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








  • Decreased activity of the L-arginine-nitric oxide metabolic pathway in patients with congestive heart failure.

    abstract:BACKGROUND:Impaired endothelium-dependent, nitric oxide (NO)-mediated vasodilation may contribute to increased vasomotor tone in patients with heart failure. Whether decreased endothelium-dependent, NO-mediated vasodilation in patients with heart failure is due to decreased synthesis or increased degradation of NO is u...


    pub_type: 杂志文章


    authors: Katz SD,Khan T,Zeballos GA,Mathew L,Potharlanka P,Knecht M,Whelan J

    更新日期:1999-04-27 00:00:00

  • Comparative effects of calcium entry-blocking drugs, beta-blocking drugs, and their combination in patients with chronic stable angina.

    abstract::For monotherapy, beta-blockers and calcium-entry blockers are effective and safe antianginal medications. For prophylaxis of myocardial ischemia, a different mechanism of action for each class of drugs is reflected by the different heart rate and rate-pressure product during exercise. In patients who continue to have ...


    pub_type: 临床试验,杂志文章


    authors: Kostuk WJ,Pflugfelder P

    更新日期:1987-06-01 00:00:00

  • Eliminating bradyarrhythmias after orthotopic heart transplantation.

    abstract:BACKGROUND:Bradycardia and sinus node dysfunction are common causes of early postoperative morbidity in orthotopic heart transplant recipients and frequently require the use of chronotropic drugs or permanent pacemakers. Several causes have been postulated, including surgical trauma to the sinus node and its blood supp...


    pub_type: 杂志文章


    authors: Rothman SA,Jeevanandam V,Combs WG,Furukawa S,Hsia HH,Eisen HJ,Buxton AE,Miller JM

    更新日期:1996-11-01 00:00:00

  • Sustained improvement in flow-mediated vasodilation after short-term administration of dobutamine in patients with severe congestive heart failure.

    abstract:BACKGROUND:In patients with severe congestive heart failure (CHF), short-term administration of dobutamine exerts sustained clinical benefits that are partially mediated by a training-like effect on skeletal muscle. Recently, physical training has been shown to enhance endothelial function in the skeletal muscle vascul...


    pub_type: 临床试验,杂志文章


    authors: Patel MB,Kaplan IV,Patni RN,Levy D,Strom JA,Shirani J,LeJemtel TH

    更新日期:1999-01-05 00:00:00

  • Inhibition of prolyl hydroxylase domain proteins promotes therapeutic revascularization.

    abstract:BACKGROUND:The hypoxia-inducible transcription factor (HIF) subunits are destabilized via the O(2)-dependent prolyl hydroxylase domain proteins (PHD1, PHD2, and PHD3). We investigated whether inhibition of PHDs via upregulating HIF might promote postischemic neovascularization. METHODS AND RESULTS:Mice with right femo...


    pub_type: 杂志文章


    authors: Loinard C,Ginouvès A,Vilar J,Cochain C,Zouggari Y,Recalde A,Duriez M,Lévy BI,Pouysségur J,Berra E,Silvestre JS

    更新日期:2009-07-07 00:00:00

  • Acute effect of intravenous dipyridamole on regional coronary hemodynamics and metabolism.

    abstract::The acute coronary hemodynamic and metabolic effects of intravenous dipyridamole were studied in 13 patients. Total left ventricular (LV), anterior (supplied by the left anterior descending coronary artery) and inferior (supplied by circumflex and right coronary arteries) regional flows and metabolic responses were as...


    pub_type: 杂志文章


    authors: Feldman RL,Nichols WW,Pepine CJ,Conti CR

    更新日期:1981-08-01 00:00:00

  • The risks of reoperative coronary artery bypass in chronic ischemic cardiomyopathy: results of the CABG Patch Trial.

    abstract:BACKGROUND:Coronary artery bypass grafting in patients with chronic ischemic cardiomyopathy is increasing in frequency, as is reoperative bypass. However, there exist very little data on early outcomes of patients with severe left ventricular dysfunction undergoing reoperation. Hence, we tested the following hypotheses...


    pub_type: 临床试验,杂志文章,随机对照试验


    authors: Kron IL,Cope JT,Baker LD Jr,Spotnitz HM

    更新日期:1997-11-04 00:00:00

  • Time-series analysis of heart rate variability during submaximal exercise. Evidence for reduced cardiac vagal tone in animals susceptible to ventricular fibrillation.

    abstract::Periodic fluctuations in the R-R interval have been used as noninvasive measures of cardiac autonomic tone. For example, a reduced heart rate variability has been shown to correlate with an increased mortality in patients recovering from myocardial infarction. The effects that physiologic perturbations such as exercis...


