Preliminary clinical studies with thromboxane synthase inhibitors and thromboxane receptor blockers. A review.


:This review of the clinical studies of thromboxane synthase inhibitors (TXSIs) and thromboxane receptor blocking drugs (TXRBs) covers the years 1981 to the present. Clinical studies on TXSIs include those in normal volunteers as well as those in patients with angina, peripheral vascular disease and Raynaud's syndrome, pulmonary hypertension, cerebral vasospasm, hepatorenal syndrome, adult respiratory distress syndrome, and those on cardiopulmonary bypass and hemodialysis. The compounds studied include dazoxiben, dazmagrel, CGS 13080, CV 4151, OKY 1581, OKY 046, and U 63557A. In volunteers, single-dose studies have demonstrated inhibition of thromboxane A2 (TXA2) formation, with some small increases in bleeding time but no marked effect on platelet aggregation. In general, the compounds tested were ineffective in both chronic stable angina and vasospastic angina but caused symptomatic improvement in patients with unstable angina. The TXSIs studied were found to produce no consistent effects in any of the other clinical conditions. Since none of the compounds tested produced a sustained inhibition of TXA2 synthesis, the disappointing clinical results with this class of drugs may be due to an incomplete blockade of thromboxane synthase with the dosage regimens used. Possible alternative or additional reasons for the general lack of success with TXSIs could be that some of the diseases studied do not involve TXA2 or that accumulating prostaglandin endoperoxides in the presence of thromboxane synthase inhibition substitute for TXA2 in causing platelet aggregation. TXRBs rely for their efficacy only on blockade of the TXA2 receptor and antagonize the deleterious effects of both TXA2 and prostaglandin H2 equally, so they represent a simpler pharmacological approach than TXSIs. Such drugs include AH 23848, GR 32191, BM 13.177, BM 13.505, and SQ 28668. All of these compounds are inhibitors of platelet aggregation induced by TXA2 or by its stable mimetic, U-46619. AH 23848 was ineffective in patients with stable angina but did benefit patients with peripheral vascular disease. BM 13.177 has also proven effective in preventing restenosis after angioplasty, occlusion of coronary artery bypass grafts, and the deleterious effects of TXA2 in renal disease. From these preliminary studies, it would appear that TXRBs may offer greater clinical potential than TXSIs. Further studies currently underway with TXRBs to resolve this question include those in unstable angina, angioplasty, peripheral vascular disease, renovascular hypertension, and cyclosporine nephrotoxicity.






Fiddler GI,Lumley P


Has Abstract


1990-01-01 00:00:00


I69-78; discussion I79-80


1 Suppl








  • Regional Systems of Care Demonstration Project: American Heart Association Mission: Lifeline STEMI Systems Accelerator.

    abstract:BACKGROUND:Up to 50% of patients fail to meet ST-segment-elevation myocardial infarction (STEMI) guideline goals recommending a first medical contact-to-device time of <90 minutes for patients directly presenting to percutaneous coronary intervention-capable hospitals and <120 minutes for transferred patients. We sough...


    pub_type: 杂志文章


    authors: Jollis JG,Al-Khalidi HR,Roettig ML,Berger PB,Corbett CC,Dauerman HL,Fordyce CB,Fox K,Garvey JL,Gregory T,Henry TD,Rokos IC,Sherwood MW,Suter RE,Wilson BH,Granger CB,Mission: Lifeline STEMI Systems Accelerator Project.

    更新日期:2016-08-02 00:00:00

  • Survival and function of bioengineered cardiac grafts.

    abstract:INTRODUCTION:Patients with congenital heart disease frequently require graft material for repair of cardiac defects. However, currently available grafts lack growth potential and are noncontractile and thrombogenic. We have developed a viable cardiac graft that contracts spontaneously in tissue culture by seeding cells...


    pub_type: 杂志文章


    authors: Li RK,Jia ZQ,Weisel RD,Mickle DA,Choi A,Yau TM

    更新日期:1999-11-09 00:00:00

  • Volumetric analysis of in-stent intimal hyperplasia in diabetic patients treated with or without abciximab: results of the Diabetes Abciximab steNT Evaluation (DANTE) randomized trial.

