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Biomedical subjects

I Maragno

Publications and source records attributed to I Maragno.

At least 37 records · Page 2Linked to original sources

[Aortic valve stenosis: current physiopathological and therapeutic aspects].

On the premise that the increased average life expectancy and a reduced incidence of rheumatic diseases have changed the epidemiological profile of valvulopathies, the paper analyses the causes, pathological anatomy, physiopathology and therapy of aortic valvular stenosis. First of all, the differences of acquired calcific stenosis, in which the orifice may be "forced" by the ventricular pump leading to a late onset of symptoms, are underlined. Clinical symptomatology must include angina, syncope or decompensation, rather than merely and elevated gradient, before surgical therapy is proposed. In addition to traditional therapeutic methods (valvular replacement) there is now the possibility of using balloon valvuloplasty which has provided good results in terms of increased valvular area and recovery of ventricular function; however, this is only a palliative step in cases where major surgery is contra-indicated.

Adult↗

[Efficacy of diltiazem in blood pressure increase caused by exertion].

After examining the properties of the 3 most widely used calcium antagonists, the paper assesses the efficacy of Diltiazem in reducing blood pressure rises after exercise in a group of 7 patients with chronic atrial fibrillation. The blood pressure response to a standard load (50 W x 3 m2) on the exercise cycle was monitored in a group of patients under chronic digitalis treatment (phase I) after which the same patients' response to varying doses of Diltiazem (180-240 mg/day) was assessed (phase II) and finally (phase III) their response to treatment with Diltiazem alone but no digitalis. A significantly greater reduction in the systolic pressure and heart rate after exercise was noted in patients given Diltiazem with or without Digoxin than in those given digitalis alone. It is therefore concluded that Diltiazem may be useful in controlled blood pressure and heart rate increases after exercise, especially in patients with ischaemic heart disease.

Aged↗

Low- and medium-dose diltiazem in chronic atrial fibrillation: comparison with digoxin and correlation with drug plasma levels.

The safety and efficacy of diltiazem were compared with digoxin maintenance therapy for control of ventricular response in 19 patients with chronic atrial fibrillation. The relationship between drug plasma levels and cardiovascular effects was also investigated. After 7 days of combined therapy with diltiazem (60 mg three times a day in 10 patients and four times a day in nine patients) and digoxin (0.125 mg/day in two patients and 0.250 mg/day in 17 patients), the 24-hour mean heart rate derived from ambulatory ECG recording was reduced by 16.3% in comparison with digoxin therapy alone; the serum digoxin level was not significantly changed (1.06 +/- 0.43 vs 1.05 +/- 0.61 ng/ml). After a standardized bicycle exercise test (50 watts for 3 minutes), maximal heart rate was reduced by 19.9%, diastolic blood pressure was decreased by 8.9%, and systolic pressure-rate product was decreased by 12.5%. Diltiazem plasma levels (mean 120.9 +/- 63.3 ng/ml) were linearly correlated with percentage variations in maximal heart rate, diastolic blood pressure, systolic blood pressure, and pressure-rate product during exercise. Eighteen patients in succession discontinued digoxin therapy; after 14 days of diltiazem alone, the 24-hour mean heart rate returned to control values of digoxin therapy, whereas maximal heart rate and pressure-rate product during exercise were significantly reduced (-17.2% and -14.1%, respectively), with no changes in blood pressure. Diltiazem plasma levels (135.0 +/- 83.2 ng/ml) showed a linear correlation with the percentage of reduction in maximal heart rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The response of isolated guinea-pig aorta to amrinone.

1. In helically cut strips of aorta from reserpine-treated guinea-pigs, cumulative concentrations (30 microM, 0.3 mM and 3 mM) of amrinone progressively reduced the basal tone of the preparations and relaxed the smooth muscle contracted by 1 microM noradrenaline or by 20 mM K+. 2. The relaxing effect was completely suppressed by tissue pretreatment with adenosine deaminase (1 U ml-1). 3. Relaxation induced by amrinone was not affected by 50 microM indomethacin or by 0.1 mM 8-phenyltheophylline and was potentiated by 5 microM quinidine. 4. Like amrinone, exogenous adenosine reduced the basal tone of the guinea-pig aorta strips and relaxed the preparations contracted by 1 microM noradrenaline or by 20 mM k+ in a concentration-dependent manner. 5. The relaxing activity of exogenous adenosine was not affected by 50 microM indomethacin, was potentiated by 5 microM quinidine and was partially antagonized by 0.1 mM 8-phenyltheophylline. 6. These results indicate the involvement of endogenous adenosine in the relaxing effect of amrinone on guinea-pig aorta strips, but the specific mechanism of amrinone-adenosine interaction remains to be elucidated.

Adenosine↗

Negative and positive influences exerted by purine compounds on isolated guinea-pig atria.

