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Biomedical subjects

S Favilla

Publications and source records attributed to S Favilla.

36 records · Page 2Linked to original sources
PubMed1991

Hemodynamic and humoral interactions between perindopril and indomethacin in essential hypertensive subjects.

To evaluate whether perindopril, a carboxyl-containing new angiotensin-converting enzyme (ACE) inhibitor, exerts its antihypertensive action through the stimulation of prostaglandin synthesis, 10 uncomplicated essential hypertensive patients randomly received indomethacin (50 mg b.i.d.) or the corresponding placebo for 1 week and the reverse treatment after 2 weeks. Perindopril alone tended to reduce serum and urinary thromboxane B2 (TxB2) and to raise urinary 6-ketoPGF1 alpha and PGE2 and inhibited serum ACE activity 24 h post dosing by about 85%. Indomethacin, which significantly inhibited serum TxB2 and urinary TxB2, 6-ketoPGF1 alpha, and PGE2 without interfering with the inhibitory effect of perindopril on ACE, significantly reduced the antihypertensive action of perindopril alone by about 30%, but decreased though not significantly that of perindopril plus placebo. Although the size of the study limits the interpretation, these findings suggest that the stimulation of prostaglandin synthesis plays only a minor role in the antihypertensive action of perindopril.

Adult↗
PubMed1991

Dipyridamole-induced myocardial ischaemia increases ANF release in man.

Atrial natriuretic factor (ANF) release is modulated by several haemodynamic factors, including ventricular and atrial wall stretch. Dipyridamole infusion, which is commonly used as a pharmacological stressor in patients with coronary artery disease, can acutely increase ventricular and atrial pressure via myocardial ischaemia. The aim of this study was to assess whether dipyridamole infusion (up to 0.84 mg kg-1 over 10') can affect ANF release in man. Nineteen patients (13 men, 6 women) with a history of chest pain were studied. Their drug regimen was interrupted and instead they were administered a dipyridamole infusion, combined with two-dimensional echocardiography and 12-lead ECG monitoring. Plasma ANF was measured by RIA while the patients rested, and after dipyridamole infusion. Eight patients had no evidence of myocardial ischaemia, as measured by electrocardiographic and/or echocardiographic criteria, during dipyridamole infusion: among them, ANF values were similar while they were at rest and at peak dipyridamole administration (23.9 +/- 9.5 vs 23.4 +/- 6.9 pg ml-1, P = ns). Eleven patients had dipyridamole-induced transient ischaemia (regional ventricular dyssynergy and/or ST segment depression): among them, ANF values rose significantly at peak dipyridamole administration (31.8 +/- 13.8 vs 65.5 +/- 36.4, P less than 0.01). We conclude that dipyridamole infusion does not increase ANF release in man in the absence of ischaemia. The induction of myocardial ischaemia acutely increases ANF release, probably through a rise in ventricular and atrial wall stress.

Atrial Natriuretic Factor↗
PubMed1990

Atrial natriuretic factor as a vasodilator agent in hypertensive patients.

To investigate the role of Atrial Natriuretic Factor (ANF) in modulating arteriolar tone in hypertension, a synthetic 25 AA human ANF-analogue (anaritide) was infused intraarterially in the forearm vascular bed of five patients with mild hypertension. A dose-dependent increase in blood flow (plethysmographic technique) was seen at rates covering a thousand-fold range (0.008, 0.08, 0.8, 8.0 micrograms/dl tissue/min x 15 minutes each). At the lowest infusion rate, the forearm blood flow increment was associated with changes in local venous ANF concentrations comparable with those reported during biological stimuli in hypertensive man and consistent with an ANF physiologic role in forearm arterioles of hypertensive patients. However, at local venous concentrations greater than 1000 pg/ml, ANF did not relax forearm vessels by more than about one-fourth of the total forearm vasodilator capacity (as assessed through a maximally active ischemic stimulus). These data confirm the low potency of ANF as an endogenous vasodilator, although vasodilator potency is not a necessary requirement for physiologic systems involved in the regulation of muscular vascular tone. Systemic arterial pressure, heart rate, and contralateral flow did not change during the study in spite of the markedly increased peripheral ANF levels recirculating from the local forearm administration. This behavior indicates that arteriolar vasodilation is apparently not the main mechanism of action of ANF on systemic hemodynamics in hypertensive patients.

