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Biomedical subjects

M Prosdocimi

Publications and source records attributed to M Prosdocimi.

At least 37 records · Page 2Linked to original sources
PubMed1992

Protective role of heparin on in vitro functional aortic response in Watanabe heritable hyperlipidemic rabbits.

The effects of prolonged in vivo heparin treatment upon vasomotor responses and content of cholesterol and energy related compounds were studied in isolated thoracic and abdominal aortas from Watanabe heritable hyperlipidemic (WHHL) rabbits. Unfractionated heparin was administered subcutaneously (2 mg/kg twice a day) to 3-month-old WHHL rabbits for a period of 6 months. A group of WHHL rabbits was treated with saline solution and considered as control. Aortic cholesterol infiltration and serum cholesterol were not significantly decreased by the prolonged heparin treatment. In heparin-treated WHHL rabbits, the in vitro aortic endothelium-dependent relaxation produced by acetylcholine or calcimycin (A 23187) was greater than in saline-treated WHHL group. ATP-induced aorta relaxation (endothelium-dependent and endothelium-independent) did not vary significantly in the two groups of WHHL rabbits, even after mechanical removal of endothelium. Also the noradrenaline-induced aorta contraction did not vary between the two groups of WHHL rabbits. No significant variation in energy-related compounds (except for ADP) was found in the aortic arch. These results suggest that heparin produces a protective effect on aortic tissue by acting mainly at endothelial level.

Adenosine Triphosphate↗
PubMed1992

Functional responses of hindlimb circulation in aged normal and WHHL rabbits.

Normal New Zealand and Watanabe heritable hyperlipidemic (WHHL) rabbits, about 24 months old, were prepared, under anaesthesia, for recording blood pressure and hindlimb blood flow. Changes in hindlimb vascular resistance were measured after local intra-arterial bolus injection of increasing doses of acetylcholine, bradykinin, serotonin, sodium nitroprusside and phenylephrine. In WHHL rabbits basal hindlimb blood flow was reduced (from 22.6 +/- 3.0 to 12.5 +/- 1.8 ml/min; P less than 0.05) and hindlimb vascular resistance was increased (from 4.6 +/- 0.5 to 8.2 +/- 1.5 mmHg/ml per min; P less than 0.05). No difference was observed in response to acetylcholine, serotonin, sodium nitroprusside and phenylephrine. The only marked alteration found in WHHL rabbits was a clear deficit to bradykinin stimulation. Morphological analysis, using scanning and transmission electron microscopy, indicated a clear damage of the femoral artery, like the presence of atherosclerotic plaques, and an abnormal distribution of patent microvessels in the WHHL muscles of the leg. Peripheral circulation in WHHL rabbits shows some peculiar features, like increased basal vascular resistance and a selective impairment of bradykinin responses. Together with these abnormalities, it seems that responses to various other dilating or contracting agents are normal, suggesting that in this interesting animal model of atherosclerosis the alterations are more specific than in other models.

Acetylcholine↗
PubMed1992

Cloricromene antagonizes antidipsogenic effects induced by endotoxin, but not by TNF alpha, in the rat.

Intravenous (640 micrograms/kg) or intracerebroventricular (0.5 and 1 microgram) injection of Escherichia coli endotoxin (LPS) causes inhibition of water intake induced by 24 hour period of water deprivation in the rat. Tumor necrosis factor alpha (TNF-alpha; 20 and 40 ng/rat) given into the lateral cerebral ventricle (i.c.v.) causes effects similar to those observed after LPS. Cloricromene, given either intravenously (1 and 2 mg/kg) or i.c.v. (250 and 500 ng), abolished the antidipsogenic effect induced by LPS (administered both i.v. and i.c.v.). Cloricromene (2 mg/kg, i.v. or 500 ng/rat, i.c.v.), on the contrary, did not modify the antidipsogenic effects induced by TNF-alpha. These data indicate that peripherally injected cloricromene (as well as that i.c.v. injected) antagonizes the effects of mediators of LPS on sites regulating thirst and suggest that cloricromene's action may be due to inhibition of brain TNF-alpha formation induced by LPS.

Animals↗
PubMed1992

Effect of cloricromene during ischemia and reperfusion of rabbit hindlimb: evidence for an involvement of leukocytes in reperfusion-mediated tissue and vascular injury.

