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Biomedical subjects

R Latini

Publications and source records attributed to R Latini.

At least 91 records · Page 5Linked to original sources
PubMed1988

Demonstration of a different sensitivity to epinephrine in isolated and in vivo hearts.

Studies in isolated preparations dealing with myocardial effects of catecholamines usually employ epinephrine concentrations 10-1,000 times higher (10(-7)-10(-5) M) than those observed during maximal cardiac adrenoceptor activation in vivo (10(-9)-5 x 10(-8) M) to obtain measurable cardiac responses. The reason for this discrepancy is still unclear, but it may reflect a diminished sensitivity to catecholamines in vitro. The main purpose of this study was to evaluate if a different myocardial sensitivity to epinephrine in vivo and in vitro does exist and to investigate which epinephrine concentrations in vitro mimic the effect of cardiac adrenoceptor activation in vivo. We compared concentration-response curves to cumulative increasing concentrations of of epinephrine, measured by high pressure liquid chromatography, in chloralose anesthetized or pithed rats (in vivo) and in isolated Langendorff perfused rat hearts (in vitro). We found that the amplitude of response to epinephrine was significantly higher in vivo at all concentrations. For example, an increase of 50 beats/min was observed at an epinephrine concentration of 29 +/- 6 nM in chloralose anesthetized, 25 +/- 4 nM in pithed rats and 149 +/- 52 nM in isolated hearts (P less than 0.05 vs. in vivo). Data on contractility closely parallel those on heart rate. These data indicate that, when methodological differences are minimized, there is a marked reduction in the amplitude of the response to epinephrine in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Pharmacokinetics and pharmacodynamics of propafenone during acute and chronic administration.

The pharmacokinetics of propafenone and 5-OH-propafenone and their relationship with the antiarrhythmic action and side effects have been studied in 10 patients with stable, frequent, premature ventricular beats (224-928 premature ventricular complexes/h). Observations were made after a single dose of propafenone 300 mg p.o., and after 1 and 3 months (only 5 out of 10 patients) of therapy with 300 mg t.d.s. After 1 month of treatment the plasma elimination half-life of propafenone (6.7 h) was almost twice as long as after a single dose (3.5 h), and the area under the plasma propafenone concentration-time curve (7620 ng.ml-1.h) was significantly larger than after single dose (3522 ng.ml-1.h); this was also true for the metabolite. The ratio of the AUCs of 5-OH-propafenone and propafenone decreased from the single dose (0.63) to 1 month (0.32). These variables remained stable up to 3 months. Eight patients had greater than or equal to 75% reduction of premature ventricular complexes after 3 days of therapy, and in 7 they were completely suppressed; the response was maintained over 1 to 3 months. Side effects were minor and in no case had the drug to be withdrawn or the dose reduced. Thus, the kinetics of propafenone were time-dependent. Its active metabolite did not accumulate greatly during chronic treatment. The lasting antiarrhythmic effect observed in some patients suggests a b.d.s. regimen instead of t.d.s. dosing in selected patients.

Adult↗
PubMed1988

Selectivity of oral aspirin as an inhibitor of platelet vs. vascular cyclooxygenase activity is reduced by portacaval shunt in rats.

Oral aspirin can be extensively hydrolyzed to salicylate in the stomach and liver before it enters the systemic circulation. "Presystemic" acetylation of platelets may thus occur during aspirin absorption. This may result in concomitant sparing of peripheral vascular cyclooxygenase mainly exposed to salicylate. We tested whether the "biochemical selectivity" of p.o. aspirin as an inhibitor of platelet rather than vascular cyclooxygenase was reduced by elimination of the "first-pass" hepatic metabolism. A portacaval shunt was inserted in anesthetized rats by connecting the portal vein to the inferior vena cava through a heparinized polyethylene "Y" cannula. Sham-operated rats acted as controls. Ninety minutes after recovery from anesthesia rats were given aspirin p.o. (10 mg/kg) and 45 min later serum thromboxane B2 and 6-keto-prostaglandin F1 alpha formation by vascular rings was evaluated by radioimmunoassay. Serum thromboxane B2 was almost suppressed completely in all animals; vascular 6-ketoprostaglandin F1 alpha was reduced significantly (by 40-60% in aorta and vena cava) in rats with the portacaval shunt but not in sham-operated animals. The results in rats with the shunt were similar to those obtained previously after i.v. aspirin. Fifteen minutes after aspirin, plasma levels of unmetabolized drug measured by high-pressure liquid chromatography were significantly higher in rats with portacaval shunt (0.56 +/- 0.16 micrograms/ml; n = 5) than in sham-operated controls (0.16 +/- 0.02 micrograms/ml; n = 5). These findings support directly the role of first-pass hepatic metabolism in the "biochemical selectivity" of p.o. aspirin.

6-Ketoprostaglandin F1 alpha↗
PubMed1988

[Digitalis intoxication in the presence of amiodarone-induced acute hepatitis].

