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Biomedical subjects

S Heptinstall

Publications and source records attributed to S Heptinstall.

At least 109 records · Page 6Linked to original sources
PubMed1985

Platelet behaviour in normal pregnancy, pregnancy complicated by essential hypertension and pregnancy-induced hypertension.

Platelet behaviour was studied throughout pregnancy in a group of women who remained normotensive and a group with essential hypertension (EHT). Women who developed pregnancy-induced hypertension (PIH) were also studied together with a group of non-pregnant female controls. We determined the sensitivity of platelets to arachidonic acid (AA) and determined the effects of dazoxiben, a thromboxane synthetase inhibitor, on AA-induced platelet behaviour. A marked increase in platelet reactivity was evident in all three groups throughout pregnancy; platelets became more sensitive to AA and less sensitive to the inhibitory effects of dazoxiben. The change was apparent as early as 16 weeks gestation. In normotensive pregnancy and in EHT platelet behaviour had returned to normal six weeks after delivery. Platelets from women who developed PIH were more sensitive to AA than those from the other pregnant women and platelet reactivity had not returned to normal six weeks after delivery. The results indicate that alterations in platelet behaviour may contribute to the vascular complications that are known to be associated with pregnancy and with PIH in particular.

Adenosine Diphosphate↗
PubMed1985

Platelet aggregation in whole blood: the role of thromboxane A2 and adenosine diphosphate.

The platelet aggregation that occurred in whole blood in response to several aggregating agents (collagen, arachidonic acid, adenosine diphosphate, adrenaline and thrombin) was measured using an Ultra-Flo 100 Whole Blood Platelet Counter. The amounts of thromboxane B2 produced were measured by radioimmunoassay. The effects of various inhibitors of thromboxane synthesis and the effects of apyrase, an enzyme that destroys adenosine diphosphate, were determined. Platelet aggregation was always accompanied by the production of thromboxane B2, and the amounts produced depended on the nature and concentration of the aggregating agent used. The various inhibitors of thromboxane synthesis--aspirin and flurbiprofen (cyclo-oxygenase inhibitors), BW755C (a cyclo-oxygenase and lipoxygenase inhibitor) and dazoxiben (a selective thromboxane synthase inhibitor)--did not markedly inhibit aggregation. Results obtained using apyrase showed that adenosine diphosphate contributed to the aggregation process, and that its role must be acknowledged when devising means of inhibiting platelet aggregation in vivo.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMed1985

The effects of PGE2 and CL 115,347, an antihypertensive PGE2 analogue, on human blood platelet behaviour and vascular contractility.

The effects of prostaglandin E2 (PGE2) and an antihypertensive PGE2 analogue, CL 115,347 (d,l-15-deoxy-16-hydroxy-16 (alpha/beta)-vinyl prostaglandin E2 methyl ester), were examined on human blood platelet behaviour in platelet-rich plasma (PRP) and in whole blood (WB). The effects on baseline tone of isolated human carotid arterial strips were also examined. PGE2 had a biphasic effect on platelet behaviour, potentiating ADP- and collagen-induced aggregation at low concentrations (10(-8)-10(-6) M) and inhibiting aggregation at higher concentrations (10(-5) M). In contrast, low concentrations of CL 115,347 (10(-9)-10(-5) M) had no effect on platelet aggregation and higher concentrations (10(-4) M) potentiated ADP- and collagen-induced aggregation. The effects of PGE2 and CL 115,347 on adrenaline-induced aggregation were different to those of the other aggregating agents since only inhibition of platelet aggregation was observed. In the presence of PGI2 (10(-9)-10(-8) M) however, PGE2 (10(-8)-10(-6) M) was able to potentiate both ADP- and adrenaline-induced aggregation. Results obtained in WB were similar to those obtained in PRP. Both PGE2 and CL 115,347 contracted isolated human carotid arterial strips in a dose-dependent manner, with PGE2 being approximately 20 times more potent than its synthetic analogue. These results indicate that CL 115,347 is less potent than PGE2 in its effects on human blood platelet behaviour and vascular contractility in vitro.

Adenylyl Cyclase Inhibitors↗
PubMed1985

Blood platelet behaviour in mothers and neonates.

Blood platelet behaviour was compared in mothers at birth and their babies, and in non-pregnant, female controls. Platelet responses to arachidonic acid (AA) and to adrenaline were measured in platelet-rich plasma and the inhibitory effects of prostacyclin (PGI2) were determined. Platelets from the mothers differed from those from the neonates and controls in that lower concentrations of AA were needed to induce platelet aggregation and a release reaction. In addition, more PGI2 was needed to inhibit AA-induced platelet aggregation. Platelets from the neonates differed from the mothers and controls in that they were almost completely insensitive to adrenaline. They did not differ from the controls in their sensitivity to AA or PGI2 but the extent of the release reaction induced by AA was significantly reduced.