The involvement of polymorphonuclear leukocytes (PMN) in reperfusion-mediated vascular injury was studied in a model of ischemia and reperfusion in rabbit hindlimb. Ischemia was induced by 4-h occlusion of the left iliac artery followed by 4-h reperfusion. Plasma creatine kinase (CK) and lactate dehydrogenase (LDH) activities, hindlimb vascular resistance (HVR), and myeloperoxidase (MPO) activity in the postischemic extensor digitorum longus (EDL) muscle were measured to evaluate the extent of vascular and skeletal muscle injury. In addition, the ischemia/reperfusion-induced injury of the hindlimb vasculature was evaluated by electron microscopy. Ischemia and reperfusion (n = 10) was associated with an increase in CK (6,380 +/- 1,346 U/L, p < 0.05) and LDH (552 +/- 76 U/L, p < 0.05) activities which were significantly greater than those observed in sham-operated control animals (CK 1,651 +/- 207 U/L, LDH 246 +/- 14 U/L; n = 6). HVR in sham-operated animals decreased by 20 +/- 3%, but increased in the ischaemic group by 56 +/- 16% (p < 0.05). MPO activity of EDL muscle increased from 7.3 +/- 3.9 U per muscle (sham) to 28.0 +/- 5.9 U per muscle (p < 0.05) after ischemia and reperfusion. Morphologic analysis did not show any alteration in the microvascular bed of the hindlimb. Moreover, 1 mg/kg/h intravenous (i.v.) cloricromene, an antithrombotic drug that inhibits superoxide anion production as well as PMN adhesion to endothelium, reduced the increase in plasma CK and LDH and the increase in MPO and HVR observed in animals subjected to hindlimb ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Effects of cloricromene on ischemia-reperfusion myocardial damage in the rabbit.

Cloricromene, a compound with several biological activities which suggest a therapeutic role in thrombosis or ischemic disease, has been studied for its effects on the extension of myocardial damage and the production of oxygen free radicals during periods of ischemia and reperfusion. In twenty rabbits the left anterior descending coronary artery (LAD) was occluded and cloricromene (3.6 micrograms/kg/min; n = 10) or placebo (n = 10) were continuously infused. After 50 min the artery was reopened and after 20 min of reperfusion a biopsy was obtained from the anterior wall of the heart in the LAD area and from the posterior wall (control myocardium) prior to sacrifice. Both samples were used for chemiluminescence measurement (free-radical production) and ultrastructural studies. In the placebo group all rabbits showed ST-segment changes during ischemia and reperfusion arrhythmias, while in the cloricromene group there were transient ST elevations in 4 animals which reverted at higher infusion rates of the drug. The chemiluminescence values were 18,017 +/- 1,956 and 8,583 +/- 918 cpm/mg protein (p < 0.001) in the anterior and posterior walls of the left ventricle, respectively, for the placebo group, and 7,767 +/- 992 and 8,333 +/- 832 cpm/mg protein (NS), respectively, for the cloricromene group. The ratio between the anterior and posterior wall was 2.27 +/- 0.37 for the placebo group versus 0.95 +/- 0.11 for the cloricromene group (p < 0.001). In ultrastructural studies, the anterior wall in the placebo group showed irreversible myocyte injury and infarction as well as mitochondrial damage. Samples from the cloricromene-treated group showed, in general, preservation of myocyte architecture or minor signs of injury. These results illustrate clearly the protective effect of cloricromene during damage induced by ischemia and reperfusion in the rabbit.

Animals↗
PubMed1992

Reduction of myocardial damage by cloricromene during ischemia-reperfusion in the rabbit.

