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Biomedical subjects

G Ambrosio

Publications and source records attributed to G Ambrosio.

At least 91 records · Page 5Linked to original sources
PubMed1993

Angiotensin II directly stimulates release of atrial natriuretic factor in isolated rabbit hearts.

BACKGROUND: Previous studies have shown that infusion of angiotensin II (Ang II) increases plasma concentrations of atrial natriuretic factor (ANF) in vivo. This phenomenon has been considered secondary to the effects of Ang II on cardiac and systemic hemodynamics. The present study was designed to assess whether Ang II may exert a direct stimulatory effect on ANF release from the heart independent of changes in hemodynamics. METHODS AND RESULTS: Isolated rabbit hearts were perfused in the Langendorff mode. Heart rate, coronary flow, and atrial and left ventricular (LV) volumes were kept constant. After stabilization, Ang II was infused intracoronary at increasing doses (10(-11) to 10(-8) M) in nine hearts and at a single dose of 10(-10) M in 10 hearts. Each infusion lasted for 5 minutes and was followed by a 10-minute washout period. Four hearts received vehicle alone for 80 minutes. Ang II induced a dose-dependent increase in coronary perfusion pressure and in LV developed pressure. ANF release, measured by radioimmunoassay on the extracts of the cardiac effluent, also increased during Ang II infusion and returned to the basal values during the 10-minute washout period. In the control group, coronary perfusion pressure, LV developed pressure, and LV end-diastolic pressure did not change appreciably over the observation period, whereas ANF release progressively decreased during perfusion. CONCLUSIONS: Ang II can directly stimulate cardiac release of ANF in isolated rabbit hearts independently of changes in hemodynamics.

Analysis of Variance↗
PubMed1993

Short-term and long-term role of platelet activating factor as a mediator of in vivo platelet aggregation.

BACKGROUND: Platelet activating factor (PAF) is a phospholipid released upon stimulation by a variety of cells and has been implicated in several pathophysiological events such as asthma and inflammatory diseases. However, although the ability to aggregate platelets in vitro was the first biological activity ascribed to PAF, its role in contributing to the in vivo formation of arterial thrombi has not been thoroughly clarified. METHODS AND RESULTS: Intravascular platelet aggregation was initiated in two different animal models of arterial stenosis and endothelial injury. An external constrictor was positioned around rabbit carotid arteries and canine coronary arteries. After placement of the constrictor, a typical pattern of flow developed in the stenotic vessels. This pattern of flow, characterized by progressive reductions of carotid or coronary blood flow followed by spontaneous or induced restorations of flow (cyclic flow variations, CFVs), is related to recurrent platelet aggregation at the site of the stenosis followed by dislodgment of the thrombus. After observing CFVs for 30 minutes, BN52021 (up to 1.2 mg/kg), a potent and selective PAF antagonist, was given intravenously to rabbits (n = 12) and dogs (n = 10). BN52021 completely inhibited CFVs in 10 of 12 rabbits, whereas it was relatively ineffective in abolishing CFVs in dogs (only 2 of 10 animals inhibited). This different effect of BN52021 was not explained by too small a dose of the drug to achieve a complete blockade of PAF receptors in dogs, since ex vivo platelet aggregation was completely inhibited in both rabbits and dogs in response to exogenous PAF at concentrations up to 10(-5) mol/L. In a second group of 10 dogs, the hypothesis that PAF may become an important mediator of CFVs in dogs only several hours after endothelial injury was tested. After 30 minutes of baseline CFVs, these animals received a bolus of BN52021 up to 1.2 mg/kg. After this treatment, CFVs were completely abolished in 2 of 10 animals. The remaining 8 dogs were followed for an additional 8-hour period, at the end of which a second bolus of BN52021 was given. At this time, BN52021 was effective, as CFVs were abolished in 6 of 8 animals. These effects of BN52021 at 8 hours were not the consequence of a cumulative dose of the compound, since ex vivo platelet aggregation in response to PAF returned to baseline values immediately before administering the second dose. To identify possible sources of PAF other than aggregating platelets at the site of arterial stenosis, dogs in a third group were killed after 30 minutes (n = 7) and after 8 hours (n = 8) of CFVs. Histological sections of the stenotic coronary artery showed a marked leukocyte infiltration in these arterial segments after 8 hours of CFVs, whereas sections from dogs killed after 30 minutes showed only moderate or no infiltration. CONCLUSIONS: These data demonstrate that PAF plays an important role as a mediator of platelet aggregation in vivo in rabbits and dogs. In the canine model, PAF appears to become more important after leukocyte infiltration of the arterial wall, as it may contribute to initiating enough platelet activation to lead to cyclic flow variations at sites of arterial stenosis and endothelial injury. Data from the present study suggest that PAF antagonists may be used as antiplatelet agents.

