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Biomedical subjects

G De Gaetano

Publications and source records attributed to G De Gaetano.

At least 19 recordsLinked to original sources
PubMed1996

Combined aortic valve replacement and left ventricular aneurysm plication in systemic lupus erythematosus.

The case of a 37-year-old female patient is reported with systemic lupus erythematosus and severe renal function impairment, and associated aortic insufficiency, obstructive coronary disease and aneurysm of the left ventricular inferior free wall. Renal failure, hematologic disorder and the need for high-dose steroid therapy to control the autoimmune disease were considered the main surgical risks. Surgery included aortic valve replacement and plication of the ventricular aneurysm. The postoperative course was free of any major complications related to surgery or SLE disease.

Adult↗
PubMed1994

Prostacyclin is required for t-PA release after venous occlusion.

The role of vascular cyclooxygenase pathway on tissue-type plasminogen activator (t-PA) release after venous occlusion was studied in anesthetized rats. After the inferior vena cava was clamped for 30 min, fibrinolytic activity increased from 143.7 +/- 14.5 to 209.5 +/- 10.3 mm2 (mean +/- SE, P < 0.002). This increase was prevented by aspirin at high (100 mg/kg i.v.) but not at low doses (1 mg/kg i.v.). Dazoxiben (10 mg/kg i.v.), an inhibitor of thromboxane synthase, was ineffective on the fibrinolytic response. Both the basal levels of 6-ketoprostaglandin F1 alpha and its increase after venous occlusion were suppressed by 100 mg/kg aspirin administration (from 0.64 +/- 0.2 to 0.05 +/- 0.002 ng/ml before occlusion, P < 0.001; and from 1.08 +/- 0.2 to 0.06 +/- 0.002 ng/kg after occlusion, P < 0.001), whereas they were both unaffected by aspirin at low doses (from 0.53 +/- 0.06 before to 1.20 +/- 0.08 ng/ml after stasis). Moreover, iloprost, a stable analogue of prostacyclin, reversed the aspirin inhibitory effects on fibrinolytic activity by restoring t-PA vascular release after venous stasis. Our results provide experimental evidence that an intact cyclooxygenase pathway in vascular wall is required for the fibrinolytic activity increase after venous occlusion in rats.

6-Ketoprostaglandin F1 alpha↗
PubMed1994

[Predictive value of the shunt-to-infarct size ratio as a surgical risk factor in patients with decompensated post-ischemic interventricular septal rupture].

Postischemic septal rupture has always been evaluated, in respect of surgical indication, as regards the time lapse between infarct and rupture, interval between rupture and operation, extension of myocardial damage and general risk factors such as age, sex and associated pathologies. But in fact the surgeon is dealing with a two sided problem, the MI and the rupture, and thus surgical results depend upon both the residual ventricular function after MI and the consequences of volume overload on a damaged muscle. Surgical indication could not be based on a single criterion only. Extension of the MI alone is not fully predictive of operative mortality because, aside the reperfusion injury, the repair further jeopardizes viable myocardium and alters ventricular geometry; although the shunt appears unrelated to mortality it certainly interferes with operative outcome at least because of the time elapsed between rupture and repair. So far an index which could correlate the extension of myocardial damage and the entity of the shunt with each other was not available. Patients with septal rupture follow an emergency protocol and are often insufficiently investigated but every patients has a least one echo-Doppler evaluation or even a ventriculography while one or more ECGs are always available. With the presumption that the Qp/Qs is roughly indicative of the right ventricular volume overload and that ecg signs of myocardial infarct are always reliable, we have reviewed among our 24 patients with septal rupture those where a full ecg tracing and a quantitative Echo or angiographic evaluation of the shunt were available.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1994

[Doppler echocardiographic evaluation of the new mechanical bileaflet Sorin Bicarbon valve prosthesis compared with St. Jude Medical].