1. In spontaneously beating atria isolated from reserpine-treated guinea-pig adenosine, AMP, ADP, ATP (2 microM) and alpha, beta-methylene ATP (0.4 microM) induced a dual effect: a short lasting negative response, characterized by a reduction in contractile force and in frequency rate, followed by a positive phase of increased inotropism and chronotropism. N6-phenylisopropyladenosine (5 nM) induced only the depressant effects whereas inosine (2 microM) was completely inactive. 2. The early, negative influences were antagonized by 8-phenyltheophylline (0.5-10 microM), an alkylxanthine that competes with purines for P1 receptors. 3. The late, positive response was potentiated by 8-phenyltheophylline (0.5-10 microM) and suppressed by quinidine (5 microM), that blocks the effects of adenine compounds mediated by P2 receptors. 4. In spontaneously beating as well as in electrically driven atria, desensitization of P2 purinoceptors by long lasting exposure to alpha, beta-methylene ATP (8 microM) abolished the late positive response to ATP. In preparations treated with both alpha, beta-methylene ATP and 8-phenyltheophylline, ATP was ineffective. 5. These results suggest that, besides P1 receptors, P2 receptors are also present in guinea-pig atria, mediating stimulatory effects of adenine compounds.

Adenine Nucleotides↗

[A clinical case].

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Angina Pectoris↗

[Hepatic injury in mitral valvular cardiopathy. Clinical and diagnostic aspects].

Liver function was studied in 38 patients with various types of mitral valve disease hospitalised with suspected "cardiac liver". Liver biopsy confirmed the suspicion in 22 cases including 4 with cardiac cirrhosis. The remaining 16 patients had other liver pathologies. No significant differences were noted in the distribution of symptoms, clinical signs and laboratory indices of liver function between the two groups of patients. Among instrumental examinations laparoscopy resulted in a diagnostic accuracy of 89.4% and liver echography of 73% when their results were compared with those of needle biopsy. In other words clinical and laboratory diagnosis of "cardiac liver" was found to be totally unreliable whereas, among instrumental examinations, liver echography proved to be a reasonably efficient alternative to laparoscopy. The diagnostic accuracy of this non-invasive test suggests that it should be used systematically for the screening and follow-up of this type of patients, whereas invasive investigations would be reserved for selected cases.

Adult↗

Verapamil-induced changes in digoxin kinetics in cirrhosis.

The influence of a single low dose of verapamil (80 mg) on the serum levels of digoxin (single dose of 0.5 mg) was studied in 6 patients with hepatic cirrhosis and in 6 healthy volunteer controls. In the cirrhotic patients verapamil increased the peak serum level and the total AUC of digoxin by 98% and 32%, respectively. There was an associated 23% decrease in the renal digoxin clearance. In normal subjects only marginal alterations in digoxin kinetics were observed following verapamil administration. The results indicate that cirrhosis magnifies the influence of verapamil on digoxin kinetics.

Adult↗

The role of calcium in amrinone action on intestinal smooth muscle.

In the guinea-pig isolated ileum amrinone (3 microM to 0.3 M) induced transient, dose-dependent contractions which were followed by pronounced relaxation only at the highest amrinone concentrations tested (30 mM to 0.3 M). The contractile effect was potentiated by eserine and abolished by scopolamine. Verapamil, at concentrations (0.1-1 microM) that did not affect basal tension of the preparations or the contractile response to exogenous acetylcholine, selectively reduced amrinone-evoked contraction, while the relaxing component was abolished by verapamil concentrations (5-10 microM) that per se reduced muscle tension as well as acetylcholine-induced contraction. Similarly, when external Ca2+ concentration was reduced from 2.5 to 1.25 and 0.5 mM, the contractile component of amrinone effect was markedly reduced, while relaxation was not significantly altered. Any further decrease of Ca2+ content in the superfusion medium (0.25 to 0 mM) also reduced the relaxing effect of amrinone and the response of the ileum to exogenous acetylcholine. The present results indicate that in guinea-pig ileum amrinone-induced contractions are sustained by acetylcholine release as well as by Ca2+ entry into smooth muscle cells through verapamil-sensitive channels, while other Ca2+ pools may play a role in the relaxing effect of the drug.

Acetylcholine↗

Effects of amiodarone on oral and intravenous digoxin kinetics in healthy subjects.

The effect of amiodarone on oral and intravenous pharmacokinetics of digoxin was studied in healthy volunteers. A single 0.5-mg dose of digoxin was administered orally to three subjects both before and after 2 weeks of oral amiodarone (200 mg daily), while three subjects received a 0.5-mg intravenous dose of the glycoside under the same experimental conditions. Two other subjects were given both oral and intravenous doses of digoxin at different times, in the absence and in the presence of amiodarone. After oral digoxin treatment, amiodarone increased peak serum concentration, total area under the serum concentration-time curve (AUC), and 5-day urinary recovery of the glycoside, without changes in peak time and absorption rate constant. During the intravenous study, no significant change occurred in AUC and urinary recovery after amiodarone administration. Absolute bioavailability, for the two subjects who received both oral and intravenous digoxin, increased by 36 and 43%, respectively, after amiodarone treatment. Bioavailability derived from the mean values of oral and intravenous AUCs was 33% greater with amiodarone treatment. Apparent volume of distribution and systemic, extrarenal, and renal clearances of oral digoxin were not modified by amiodarone, when corrected for the bioavailability factor. Amiodarone had no effect on these pharmacokinetic parameters during the intravenous study with the glycoside. Our data indicate that increased oral bioavailability is the most relevant change in digoxin pharmacokinetics during the interaction with amiodarone and this can account for the increase in the glycoside concentrations.