    abstract:BACKGROUND:In diabetic patients in the Evaluation of Platelet IIb/IIIa Inhibitor for Stenting (EPISTENT) trial, abciximab reduced target vessel revascularization by approximately 50% compared with placebo. Whether this is a result of a lower restenosis rate caused by inhibition of intimal hyperplasia remains to be defi...


    pub_type: 临床试验,杂志文章,随机对照试验


    authors: Chaves AJ,Sousa AG,Mattos LA,Abizaid A,Staico R,Feres F,Centemero M,Tanajura LF,Abizaid A,Pinto I,Maldonado G,Seixas A,Costa MA,Paes A,Mintz GS,Sousa JE

    更新日期:2004-02-24 00:00:00

  • Association between apolipoprotein E alleles and calcific valvular heart disease.

    abstract:BACKGROUND:Studies on apolipoprotein E (apoE) alleles have reported an increased risk of coronary heart disease in patients with the apoE4 allele. Given the risk factor and histological similarities between coronary and calcific valvular heart disease (aortic stenosis [AS] and mitral annular calcification [MAC]), we po...


    pub_type: 杂志文章


    authors: Novaro GM,Sachar R,Pearce GL,Sprecher DL,Griffin BP

    更新日期:2003-10-14 00:00:00

  • Significance of chronic bifascicular block without apparent organic heart disease.

    abstract::Eighty-six of 452 patients (19%) with chronic bifascicular block were found to have no clinically apparent associated organic heart disease (OHD) and were defined as having primary conduction disease (PCD). Comparison of patients with PCD and OHD revealed a significantly lower incidence of the following clinical varia...


    pub_type: 杂志文章


    authors: Dhingra RC,Wyndham C,Bauernfeind R,Denes P,Wu D,Swiryn S,Rosen KM

    更新日期:1979-07-01 00:00:00

  • Apoptosis of endothelial cells precedes myocyte cell apoptosis in ischemia/reperfusion injury.

    abstract:BACKGROUND:Apoptosis contributes to cell loss after ischemia/reperfusion injury in the heart. This study describes the time course and level of apoptosis in different cell types in the intact heart during ischemia/reperfusion injury. METHODS AND RESULTS:Isolated Langendorff-perfused rat hearts were subjected to perfus...


    pub_type: 杂志文章


    authors: Scarabelli T,Stephanou A,Rayment N,Pasini E,Comini L,Curello S,Ferrari R,Knight R,Latchman D

    更新日期:2001-07-17 00:00:00

  • Intracellular calcium and vulnerability to fibrillation and defibrillation in Langendorff-perfused rabbit ventricles.

    abstract:BACKGROUND:The role of intracellular calcium (Ca(i)) in defibrillation and vulnerability is unclear. METHODS AND RESULTS:We simultaneously mapped epicardial membrane potential and Ca(i) during shock on T-wave episodes (n=104) and attempted defibrillation episodes (n=173) in 17 Langendorff-perfused rabbit ventricles. U...


    pub_type: 杂志文章


    authors: Hwang GS,Hayashi H,Tang L,Ogawa M,Hernandez H,Tan AY,Li H,Karagueuzian HS,Weiss JN,Lin SF,Chen PS

    更新日期:2006-12-12 00:00:00

  • Contribution of endothelium-derived nitric oxide to exercise-induced vasodilation.

    abstract:BACKGROUND:Endothelium-derived nitric oxide is an important modulator of resting vascular tone in animals and humans. However, the contribution of nitric oxide to exercise-induced vasodilation is unknown. METHODS AND RESULTS:The effect of NG-monomethyl-L-arginine (L-NMMA), an inhibitor of nitric oxide synthesis, on ex...


    pub_type: 杂志文章


    authors: Gilligan DM,Panza JA,Kilcoyne CM,Waclawiw MA,Casino PR,Quyyumi AA

    更新日期:1994-12-01 00:00:00

  • Platelets, thromboembolism and mitral valve prolapse.

    abstract::Cerebral and retinal ischemic events have been described in mitral valve prolapse. To determine whether platelets play a part in the pathogenesis of thromboembolism we studied 29 patients with mitral valve prolapse, including nine (group I) with thromboembolism (cerebral, retinal and deep venous), eight (group II) wit...