BACKGROUND: Despite the Bicarbon valve has been marketed for more than two years, no systematic Doppler evaluation of its normal functioning has yet been published. Therefore, the aims of this study were to establish the normal flow characteristics for the Bicarbon bileaflet prosthetic heart valve and to compare them with those obtained from the St. Jude Medical valve prosthesis. METHODS: Doppler echocardiographic characteristics of normally functioning Bicarbon prostheses were prospectively assessed in 76 consecutive patients (44 males and 32 females, mean age 60 +/- 10 years) with 79 valves in mitral (n = 29) and aortic (n = 50) position whose function was considered normal by clinical and echocardiographic evaluation. In addition, Doppler characteristics of the Bicarbon valves in aortic position were compared to those of 27 normal functioning St. Jude Medical implanted during the same period. RESULTS: For the mitral valve prostheses, we found non significant difference among prosthesis sizes in terms of transprosthetic gradients or pressure half time. Peak and mean gradients were similar in the 27-mm and 31-mm size valves (from 11 +/- 4 to 11 +/- 2 mm Hg and from 5 +/- 2 to 5 +/- 1 mm Hg, respectively; p = NS for both). Similarly, the pressure half time was similar in the 27-mm and in the 31-mm size valve (85 +/- 16 and 76 +/- 13 msec; p = NS). Conversely, for the aortic valve prostheses, there was a significant decrease in transprosthetic gradients and an increase in effective orifice areas as prosthesis size increased. Mean gradient was 13 +/- 1 mm Hg in 19-mm size valves, and it decreased to 6 +/- 2 mm Hg in the 29-mm size. Effective prosthetic valve area calculated using the continuity equation, ranged between 1.0 +/- 0.3 cm2 for 19-mm size valves to 3.5 +/- 0.7 cm2 for 29-mm size. With analysis of variance, effective prosthetic aortic valve area differentiated various valve sizes (F = 23.3; p < 0.0001) better than peak (F = 3.2; p = 0.017) or mean (F = 4.19; p = 0.0035) gradients alone did. Furthermore, effective prosthetic aortic valve area correlated better than peak and mean gradients with prosthetic size (r = 0.87, r = -0.58 and r = -0.57; respectively). In addition, peak and mean transprosthetic gradients and effective prosthetic aortic valve areas did not show any statistically significant difference between the Bicarbon and the St. Jude Medical valves in aortic position, either in 19 and 21 mm (25 +/- 8 mm Hg, 13 +/- 4 mm Hg, 1.3 +/- 0.3 cm2 and 32 +/- 11 mm Hg, 17 +/- 6 mm Hg, 1.2 +/- 0.4 cm2, respectively; p = NS), or in 23 and 25 mm (21 +/- 8 mm Hg, 11 +/- 4 mm Hg, 2.1 +/- 0.5 cm2 and 24 +/- 11 mm Hg, 12 +/- 5 mm Hg, 1.8 +/- 0.4 cm2, respectively; p = NS) or in 27 and 29 mm (12 +/- 2 mm Hg, 7 +/- 1 mm Hg, 2.8 +/- 0.9 cm2 and 16 +/- 5 mm Hg, 7 +/- 2 mm Hg, 2.6 +/- 0.4 cm2, respectively; p = NS). CONCLUSIONS: This study suggest that the Bicarbon valve prosthesis offers relatively little resistance to forward flow except at a small anulus diameter. Furthermore, these is no statistically significant difference between the Bicarbon and the St. Jude Medical in aortic position with regard to early hemodynamic performances.

Aged↗
PubMed1993

Antiplatelet activity of 2-(6-carboxyhexyl)-3-n-hexylcyclohexylamine (IBI P-05006), a thromboxane receptor antagonist.

2-(6-Carboxyhexyl)-3-n-hexylcyclohexylamine (IBI P-05006) is a molecule with cytoprotective and antisecretory actions. Since its chemical structure resembles that of the prostanoid nucleus of thromboxane (Tx) A2, the possibility of antiplatelet activity was investigated. The aims of our study were to evaluate a possible inhibitory effect of IBI P-05006 on in vitro platelet aggregation induced by different stimuli and to characterize its mechanism of action. For this purpose, selected mechanisms of platelet function were evaluated. IBI P-05006 inhibited platelet aggregation induced by arachidonic acid or U46619, at concentrations ranging from 0.4 to 4 microM, dose dependently, without interfering with arachidonic acid metabolism. The possibility that the compound acts through adenylate cyclase stimulation was ruled out by measurement of cAMP levels, which were not increased. Receptor binding studies indicated competitive inhibition by IBI P-05006 of the binding of the ligand [3H]SQ29548 to the TxA2/(prostaglandin) PG-cyclic endoperoxides receptor with IC50 in the range of concentrations active on platelet aggregation. In conclusion, IBI P-05006 inhibits in vitro human platelet aggregation through a specific mechanism of competition for the TxA2/PG-cyclic endoperoxides receptor.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1993

Current concepts of platelet physiopathology.

