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Article: The effects of thromboxane receptor blockade on platelet aggregation and digital skin blood flow in patients with secondary Raynaud's syndrome

TitleThe effects of thromboxane receptor blockade on platelet aggregation and digital skin blood flow in patients with secondary Raynaud's syndrome
Authors
Issue Date1991
PublisherSpringer Verlag. The Journal's web site is located at http://link.springer.de/link/service/journals/00296/index.htm
Citation
Rheumatology International, 1991, v. 11 n. 4-5, p. 163-168 How to Cite?
AbstractRaynaud's syndrome (RS) is characterized by intense blood vessel spasm resulting in finger blanching. Treatment primarily involves vasodilation. Thromboxane A2 (TXA2) has been shown to be a potent vasoconstrictor and platelet aggregant. It may be possible to produce a vasodilatory and anti-thrombotic effect by blockade of the TXA2 receptors. ICI 192,605 is a potent TXA2 receptor antagonist and we studied its effects on platelet aggregation and digital blood flow in patients with RS. Sixteen patients with RS completed this double-blind, randomized, placebo controlled study. Each patient was seen on three separate occasions and was given ICI 192,605 (100 mg orally) on one occasion and matching placebo tablets on the other two. We measured platelet aggregation using platelet rich plasma (PRP) stimulated by U46619, a thromboxane (TX) mimetic. The concentration of U46619 required to cause just over 50% platelet aggregation before the administration of either ICI 192,605 or placebo (pre-dose) was noted. The same concentration of U46619 was used to stimulate the PRP sample at 1 h after the administration of ICI 192,605 or placebo (post-dose) and the percentage of platelet aggregation was again noted. Fingertip skin blood flow was also measured 1.25 h post-dose using a laser Doppler flowmeter. Patients were seated in a temperature controlled chamber which was initially heated to 40 °C to induce centrally mediated vasodilatation. The temperature was then lowered to 12 °C followed by rewarming to 40 °C. Steady blood flow values at these temperatures were measured and the rates of cooling and rewarming were also noted. There was significant inhibition of platelet aggregation 1 h following the administration of ICI 192,605 {post-dose % platelet aggregation [mean (standard deviation)] = 4.8 (12.7)% vs control values of 65.6 (10.5)% and 62.7 (21.3)%, P < 0.0001 (Analysis of covariance)}. No demonstrable evidence of improved fingertip skin blood flow was observed and it may be that more prolonged dosing is required. As platelet aggregation is increased in Raynaud's phenomenon further evaluation of this group of drugs in patients with RS is required.
Persistent Identifierhttp://hdl.handle.net/10722/161852
ISSN
2015 Impact Factor: 1.702
2015 SCImago Journal Rankings: 0.638
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLau, CSen_US
dc.contributor.authorKhan, Fen_US
dc.contributor.authorMclaren, Men_US
dc.contributor.authorBancroft, Aen_US
dc.contributor.authorWalker, Men_US
dc.contributor.authorBelch, JJFen_US
dc.date.accessioned2012-09-05T05:15:31Z-
dc.date.available2012-09-05T05:15:31Z-
dc.date.issued1991en_US
dc.identifier.citationRheumatology International, 1991, v. 11 n. 4-5, p. 163-168en_US
dc.identifier.issn0172-8172en_US
dc.identifier.urihttp://hdl.handle.net/10722/161852-
dc.description.abstractRaynaud's syndrome (RS) is characterized by intense blood vessel spasm resulting in finger blanching. Treatment primarily involves vasodilation. Thromboxane A2 (TXA2) has been shown to be a potent vasoconstrictor and platelet aggregant. It may be possible to produce a vasodilatory and anti-thrombotic effect by blockade of the TXA2 receptors. ICI 192,605 is a potent TXA2 receptor antagonist and we studied its effects on platelet aggregation and digital blood flow in patients with RS. Sixteen patients with RS completed this double-blind, randomized, placebo controlled study. Each patient was seen on three separate occasions and was given ICI 192,605 (100 mg orally) on one occasion and matching placebo tablets on the other two. We measured platelet aggregation using platelet rich plasma (PRP) stimulated by U46619, a thromboxane (TX) mimetic. The concentration of U46619 required to cause just over 50% platelet aggregation before the administration of either ICI 192,605 or placebo (pre-dose) was noted. The same concentration of U46619 was used to stimulate the PRP sample at 1 h after the administration of ICI 192,605 or placebo (post-dose) and the percentage of platelet aggregation was again noted. Fingertip skin blood flow was also measured 1.25 h post-dose using a laser Doppler flowmeter. Patients were seated in a temperature controlled chamber which was initially heated to 40 °C to induce centrally mediated vasodilatation. The temperature was then lowered to 12 °C followed by rewarming to 40 °C. Steady blood flow values at these temperatures were measured and the rates of cooling and rewarming were also noted. There was significant inhibition of platelet aggregation 1 h following the administration of ICI 192,605 {post-dose % platelet aggregation [mean (standard deviation)] = 4.8 (12.7)% vs control values of 65.6 (10.5)% and 62.7 (21.3)%, P < 0.0001 (Analysis of covariance)}. No demonstrable evidence of improved fingertip skin blood flow was observed and it may be that more prolonged dosing is required. As platelet aggregation is increased in Raynaud's phenomenon further evaluation of this group of drugs in patients with RS is required.en_US
dc.languageengen_US
dc.publisherSpringer Verlag. The Journal's web site is located at http://link.springer.de/link/service/journals/00296/index.htmen_US
dc.relation.ispartofRheumatology Internationalen_US
dc.subject.meshAdulten_US
dc.subject.meshAgeden_US
dc.subject.meshCold Temperatureen_US
dc.subject.meshDioxanes - Pharmacologyen_US
dc.subject.meshDouble-Blind Methoden_US
dc.subject.meshFemaleen_US
dc.subject.meshFingersen_US
dc.subject.meshHumansen_US
dc.subject.meshLasers - Diagnostic Useen_US
dc.subject.meshMaleen_US
dc.subject.meshMiddle Ageden_US
dc.subject.meshPlatelet Aggregation - Drug Effects - Physiologyen_US
dc.subject.meshRaynaud Disease - Blood - Physiopathologyen_US
dc.subject.meshReceptors, Prostaglandin - Antagonists & Inhibitorsen_US
dc.subject.meshReceptors, Thromboxaneen_US
dc.subject.meshRegional Blood Flow - Drug Effectsen_US
dc.subject.meshSkin - Blood Supplyen_US
dc.titleThe effects of thromboxane receptor blockade on platelet aggregation and digital skin blood flow in patients with secondary Raynaud's syndromeen_US
dc.typeArticleen_US
dc.identifier.emailLau, CS:cslau@hku.hken_US
dc.identifier.authorityLau, CS=rp01348en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1007/BF00332555-
dc.identifier.pmid1838424-
dc.identifier.scopuseid_2-s2.0-0025719259en_US
dc.identifier.volume11en_US
dc.identifier.issue4-5en_US
dc.identifier.spage163en_US
dc.identifier.epage168en_US
dc.identifier.isiWOS:A1991GT14100004-
dc.publisher.placeGermanyen_US
dc.identifier.scopusauthoridLau, CS=14035682100en_US
dc.identifier.scopusauthoridKhan, F=7402008077en_US
dc.identifier.scopusauthoridMcLaren, M=7005471705en_US
dc.identifier.scopusauthoridBancroft, A=7004599092en_US
dc.identifier.scopusauthoridWalker, M=7403869191en_US
dc.identifier.scopusauthoridBelch, JJF=7101752870en_US

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