Administration, Oral↗

Possible role of adenosine in the relaxant effect of amrinone on guinea-pig ileum.

In isolated segments of guinea-pig ileum, amrinone (0.3 mM-0.3 M) caused a transient contraction followed by a concentration-dependent relaxation. Theophylline (0.1-0.5 mM) mimicked the effects of amrinone but apparently inhibited relaxation induced by the latter. However the total decrease of muscle tension measured in preparations exposed to amrinone before and after theophylline treatment was quantitatively comparable. Dipyridamole (0.1 microM) potentiated the relaxing effect of amrinone. The stimulatory response of the ileum to high concentrations of adenosine (10-50 mM) was abolished by amrinone. In preparations treated with adenosine deaminase (10 U/ml) the basal tone was decreased and both amrinone and theophylline were ineffective. In rat ileum, amrinone exerted a marked relaxing effect that was abolished by adenosine deaminase. Thus amrinone appears to cause relaxation of intestinal smooth muscle from different species by hindering the stimulatory effect of endogenous adenosine. The possible intracellular localization of the amrinone-adenosine interaction site is discussed.

Acetylcholine↗

Amrinone action on guinea-pig isolated stomach fundus.

In the guinea-pig stomach fundus strips, set in cascade, amrinone (3 microM to 0.3 mM) induced contractions which were followed by relaxation only at the highest amrinone concentrations tested (30 mM to 0.3 M). Contractions were transient and scarcely related to the drug concentration used, whereas relaxation was the most pronounced and concentration-dependent effect. The transient contraction elicited by amrinone was abolished by scopolamine, indicating activation of cholinergic receptors, but it was unaffected by low temperature or hemicholinium-3. The relaxing effect induced by amrinone was unaffected by low temperature, by the receptor inhibitors used (scopolamine, phenoxybenzamine, propranolol, methysergide, pyrilamine) and by indomethacin. It was potentiated by dipyridamole (0.1 microM) and completely suppressed by tissue pretreatment with adenosine deaminase (10 U/ml). Inhibition of this effect was also obtained by reducing Ca2+ concentration in the perfusion fluid or by pretreating the preparations with verapamil. These results indicate the involvement of endogenous adenosine in the relaxing effect of amrinone and the requirement of Ca2+ influx through plasma membrane for this effect.

Adenosine↗

Variability of positive inotropic response to acute amrinone administration in chronic cardiac failure.

To determine the factors conditioning the variability of positive inotropic response after intravenous acute amrinone administration, 14 patients with chronic cardiac failure were studied by quantitative M-mode and cross-sectional echocardiography. Six patients had idiopathic dilated cardiomyopathy and 8 patients had severe chronic aortic insufficiency. Myocardial contractility (evaluated as peak arterial systolic pressure/end-systolic volume ratio: PAP/ESV) did not change in patients with idiopathic cardiomyopathy, a significant increase of myocardial contractility occurred in patients with aortic regurgitation only if the control value of PAP/ESV was greater than 1. Mean systolic wall stress decreased significantly in all patients, independent of aetiology of cardiac failure and was the factor determining the improvement of left ventricular performance (evaluated as fractional shortening) in patients without changes in myocardial contractility. Maximum improvement in left ventricular performance occurred 10 minutes after amrinone administration. It is concluded that the possibility of detecting the positive inotropic properties of amrinone in man depends on the aetiology of the cardiac failure and on the basal level of myocardial contractility.

Adult↗

Interaction of amrinone with endogenous adenosine in guinea-pig atria.

In spontaneously beating atria from reserpine-treated guinea-pigs, amrinone (10 microM to 2 mM) induced a positive inotropic and chronotropic effect that was preceded by a transient reduction in contractile force and in frequency. Both the positive and negative effects were concentration-dependent. The inotropic action of amrinone was antagonized by low concentrations of 8-phenyltheophylline that compete with adenosine at R-receptors on plasma membrane without significantly influencing phosphodiesterase activity. Cumulative concentrations of amrinone (1 mM) antagonized the reduction of rate of contraction and amplitude induced by dipyridamole 1 microM in spontaneously beating atria and restored the maximum contractile effect reached in the absence of dipyridamole. In spontaneously beating preparations incubated in the presence of adenosine deaminase (1 u ml-1), amrinone lost its positive effects on the atria and only reduction of rate and contractile force was evident. Both effects were antagonized by scopolamine 1 mM thus indicating their cholinergic nature. Adenosine at 0.1 microM and 0.5 microM significantly inhibited the inotropic effect induced by amrinone (0.03 to 3 mM) and the concentration-effect curves of amrinone obtained in the absence and presence of adenosine clearly indicate a competitive antagonism between the two drugs. Thus the contractile activity of amrinone in spontaneously beating atria from reserpine-treated guinea-pigs originates from a displacement of adenosine from its R-receptor sites in the cardiac cell.

Adenosine↗