Animals↗
PubMed1993

[Anti-angina activity of potassium-channel activators].

Recently, a new class of drugs has been developed with unique properties with regard to cardiovascular pharmacology: K(+)-channel openers. The increased K+ efflux from smooth muscle cells induced by these drugs is accompanied by a reduced intracellular availability of free Ca++, which in turn induces vascular relaxation. This property is currently being exploited to achieve peripheral and coronary artery dilatation in patients with ischemic heart disease. Cromakalim, pinacidil, and nicorandil, are the most extensively investigated agents in this class. Nicorandil, in addition to its K(+)-channel opener property, also shows a nitrate-like activity on guanylate cyclase of vascular smooth muscle cells. Clinical trials demonstrate that chronic administration of nicorandil can significantly increase exercise tolerance in patients with coronary artery disease. In experimental studies, this drug has also shown protective effects against myocardial injury induced by ischemia and reperfusion, by mechanisms partly independent of its vasodilating properties. These results suggest that K(+)-channel openers may have a relevant place in the pharmacological treatment of patients with ischemic heart disease.

Angina Pectoris↗
PubMed1993

Hindbrain hernia headache and syncope in type I Arnold-Chiari malformation.

We describe two young women affected with syncopal episodes and occipital headache exacerbated by cough, sneezing, rising, or effort. MRI revealed in both patients type I Arnold-Chiari malformation. A craniospinal pressure dissociation with brainstem compression may be involved in the pathogenesis of headache and syncope.

Adult↗
PubMed1993

Cerebellar vermis hypoplasia in a case of cri-du-chat syndrome.

We describe a 6-year-old child who presented the phenotype of cri-du-chat disease. The study of her caryotype confirmed an interstitial deletion of the short arm of chromosome 5. The neurological examination showed mental retardation, behavioral disturbances and features of cerebellar and cortico-spinal impairment. The MRI scan of the brain showed hypoplasia of the vermis associated with dysgenesia of the corpus callosum. This is the first report of vermian hypoplasia in cri-du-chat disease. We suggest that the most likely pathogenesis of this malformation is a midline dysraphia.

Cerebellum↗
PubMed1993

Hibernating and stunned myocardium.

The term "hibernating" myocardium has been introduced to indicate the presence of regional asynergy due to persistent hypoperfusion, which can be reversed after revascularization. The mechanisms underlying the prolonged functional adaptation of myocardial cells to hypoperfusion are still not clear, although preliminary experimental data indicate that a reduced availability of intracellular Ca++ may play an important role. The identification of hibernating myocardium may have therapeutic implications, since it has been demonstrated that the revascularization of hibernating myocardial territories may lead to regional and global improvement of systolic left ventricular function. The noninvasive identification of hibernating myocardium can be accomplished by positron emission tomography, which demonstrates the presence of preserved metabolic activity in hibernating myocardial territories. However, exercise 201thallium scintigraphy, using the reinjection technique, with a quantitative regional analysis of 201thallium uptake, has also been reported to provide information comparable to that obtained by positron emission tomography. "Stunning" of the myocardium indicates a condition of transient impaired regional systolic function, following an episode of ischemia. The mechanisms determining the slow recovery of function after ischemia are still not completely understood. Experimental data suggest in this case a reduced Ca++ affinity of the myofibrils and a reduced maximal calcium-activated force.

Animals↗
PubMed1993

The in vivo antiplatelet effects of thromboxane A2 synthase inhibitors are potentiated by simultaneous thromboxane A2/prostaglandin H2 receptor blockade.

