Combined thromboxane A2synthase inhibition and prostaglandin endoperoxide receptor antagonism limits myocardial infarct size after mechanical coronary occlusion and reperfusion at doses enhancing coronary thrombolysis by streptokinase

Vandeplassche, G; Hermans, Carlo; Somers, Yves; Werf, Frans Van de; Clerck, Fred De

doi:10.1016/0735-1097(93)90256-z

Cited by 12 publications

(4 citation statements)

References 32 publications

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“…A large number of publications report the use of thrombolytics in experimental arterial thrombosis models in dogs (LOE 3), but lack suitable controls thereby precluding their use to address the PICO question 26–86 . In most of these studies, thrombolytics were administered within 60 minutes of thrombosis, 10,18,26–29,31,33,34,36,39–41,45–58,61,64–69,73–76,78–82,84,85,87–94 with fewer studies investigating thrombolytics administered 90 minutes, 43,44,86,95 2 hours, 30,38,62,72,77 3 hours, 63,70 or 6 hours 96 after thrombosis.…”

Section: Resultsmentioning

confidence: 99%

“…Additionally, case series and case reports have reported the use of aspirin 116 or clopidogrel 97,98 in association with thrombolytics in dogs with naturally occurring thrombosis but did not directly address the PICO question as there was no comparator group. Studies assessing antiplatelet drugs that are not commercially available pharmaceuticals such as ridogrel, 66 DMP728, 86,123 CRL42796, 37 BIBU 52ZW (Fradafiban), 31 RPR109891, 40 and TP‐9201 124 were not included in the systematic review.…”

Section: Resultsmentioning

confidence: 99%

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2022 Update of the Consensus on the Rational Use of Antithrombotics and Thrombolytics in Veterinary Critical Care (CURATIVE) Domain 6: Defining rational use of thrombolytics

Sharp

Blais

Boyd

et al. 2022

J Vet Emergen Crit Care

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ObjectivesTo systematically review available evidence and establish guidelines related to the use of thrombolytics for the management of small animals with suspected or confirmed thrombosis.DesignPICO (Population, Intervention, Control, and Outcome) questions were formulated, and worksheets completed as part of a standardized and systematic literature evaluation. The population of interest included dogs and cats (considered separately) and arterial and venous thrombosis. The interventions assessed were the use of thrombolytics, compared to no thrombolytics, with or without anticoagulants or antiplatelet agents. Specific protocols for recombinant tissue plasminogen activator were also evaluated. Outcomes assessed included efficacy and safety. Relevant articles were categorized according to level of evidence, quality, and as to whether they supported, were neutral to, or opposed the PICO questions. Conclusions from the PICO worksheets were used to draft guidelines, which were subsequently refined via Delphi surveys undertaken by the Consensus on the Rational Use of Antithrombotics and Thrombolytics in Veterinary Critical Care (CURATIVE) working group.ResultsFourteen PICO questions were developed, generating 14 guidelines. The majority of the literature addressing the PICO questions in dogs is experimental studies (level of evidence 3), thus providing insufficient evidence to determine if thrombolysis improves patient‐centered outcomes. In cats, literature was more limited and often neutral to the PICO questions, precluding strong evidence‐based recommendations for thrombolytic use. Rather, for both species, suggestions are made regarding considerations for when thrombolytic drugs may be considered, the combination of thrombolytics with anticoagulant or antiplatelet drugs, and the choice of thrombolytic agent.ConclusionsSubstantial additional research is needed to address the role of thrombolytics for the treatment of arterial and venous thrombosis in dogs and cats. Clinical trials with patient‐centered outcomes will be most valuable for addressing knowledge gaps in the field.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

2022 Update of the Consensus on the Rational Use of Antithrombotics and Thrombolytics in Veterinary Critical Care (CURATIVE) Domain 6: Defining rational use of thrombolytics

Sharp

Blais

Boyd

et al. 2022

J Vet Emergen Crit Care

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“…The most studied of these compounds are samixogrel and ridogrel. Ridogrel is effective in models of coronary thrombosis, it shortens the time of reperfusion when used in combination with tPA (tissue plasminogen activator) and reduces infarct size [53,54]. It has been tested as anti-thrombotic and anti-inflammatory agent in clinical trials [55,56], but has never been evaluated for its capacity to inhibit angiogenesis.…”