The genesis of the modern concept of platelet physiopathology can be traced historically to many individuals and developments, including the pioneering work of Giulio Bizzozero over 100 years ago. Much knowledge has since been gained to the point that we can now define many of the elements of the platelet function in relation to the hemostatic process in terms of their molecular biology. This presentation will attempt to synthesize a simple, understandable, yet global perspective of platelet function and of its participation to the pathogenesis of arterial thrombosis. Focus will be placed on the crucial importance of cell-cell interaction. A symbolic representation of platelet plug formation using simple mathematical figures like the line, point, and triangle is helpful. The line represents the vascular system with intact endothelial cell linings. The irritation/disruption of vascular endothelium can be viewed as a point on the line representative of a localized event. From this initial (often small) stimulus, amplification occurs rapidly to produce an appropriate cellular and humoral response, represented by a triangle. Each component (vessel wall, platelets, leukocytes, coagulation and fibrinolysis systems) of this complicated response has biological characteristics which localize and amplify subsequent reactions to the site of primary injury until bleeding is arrested and the wound is healed or arterial thrombosis progresses to vascular occlusion.

Arteriosclerosis↗
PubMed1993

[Doppler echocardiographic evaluation of functional parameters of mechanical and biological valve prostheses].

We studied and compared functional parameters in 314 valvular prostheses. The following parameters have been calculated: mean transvalvular gradients for aortic and mitral prostheses and functional area by Pht (pressure half time) for mitral prostheses. All patients with important depression in myocardial function, tachycardia or malfunctioning prostheses were excluded. 173 prostheses were in aortic position and 141 in mitral position. Mitral prostheses were: 31 biological and 110 mechanical. We subdivided mechanical prostheses in monoleaflet (Omnicarbon, Sorin-Carbocast and Allcarbon, Medtronic, Bjork-Shiley) and bileaflet (Sorin-Bicarbon, St. Jude). These three groups were compared: mean transvalvular gradients and area showed no differences. Aortic prostheses were: 33 biological and 140 mechanical; mechanical prostheses were subdivided in two groups: monoleaflet (Sorin Allcarbon e Carbocast, Bjork-Shiley, Medtronic, Omnicarbon) and bileaflet (Sorin-Bicarbon, St. Jude). Mean transvalvular gradients of these three groups were compared within each group for every size: bileaflet prostheses demonstrated inferior gradients than biological and monoleaflet for 19-21 and 23 sizes; in superior sizes there were no significant differences. Further analysis showed a significant correlation among gradients and body surface area in the 21 size prostheses (p = 0.004). Bileaflet prostheses in this subgroup showed less increase in mean gradient with surface area than mechanical and biological ones.

Aortic Valve↗
PubMed1992

Inhibition by heparin of platelet activation induced by neutrophil-derived cathepsin G.

Heparin is the most widely used anticoagulant drug for prevention and treatment of thrombosis. However, inhibition of blood coagulation might not fully explain the antithrombotic activity of this drug. The present study shows that different heparin preparations (50 nM) completely prevent human platelet aggregation, serotonin release and thromboxane B2 production induced by purified neutrophil-derived cathepsin G (E.C. No. 3.4.21.20). This inhibitory effect was not related to the anticoagulant property of the compounds, since a heparin preparation with an inactivated active for antithrombin III was also effective. Heparins inhibited the protease activity of the enzyme over the same range of concentrations. Since the effect of cathepsin G on platelets requires an intact proteolytic active site, the inhibitory effect of the drugs on cathepsin G-induced platelet activation may be explained by a blockade of protease activity. Heparins were also shown to reduce platelet activation induced by cathepsin G released from activated polymorphonuclear leucocytes in mixed cell suspensions. As polymorphonuclear leucocytes might contribute to both arterial and venous thrombosis through platelet activation induced by the release of cathepsin G, this novel property of heparin could be used to optimize its antithrombotic efficacy.