    pub_type: 杂志文章


    authors: Billman GE,Hoskins RS

    更新日期:1989-07-01 00:00:00

  • Cellular basis for the ECG features of the LQT1 form of the long-QT syndrome: effects of beta-adrenergic agonists and antagonists and sodium channel blockers on transmural dispersion of repolarization and torsade de pointes.

    abstract:BACKGROUND:This study examines the cellular basis for the phenotypic appearance of broad-based T waves, increased transmural dispersion of repolarization (TDR), and torsade de pointes (TdP) induced by beta-adrenergic agonists under conditions mimicking the LQT1 form of the congenital long-QT syndrome. METHODS AND RESU...


    pub_type: 杂志文章


    authors: Shimizu W,Antzelevitch C

    更新日期:1998-11-24 00:00:00

  • The cellular electrophysiologic changes induced by ablation: comparison between argon laser photoablation and high-energy electrical ablation.

    abstract::The cellular electrophysiologic effects of myocardial ablation performed in vitro with argon laser energy were compared with those of high-energy electrical shocks. A border zone of injured but nonnecrotic tissue surrounding the site of energy delivery was present after tissue ablation by both energy modalities. A dec...


    pub_type: 杂志文章


    authors: Levine JH,Merillat JC,Stern M,Weisman HF,Kadish AH,Moore EN,Spear JF,Fonger J,Guarnieri T

    更新日期:1987-07-01 00:00:00

  • Preservation of myocardial function with mannitol reperfusate.

    abstract::Reperfusion of the globally ischemic myocardium with mannitol has been shown to preserve myocardial function. However, it remains unclear whether the mechanism of mannitol protection relates to its hyperosmolar or free radical scavenging properties. Three groups of isolated, perfused rabbit hearts underwent 45 min of ...


    pub_type: 杂志文章


    authors: Ouriel K,Ginsburg ME,Patti CS,Pearce FJ,Hicks GL

    更新日期:1985-09-01 00:00:00

  • Randomized trial of simple versus complex drug-eluting stenting for bifurcation lesions: the British Bifurcation Coronary Study: old, new, and evolving strategies.

    abstract:BACKGROUND:The optimal strategy for treating coronary bifurcation lesions remains a subject of debate. With bare-metal stents, single-stent approaches appear to be superior to systematic 2-stent strategies. Drug-eluting stents, however, have low rates of restenosis and might offer improved outcomes with complex stentin...


    pub_type: 杂志文章,多中心研究,随机对照试验


    authors: Hildick-Smith D,de Belder AJ,Cooter N,Curzen NP,Clayton TC,Oldroyd KG,Bennett L,Holmberg S,Cotton JM,Glennon PE,Thomas MR,Maccarthy PA,Baumbach A,Mulvihill NT,Henderson RA,Redwood SR,Starkey IR,Stables RH

    更新日期:2010-03-16 00:00:00

  • A randomized trial of beta-blockade in heart failure. The Cardiac Insufficiency Bisoprolol Study (CIBIS). CIBIS Investigators and Committees.

    abstract:BACKGROUND:Functional benefit in heart failure due to idiopathic dilated cardiomyopathy has been observed after beta-blockade, but improvement in survival has not been established in a large-scale randomized trial. This was the main objective of the Cardiac Insufficiency Bisoprolol Study (CIBIS). METHODS AND RESULTS:S...


    pub_type: 临床试验,杂志文章,多中心研究,随机对照试验



    更新日期:1994-10-01 00:00:00

  • Transfer of CD4(+) T cells aggravates atherosclerosis in immunodeficient apolipoprotein E knockout mice.

    abstract:BACKGROUND:Atherosclerosis is associated with immune responses to oxidized lipoproteins and certain microorganisms, but the role of specific immunity has remained unclear. METHODS AND RESULTS:To study the role of immunity in atherosclerosis, we crossed atherosclerosis-prone apoE(-/-) mice with immunodeficient scid/sci...


    pub_type: 杂志文章


    authors: Zhou X,Nicoletti A,Elhage R,Hansson GK

    更新日期:2000-12-12 00:00:00

  • Adenosine-induced coronary vasodilation during transesophageal Doppler echocardiography. Rapid and safe measurement of coronary flow reserve ratio can predict significant left anterior descending coronary stenosis.

    abstract:BACKGROUND:Less invasive methods are replacing traditional invasive means of measuring coronary flow reserve (CFR). Transesophageal echocardiography (TEE) is becoming a useful tool for evaluation of coronary artery disease and has recently been used to measure CFR. This has always been done using dipyridamole, but aden...


    pub_type: 临床试验,杂志文章


    authors: Redberg RF,Sobol Y,Chou TM,Malloy M,Kumar S,Botvinick E,Kane J

    更新日期:1995-07-15 00:00:00

  • Forecasting the future of cardiovascular disease in the United States: a policy statement from the American Heart Association.