In this report, we describe a case of acute atypical hepatitis during chronic treatment with amiodarone in a patient in which symptoms of digitalis toxicity also developed. The sudden onset of these side effects, whose mechanisms are herein discussed, stresses the importance of a careful monitoring of patients treated with amiodarone.

Aged↗
PubMed1987

Amiodarone induced phospholipidosis. Biochemical, morphological and functional changes in the lungs of rats chronically treated with amiodarone.

Amiodarone, an antiarrhythmic drug, causes pulmonary fibrosis in some patients during chronic treatment but the mechanism is unknown. We studied the effects of amiodarone on pulmonary biochemistry, morphology and function at doses of 25 and 50 mg/kg/12 hr given to rats by gavage for four weeks. Plasma and pulmonary phospholipids were significantly augmented, 13% and 88% respectively, in the group given amiodarone 50 mg/kg/12 hr compared to pair-fed controls. Typical phospholipidosis-like light and electron microscopic alterations were seen in the lung, their severity related to the extent of biochemical changes induced by amiodarone. Pulmonary function tests revealed mild but not significant changes in O2 and CO2 alveolar exchange efficiency and lung compliance (P-V curve) of treated animals in comparison to pair fed controls. Plasma average concentrations of amiodarone and its main metabolite, desethylamiodarone, after four weeks were 2.46 +/- 0.18 and 0.73 +/- 0.13 micrograms/ml, respectively, in the 50 mg/kg/12 hr group. In the same group amiodarone and desethylamiodarone concentrations in lung were 163 +/- 26 and 569 +/- 153 times higher than those in plasma. A highly significant correlation was found between amiodarone concentrations in plasma and lung and phospholipid content in the lung. A subgroup of animals received amiodarone 50 mg/kg/12 hr for 8 weeks. The pulmonary phospholipidosis-like lesions were similar to those observed after one month of treatment, no fibrosis was evident on light microscopic examination.

Amiodarone↗
PubMed1987

Distribution of amiodarone and desethylamiodarone in a patient with acute myocardial infarction after intravenous administration.

The autopsy tissues concentration of amiodarone and desethylamiodarone of a man with acute myocardial infarction treated acutely with intravenous amiodarone is reported. Our data indicate that amiodarone is quickly distributed into all highly perfused tissues after intravenous administration with a high amiodarone/desethylamiodarone ratio. We also report here the autopsy case of a woman who died after 30 days of oral therapy with amiodarone. The increase in heart/plasma ratio of amiodarone and desethylamiodarone concentrations and the decrease in amiodarone/desethylamiodarone ratio after one month of therapy could explain the latency in the antiarrhythmic action of the drug.

Amiodarone↗
PubMed1987

Metabolism of caffeine to 6-amino-5-[N-methylformylamino]-1,3-dimethyluracil in the isolated, perfused liver from control or phenobarbital-, beta-naphthoflavone- and 3-methylcholanthrene-pretreated rats.

Caffeine metabolism to 6-amino-5-[N-methylformylamino]-1,3-dimethyluracil was studied in the isolated, perfused rat liver. The [2-14C]-labelled drug and metabolites were separated by thin-layer chromatography or high-pressure liquid chromatography. The chemical structure of 6-amino-5-[N-methylformylamino]-1,3-dimethyluracil was confirmed by mass spectrometry and it was quantitatively determined by liquid scintillation counting. 6-Amino-5-[N-methylformylamino]-1,3-dimethyluracil is one of the major metabolites of caffeine found in the perfusion medium. The kinetics of caffeine elimination and of the uracil metabolite formation were studied up to 2 h perfusion time using livers from control rats and rats pretreated with phenobarbital, beta-naphthoflavone or 3-methylcholanthrene. Phenobarbital pretreatment did not modify the rate of caffeine elimination or the extent of 6-amino-5-[N-methylformylamino]-1,3-dimethyluracil formation. In contrast, there was a highly significant inducing effect on both drug elimination and formation of the uracil metabolite in perfusions of livers from beta-naphthoflavone- and 3-methylcholanthrene-pretreated animals.

Animals↗
PubMed1987

Pharmacokinetics of enteric-coated aspirin and inhibition of platelet thromboxane A2 and vascular prostacyclin generation in humans.

We evaluated whether an enteric-coated aspirin formulation showed a "presystemic" component in its antiplatelet effect and if so would spare vascular cyclooxygenase. In six healthy volunteers, 30 to 45 minutes after ingestion of 325 mg enteric-coated aspirin, platelet thromboxane A2 generation was inhibited by about 20% before any drug could be detected in the peripheral venous blood. A further decline in thromboxane A2 generation occurred with appearance of aspirin in blood between 60 and 240 minutes. No presystemic component could be detected after 325 mg aspirin tablets. Ten patients undergoing saphenectomy received 325 mg of either aspirin tablet or enteric-coated aspirin; 12 hours later platelet thromboxane A2 and peripheral vascular prostacyclin generation were significantly reduced by 98% and 58%, respectively. The effects of the two aspirin formulations were not different. Aspirin formulations with "presystemic" component in their antiplatelet effect may not necessarily result in sparing of peripheral vascular cyclooxygenase.