The aim of the present study was twofold: 1) to assess whether inhibition of thromboxane A2 (TxA2) synthase exerts more potent antiplatelet effects when applied concomitantly with TxA2 and prostaglandin (PG)H2 receptor blockade and 2) whether these effects are mediated through redirection of PG endoperoxides toward the synthesis of antiplatelet PGs, such as PGI2 and PGE2. Thus, cyclic flow variations (CFVs), due to recurrent platelet aggregation, were initiated in the stenotic, endothelially injured carotid arteries of 39 rabbits. After 30 min of CFVs, the animals received: 1) SQ29548 (up to 0.6 mg/kg bolus + 0.2 mg kg-1 hr-1, n = 13), a TxA2/PGH2 receptor antagonist; 2) dazoxiben (up to 15 mg/kg bolus + 5 mg kg-1 hr-1, n = 13), a TxA2 synthase inhibitor and 3) picotamide (up to 20 mg/kg bolus + 20 mg kg-1 hr-1, n = 13), a drug with simultaneous TxA2 synthase and receptor blocking properties. CFVs were abolished in 6, 7, and 12 animals treated with SQ29548, dazoxiben, and picotamide, respectively (P < .01 for picotamide versus SQ29548 and dazoxiben). The animals in which CFVs were not abolished by SQ29548 or dazoxiben received the other drug at the same dose. CFVs were abolished by dazoxiben in five of seven rabbits that initially did not respond to SQ29548 and by SQ29548 in five of six animals that did not respond to dazoxiben. All animals that responded to the combination of SQ29548 and dazoxiben, as well as those that responded to picotamide, received increasing intravenous infusions of epinephrine to restore CFVs.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Experimental carotid stenosis and endothelial injury in the rabbit: an in vivo model to study intravascular platelet aggregation.

Previous studies have shown that experimental canine coronary artery stenosis associated with endothelial injury results in a typical pattern of coronary flow characterized by gradual decreases in coronary flow to almost zero values followed by restorations of flow to normal values. This pattern of flow, called cyclic flow reductions (CFRs), is the consequence of recurrent platelet aggregation at the site of the stenosis and endothelial injury and subsequent dislodgement of the thrombus. In the present study, platelet activation and aggregation in vivo was induced by placing an external constrictor around carotid arteries with endothelial injury in anesthetized rabbits. Carotid blood flow velocity was measured continuously with a Doppler flow probe positioned proximally to the constrictor. After placement of the constrictor, CFRs developed in 14 of 14 rabbits with a mean frequency of 16.5 +/- 2.3 cycles/h. CFRs were observed for 30 min, and the animals were treated with either an i.v. bolus of aspirin (10 mg/kg) or R 68070 (20 mg/kg), a drug with simultaneous TxA2 synthase and TxA2/PGH2 receptor blocking properties. Aspirin completely inhibited CFRs in 4 of 7 rabbits, whereas R 68070 eliminated CFRs in 7 of 7 animals. In the 3 animals that did not respond to aspirin, administration of ketanserin (0.25 mg/kg i.v.), a selective serotonin S2 receptor antagonist, completely abolished CFRs. Both aspirin and R 68070 resulted in a marked reduction in serum TxB2 formation and in a complete inhibition of ex vivo platelet aggregation in response to arachidonic acid, whereas aggregation in response to U46619, a TxA2 mimetic, was inhibited only in R 68070-treated rabbits.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Effects of the superoxide radical scavenger superoxide dismutase, and of the hydroxyl radical scavenger mannitol, on reperfusion injury in isolated rabbit hearts.

