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L Favalli

Publications and source records attributed to L Favalli.

At least 37 records · Page 2Linked to original sources
PubMed1986

Myocardial contractility and heart pharmacokinetics of adriamycin following a single administration in rat.

A single administration of adriamycin (DXR) 6.0 mg/kg i.v. to rats brings about a biphasic impairment of the maximal myocardial contractile performance, measured as dF/dt of ex vivo isolated atria incubated in the presence of calcium concentrations varying up to 12 mM. The initial impairment of the contractile performance peaks 1 week after DXR administration and recovers within 3 weeks (acute phase of cardiotoxicity). After this time and up to the end of the observation period (8 weeks after treatment), delayed cardiotoxicity occurs, showing a progressive and irreversible impairment of the contractile performance of the atria. This behaviour parallels the previously shown ECG and morphological abnormalities. Tissue determinations of DXR showed that the drug is present in myocardium during the acute phase of cardiotoxicity, while the metabolite adriamycinol is not detectable 1 week after DXR administration. These data show that the presence of DXR and/or metabolites in heart muscle is not necessary for the delayed form of cardiotoxicity to become apparent and suggest that this form of cardiotoxicity is related to a mechanism different from that involved in acute cardiotoxicity.

Animals↗
PubMed1986

Effect of suloctidil on cerebral circulation patterns of conscious rabbits.

Suloctidil (SUL) produces calcium antagonistic and antispasmodic effects on peripheral and pial arteries. The present studies were performed with the aim of evaluating the action of SUL on cerebral blood flow (CBF), which was taken as an index for evaluating the cerebral circulation. The drug was administered by rapid intravenous injection to groups of unanaesthetized rabbits at doses of 100-200 micrograms/kg and by intravenous infusion at doses of 10-20 micrograms/kg/min. In other experiments, SUL was chronically administered p.o. to normal rabbits and to rabbits receiving Kritchevsky's atherogenic diet; the daily dose of the drug was about 16 mg/kg. Cerebral blood flow and its compartmental distribution were determined in unanaesthetized animals by the intracarotid 133Xe clearance method. The data demonstrate that the atherogenic diet brings about a significant impairment of CBF; SUL is inactive in normal rabbits, while in the atherosclerotic rabbits it induces a pronounced increase in cerebral blood flow in the grey matter and an enhancement of the corresponding circulatory compartment. These changes are less evident in the white matter.

Anesthesia↗
PubMed1985

Flunarizine, cerebral blood flow and reversion of experimental atherosclerosis in rabbit.

Flunarizine is a calcium entry blocker active in the treatment of peripheral vascular disease. The present study was performed to evaluate the effect of flunarizine on cerebral blood flow (CBF) and lipidic patterns in rabbits with dietary experimental atherosclerosis. Since it is well known that there is only a slight correlation between the severity of atheromatous lesions ascertained at necroscopy and the severity of clinical symptoms of cerebral vascular disease, the effect of the drug was assessed by measuring the CBF and compartmental distribution of blood flow in unanaesthetized rabbits by the intracarotid Xe-133 clearance method; blood pressure, plasma lipids and tissue fat infiltration were also checked. An atherogenic diet brings about significant impairment of CBF. Flunarizine is inactive in normal rabbits if chronically administered at the daily dose of 10 mg/kg p.o. In atherosclerotic rabbits chronic treatment with flunarizine induced a pronounced increase in cerebral haemodynamic parameters. Arterial pressure and blood pCO2 were not significantly modified. Lipidic patterns were not markedly improved by flunarizine treatment in comparison with values for atherosclerotic animals. These data demonstrate that flunarizine treatment counteracts the haemodynamic effects of cerebral atherosclerosis. The pronounced activity on the cerebral vessels is accompanied by a weak antilipaemic effect.

Animals↗
PubMed1983

Role of the fast-exchanging calcium compartment in the early cardiotoxicity of anthracycline analogs.

Two new anthracycline analogs, 4'-epi-doxorubicin and 4'-deoxydoxorubicin, were tested for their cardiotoxicity and their activity on calcium turnover in guinea pig heart. The df/dt was used as an index of contractile force; calcium turnover was studied by means of a radioisotopic technique. 4'-Epi-doxorubicin was found less cardiotoxic than doxorubicin, whereas 4'-deoxydoxorubicin was found almost completely devoid of cardiotoxicity. The different cardiotoxic activity was found to be linearly correlated with the relative capacity to inhibit the fast-exchanging calcium compartment in cardiac muscle: doxorubicin greater than 4'-epi-doxorubicin greater than 4'-deoxydoxorubicin. This result supports that the inhibition of calcium exchange is involved in development of the early cardiotoxicity of anthracyclines.

Animals↗
PubMed1983

Interaction between doxorubicin and mitomycin C on mortality and myocardial contractility in guinea pig.

The present investigations were carried out in guinea pig to ascertain whether mitomycin C has a direct cardiotoxic effect or interacts with doxorubicin-induced cardiotoxicity. I.p. administration of mitomycin C did not modify the survival rate up to 30 days, whereas the combined administration of doxorubicin and mitomycin C significantly decreased the survival time in comparison to the doxorubicin-treated group. On isolated atria, mitomycin C did not cause significant inhibition of the contractile force or an enhancement of the doxorubicin-induced negative inotropic effect. These results do not support the possibility that mitomycin C potentiates the acute cardiotoxic effects produced by doxorubicin.

