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Biomedical subjects

R Abbate

Publications and source records attributed to R Abbate.

At least 181 records · Page 10Linked to original sources
PubMed1985

Heparin does not interfere with prostacyclin and prostaglandin D2 binding to platelets.

Heparin has been reported to antagonize the platelet antiaggregating activity of prostacyclin (PGI2) and prostaglandin D2 (PGD2). To investigate whether heparin interferes with PGI2 and/or PGD2 binding to the specific membrane platelet receptors, the number and the affinity of binding sites for tritiated PGI2 and PGD2 were determined in 8 healthy subjects (aged 25-32; 4 for PGI2 and 4 for PGD2 studies) in the absence and in the presence of heparin. Preliminary aggregation tests indicated that the heparin concentration tested (2 I.U./ml) reduced the antiaggregating activity of PGI2 and PGD2. Heparin, when preincubated with platelet suspension, did not induce any significant change in the number/platelet (bs/plt) and affinity (Kd) of PGI2 and PGD2 binding sites (bs) in comparison to control values (PGI2 high affinity bs: bs/plt = 106 +/- 12 vs 107 +/- 17 - Kd = 9.7 +/- 3.1 vs 10.0 +/- 2.3 nM; PGI2 low affinity bs: bs/plt = 3551 +/- 233 vs 3670 +/- 465 - Kd = 877 +/- 125 +/- 125 vs 833 +/- 104 nM; PGD2 bs: bs/plt = 228 +/- 14 vs 234 +/- 24 - Kd = 68 +/- 10 vs 73 +/- 7 nM; p greater than 0.4 for all the differences). No significant binding modification was also observed when heparin was preincubated with 3H-PGI2 and 3H-PGD2. The present demonstration that heparin does not interfere with PGI2 and PGD2 binding to platelets is consistent with the hypothesis that heparin reduces the antiaggregating effects of PGI2 and PGD2 by directly potentiating platelet aggregation.

Adenosine Diphosphate↗
PubMed1985

Spontaneous and cold pressor test-induced prostaglandin biosynthesis by human heart.

To investigate prostaglandin biosynthesis by the heart, 21 patients undergoing cardiac catheterization and coronary angiography for congenital or acquired heart diseases other than coronary artery disease were investigated. Prostacyclin (as 6-keto-PGF1 alpha), PGE2, PGF2 alpha and TxA2 (as TxB2) were measured by specific radioimmunoassay in blood from coronary sinus, aorta, and a peripheral vein under resting conditions and following cold pressor test (CPT). PGF2 alpha was always found undetectable. In resting conditions, no significant differences in plasma 6-keto-PGF1 alpha, PGE2, or TxB2 concentrations were found among coronary sinus, aorta, and peripheral venous blood and no transcardiac gradient existed (mean: +0.4 +/- 1.2 pg/ml for 6-keto-PGF1 alpha, +0.1 +/- 0.6 pg/ml for PGE2, and -0.4 +/- 9.9 pg/ml for TxB2). CPT was able to induce a significant increase in 6-keto-PGF1 alpha and PGE2 concentration in blood from the different sampling sites and a significant transcardiac gradient was found following CPT (+11.6 +/- 7.4 pg/ml for 6-keto-PGF1 alpha (p less than 0.01) and +5.2 +/- 3.6 pg/ml for PGE2 (p less than 0.001). TxB2 levels significantly increased in peripheral venous blood (from 18.3 +/- 6.2 to 29.2 +/- 20.3 pg/ml, p less than 0.05), but they did not increase either in coronary sinus (from 21.9 +/- 9.7 to 22.9 +/- 9.8 pg/ml) or in aorta (from 22.3 +/- 4.7 to 19.1 +/- 6.5 pg/ml). Present results indicate that a cardiocoronary prostacyclin and PGE2 synthesis is inappreciable under resting conditions but it becomes remarkable following sympathetic stimulation. On the contrary, no TxA2 cardiocoronary biosynthesis seems to occur in patients free from coronary artery disease.

Adult↗
PubMed1985

Abnormal cardiocoronary thromboxane A2 production in patients with unstable angina.

Thromboxane B2 (TXB2), the stable metabolite of thromboxane A2 (TXA2), was measured in the coronary sinus and in aortic blood before and after cold pressor test (CPT) in 21 patients suffering from ischemic heart disease (7 affected by stable effort angina and 14 by unstable angina) and in 12 patients not suffering from myocardial ischemia (control group) during coronary angiography. Aspirin (10 mg/kg intravenously) was administered before catheterization in order to prevent platelet and leukocyte TXA2 formation. Control subjects and patients with effort angina had TXB2 resting levels lower than unstable angina patients without a transcardiac gradient which, on the contrary, was found in unstable angina patients. Only in these patients CPT resulted in a significant TXB2 increase more marked in the coronary sinus (from 50.0 +/- 18.9 pg/ml to 73.0 +/- 35.1 pg/ml, p less than 0.001) than in the aorta (from 33.4 +/- 17.1 pg/ml to 42.6 +/- 24.0 pg/ml, p less than 0.05), so that the transcardiac TXB2 gradient significantly increased. In all but two unstable angina patients, TXB2 elevation was not associated with a fall of cardiac lactate extraction. The resting and CPT-induced TXB2 gradients were unrelated to the presence and severity of coronary angiographic lesions. These results indicate that unstable angina patients show an abnormal cardiocoronary capacity to synthesize TXA2, which seems not to be elicited by the occurrence of myocardial ischemia.