Hydroxyl radical formation, secondary to superoxide radical generation, has been advocated as the actual mechanism of oxygen radical-mediated damage in biological systems. The present study was designed to compare the efficacy of administration of the hydroxyl radical scavenger mannitol vs. that of the superoxide radical scavenger superoxide dismutase (SOD) in reducing myocardial reperfusion injury, and to test whether combined treatment with both agents would confer better tissue protection compared with either intervention alone. Rabbit hearts perfused within a 31P nuclear magnetic resonance (31P-NMR) spectrometer were subjected to 30 minutes of total global ischemia at 37 degrees C. At reflow, 12 hearts in each group received either (a) a bolus of standard perfusion buffer, followed by 45 minutes of reperfusion (controls); (b) the superoxide radical scavenger recombinant human SOD (h-SOD, as a 60,000 U bolus followed by a 100 U/ml infusion for 15 minutes); (c) the hydroxyl radical scavenger mannitol (50 mM bolus followed by 15 minutes of 50 mM infusion; or (d) a combination of both agents. All treated hearts were switched to standard buffer for the remaining 30 minutes of reperfusion. Treatment with h-SOD alone was associated with a significant improvement in the recovery of cardiac contractility and coronary flow, as well as of ATP content, compared to control hearts. In contrast, mannitol treatment resulted in a small, nonsignificant improvement in these parameters. The addition of mannitol to h-SOD did not result in further significant improvement of contractility and ATP recovery compared to h-SOD alone. These data demonstrate that under our experimental conditions significant protection against reperfusion injury can be achieved by the administration of h-SOD alone, without the need for additional hydroxyl radical scavenger therapy with mannitol. These results do not exclude that significant tissue protection may be achieved by different doses of mannitol or by other agents. However, they suggest that under definite experimental conditions prevention of hydroxyl radical formation, rather than attempts to minimize hydroxyl radical toxicity, might be a more efficient method to prevent oxygen radical-mediated reperfusion injury in isolated hearts.

Adenosine Triphosphate↗
PubMed1992

Effects of ischemia and reperfusion on cardiac tolerance to oxidative stress.

Oxidative stress may affect cardiac function and metabolism. Oxidants are normally inactivated by reacting with reduced glutathione (GSH), with resulting formation and release of oxidized glutathione (GSSG). However, ischemia might affect glutathione metabolism. This might render ischemic hearts less resistant against subsequent oxidant injury during reperfusion, and it might also affect the reliability of GSSG measurements as a means to investigate oxidative stress in reperfused hearts. We compared the metabolic and functional consequences of an oxidant load in control rabbit hearts and in hearts reperfused after 30 min of normothermic total ischemia. In controls, H2O2 infusion (H2O2; 5-30 microM) induced a dose-dependent stimulation of GSSG release and a progressive impairment of cardiac function. At these doses, H2O2 challenge of postischemic hearts resulted in biochemical and functional changes identical to those observed in controls. Release of lactate dehydrogenase (LDH) and of GSH was negligible, similar in both groups. In additional experiments, infusion of H2O2 at a much higher dose (200 microM) elicited a further increase in GSSG release from both groups, although GSSG concentrations were lower in postischemic hearts. The functional effects of the 200 microM H2O2 infusion were similar in both groups, all hearts showing rapid and irreversible deterioration of function. Occurrence of irreversible cell injury was also manifested by a large release of LDH and GSH to a similar extent in both groups. These data demonstrate that cardiac tolerance toward oxidants is largely unaffected by a relatively brief episode of severe ischemia and indicate that GSSG release can be reliably used to investigate oxidative stress in reperfused hearts.

Animals↗
PubMed1992

Endothelium-derived relaxing factor modulates platelet aggregation in an in vivo model of recurrent platelet activation.