Animals↗
PubMed1980

Relationship between the effect on calcium turnover and early cardiotoxicity of doxorubicin and 4'-epi-doxorubicin in guinea pig heart muscle.

Doxorubicin and 4'-epi-doxorubicin, two anthracycline derivatives with different cardiotoxic effects in experimental models, were found to decrease myocardial contractility in isolated guinea pig atria by significantly modifying calcium turnover. This effect seems to be mainly localized on the fast exchanging membrane-bound calcium, while these drugs do not significantly influence the intracellular stores of calcium. 4'-epi-doxorubicin, which induces a less negative inotropic effect than doxorubicin, produces a smaller inhibition of calcium turnover. This supports the hypothesis that the inhibition of calcium turnover and particularly of the fast exchanging calcium compartment is a general mechanism involved in the early anthracycline-induced cardiotoxicity.

Animals↗
PubMed1980

Method for the determination of cerebral blood flow in conscious rabbits.

A procedure for the determination of cerebral blood flow by the local clearance method after intracarotid injection of 133Xe in the conscious rabbit is described. The inert radioactive indicator is injected into a permanent nylon catheter equipped with a two-way Gordth's needle inserted into the common carotid artery and filled with heparin, emerging behind the shoulders of the animals. All branches of the homolateral common carotid artery except the internal carotid artery were ligated. Studies of the distribution of colored tracers (dark blue ink) and radioactive tracers (99mTc albumin microspheres) show that the main localization of the injected indicator is within the homolateral hemisphere. Brain to blood partition coefficients of 133Xe are worked out for rabbit's gray matter (0.576 +/- 0.048) and white matter (0.808 +/- 0.023). The slope method for first and second component of the wash-out Xenon curve is used for CBF calculations. CBF determinations in 9 normal rabbits result in 84.27 +/- 5.59 and 16.69 +/- 2.44 ml/min x 100 g tissue, respectively, for the fast and slow component. Significant changes do not occur in serial determinations within 2 hr.

Anesthesia↗
PubMed1980

Uptake and intracellular distribution of lanthanum.

The present investigation of the cellular distribution of lanthanum was undertaken in order to control the validity of the "Lanthanum method" used for the study of the cell calcium compartments. The presence of lanthanum was evaluated in the isolated guinea-pig heart and its subcellular fractions perfused with a lanthanum-containing Tyrode solution. Lanthanum was determined by instrumental neutron activation analysis. Under the adopted experimental conditions (30-min incubation in the presence of 12.5 microM lanthanum), lanthanum is carried across the cell membrane and is taken up by subcellular organelles. These results confirm the limited validity of investigations based on of the "Lanthanum method".

Animals↗
PubMed1977

Experimental investigations on the contraction induced by lead in arterial smooth muscle.

Previous observations suggested that the turnover of tissue calcium might be involved in the mechanism of smooth muscle contraction induced by lead. In the present investigations, the effect of lead on calcium exchangeability has been studied in the isolated rat tail artery. Experimental results suggest that the mechanism of lead action might be identified with a tissue calcium accumulation and with a lead-to-calcium competition. Evidence exists that the site of action is located in the cell membrane, where lead inhibits the processes of calcium extrusion, and in the intracellular calcium stores, whose calcium binding capacity is lowered; both processes induce an increase of the cellular exchangeable calcium available for contraction.

Animals↗
PubMed1977

Effect of lanthanum on the turnover of calcium in rat uterus.

Previous investigations suggest that lanthanum might enter uterine smooth muscle cells and work as intracellular calcium displacing agent. The present investigation had been carried out in order to confirm if lanthanum develops an intracellular effect. Experiments show that lanthanum brings about a marked increase of the intracellular calcium; the comparison of the uptake and of the wash-out curve of 45Ca shows that lanthanum induces a lowering of the rapid phase of 45Ca release from rat uterus, while the uptake of the labelled ion is not modified or is even enhanced. The present data demonstrate that the action of lanthanum in rat uterus is limited to the cell membrane, whose calcium extruding properties are inhibited.

Animals↗
PubMed1977

[Direct effect of reserpine. II. Response of the rat vas deferens to calcium].

It has been shown that reserpine competitively antagonises the response of the isolated rat vas deferens to Ca2+. It has also been shown that reserpine does not modify uptake of Ca2+ from the external medium. On the basis of the results obtained and bearing in mind the uncoupling effect of reserpine on oxidative phosphorylation, it is suggested that reserpine owes its "direct" action to reduced availability of Ca2+ for contraction due to metabolic block.

Animals↗
PubMed1975

Microbiologic and pharmacologic properties of a new ampicillin derivative: Ampicillin-guaiacolsulfonate.

Ampicillin-guaiacolsulfonate, a new derivative of ampicillin, preserves the antibacterial properties of ampicillin, is suitable for infection owing to its good water solubility and it has far higher stability in dry state than has sodium ampicillin. Ampicillin-guaiacolsulfonate is better orally absorbed in rabbit than is ampicillin. In vitro experiments carried out with the model system by Rosano and Schulman, and measurements of the intestinal absorption in the everted sac jejunal preparation, carried out with 14C-labelled compounds, demonstrate that the new ampicillin derivative is better absorbed by the intestine because of an increase in the intestinal permeability of the molecule itself.

Ampicillin↗