We studied the effect of cloricromene on myocardial damage during ischemia and reperfusion. The left anterior descending coronary artery was occluded in 20 rabbits and cloricromene (6.2 micrograms/kg/min) (n = 10) or placebo (n = 10) were continuously infused. After 10 minutes of occlusion, a first biopsy was obtained from the apex. After 30 minutes, the artery was reopened and after 10 minutes a second biopsy was taken. Both samples were used for chemiluminescence and electron microscopy. The group given placebo showed displacement of the ST segment throughout the ischemic period and arrhythmias during reperfusion; while, in the group given cloricromene, there were transient ST segment elevations in 5 animals, which reverted as the infusion was increased. The chemiluminescence values were 7100 +/- 1300 cpm/mg protein and 14900 +/- 2300 (p less than 0.01) for the first and second biopsies of the control group and 5900 +/- 900 and 6100 +/- 900 (NS) for the first and second biopsies of the cloricromene-treated group. In the group given placebo, the second biopsy showed early signs of irreversible myocyte injury and infarction, whereas samples from the group given cloricromene showed a preservation of myocyte architecture. During ischemia, the percentage of normal mitochondria was lower in the placebo group (p less than 0.0001); and, on reperfusion, the percentage of severely damaged mitochondria was increased in the placebo group (p less than 0.0001). The direct addition of cloricromene in vitro to myocardial homogenates did not reduce hydroperoxide-induced chemiluminescence.

Animals↗
PubMed1991

Polymorphonuclear leukocyte-dependent modulation of platelet function: effect of cloricromene.

Cloricromene inhibits the activation of platelets and polymorphonuclear leukocytes (PMN) induced by specific stimuli. We report here that cloricromene caused a concentration-dependent reduction of platelet aggregation, beta-thromboglobulin (beta-TG) release and cytoplasmic Ca2+ movements induced by PMN stimulated with N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP), and enhanced the inhibitory action of unstimulated PMN on platelet responses to the stable endoperoxide analog U46619. These effects may be of pharmacological interest in view of the multiple interactions between platelets and leukocytes that occur in thrombotic and inflammatory diseases.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1991

Acute carotid artery occlusive thrombosis and its pharmacological prevention in the rabbit.

A simple and reproducible method to induce an occlusive thrombus in rabbit carotid artery is reported. Rabbits were anesthetized and prepared to record arterial pressure, heart rate, and carotid blood flow. A critical stenosis of a damaged carotid artery was obtained using an external plastic cylinder. Complete occlusion occurred within 6 to 12 minutes, as measured by the decrease in blood flow. Both stenosis of the vessel and deliberate damage (clamping by surgical forceps) were found essential to occlusion. Occlusion was prevented by administration of heparin (200 IU/kg), tissue plasminogen activator (300 micrograms/kg), iloprost (10 micrograms/kg) or the synthetic thrombin inhibitor, FPRCH2Cl (0.5 mg/kg), while ASA (100 mg/kg) was uneffective. The procedure permits an easy and rapid evaluation of thrombus formation and of anti-thrombotic drugs affecting the hemostatic process.

Acute Disease↗
PubMed1991

Impaired heart rate variability in patients with chronic Chagas' disease.

Spectral analysis of heart rate variability was used to investigate the possible alteration in sympathovagal control of heart rate in patients with Chagas' disease. The study included 31 subjects, divided into three groups: controls, Chagas' 1 (subjects with only positive serology for Chagas' disease) and Chagas' 2 (subjects with positive serology and electrocardiographic abnormalities that are usually found in this disease). The subjects were studied during rest, while standing, and during handgrip exercise. With this approach, the low frequency (approximately 0.1 Hz) spectral component of R-R interval variability is considered to be a marker primarily of sympathetic activity, whereas the high frequency (approximately 0.25 Hz) component, which is related to respiration, seems mainly to reflect vagal activity. We observed significant (p less than 0.05) differences among the three groups during standing: although in the control subjects the low-frequency component increased (delta = 30 +/- 5 normalized units, nu), there was no increase in Chagas' 1 (delta = -1 +/- 8 nu) and Chagas' 2 (delta = -2 +/- 8 nu) patients. During handgrip exercise, another test that is capable of exciting sympathetic outflow, there was an increase of low frequency only in control subjects. These results confirm the occurrence of quantitative and assessable abnormalities in the neural control of heart rate variability in Argentinian patients with chronic Chagas' disease, even in the absence of heart failure.

Chagas Disease↗
PubMed1991

Inner ester derivatives of gangliosides protect autonomic nerves of alloxan-diabetic rats against Na+, K(+)-ATPase activity defects.