Adult↗
PubMed1987

Flecainide distribution in human tissues.

The distribution of antiarrhythmic drugs in human tissues may yield a better understanding of their therapeutic action and side effects. We report tissue distribution of flecainide in a patient who died suddenly while being treated chronically with the drug. Lungs showed the highest concentration of flecainide (143 micrograms g-1 wet tissue); liver, kidney and heart, in decreasing order, have good affinity for the drug. Flecainide was present also in the central nervous system in lower concentrations. The lowest concentration was found in the adipose tissue.

Flecainide↗
PubMed1987

Effects of three new anthracyclines and doxorubicin on the rat isolated heart.

The acute cardiac toxicity of three second-generation anthracycline analogues and doxorubicin was compared in a model of the rat isolated Langendorff perfused heart. The drugs, doxorubicin (DX), 4-epi-doxorubicin (4'EDX), 4-demethoxy-daunorubicin (4DMDR) and 4'-deoxy-doxorubicin (4'dxDX) were infused for 40 min at a concentration of 26 microM into the isolated hearts. All four compounds significantly reduced cardiac work and its first derivative. The time to 50% decrease in work (TW50) was respectively 36, 23, 9 and 7 min for DX, 4'EDX, 4'dxDX and 4DMDR. The three anthracycline derivatives, but not DX, significantly increased coronary resistance. Heart rate was reduced by all compounds compared with baseline, but not compared with controls. Rhythm disturbances were seen with all five hearts perfused with 4DMDR, which stopped beating before 40 min; 2/5 hearts in the 4'EDX group and 1/5 hearts in the 4'dxDX group also stopped before the end of perfusion. All the compounds reached concentrations in the myocardium 8 to 50 times higher than in the perfusing medium. The more cardiotoxic the compound, the higher was its myocardial concentration; a significant correlation was found for all four agents. Noradrenaline was never measurable in the perfusate of control and DX hearts; perfusion with the three anthracycline derivatives caused some release, but the pattern was not clearcut and the maximum concentrations attained in the perfusate were relatively low (less than or equal to 1.6 X 10(-9) M). In conclusion, in the rat isolated perfused heart, the early cardiotoxicity induced by equimolar concentrations of the three anthracycline compounds was greater than that induced by DX and was directly related to drug accumulation in the myocardium. Catecholamines do not seem to have a major role in the development of toxicity in this model.

Animals↗
PubMed1987

Amiodarone and desethylamiodarone tissue uptake in rats chronically treated with amiodarone is non-linear with the dose.

Four groups of rats were given amiodarone chronically at 25, 37.5, 50, 75 mg kg-1/12 h for 3 weeks; on day 21 the animals were killed and blood, plasma, heart, lung, liver and fat were collected and assayed for amiodarone and desethylamiodarone. Amiodarone plasma concentrations ranged from 0.74 to 4.68 micrograms mL-1 and desethylamiodarone from 0.08 to 2.05 micrograms mL-1. Plasma, blood and tissue concentrations of amiodarone and desethylamiodarone increased significantly with the dose. Blood/plasma and tissue/plasma partition ratios of amiodarone and desethylamiodarone increased significantly at the higher doses. Blood/plasma ratio was a good predictor of tissue/plasma ratios of amiodarone and its metabolite, except in fat. Total phospholipid concentrations in lung were correlated with amiodarone and desethylamiodarone concentrations in plasma, blood and lung.

Amiodarone↗
PubMed1987

[Hypotensive efficacy of verapamil alone and in combination with a diuretic in the treatment of essential hypertension in geriatric patients].

To evaluate the hypotensive efficacy of Verapamil alone and combined with diuretic, in the treatment of essential hypertension in elderly patients, we studied 54 patients, mean age 67.2 +/- 4.7 years, with essential hypertension, I-II WHO class. After a two-week wash-out from previous hypotensive therapies, patients were divided, at random, into three groups and, in double-blind conditions; they were treated as follows: the first group was treated with Verapamil (V) slow-release 240 mg/die, the second group with Chlorthalidone (C) 50 mg/die and the third group with the combination of Verapamil slow-release 240 mg/die and Chlorthalidone 50 mg/die (V + C). In the first group, the therapy (V) statistically reduced (p less than 0.001) either PAS or PAD values in supine position, (respectively -13 +/- 9 mmHg and -12 +/- 4 mmHg) and PAS-PAD values in upright position (respectively -16 +/- 3 mmHg and -10 +/- 3 mmHg). In the group treated with C, a statistically significant reduction (p less than 0.001) of PAS (-12 +/- 3 mmHg in supine position and -16 +/- 3 mmHg in upright position) and of PAD (-11 +/- 5 in supine and -9 +/- 4 mmHg in upright position). In the third group, V + C treatment induced a statistically bigger reduction of PAS and PAD (p less than 0.001) than that of the other two groups either in supine (-24 +/- 3 and -21 +/- 5 mmHg, respectively) or in upright position (-26 +/- 4 and -20 +/- 5 mmHg, respectively). Three patients interrupted the therapy for scarse compliance (I-II group).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