Adult↗
PubMed1989

The influence of dopamine-1 receptor blockade on the humoral and renal effects of low-dose atrial natriuretic factor in human hypertensives.

To test whether dopaminergic mechanisms can modulate the humoral and renal effects of atrial natriuretic factor (ANF), seven untreated, mildly hypertensive patients without complications were given a placebo (saline for 60 min) followed by a low dose of ANF (0.005 microgram/kg per min), or D-sulpiride (0.05 mg/kg per min), a specific dopamine-1 antagonist, or ANF + D-sulpiride at the same doses, for 60 min. The sequence of the three treatments was random, with a 72-h interval between treatments. The ANF infusion, which increased plasma ANF within the physiological range, significantly increased urinary sodium excretion, fractional sodium excretion and haematocrit; it reduced plasma aldosterone and tended to reduce plasma renin activity without changing blood pressure, the heart rate, renal plasma flow or the glomerular filtration rate. D-Sulpiride, when given alone, significantly increased mean blood pressure and reduced absolute and fractional sodium excretion without changing the heart rate, glomerular filtration rate, renal plasma flow, haematocrit, plasma renin activity or plasma aldosterone. When infused with D-sulpiride, ANF did not change absolute or fractional sodium excretion or haematocrit. This study provides evidence that dopaminergic mechanisms play a role in the natriuretic and plasma volume effects of a synthetic human ANF analogue infused at a low dose in patients with essential hypertension.

Adult↗
PubMed1989

Low dose atrial natriuretic factor in primary aldosteronism: renal, hemodynamic, and vascular effects.

Whether atrial natriuretic factor (ANF) plays a physiological role in primary aldosteronism has yet to be determined. In the present study, the renal, hemodynamic, humoral, and vascular effects of a synthetic (WY-47663) human analogue were studied in five water-loaded (15 ml H2O/kg) patients with adenomatous primary aldosteronism, a salt-sensitive, low renin, volume-expanded syndrome. ANF was infused for 3 hours at a low rate (0.005 micrograms/kg/min), which approximately doubled circulating immunoreactive ANF. Glomerular filtration rate and renal blood flow (inulin and para-aminohippurate clearance) remained stable, but sodium excretion increased significantly suggesting a dissociation between renal hemodynamics and natriuresis as well as a direct inhibitory effect on tubular sodium reabsorption by ANF. Intra-arterial diastolic blood pressure, heart rate, forearm blood flow (plethysmographic method), and arterial plasma norepinephrine did not change, but systolic blood pressure declined and hematocrit rose suggesting plasma volume contraction by ANF. Plasma aldosterone levels were unchanged indicating a loss of ANF-mediated aldosterone inhibition, possibly related to qualitative or quantitative alterations of ANF receptors in tumoral adrenal tissue. Infusion of the analogue into the brachial artery was at a rate of 0.005 micrograms/dl forearm tissue/min x 30 minutes, which also doubled local immunoreactive venous ANF concentrations and vasodilated forearm arterioles. These data suggest a physiological role for ANF in modulating body fluid volume even in human primary aldosteronism.

Adult↗
PubMed1988

Increased protein C and fibrinopeptide A concentration in patients with angina.

Protein C and fibrinopeptide A (FpA) levels in plasma were measured in 30 controls and in two groups of patients with angina. The first group was formed by 27 patients suffering from spontaneous ischemic attacks (active angina). The second one was formed by patients who had previously suffered from angina, but were free from myocardial ischemic attacks for at least one month (inactive angina). Protein C (measured by electroimmunoassay) and FpA (radioimmunoassay) were higher than controls in both groups but were significantly higher in patients with active angina than in patients with inactive angina. A clear trend toward a linear correlation existed between protein C and FpA levels, though it did not reach the statistical significance. These results confirm a significant involvement of blood clotting system in ischemic heart disease and specially in active angina.

Adult↗
PubMed1988

Platelet synthesis of cyclooxygenase and lipoxygenase products in type I and type II diabetes.