Bovine brain gangliosides have been shown to prevent decay in Na+,K(+)-ATPase activity in sciatic and optic nerves of alloxan- and streptozotocin-diabetic rats. In the search for a drug with greater bioavailability and increased incorporation into neural tissue, ganglioside inner ester derivatives (AGF1) were recently developed. We evaluated the effect of AGF1 treatment on Na+,K(+)-ATPase activity in homogenates of vagus nerve from alloxan-diabetic rats (100 mg/kg s.c.). Animals were treated with AGF1: 10 mg/kg 6 days/week i.p., or 30 mg/kg biweekly i.p. Treatment began 10 d post-alloxan and continued for 8 consecutive weeks. Normal age- and sex-matched rats were used as controls. Alloxan intoxication produced a 39% decrease in Na+,K(+)-ATPase activity of the vagus nerve, which was completely restored (96-97% recovery) by both AGF1 regimes. Results suggest that ganglioside inner ester derivatives may be used in the clinical setting for the management of diabetic autonomic neuropathy.

Animals↗
PubMed1991

Protective effect of cloricromene, a coumarine derivative, in hypovolemic hemorrhagic shock in the rat.

Hypovolemic hemorrhagic shock was induced in male anesthetized rats by intermittently withdrawing blood from an iliac catheter over a period of 20 min until mean arterial pressure (MAP) fell to 30 mm Hg. Survival rate, MAP, plasma myocardial depressant factor (MDF) activity and plasma levels of both TxB2 and 6-keto PGF1 alpha were then evaluated. Cloricromene (0.5, 1, and 2 mg/kg) or an equal volume of vehicle (0.9% NaCl solution) were injected intravenously 5 min after the end of the bleeding. Hemorrhagic shocked rats showed enhanced plasma levels of MDF, TxB2 and 6-keto PGF1 alpha. All vehicle-treated rats died within 25 min. Cloricromene (1 and 2 mg/kg) given curatively significantly increased survival rate and blunted the rise in plasma MDF and TxB2. Moreover, cloricromene reversed the severe hypotension and the ST-segment elevation occurring during hemorrhagic shock. The data suggest that cloricromene exerts beneficial effects in experimental hypovolemic shock, probably reversing myocardial failure.

6-Ketoprostaglandin F1 alpha↗
PubMed1990

Cloricromene inhibits the activation of human platelets by ADP alone or in combination with adrenaline.

Cloricromene may inhibit platelet activation induced by several agonists. In this study we report that ADP and adrenaline synergistically promote platelet aggregation and cytoplasmic Ca2+ movements in aequorin-loaded platelets. Cloricromene caused dose-dependent reduction in platelet aggregation and cytoplasmic Ca2+ movements after exposure of the cells to a low concentration of ADP (2 microM) or to a combination of ADP (2 microM) and adrenaline (10 microM). Cloricromene's inhibitory action may be of considerable pharmacological interest since platelet activation by a combination of agonists may mimic the conditions under which thrombosis occurs in vivo.

Adenosine Diphosphate↗
PubMed1990

The coumarin derivative AD6 inhibits the release of arachidonic acid by interfering with phospholipase A2 activity in human platelets stimulated with thrombin.

AD6 is a coumarin derivative which is able to inhibit platelet aggregation and release due to various agonists as adrenaline, PAF, Ca++ ionophore and others. It has been demonstrated that this compound reduces the production of free arachidonate and diglyceride from human platelets pulse-labeled with radioactive arachidonic acid thus suggesting a possible interference with the activity of phospholipase A2 and/or phospholipase C. The present report indicates that the drug has no effect on the increase of the labeling of phosphatidic acid which takes place when platelets pulse-labeled with arachidonic acid are stimulated with thrombin. Furthermore, AD6 is not able to cause changes on the metabolism of phosphoinositides monitored using platelets pre-labeled with [3H] inositol. These observations exclude the possibility that AD6 interferes with phospholipase C activity. Experiments with platelets pulse-labeled with arachidonate suggest that AD6 inhibits phospholipase(s) A2 activity or modulate negatively one or more processes involved in its activation.

Arachidonic Acid↗
PubMed1990

Effects of sympathetic activation on heart rate variability in Chagas' patients.

To assess the alterations present in neural control of heart rate in patients with signs of Chagas' disease we studied the spectral components of heart rate variability in 10 Chagas' patients, without cardiac failure, and in 10 control subjects during supine and standing position. Chagas' patients during standing did not present the changes in the spectral components of heart rate variability which normally accompany sympathetic activation and vagal withdrawal.

Arrhythmias, Cardiac↗