Amino Acid Sequence↗
PubMed1992

Ten years of surgery of aortic dissections and aneurysms. Clinical experience and original contributions.

From January '82 to April '91, 117 patients with aortic disease were operated upon at our University Hospital in Genoa, Italy. Thirty-seven had arch dissections or aneurysms; 66 had acute aortic dissection type A and 14 had aortic dissections or aneurysms type B, acute and chronic. Patients with arch or type B aortic pathology but without surgical indication and cases of post-traumatic aortic transections are not included. There were 84 male and 33 female patients with a mean age of 52 (6 min and 74 max). In the acute patients, the mean interval between clinical onset and surgery was 34 hours (6 min-72 max). All patients with primary arch disease had surgical repair with the aid of deep hypothermia and circulatory arrest (17-96 min). Type A dissections were treated with standard CPBP at 28 degrees C. Surgical techniques included direct suture of intimal tear alone, direct suturing of the two aortic stumps; interposition of Dacron tubular prosthesis; Bentall repair; separated valve and aortic replacement; an original aortic bulb aortoplasty with valve repair; arch replacement with resuturing of one or more aortic trunks. Human fibrin glue (Tissucol) was employed either as haemostatic agent, widely spread over the suture lines or as tissue adhesion agent between dissected aortic layers. Human fibrin glue is adopted because it gathers high glueing capacity and maintenance of the elastic property of the vessel wall. Hospital mortality (30 days) has been 25% in ascending aortic dissections (16/66 patients) and 50% in patients with arch disease (18/37 patients) who needed circulatory arrest. Late mortality 5/83 (6%). Reoperations for aortic valve insufficiency or re-dissection have been 7 (8.4%). Early diagnosis (increasing reliability of 2D-Echo and CT scans), aggressive surgery, meticulous myocardial and cerebral protection and introduction in clinical use of biological glues seem to be the milestones of present and further improvements in surgical results.

Acute Disease↗
PubMed1992

[Acute surgically-treated complications of myocardial infarct. Clinical experience and discussion of surgical indications].

Post-infarction free-wall, papillary muscle and septal myocardium rupture yields a lowering mortality, not only due to the improved surgical technique but also to a more careful selection of surgical candidates. The value of pericardial decompression in cases of free-wall rupture is discussed. Echocardiographic evidence of blood in the pericardium after a myocardial infarction is not a direct indication for a diagnostic sampling, decompression or surgery. Pericardiocentesis is not a risk-free procedure and should be limited to patients with life-threatening acute tamponade. Clinical results of 34 patients operated upon for myocardial rupture, regardless of adopted technique or timing of surgery, confirm that the decision about a patient's operability should follow a careful evaluation of the following risk factors in this order: infarct size, age, cardiogenic shock, multiorgan failure, rupture site, cardiac failure and associated diseases.

Aged↗
PubMed1990

Platelet activation by polymorphonuclear leukocytes exposed to chemotactic agents.

Human platelets were loaded with aequorin, a Ca2(+)-sensitive photoprotein, and tested in the platelet-ionized calcium aggregometer for simultaneous recording of platelet aggregation and intraplatelet Ca2+ levels both in the presence and in the absence of autologous polymorphonuclear leukocytes. Cells were exposed to one of three chemotactic stimuli: platelet-activating factor (PAF), N-formyl-methionyl-leucyl-phenylalanine (FMLP), or leukotriene B4 (LTB4). Platelets alone aggregated and showed intracellular Ca2+ movement only when exposed to PAF. Amplification of both platelet aggregation and intraplatelet Ca2+ movement was induced by PAF in the presence of leukocytes. Aggregation and intraplatelet Ca2+ mobilization were also observed in the presence of leukocytes activated by either FMLP or LTB4. Both parameters increased with the concentration of the stimuli and/or the number of leukocytes. Platelet thromboxane B2 production was also significantly increased in the presence of leukocytes. Addition of platelets at different times after leukocyte activation resulted in progressively reduced cytoplasmic Ca2+ increase. Cell-free supernatants prepared from FMLP-stimulated leukocytes were able to induce platelet aggregation, thromboxane B2 generation, and Ca2+ mobilization, although at a reduced degree as compared with intact leukocyte addition. The activity of leukocyte supernatants was stable at 37 degrees C for up to 30 min and was suppressed by trypsin inhibitor. Our study indicates that stimulated leukocytes release a soluble enzymatic activity able to activate platelets; cell-to-cell interaction may also play a role in this phenomenon. Platelet-leukocyte interaction could have physiopathological relevance and constitutes a new model for studying old and new platelet inhibitory drugs.