    pub_type: 杂志文章


    authors: Walsh PN,Kansu TA,Corbett JJ,Savion PJ,Goldburgh WP,Schatz NJ

    更新日期:1981-03-01 00:00:00

  • Myocardial lesions of progressive systemic sclerosis. A cause of cardiac dysfunction.

    abstract::The nature, prevalence, functional significance, and indeed existence of myocardial disease in progressive systemic sclerosis (PSS) has been debated. In this study the clinical and pathological features of 52 autopsied patients were analyzed in an attempt to resolve these questions. A distinctive focal myocardial lesi...


    pub_type: 杂志文章


    authors: Bulkley BH,Ridolfi RL,Salyer WR,Hutchins GM

    更新日期:1976-03-01 00:00:00

  • Comparison of Events Across Bleeding Scales in the ENGAGE AF-TIMI 48 Trial.

    abstract:BACKGROUND:Numerous scales exist for the classification of major bleeding events. Limited data compare the most commonly used bleeding scales within a single at-risk cohort of patients with atrial fibrillation. Here, we analyze bleeding outcomes according to the ISTH (International Society on Thrombosis and Hemostasis)...


    pub_type: 临床试验,杂志文章,多中心研究


    authors: Bergmark BA,Kamphuisen PW,Wiviott SD,Ruff CT,Antman EM,Nordio F,Kuder JF,Mercuri MF,Lanz HJ,Braunwald E,Giugliano RP

    更新日期:2019-11-26 00:00:00

  • Reduced mortality and strokes with off-pump coronary artery bypass grafting surgery in octogenarians.

    abstract:BACKGROUND:Off-pump coronary artery bypass surgery (OPCAB) has been revived and has gained popularity, although the exact subsets of patients who might benefit most from this technique are unknown. The aim of this retrospective study was to compare the results of coronary artery bypass grafting surgery (CABG) in octoge...


    pub_type: 杂志文章


    authors: Demaria RG,Carrier M,Fortier S,Martineau R,Fortier A,Cartier R,Pellerin M,Hébert Y,Bouchard D,Pagé P,Perrault LP

    更新日期:2002-09-24 00:00:00

  • Expansion of acute myocardial infarction: an experimental study.

    abstract::Expansion (regional dilatation and thinning) of acutely infarcted myocardium in man has been shown to correlate with overall cardiac dilatation and rupture. We studied gross and histopathologic features and the time course of expansion in rats. Infarcts were produced in 84 rats by ligation of the left coronary artery ...


    pub_type: 杂志文章


    authors: Hochman JS,Bulkley BH

    更新日期:1982-06-01 00:00:00

  • Effects of neuronal nitric oxide synthase on human coronary artery diameter and blood flow in vivo.

    abstract:BACKGROUND:Nitric oxide (NO)-mediated local regulation of vascular tone is considered to involve endothelial NO synthase (eNOS). However, we recently reported that human forearm basal microvascular tone in vivo is tonically regulated by neuronal NO synthase (nNOS), in contrast to an acetylcholine-stimulated reduction i...


    pub_type: 杂志文章


    authors: Seddon M,Melikian N,Dworakowski R,Shabeeh H,Jiang B,Byrne J,Casadei B,Chowienczyk P,Shah AM

    更新日期:2009-05-26 00:00:00

  • Influence of nitric oxide synthase and adrenergic inhibition on adenosine-induced myocardial hyperemia.

    abstract:BACKGROUND:Myocardial perfusion during adenosine-induced hyperemia is used both in clinical diagnosis of coronary heart disease and for scientific investigations of the myocardial microcirculation. The objective of this study was to clarify whether adenosine-induced hyperemia is dependent on endothelial NO production o...


    pub_type: 临床试验,杂志文章


    authors: Buus NH,Bøttcher M,Hermansen F,Sander M,Nielsen TT,Mulvany MJ

    更新日期:2001-11-06 00:00:00

  • Identification of alpha- and beta-cardiac myosin heavy chain isoforms as major autoantigens in dilated cardiomyopathy.

    abstract:BACKGROUND:Immunization with cardiac myosin induces experimental autoimmune heart disease in genetically predisposed mice. These mice produce heart-specific autoantibodies, some of which are directed against the cardiac myosin isoform. METHODS AND RESULTS:We have reported the presence of circulating heart-specific aut...


