to acetylcholine, etozoline did not influence basal vascular tone either in the absence or in the presence of superoxide-dismutase. In the same preparation, the diuretic inhibited vascular contractions induced by the three spasmogenic agents used, i.e. noradrenaline, histamine and serotonin. This inhibition occurred at concentrations of etozoline ranging from 10 microM to 1 mM and was uninfluenced by indomethacin (10 microMs). In isolated rings of rat aorta, the contractile effect of noradrenaline was not influenced by the addition of either 100 microM pyrogallol, or 10 microM methylene blue or 100 U/ml superoxide-dismutase, while the contractile responses to histamine and to serotonin were potentiated by pyrogallol and by methylene blue and reduced by superoxide-dismutase. This indicates that, in rat aorta, noradrenaline evokes only a direct contractile response, whereas both serotonin and histamine have a double effect: direct contraction of vascular smooth muscle and release of a relaxing factor from the endothelium. The inhibitory activity of etozoline towards serotonin- and histamine-induced contractions was reduced by pyrogallol and by methylene blue, whereas it was potentiated by superoxide-dismutase. The ability of etozoline to reverse the noradrenaline-induced contraction was unaffected by pyrogallol, methylene blue or superoxide-dismutase. These results emphasize the spasmolytic activity of etozoline, which seems to involve only the muscular component of rat and guinea-pig aorta.

Acetylcholine↗