Blood Platelets↗
PubMed1987

Aspirin and risk of bleeding in patients with thrombocythemia.

Thirty-two patients with thrombocythemia associated with myeloproliferative syndromes were selected on the basis of normal bleeding time and absence of hemorrhagic or thrombotic history. Twenty-five control subjects were studied simultaneously. They were all given a single intravenous infusion of 500 mg of aspirin (lysine acetylsalicylate), and bleeding time was measured two hours later. Both in the control group and in the patient group, aspirin significantly prolonged the bleeding time, but the average prolongation was significantly more pronounced in the patients. In comparison with the control subjects, the patients had a statistically significant reduction of platelet serotonin content and no difference in the production of platelet lipoxygenase derivative 12-HETE or plasma von Willebrand factor properties. Fourteen patients had abnormal platelet aggregation in response to adenosine diphosphate, adrenaline (epinephrine), or collagen. In six of them, all with very low serotonin content, the bleeding time was prolonged above the upper limit of the post-aspirin values in the control group. Thus, cyclooxygenase inhibition by aspirin unmasked a bleeding tendency in patients with a severe reduction in platelet dense bodies content. These findings might be relevant in relation to the use of antiplatelet drugs.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1985

Coronary and systemic 6-ketoprostaglandin F1 alpha and thromboxane B2 during myocardial ischemia in dog.

The left anterior descending coronary artery (LAD) of five dogs was ligated, and blood was withdrawn from the great cardiac vein, left marginal cardiac vein, femoral vein, and aorta. After ligation, immunoreactive 6-ketoprostaglandin (PG) F1 alpha rose from less than 0.1 to a mean value of 1.2 pmol/ml plasma in the great cardiac vein (GCV) and 0.88 pmol/ml in the left marginal vein, with no change in peripheral circulation. Immunoreactive thromboxane (TX) B2 remained below 0.075 pmol/ml throughout the experiments. LAD of 11 dogs was stenosed 60-80% with consequent cyclical reductions in blood flow. 6-Keto-PGF1 alpha in GCV rose in seven dogs (range 0.5-2.2 pmol/ml) and remained unchanged in four. No change was observed in peripheral plasma levels of 6-keto-PGF1 alpha. In these experimental conditions TXB2 remained below 0.075 pmol/ml. Lactate concentrations rose in both experimental conditions in GCV but not in peripheral circulation or in the left marginal vein. This study confirms a link between cardiac ischemia and increased coronary prostacyclin release, but we were unable to detect a similar correlation with TXB2 in plasma.

6-Ketoprostaglandin F1 alpha↗
PubMed1984

Prolongation of rat tail bleeding time by ketanserin: mechanisms of action.

Serotonin (5-HT) may play a regulatory role in platelet-vessel wall interaction. This can be reliably investigated by measuring bleeding time. Ketanserin is a recently developed selective 5-HT2 receptor antagonist, reportedly effective against both platelet and vascular 5-HT activation. Ketanserin (5-10 mg/kg) significantly prolonged tail bleeding time measured in conscious rats by two different techniques. While mianserin (a 5-HT2 receptor antagonist exhibiting alpha-adrenolytic activity) also prolonged bleeding time, methysergide, metergoline and cyproheptadine did not. All three compounds acted as 5-HT2 receptor antagonists with appreciable affinity for 5-HT1 receptors. On the other hand, bleeding time was prolonged by either prazosin (a selective alpha 1-adrenoceptor antagonist) or labetalol (an alpha 1- and beta-receptor antagonist). In contrast it was not affected by phentolamine or nicergoline (alpha 1-alpha 2-receptor antagonists) nor by propranolol (a beta-receptor antagonist). The effect of prazosin was significantly increased by combining it with either ketaserin or metergoline. Depletion of platelet serotonin by reserpine did not result in any modification of bleeding time, unless reserpine was combined with an inhibitor of 5-HT synthesis. Platelet activation by 5-HT was neither potentiated by norepinephrine nor prevented by prazosin or phentolamine whereas ketanserin and methysergide were equally effective inhibitors. These findings argue against a role of platelet and/or vascular 5-HT2 receptors in the antihemostatic effect of ketanserin in rats. This drug prolongs bleeding time by antagonising vascular adrenoceptors (prazosin-like effect) and/or by preventing a synergistic interaction between 5-HT and catecholamines at the vascular level.