    pub_type: 杂志文章


    authors: Caforio AL,Grazzini M,Mann JM,Keeling PJ,Bottazzo GF,McKenna WJ,Schiaffino S

    更新日期:1992-05-01 00:00:00

  • Congenital aneurysms of the left atrium: recognition by cross-sectional echocardiography.

    abstract::The two-dimensional echocardiographic features of three patients with congenital aneurysms of the left atrium are described. The aneurysm arose from the left atrial appendage in two patients and from the posterior left atrial wall in one. The aneurysms were characterized by their origin from an otherwise normal left a...


    pub_type: 杂志文章


    authors: Foale RA,Gibson TC,Guyer DE,Gillam L,King ME,Weyman AE

    更新日期:1982-11-01 00:00:00

  • The isovolumic contraction time of the left ventricle. An echographic study.

    abstract::The echographic isovolumic contraction time (ICT) of the left ventricle (LV) was measured in order to assess alterations of LV performance in children with various forms of cardiac disease. The echographic ICT was defined as the interval between coaptation of the anterior and posterior mitral valve leaflets and aortic...


    pub_type: 杂志文章


    authors: Hirschfeld S,Meyer R,Korfhagen J,Kaplan S,Liebman J

    更新日期:1976-11-01 00:00:00

  • The Münster Heart Study (PROCAM): total mortality in middle-aged men is increased at low total and LDL cholesterol concentrations in smokers but not in nonsmokers.

    abstract:BACKGROUND:Some large epidemiological studies have shown an increase in mortality at low levels of total and LDL cholesterol. It has been speculated that low cholesterol levels may play a causative role in this association. To investigate this question, we analyzed all deaths occurring among middle-aged men in the Müns...


    pub_type: 杂志文章,多中心研究


    authors: Cullen P,Schulte H,Assmann G

    更新日期:1997-10-07 00:00:00

  • Plasma endothelin in chronic heart failure.

    abstract:BACKGROUND:Endothelins are recently characterized vasoconstrictor peptides. As chronic heart failure (CHF) is characterized by peripheral arteriolar and renal vasoconstriction, we have measured venous plasma endothelin-like immunoreactivity ("endothelin") in patients with this syndrome. METHODS AND RESULTS:Compared wi...


    pub_type: 杂志文章


    authors: McMurray JJ,Ray SG,Abdullah I,Dargie HJ,Morton JJ

    更新日期:1992-04-01 00:00:00

  • Attenuation of exercise-induced myocardial ischemia in dogs with recruitment of coronary vasodilator reserve by nifedipine.

    abstract::There is now evidence that under resting conditions coronary vasodilator reserve exists even in the presence of myocardial ischemia. Therefore, we tested the hypothesis that a vasodilator reserve may exist during exercise so that during exercise-induced ischemia a reduction in coronary constrictor tone can be produced...


    pub_type: 杂志文章


    authors: Heusch G,Guth BD,Seitelberger R,Ross J Jr

    更新日期:1987-02-01 00:00:00

  • Transluminal angioplasty: correlation of morphologic and angiographic findings in an experimental model.

    abstract::The morphologic consequences of transluminal angioplasty of stenotic atherosclerotic coronary arteries are unknown. This study describes the production of aortoiliac atherosclerosis in rabbits and reports the morphologic changes after transluminal angioplasty of stenotic arterial lesions. Atherosclerotic lesions were ...


    pub_type: 杂志文章


    authors: Block PC,Baughman KL,Pasternak RC,Fallon JT

    更新日期:1980-04-01 00:00:00

  • Visceral adiposity and the prevalence of hypertension in Japanese Americans.

    abstract:BACKGROUND:Visceral adiposity is generally considered to play a key role in the metabolic syndrome, including hypertension. The purpose of this study was to evaluate cross-sectionally whether visceral adiposity is associated with prevalence of hypertension independent of other adipose depots and fasting plasma insulin....


    pub_type: 杂志文章


    authors: Hayashi T,Boyko EJ,Leonetti DL,McNeely MJ,Newell-Morris L,Kahn SE,Fujimoto WY

    更新日期:2003-10-07 00:00:00

  • Endothelial cell activation by pore-forming structures: pivotal role for interleukin-1alpha.