It has been shown that endothelium-derived relaxing factor (EDRF) may inhibit platelet aggregation in vitro through activation of platelet-soluble guanylate cyclase. To assess whether EDRF may also affect platelet function in vivo, intravascular platelet aggregation was initiated by placing an external constrictor around endothelially injured rabbit carotid arteries. Carotid blood flow velocity was measured continuously by a Doppler flow probe placed proximal to the constrictor. After placement of the constrictor, cyclic flow reductions (CFRs), due to recurrent platelet aggregation, developed at the site of the stenosis. After CFRs were observed for 30 minutes, a solution of authentic nitric oxide (NO, n = 10) was infused into the carotid artery via a small catheter placed proximally to the stenosis. Before infusion of NO, CFR frequency averaged 18.3 +/- 2.9 cycles per hour, and CFR severity (lowest carotid blood flow as percentage of baseline values) was 6 +/- 1%. NO completely inhibited CFRs in all animals, as shown by the normal and constant pattern of carotid blood flow (CFR frequency, 0 cycles per hour, p < 0.001; carotid blood flow, 92 +/- 5%, p = NS versus baseline). These effects were transient; CFRs were restored spontaneously within 10 minutes after cessation of NO infusion. After CFRs returned, S-nitroso-cysteine (S-NO-cys), a proposed form of EDRF, was infused into the carotid artery. S-NO-cys also abolished CFRs in all animals but at a significantly lower dose than NO (0.3 +/- 0.1 versus 12 +/- 4 nmol/min). The role of endogenously released EDRF in modulating in vivo platelet function was then tested in additional experiments. In 10 animals, endogenous release of EDRF was stimulated by infusing acetylcholine into the aortic root during CFRs. Infusion of acetylcholine was also associated with a complete inhibition of CFRs, similar to that observed during exogenous infusion of NO or S-NO-cys. These antithrombotic effects of acetylcholine were completely lost when EDRF synthesis was prevented by administration of the L-arginine analogue NG-monomethyl L-arginine (L-NMMA). Furthermore, in six additional rabbits the basal release of EDRF was blocked by L-NMMA after CFRs had been previously abolished with aspirin or the combination of aspirin and ketanserin, a serotonin S2 receptor antagonist. L-NMMA caused restoration of CFRs in all animals, indicating that even the basal release of EDRF is important in modulating platelet reactivity in vivo. Taken together, the data of the present study demonstrate that endogenous EDRF might importantly contribute to the modulation of platelet function in vivo.

Acetylcholine↗
PubMed1992

Calcium antagonists and experimental myocardial ischemia reperfusion injury.

A number of previous studies have reported that administration of calcium antagonists reduces acute ischemic injury in a variety of experimental models. More recently, however, it has been suggested that the beneficial effects of reperfusing the ischemic myocardium might be blunted by the paradoxical occurrence of a specific form of reperfusion-mediated injury. Although the ultimate mechanisms responsible for this phenomenon have not been completely elucidated, it has been suggested that oxygen radical generation, neutrophil activation, and calcium overload, may all contribute to the development of myocardial damage in postischemic hearts. Several experimental studies suggest that, in addition to their well-known effects on ischemic injury, calcium antagonists may variably affect these mechanisms of reperfusion-mediated cell damage. In particular, evidence has been provided that suggests these drugs may inhibit oxygen radical-mediated peroxidation of membrane lipids and may also reduce activation of stimulated neutrophils. Furthermore, calcium-channel blockers might also prevent calcium overload in reperfused hearts, and they might interfere with reperfusion injury indirectly, secondary to a reduction in the severity of ischemia. From the experimental data available it can be speculated that calcium antagonists might contribute to reducing oxygen radical damage following reflow. At the same time, these drugs may allow the extension of the time window of reperfusion therapy, thus further expanding the benefits of thrombolysis.

Animals↗
PubMed1992

[Evaluation of the therapeutic efficacy of pravastatin in monothereapy and in association with gemfibrozil in hypercholesterolemia associated with moderate hyperglyceridemia].

Pravastatin is a new drug that inhibits 3-hydroxy-3-methylglutaryl-coenzyme A reductase, the key enzyme in cholesterol synthesis. It prevents mevalonate synthesis, thus reducing cholesterol. Pravastatin also stimulates the expression of LDL receptors, leading to an activation of this specific pathway of LDL catabolism. Gemfibrozil is a fibrate drug. Although the mechanism of hypolipidemic action of fibrates is not conclusively elucidated, it seems to involve reduction of LDL cholesterol secondary to decreased VLDL production and increased VLDL catabolism. Therefore, it might be hypothesized that combination therapy with both agents could afford greater reduction of cholesterol levels as compared to pravastatin alone. This study compared the efficacy and safety of pravastatin in monotherapy or in combination with gemfibrozil in the treatment of primary hypercholesterolemia with moderate hypertriglyceridemia. Thirty-eight subjects (aged 57 +/- 15 years, 25 M and 13 F) with baseline cholesterol levels > 220 mg/dl, were included in the study. Serum triglyceride levels were greater than 170 mg/dl and lower than 250 mg/dl. All patients initially followed 4 weeks of hypolipidemic diet. The patients were there assigned to receive either 20 mg once a day of pravastatin alone (n 13) or 20 mg of pravastatin in association with 600 mg of gemfibrozil daily (n 11). Fourteen additional patient, treated with diet only, served as a control group. The treatment plan provided 18 months of active treatment with clinical and laboratory controls every month. Both groups of treated patients showed a reduction of total and LDL-cholesterol levels. The HDL-cholesterol levels increased significantly both with pravastatin and with gemfibrozil.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