Arachidonic Acid↗
PubMed1985

Extracts of feverfew inhibit granule secretion in blood platelets and polymorphonuclear leucocytes.

Extracts of feverfew (Tanacetum parthenium) inhibited secretory activity in blood platelets and polymorphonuclear leucocytes (PMNs). Release of serotonin from platelets induced by various aggregating agents (adenosine diphosphate, adrenaline, sodium arachidonate, collagen, and U46619) was inhibited. Platelet aggregation was consistently inhibited but thromboxane synthesis was not. Feverfew also inhibited release of vitamin B12-binding protein from PMNs induced by the secretagogues formyl-methionyl-leucyl-phenylalanine, sodium arachidonate, and zymosan-activated serum. Feverfew did not inhibit the secretion induced in platelets or PMNs by the calcium ionophore A23187. The pattern of the effects of the feverfew extracts on platelets is different from that obtained with other inhibitors of platelet aggregation and the effect on PMNs is more pronounced than has been obtained with very high concentrations of non-steroidal anti-inflammatory agents.

Blood Platelets↗
PubMed1985

Effects of diamide and iodoacetamide on the expression of the glycoprotein IIb/IIIa complex on blood platelets.

We have examined the effects of two agents that alter platelet thiol-disulphide status on platelet aggregation and on the ability of platelets to bind a monoclonal antibody (M148) that is directed toward an epitope on the glycoprotein IIb/IIIa complex. The immediate effect of both diamide and iodoacetamide is to enhance aggregation but after further incubation diamide, but not iodoacetamide, inhibits platelet aggregation. Incubation of platelets with diamide, but not iodoacetamide, is accompanied by a marked increase in the amount of M148 that binds to platelets. This is presumably a reflection of an altered distribution of glycoproteins on the platelet surface. It is known that diamide, but not iodoacetamide, leads to polymerisation of cytoskeletal proteins in platelets. Thus evidence is provided that agents that interact with the cytoskeleton inhibit platelet behaviour via an effect on surface glycoproteins.

Antibodies, Monoclonal↗
PubMed1985

Effects of prostacyclin and of the stable prostacyclin analogue ZK 36374 on forearm blood flow and blood platelet behaviour in man.

PGI2 and ZK 36374 were each infused into volunteers and the effects on forearm blood flow and on platelet behaviour were determined. Infusions of PGI2 or ZK 36374 did not alter resting forearm blood flow but both agents reduced the extent of the vasoconstriction that occurred in response to cold. ZK 36374 appeared to be a much more potent inhibitor of platelet behaviour than PGI2 when blood was taken while the infusions were in progress, but the effects of both agents were no longer evident one hour after the infusions were terminated. There was an inverse relationship between the extent of cold-induced vasoconstriction and the concentration of sodium arachidonate that was needed to induce platelet aggregation for different individuals. Infusions of PGI2 affected both parameters equally but ZK 36374 had a greater effect on platelet behaviour than on blood flow. It is possible that very low doses of ZK 36374 would result in inhibition of platelet behaviour without producing adverse haemodynamic effects.

Adult↗
PubMed1985

The effects of dazoxiben, an inhibitor of thromboxane synthetase, on cold-induced forearm vasoconstriction and platelet behaviour in different individuals.

The effect of dazoxiben, a thromboxane synthetase inhibitor, on cold-induced forearm vasoconstriction was determined in two groups of human volunteers, those in whom dazoxiben abolished the platelet aggregation and release reaction induced by sodium arachidonate (group I) and those in whom it did not (group II). Dazoxiben abolished cold-induced forearm vasoconstriction in group I volunteers but not in those of group II. These results imply a correlation between platelet behaviour and cold-induced changes in vascular tone. In the group I volunteers the effect of dazoxiben on cold-induced vasoconstriction was abolished by 1800 mg of aspirin, but not by 40 mg. Since the lower dose of aspirin inhibits platelet cyclo-oxygenase but has no effect on cyclo-oxygenase in blood vessel walls, it is possible that platelets play no part in the modulation of vascular tone by dazoxiben. It is more likely that the effects of dazoxiben are confined to the vessel wall.

Adult↗
PubMed1984

The expression of glycoproteins on single blood platelets from healthy individuals and from patients with congenital bleeding disorders.

Glycoproteins present on the surface of blood platelets are fundamental to normal blood platelet behaviour. We have used monoclonal antibodies and flow cytofluorimetry to study the expression of glycoproteins on single platelets from normal subjects, and from patients with Glanzmann's thrombasthenia and the Bernard-Soulier syndrome. We show that normal platelets are heterogeneous in that individual cells display markedly different numbers of glycoprotein IIb/IIIa complex and glycoprotein Ib molecules. We also show that the two congenital bleeding disorders are associated with markedly reduced numbers of glycoprotein IIb/IIIa complex or glycoprotein Ib molecules on all the platelets rather than the difference residing in a sub-population.