    abstract:BACKGROUND:Interaction of complement with endothelial cells (ECs) underlies the development of inflammation and coagulation in disease. Assembly of the membrane attack complex (MAC) of complement on EC membrane, like stimulation with cytokines, upregulates tissue factor and cyclooxygenase-2 but does so via the intermed...


    pub_type: 杂志文章


    authors: Saadi S,Holzknecht RA,Patte CP,Platt JL

    更新日期:2000-04-18 00:00:00

  • The role of right and left ventricular function in the ventilatory response to exercise in chronic heart failure.

    abstract:BACKGROUND:Right ventricular function may be an important determinant of exercise capacity, peak oxygen consumption (VO2), and the ventilatory response to carbon dioxide production (VE/VCO2 relation) in patients with chronic heart failure (CHF). METHODS AND RESULTS:We studied the role of right ventricular function in ...


    pub_type: 杂志文章


    authors: Clark AL,Swan JW,Laney R,Connelly M,Somerville J,Coats AJ

    更新日期:1994-05-01 00:00:00

  • Coagulant activities of platelets in coronary artery disease.

    abstract::Platelets have been implicated in the pathogenesis of coronary artery disease, and a number of studies have examined platelet function and coagulation parameters in such patients. We have examined platelet coagulant activities, volumes, and aggregate ratios in 23 patients with chest pain, seven of whom had normal coro...


    pub_type: 杂志文章


    authors: Rao AK,Mintz PD,Lavine SJ,Bove AA,McDonough MT,Spann JF,Walsh PN

    更新日期:1984-01-01 00:00:00

  • Evidence implicating nonmuscle myosin in restenosis. Use of in situ hybridization to analyze human vascular lesions obtained by directional atherectomy.

    abstract:BACKGROUND:Identification of genes that are specifically activated in restenosis lesions after percutaneous transluminal angioplasty represents a necessary step toward molecular manipulation designed to inhibit cellular proliferation responsible for such lesions. Whereas quiescent smooth muscle cells (contractile pheno...


    pub_type: 杂志文章


    authors: Leclerc G,Isner JM,Kearney M,Simons M,Safian RD,Baim DS,Weir L

    更新日期:1992-02-01 00:00:00

  • Evidence for increased collagenolysis by interstitial collagenases-1 and -3 in vulnerable human atheromatous plaques.

    abstract:BACKGROUND:Several recent studies attempted to classify plaques as those prone to cause clinical manifestations (vulnerable, atheromatous plaques) or those less frequently associated with acute thrombotic complication (stable, fibrous plaques). Defining the cellular and molecular mechanisms that underlie these morpholo...


    pub_type: 杂志文章


    authors: Sukhova GK,Schönbeck U,Rabkin E,Schoen FJ,Poole AR,Billinghurst RC,Libby P

    更新日期:1999-05-18 00:00:00

  • Targeting lymphatic vessel activation and CCL21 production by vascular endothelial growth factor receptor-3 inhibition has novel immunomodulatory and antiarteriosclerotic effects in cardiac allografts.

    abstract:BACKGROUND:Lymphatic network and chemokine-mediated signals are essential for leukocyte traffic during the proximal steps of alloimmune response. We aimed to determine the role of lymphatic vessels and their principal growth signaling pathway, vascular endothelial growth factor (VEGF)-C/D/VEGFR-3, during acute and chro...


    pub_type: 杂志文章


    authors: Nykänen AI,Sandelin H,Krebs R,Keränen MA,Tuuminen R,Kärpänen T,Wu Y,Pytowski B,Koskinen PK,Ylä-Herttuala S,Alitalo K,Lemström KB

    更新日期:2010-03-30 00:00:00

  • Reducing consumption of sugar-sweetened beverages is associated with reduced blood pressure: a prospective study among United States adults.

    abstract:BACKGROUND:Increased consumption of sugar-sweetened beverages (SSBs) has been associated with an elevated risk of obesity, metabolic syndrome, and type II diabetes mellitus. However, the effects of SSB consumption on blood pressure (BP) are uncertain. The objective of this study was to determine the relationship betwee...


    pub_type: 杂志文章,多中心研究,随机对照试验


    authors: Chen L,Caballero B,Mitchell DC,Loria C,Lin PH,Champagne CM,Elmer PJ,Ard JD,Batch BC,Anderson CA,Appel LJ

    更新日期:2010-06-08 00:00:00