Animals↗
PubMed1984

Inhibition of human platelet cyclo-oxygenase activity by sulfinpyrazone and three of its metabolites.

Sulfinpyrazone and three of its major metabolites were compared in vitro for their inhibitory effect on human platelet cyclo-oxygenase activity. Sulfinpyrazone appeared to be about 15-20 times less potent than its sulfide metabolite (G25671) and 6-7 times less potent than the other two compounds, the sulfone metabolite (G31442) and p-hydroxysulfide (G33378). All four compounds were apparently competitive inhibitors of platelet cyclo-oxygenase activity. Comparison of the potency of sulfinpyrazone and its metabolites, as determined in the present study and the plasma levels previously measured in man, indicates that sulfinpyrazone and G33378 were not potent enough to be effective in man. G31442 showed inhibitory potency slightly lower than its corresponding plasma levels, whereas G25671 was effective at concentrations well below those found in human plasma. This study supports the hypothesis that sulfinpyrazone metabolites (in particular the sulfide) rather than the drug itself affect platelet function when administered therapeutically.

Arachidonic Acid↗
PubMed1983

Salicylate fails to prevent the inhibitory effect of 5,8,11,14-eicosatetraynoic acid on human platelet cyclo-oxygenase and lipoxygenase activities.

Sodium salicylate is inactive both on cyclo-oxygenase and lipoxygenase prepared from human platelets. It prevents the inhibition of cyclo-oxygenase induced by aspirin, but does not counteract the inhibitory effect of 5,8,11,14-eicosatetraynoic acid on both enzymes. It also fails to interfere with the inhibitory activity of nordihydroguaiaretic acid on lipoxygenase. These data indicate that, unlike eicosatetraynoic acid, non-steroidal anti-inflammatory drugs interact with a site on cyclo-oxygenase distinct from the catalytic site, although related to it. Such a supplementary binding site is lacking on lipoxygenase.

5,8,11,14-Eicosatetraynoic Acid↗
PubMed1983

Prostacyclin production by human endothelial and bovine smooth muscle cells in culture. Effect of repeated stimulation with arachidonic acid, thrombin and ionophore A23187.

Prostacyclin (prostaglandin I2) is the major product of arachidonic acid metabolism in vascular cells. Its physiological role may be linked to the ability of the cells to respond continuously with prostaglandin I2 production to a variety of stimuli. We report that human endothelial cells or bovine smooth muscle cells in culture respond with prostaglandin I2 synthesis to a first but not to a second stimulation with arachidonic acid. The development of this refractoriness was independent of the arachidonic acid concentration used (6.6-25 microM) and lasted for about 6 h. The same time was required for the cells to recover completely after inhibition of cyclooxygenase activity by aspirin. Neither cis-polyunsaturated fatty acids (linoleic or oleic acids) nor stearic acid (a long-chain saturated fatty acid) prevented the generation of prostaglandin I2 by arachidonic acid. Similarly to arachidonic acid, thrombin and ionophore A23187 could elicit vascular prostaglandin I2 synthesis only once. Pretreatment of the cells with arachidonic acid rendered the cells unresponsive to any other stimulus. These results indicate that the mechanism of the refractoriness induced by arachidonic acid was different from that induced by the other stimuli. It is proposed that vascular cells cannot be stimulated continuously to produce prostaglandin I2, but this process is regulated by different feedback mechanisms.

Animals↗