In 24 type I and 22 type II diabetic patients without vascular complications and in 25 controls platelet thromboxane A2 (TxA2) and prostaglandin E2 (PGE2) production (by radioimmunoassay-RIA) and 1-14C arachidonic acid (AA) metabolism (by high pressure liquid chromatography-HPLC) after thrombin stimulation were studied. Platelets both from type I and type II diabetics generated larger amounts of TxB2 (p less than 0.001) and PGE2 (p less than 0.005) than controls, independently of the presence of retinopathy. No significant differences in platelet AA uptake or metabolism via the cyclooxygenase (CO) route, after thrombin stimulation (5 NIH U/ml), were observed in diabetic patients: lipoxygenase metabolites were found to be slightly, but significantly decreased. A positive linear relationship (r = 0.64, p less than 0.001) was found between HbA-1c and TxB2 production, but not with fasting plasma glucose. These results indicate that metabolic alterations can affect platelet function independently of vascular complications. The absence of alterations in intraplatelet 1-14C AA metabolism via CO, in the presence of increased TxB2 and PGE2 production from endogenous AA, suggests that the activation of CO is not the only possible mechanism of platelet activation and that probably an increased availability of platelet AA plays an important role in the enhanced platelet aggregation commonly found in diabetics.

Adult↗
PubMed1987

Altered intraplatelet arachidonic acid metabolism during the acute state of unstable angina.

Thromboxane A2 (TxA2) generation and 1-14C arachidonic acid (AA) metabolism by platelets (stimulated with thrombin) were studied in vitro in 16 patients with unstable angina both during the acute and chronic inactive phase of the angina. Eight patients with stable effort angina and 21 controls were also investigated. In acute unstable angina 1-14C AA metabolism was significantly increased through cyclooxygenase pathway resulting in a higher selective TxA2 generation than in stable effort angina and in controls (p less than 0.01). No differences were found between patients with stable effort angina and controls. The alterations in AA metabolism were no longer found when patients reverted to the inactive phase of angina. TxA2 generation by platelets was independent of the number of the daily ischemic attacks (r = 0.17, ns) in patients with unstable angina. Present results indicate that an altered intraplatelet AA metabolism leading to the increased TxA2 synthesis occurs simultaneously with the conversion of angina from the chronic to the acute phase.

Acute Disease↗
PubMed1987

The interference of indomethacin and of imidazole salicylate on blood pressure control of essential hypertensive patients treated with atenolol. Preliminary report.

To evaluate whether imidazole salicylate, a recently developed NSAID, can interfere with the antihypertensive effect of atenolol and to compare its action with that of indomethacin, 9 essential hypertensives, while on prolonged (more than 1 month) treatment with atenolol (100 mg qd) received, according to a double-blind cross-over study, imidazole salicylate (750 mg t.i.d.) or indomethacin (50 mg b.i.d. plus a placebo tablet) for 1 week, reverting the treatment after a 2-week wash-out period. While indomethacin addition significantly increased blood pressure, when compared to atenolol alone, imidazole salicylate did not change it. These data show that imidazole salicylate, unlike indomethacin, does not reduce the antihypertensive effect of atenolol.

Adult↗
PubMed1986

Factors influencing platelet aggregation in whole blood.

In order to evaluate the interference of blood cells on platelet aggregation, spontaneous platelet aggregation (SPA), ADP, and collagen-induced platelet aggregation were investigated in whole blood by the impedance method and in platelet-rich plasma (PRP) by densitometric and impedance aggregometers. Stirring of the sample induced a significant decrease of neutrophils (P less than 0.001) but no changes of red blood cell (RBC) and platelet count. After collagen addition, a further decrease of neutrophils was observed, while RBC count was unmodified. The occurrence of SPA was not different in whole blood and in PRP. Platelet number and hematocrit did not affect either spontaneous or collagen-induced aggregation. A significant linear relation (r = -0.60, P less than 0.01) between neutrophil count and collagen whole blood platelet aggregation was found. Collagen- and ADP-induced aggregation were significantly higher and lower, respectively, in whole blood than in PRP using the densitometric method. No differences were observed in SPA and collagen platelet aggregation according to age and sex.

Adult↗
PubMed1984

In vitro investigation on the antiaggregating activity of ditazole.