Adult↗
PubMed1985

Decreased number of PGD2 binding sites on platelets from patients with type IIa hyperlipoproteinemia.

Platelets from patients with familial hypercholesterolemia (type IIa hyperlipoproteinemia), a condition associated with a high prevalence of atherosclerosis and its ischemic complications, are claimed to be hyperresponsive to aggregating stimuli. We investigated the platelet responsiveness to and the binding of PGD2, a potent endogenous inhibitor of platelet aggregation via stimulation of adenylate cyclase, in a group of 7 patients affected by IIa hyperlipoproteinemia (IIa HLP) and in a control group of 10 healthy subjects. Inhibition by PGD2 of ADP-induced platelet aggregation was significantly lower in IIa HLP patients than in controls. The number of binding sites for PGD2 of platelets from IIa HLP patients was significantly reduced in comparison with that from controls (93 +/- 19 and 232 +/- 23 receptors/platelet, respectively), whereas the affinity for PGD2 was comparable to that of controls (Kd = 68.8 +/- 19.8 nM in patients and 66.1 +/- 15.9 nM in controls). The reduced number of platelet PGD2 binding sites in IIa HLP patients may account for the impaired sensitivity to PGD2 shown in vitro by platelets and may contribute to the increased tendency to thrombotic manifestations observed in IIa HLP.

Adolescent↗
PubMed1985

Age related changes of platelet prostacyclin receptors in humans.

Platelet receptors for PGI2 were investigated in eighteen healthy volunteers divided in two classes of age: nine were 18-40 years old and nine were 41-65 years old. PGI2 platelet receptors were found to decrease significantly with age; the young subjects had 106 +/- 16 (mean +/- SD) high affinity receptors/platelet and 3509 +/- 529 low affinity receptors/platelet whereas the old subjects had 86 +/- 14 high affinity receptors/platelet (P less than 0.02) and 2471 +/- 640 low affinity receptors/platelet (P less than 0.005). The cumulated data from all the subjects yielded a significant negative correlation with age (r = -0.71, P less than 0.001 for the high affinity class and r = -0.65, P less than 0.01 for the low affinity class). The affinity of receptor sites for the ligand did not statistically change with aging (P less than 0.30 and P less than 0.90 respectively for high and low affinity receptors).

Adolescent↗
PubMed1984

Reduction in prostacyclin platelet receptors in active spontaneous angina.

The number and affinity of binding sites for tritiated prostacyclin (PGI2) in platelets were investigated in twenty-eight patients with spontaneous angina (fourteen in the active and fourteen in the inactive phase) and in nine healthy controls of similar age. Active-phase patients had significantly lower numbers of both classes of platelet PGI2 receptors (high affinity and low affinity) than controls or inactive-phase patients. In contrast, the affinity for PGI2 was not significantly different in the three groups. In six active-phase patients restudied in the inactive phase the previously low number of PGI2 receptors had returned to normal. These results suggest that the instability of angina is associated with functional changes not confined to the coronary vasculature.

Angina Pectoris↗
PubMed1983

TxA2 production by human arteries and veins.

Human arterial and venous segments from patients under-going operations when incubated in Tris buffer both alone and with arachidonic acid were able to produce thromboxane B2 (assessed by radioimmunoassay). Thromboxane B2 (TxB2) production was progressive in time (till 40 min.) and was enhanced by the addition of 1mM norepinephrine. Contamination of tissues by platelet was checked and platelets did not contribute to thromboxane formation. The investigation of the conversion of 1-14C arachidonic acid by vascular tissue indicated that human vascular tissues produce the metabolites of the cyclooxygenase dependent pathway and that prostacyclin is the main metabolite with a PGI2/TxA2 ratio of 4:1. The arterial wall was found to possess an active lipoxygenase dependent pathway. Thromboxane production by intimal cells was negligible and the main source of thromboxane was the media. The production of thromboxane did not change in relation to age, but arterial segments from men produced significantly larger amounts of thromboxane than those from women.

Adult↗
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↗
PubMed1982

Platelet aggregation and thromboxane A2 production after adrenergic stimulation in young healthy humans.

The effects of adrenergic stimulation on platelet aggregation (platelet aggregation ratio; PAR), beta-thromboglobulin (beta-TG) release and plasma thromboxane B2 (TxB2) levels were investigated in 25 healthy young volunteers. Adrenergic stimulation induced by cold application was checked by evaluating the changes in the calculated vascular resistance in the forearm. A prompt increase in platelet aggregates and plasma beta-TG and TxB2 concentrations was observed after adrenergic stimulation. PAR changed from resting values of 0.97 +/- 0.05 to 0.75 +/- 0.08 (p less than 0.001) at the end of cold application. At the same time, beta-TG plasma concentration increased from 32.09 +/- 19.64 to 135.48 +/- 37.97 ng/ml (p less than 0.001) and TxB2 plasma levels changed from 0.49 +/- 0.24 to 0.99 +/- 0.39 pmol/ml (p less than 0.001). TxB2 levels, but not PAR and beta-TG concentration came back to the resting values at the end of the observation period (10 min). Aspirin, as the lysine acetylsalicylate equivalent to 5 mg/kg i.v. of acetylsalicylic acid, although able to completely inhibit platelet cyclooxygenase failed to inhibit the plasma TxB2 increase induced by adrenergic stimulation. This strongly suggests that the increase in plasma TxB2 following adrenergic stimulation is of extraplatelet origin. Also beta-TG and PAR changes were not affected by aspirin administration.

Adolescent↗
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↗