[Calcium channel blockers inhibit human low-density lipoprotein peroxidation induced by oxygen free radicals in vitro].

Previous studies have shown that calcium-antagonists may reduce the development of experimental atherosclerosis, and that nifedipine may slow progression of coronary atherosclerosis in man. The mechanisms responsible for this effect are still unclear. It has been recently proposed that oxygen-free radicals can induce peroxidation of human low-density lipoproteins (LDL), and that peroxidized LDL may be an atherogenic stimulus. Chemical modified LDL are internalized by macrophages via specific cell surface receptor that was termed the scavenger receptor, and could induce foam cells transformation in vivo. Previous studies on other systems have shown that calcium-antagonists may effectively inhibit oxygen radical-induced lipid peroxidation. These drugs, though differing widely in their chemical structure, are lipophilic to various degrees and presumably would concentrate in the lipid domain of the phospholipid-rich membranes. Therefore, the aim of the present study was to investigate whether calcium-channel blockers may reduce human LDL peroxidation. Purified human LDL were exposed to oxygen radicals generated by xanthine-xanthine oxidase (18 hours) after a pre-incubation (30 min) in presence of different concentrations of nifedipine, diltiazem and verapamil. Peroxidation was measured from malonyldialdehyde production. The results show that calcium-antagonists prevent LDL peroxidation. Thus, calcium-antagonists may reduce peroxidation of human LDL in vitro, at clinically relevant concentrations. These data suggest that reduced formation of atherogenic peroxidized LDL may be an additional mechanism for the anti-atherosclerotic effects of calcium-antagonists in vivo.

Arteriosclerosis↗
PubMed1992

Spinal cord injury: some epidemiological data. A review of 233 cases.

Two hundred thirty-three consecutive cases of traumatic para- and tetraplegia admitted to a department of Neurosurgery in Naples within ten years were reviewed and categorized according to etiology, level of lesion and clinical features. The age of the patients at the time of injury varied from 7 to 74 years with a mean age of 37.1 +/- 17.1 (male mean age = 35.8 +/- 16.7; female mean age = 41.5 +/- 18.2). The male/female sex ratio was 4.8. Of these patients 66 were paraplegic and 167 were tetraplegic. The analysis of the various causes of the spinal cord injury showed that the occupational activities take the first place (32.2%); injuries in recreational activities and road accidents accounted for the majority of the remaining cases.

Adolescent↗
PubMed1992

[Psychic disorders. An unknown complication of surgery of the posterior cranial fossa].

Psychic trouble is not generally recognised as a possible complication of posterior fossa surgery. Reviewing a series of 63 pediatric patients operated on for posterior fossa intraxial tumors, the Authors found 21 cases of psychic troubles in the post-operative period. The incidence was higher in: a) medulloblastoma; b) rostral vermis location; c) supracerebellar infratentorial and transvermian approach. The neuropathophysiological basis of the phenomenon is discussed.

Brain Neoplasms↗
PubMed1992

[Complications of intracranial neoplastic pathology].

Post-surgical complications in the treatment of intracranial tumors, independently of their location, are summarized in 5 essential points: a) edema; b) hemorrhages; c) ischemias; d) infections; e) alterations of the liquoral dynamics. According to our experience, it is possible to minimize these complications by using convenient intraoperative surgical procedures. On this subject, in addition to the traditional microsurgical techniques, the use of the high technologies (Cusa, laser) is very advantageous. In conclusion the important role of neuroanaesthesia and of the post-operative intensive care is underlined.

Brain Neoplasms↗