The antiaggregating activity of ditazole, a non-steroidal antiinflammatory drug, was assayed in vitro on platelets from 16 subjects at high risk of thrombosis and from 14 healthy control subjects. This study was performed by the photometric method (Born) on platelet rich plasma (PRP), preincubated with ditazole at final concentrations of 1, 2.5, 4 and 40 micrograms/ml. Aggregation was induced by 1 and 2 microM ADP, 1 and 10 microM adrenaline and by 1 and 2 mM arachidonic acid (AA). Ditazole (1 microgram/ml) inhibited platelet aggregation induced by ADP (1 and 2 microM) in both groups and significantly reduced at all concentrations tested adrenaline (10 microM) induced aggregation in subjects at risk, but only at 2.5 micrograms/ml concentration in control subjects. Arachidonic acid (1 mM)-induced aggregation was significantly reduced by ditazole at all concentrations tested in control subjects but only at 2.5 micrograms/ml or more in subjects at risk. In both groups, however, aggregation induced by 2 mM AA was significantly reduced by ditazole at all concentrations tested.

Adenosine Diphosphate↗
PubMed1983

Hemodialysis leukopenia and complement function with different dialyzers.

The relationship between leukopenia and the complement system during hemodialysis was re-examined by studying not only the in vivo effects of four different dialyzer membranes (cellulose hydrate, cuprophan, cellulose acetate, and polyacrilonitrile) on leukocyte counts and complement levels, but especially by investigating the effects of these membranes on complement function in vitro. Whereas from in vivo studies no definite conclusions could be drawn, in vitro investigations provided clear-cut information. When more sophisticated technical approaches were undertaken, it became evident that hemodialysis leukopenia has to be thought of in terms of chemotactic factor generation. In fact, a strict correlation was demonstrated between the degree of leukopenia induced by the dialyzers tested and the ability of the relative membrane to generate chemotactic activity in vitro. Moreover, the previously observed ability of polyacrilonitrile membrane to induce a decrement in complement function was due to the ability of polyacrilonitrile to adsorb complement activity and did not correspond to effective complement consumption. This finding explained why polyacrilonitrile dialysis is not accompanied by a decrease in circulating granulocytes. Taken together, our data strongly point to a pivotal role of complement system in the pathogenesis of hemodialysis leukopenia.

Acrylic Resins↗
PubMed1983

Ticlopidine activity on platelet function in patients with enhanced platelet aggregation. A short-term crossover study.

In a single-blind crossover study, the effect of ticlopidine (250 mg t.i.d.) on platelet function was investigated in 16 patients, with enhanced platelet aggregation, before treatment, on the third and seventh day of treatment with the drug or the placebo. Bleeding time was significantly lengthened by ticlopidine administration. Platelet aggregation, both in vivo and in vitro, was significantly inhibited during the week on ticlopidine. Beta-thromboglobulin concentration was on an average significantly decreased. The inhibition by PGI2 of platelet aggregation by PGD2 was slightly but not significantly increased. Platelet TxB2 production after stimulation with thrombin was unchanged during ticlopidine administration, whereas conversion of exogenous arachidonic acid into TxB2 was slightly but significantly reduced. The present results confirm that ticlopidine acts in vivo as a powerful antiaggregating agent. The antiaggregating activity seems to be due to an interference of ticlopidine with platelet membrane and, as a consequence, with various platelet membrane receptors and activities.

Adenosine Diphosphate↗
PubMed1981

Increased fibrinopeptide A formation and thromboxane A2 production in patients with ischemic heart disease: relationships to coronary pathoanatomy, risk factors, and clinical manifestations.

In 98 patients with ischemic heart disease (IHD), independent of their clinical status (previous myocardial infarction, spontaneous angina or effort angina), a hypercoagulable state (indicated by significant elevation of fibrinopeptide A plasma level) and an increased platelet biologic activity were observed. Moreover, plasma fibrinopeptide A concentration and platelet aggregation were remarkably higher in patients with frequently occurring spontaneous clinical manifestations (active disease) than in IHD patients with relatively quiescent symptoms. Abnormalities of blood clotting and platelet changes were not significantly altered by the presence of severity of coronary angiographic fixed obstruction in IHD. Multiple regression analysis indicated that hypercoagulability and increased platelet biologic activity were not a consequence of differences in risk factor patterns in IHD patients compared to control subjects.

Blood Coagulation↗