    abstract:BACKGROUND:Cardiovascular disease (CVD) is the leading cause of death in the United States and is responsible for 17% of national health expenditures. As the population ages, these costs are expected to increase substantially. METHODS AND RESULTS:To prepare for future cardiovascular care needs, the American Heart Asso...


    pub_type: 共识发展会议,杂志文章


    authors: Heidenreich PA,Trogdon JG,Khavjou OA,Butler J,Dracup K,Ezekowitz MD,Finkelstein EA,Hong Y,Johnston SC,Khera A,Lloyd-Jones DM,Nelson SA,Nichol G,Orenstein D,Wilson PW,Woo YJ,American Heart Association Advocacy Coordinating

    更新日期:2011-03-01 00:00:00

  • Pathophysiology of Takotsubo Syndrome.

    abstract::Originally described by Japanese authors in the 1990s, Takotsubo syndrome (TTS) generally presents as an acute myocardial infarction characterized by severe left ventricular dysfunction. TTS, however, differs from an acute coronary syndrome because patients have generally a normal coronary angiogram and left ventricul...


    pub_type: 杂志文章,评审


    authors: Pelliccia F,Kaski JC,Crea F,Camici PG

    更新日期:2017-06-13 00:00:00

  • Intermittent perfusion of ischemic myocardium. Possible mechanisms of protective effects on mechanical function in isolated rat heart.

    abstract::Intermittent restoration of coronary flow during ischemia reduced myocardial damage and improved recovery of function. The mechanisms of the protective effects of intermittent perfusion were investigated in isolated rat hearts. Ventricular function was assessed as the product of developed pressure (left ventricular sy...


    pub_type: 杂志文章


    authors: Tani M,Neely JR

    更新日期:1990-08-01 00:00:00

  • Vascular signal transducer and activator of transcription-3 promotes angiogenesis and neuroplasticity long-term after stroke.

    abstract:BACKGROUND:Poststroke angiogenesis contributes to long-term recovery after stroke. Signal transducer and activator of transcription-3 (Stat3) is a key regulator for various inflammatory signals and angiogenesis. It was the aim of this study to determine its function in poststroke outcome. METHODS AND RESULTS:We genera...


    pub_type: 杂志文章


    authors: Hoffmann CJ,Harms U,Rex A,Szulzewsky F,Wolf SA,Grittner U,Lättig-Tünnemann G,Sendtner M,Kettenmann H,Dirnagl U,Endres M,Harms C

    更新日期:2015-05-19 00:00:00

  • The structure of cardiological revolutions. James B. Herrick Lecture.

    abstract::Four revolutions are transforming the cardiology of our day. The first is a social revolution. It has resulted in plummeting esteem for the medical profession reflecting disenchantment coupled with the rapid emergence of the recognition that health care is a right rather than a privilege. The second revolution, interv...


    pub_type: 传,历史文章,杂志文章


    authors: Sobel BE

    更新日期:1993-06-01 00:00:00

  • Improvement in coronary flow reserve determined by positron emission tomography after 6 months of cholesterol-lowering therapy in patients with early stages of coronary atherosclerosis.

    abstract:BACKGROUND:Early stages of coronary atherosclerosis are characterized by a mainly functional impairment of coronary vasodilator capacity under the impact of such risk factors as hypercholesterolemia. The goal of this study was to determine whether 6-month cholesterol-lowering therapy improves coronary flow reserve in p...


    pub_type: 临床试验,杂志文章


    authors: Baller D,Notohamiprodjo G,Gleichmann U,Holzinger J,Weise R,Lehmann J

    更新日期:1999-06-08 00:00:00

  • Non-transferrin-bound iron and risk of coronary heart disease in postmenopausal women.

    abstract:BACKGROUND:Epidemiological studies aimed at correlating coronary heart disease (CHD) with serum ferritin levels have thus far yielded inconsistent results. We hypothesized that a labile iron component associated with non-transferrin-bound iron (NTBI) that appears in individuals with overt or cryptic iron overload might...


    pub_type: 杂志文章


    authors: van der A DL,Marx JJ,Grobbee DE,Kamphuis MH,Georgiou NA,van Kats-Renaud JH,Breuer W,Cabantchik ZI,Roest M,Voorbij HA,van der Schouw YT

    更新日期:2006-04-25 00:00:00

  • Cardiomyocyte-specific overexpression of human stem cell factor improves cardiac function and survival after myocardial infarction in mice.

    abstract:BACKGROUND:Soluble stem cell factor (SCF) has been shown to mobilize bone marrow stem cells and improve cardiac repair after myocardial infarction (MI). However, the effect of membrane-associated SCF on cardiac remodeling after MI is not known. The present study investigated the effects of cardiomyocyte-specific overex...