Blood Platelets↗
PubMed1984

Correlation between platelet behaviour and cold-induced vasoconstriction in man, and the effects of epoprostenol infusion.

Drugs that cause vasodilatation tend to inhibit platelet behaviour whereas compounds that cause vasoconstriction stimulate platelet behaviour. Thus there appears to be a similarity between platelet behaviour and vascular tone. To investigate this relationship we have compared the maximum vasoconstrictor response in the forearm induced by cold stimulation with some aspects of platelet behaviour. In 26 normal volunteers there was a close correlation between the maximum vasoconstrictor response to cold and the threshold concentration of sodium arachidonate that was needed to induce platelets from each individual to aggregate and to undergo a release reaction (r = 0.774, P less than 0.001). Infusion of epoprostenol (prostacyclin) in five volunteers altered both the maximum vasoconstrictor response to cold and the threshold concentration of sodium arachidonate needed to induce platelet aggregation in a manner parallel to this relationship.

Adult↗
PubMed1983

ADP-induced platelet release reaction in acute stroke.

The extent of the ADP-induced platelet release reaction has been determined in 107 patients admitted to hospital with acute stroke. In 43 of the patients a precise diagnosis was obtained and in those with proven thromboembolic stroke the mean extent of the release reaction was significantly higher than for those with either primary haemorrhagic stroke or those with subarachnoid haemorrhage. Enhanced platelet reactivity was also found in the patients in whom a precise diagnosis could not be obtained, most of whom probably had cerebral infarction. Comparison of the results obtained for patients with stroke with those obtained for individuals who had not experienced a stroke showed that thromboembolic stroke is associated with platelet hyperactivity while haemorrhagic stroke is associated with platelet hypoactivity. The part that abnormalities of platelet behaviour, whether causal or consequential, might play in occlusive stroke and intra-cranial haemorrhage is discussed and the need for large scale prospective studies is emphasised.

Acute Disease↗
PubMed1983

Effects of ketanserin and mepyramine on platelet aggregation and on the uptake of 5-hydroxytryptamine into platelets.

We have determined the effects of ketanserin, a 5HT2 antagonist, and of mepyramine, a histamine H1 antagonist, on the aggregation induced in platelet rich plasma by 5-hydroxytryptamine (5HT), adenosine diphosphate (ADP), and by combinations of 5HT and ADP. Both ketanserin and mepyramine inhibited 5HT-induced aggregation and the 5HT component of the aggregation induced by combinations of 5HT and ADP. Both agents also inhibited the second phase of the aggregation induced by ADP alone but higher concentrations of the agents were required. On a molar basis, ketanserin was always a more potent inhibitor of aggregation than mepyramine. Ketanserin did not consistently inhibit the ADP-induced release reaction nor did it inhibit ADP-induced aggregation in aspirin-treated platelets that were unable to undergo a release reaction. The results suggest that 5HT2 receptors are involved in 5HT-induced aggregation and that the platelets' endogenous 5HT may contribute to the second phase of ADP-induced aggregation. We have also compared the effects of ketanserin and mepyramine on 5HT uptake into platelets. In this case mepyramine was a much more potent inhibitor than ketanserin. The different effectiveness of ketanserin and mepyramine as inhibitors of aggregation and 5HT uptake provides further evidence for different 5HT receptors for these two processes, and indicates that those involved in the 5HT uptake may be more akin to histamine H1 receptors.

Adenosine Diphosphate↗
PubMed1983

Human blood platelet behaviour after inhibition of thromboxane synthetase.

1 We have determined the extent to which sodium arachidonate (NaAA) induces a release reaction in platelet-rich plasma (PRP) from different individuals and have studied the ability of the thromboxane synthetase inhibitor UK 34787 to modify this release. We have also determined the extent of the platelet release reaction induced in PRP from different individuals by preparations of platelet-derived thromboxane A2 (TXA2). 2 The release of [14C]-serotonin induced by NaAA is more extensive in PRP from some individuals than from others. 3 There is a direct relation between the extent of the release reaction induced in different PRPs by NaAA and TXA2. 4 UK 34787 prevents the NaAA-induced release reaction in PRP from some individuals ("responders") but not in PRP from others ("non-responders"). 5 The mean extent of the NaAA-induced release reaction for the "non-responders" was significantly higher than that for the "responders" even in the absence of UK 34787, but there was some overlap between the individual results. 6 Platelets from "responders" and "non-responders" did not differ in the amount of malondialdehyde (MDA) produced or in the effectiveness with which UK 34787 inhibited MDA production. 7 Platelet-derived TXA2 from "responders" and "non-responders" did not have markedly different effects when tested in a single preparation of PRP.

Arachidonic Acid↗