    pub_type: 杂志文章


    authors: Xiang FL,Lu X,Hammoud L,Zhu P,Chidiac P,Robbins J,Feng Q

    更新日期:2009-09-22 00:00:00

  • Glutathione reverses endothelial damage from peroxynitrite, the byproduct of nitric oxide degradation, in crystalloid cardioplegia.

    abstract:BACKGROUND:NO has been advocated as an adjunct to cardioplegia solutions. However, NO undergoes a rapid biradical reaction with superoxide anions to produce peroxynitrite (ONOO(-)). ONOO(-) in crystalloid cardioplegia solution induces injury to coronary endothelium and to systolic function after cardioplegia and reperf...


    pub_type: 杂志文章


    authors: Nakamura M,Thourani VH,Ronson RS,Velez DA,Ma XL,Katzmark S,Robinson J,Schmarkey LS,Zhao ZQ,Wang NP,Guyton RA,Vinten-Johansen J

    更新日期:2000-11-07 00:00:00

  • Ultrafast computed tomography as a diagnostic modality in the detection of coronary artery disease: a multicenter study.

    abstract:BACKGROUND:Ultrafast computed tomography (CT), by acquiring images of the proximal coronary arteries, detects coronary calcifications and has been demonstrated to be highly sensitive for the detection of coronary artery disease in many small studies. The aim of this study was to determine the relationship between ultra...


    pub_type: 临床试验,杂志文章,多中心研究


    authors: Budoff MJ,Georgiou D,Brody A,Agatston AS,Kennedy J,Wolfkiel C,Stanford W,Shields P,Lewis RJ,Janowitz WR,Rich S,Brundage BH

    更新日期:1996-03-01 00:00:00

  • Edge-to-edge mitral valve repair without ring annuloplasty for acute ischemic mitral regurgitation.

    abstract:BACKGROUND:Alfieri edge-to-edge mitral repair has been used clinically with ring annuloplasty to correct ischemic mitral regurgitation (IMR), but its efficacy without concomitant ring annuloplasty has not been described in this setting. METHODS:Seventeen sheep underwent implantation of 9 radiopaque markers on the left...


    pub_type: 杂志文章


    authors: Timek TA,Nielsen SL,Lai DT,Tibayan FA,Liang D,Rodriguez F,Daughters GT,Ingels NB Jr,Miller DC

    更新日期:2003-09-09 00:00:00

  • Effects of platelet glycoprotein IIb/IIIa blockade with tirofiban on adverse cardiac events in patients with unstable angina or acute myocardial infarction undergoing coronary angioplasty. The RESTORE Investigators. Randomized Efficacy Study of Tirofiban

    abstract:BACKGROUND:Adverse cardiovascular events associated with thrombotic occlusion occur in 4% to 12.8% of patients after coronary angioplasty. Recently, potent antiplatelet agents have been used to reduce those thrombotic complications. Tirofiban is a highly selective, short-acting inhibitor of fibrinogen binding to platel...


    pub_type: 临床试验,杂志文章,随机对照试验



    更新日期:1997-09-02 00:00:00

  • Thromboxane A2, prostacyclin and aspirin: effects on vascular tone and platelet aggregation.

    abstract::Novel compounds that induce or inhibit platelet aggregation and constrict or dilate blood vessels were recently discovered. These compounds are all derivatives of arachidonic acid and include prostaglandin endoperoxides, thromboxane A2, prostaglandin E2, prostaglandin D2 and prostacyclin. Thromboxane A2 (TxA2) could b...


    pub_type: 杂志文章,评审


    authors: Smith JB,Araki H,Lefer AM

    更新日期:1980-12-01 00:00:00

  • Ultrasonic tissue characterization: detection of acute myocardial ischemia in dogs.

    abstract::Ultrasonic tissue characterization is a new area of investigation in the field of cardiac ultrasound. The amplitude and frequency of the ultrasound signal are normally altered as the signal penetrates through tissue. It is assumed that the amplitude distribution and frequency shift of diseased or edematous tissue are ...


    pub_type: 杂志文章


    authors: Schnittger I,Vieli A,Heiserman JE,Director BA,Billingham ME,Ellis SG,Kernoff RS,Takamoto T,Popp RL

    更新日期:1985-07-01 00:00:00

  • Prognostic significance of microvascular obstruction by magnetic resonance imaging in patients with acute myocardial infarction.

    abstract:BACKGROUND:The extent of microvascular obstruction during acute coronary occlusion may determine the eventual magnitude of myocardial damage and thus, patient prognosis after infarction. By contrast-enhanced MRI, regions of profound microvascular obstruction at the infarct core are hypoenhanced and correspond to greate...


    pub_type: 杂志文章


    authors: Wu KC,Zerhouni EA,Judd RM,Lugo-Olivieri CH,Barouch LA,Schulman SP,Blumenthal RS,Lima JA

    更新日期:1998-03-03 00:00:00