Section: Dual Thromboxane Synthase Inhibi-tor/thromboxane Receptor Anmentioning

confidence: 99%

Emerging Therapeutic Approaches Multi-Targeting Receptor Tyrosine Kinases and G Protein-Coupled Receptors in Cardiovascular Disease

Flordellis¹,

Papathanasopoulos

Lymperopoulos³

et al. 2007

CHAMC

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Advances in molecular biology and functional genomics have demonstrated that the "one gene-one phenotype-one drug" paradigm, that has dominated pharmaceutical industry and clinical pharmacology thinking, is too simplistic for management of complex polygenic traits. The traditional highly specific drugs with unique target have proven their clinical usefulness. However, they do not always display the required efficacy versus side-effect profile, in major part because polygenic traits are determined by redundant mechanisms. Simultaneously modulating multiple targets may enhance therapeutic efficacy in the treatment of a range of disorders. Multi-targeting can be achieved by the combination of different drugs having specific single target activity. This approach introduces potential problems with pharmacokinetic interactions, toxicity and patient compliance. High efficacy can be achieved, alternatively, by administering selectively non-selective drugs with complex pharmacological profiles directed towards various molecular targets and affording pleiotropic actions. Dual- or multiple-ligands can be discovered accidentally, but can also be rationally designed according to validated medicinal chemical approaches. The merits of multiple-target versus single-target approaches for cardiovascular disease traits are assessed in the present review. The main aim is to make evident the molecular biological basis of the possibility for targeting multiple sites and the subsequently emerging strategies for interventions with superior clinical value by harnessing receptor tyrosine kinases (RTKs) such as VEGFR, PDGFR, bFGFR, as well as G protein-coupled receptors (GPCRs). The premises for lead discovery in this new area and the challenges of medicinal chemistry behind the rational design of multitasked ligands are also discussed.

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“…However, specific inhibitors of TXA 2 synthase are also responsible for increasing generation of prostanoids such as prostaglandin I 2 , which can be beneficial by attenuating platelet activation and decreasing vascular resistance. Therefore, efforts to modulate the actions of TXA 2 focused on agents able to block biosynthesis of TXA 2 and to antagonize both PGH 2 and TXA 2 at their common receptor (Oates et al, 1988;Vandeplassche et al, 1991;Vandeplassche et al, 1993).…”

Section: Introductionmentioning

confidence: 99%

Effects of U-46619 on Pulmonary Hemodynamics Before and After Administration of BM-573, a Novel Thromboxane A2 Inhibitor

Lambermont¹,

Kolh

Dogné³

et al. 2003

Archives of Physiology and Biochemistry

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We studied the effects on pulmonary hemodynamics of U-46619, a thromboxane A 2 (TXA 2 ) agonist, before and after administration of a novel TXA 2 receptor antagonist and synthase inhibitor (BM-573). Six anesthetized pigs (Ago group) received 6 consecutive injections of U-46619 at 30-min interval and were compared with six anesthetized pigs (Anta group) which received an increasing dosage regimen of BM-573 10 min before each U-46619 injection. Consecutive changes in pulmonary hemodynamics, including characteristic resistance, vascular compliance, and peripheral vascular resistance, were continuously assessed during the experimental protocol using a four-element Windkessel model. At 2 mg/kg, BM-573 completely blocked pulmonary hypertensive effects of U-46619 but pulmonary vascular compliance still decreased. This residual effect can probably be explained by a persistent increase in the tonus of the pulmonary vascular wall smooth muscles sufficient to decrease vascular compliance but not vessel lumen diameter. Such molecule could be a promising therapeutic approach in TXA 2 mediated pulmonary hypertension as it is the case in pulmonary embolism, hyperacute lung rejection and endotoxinic shock.

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Combined thromboxane A2synthase inhibition and prostaglandin endoperoxide receptor antagonism limits myocardial infarct size after mechanical coronary occlusion and reperfusion at doses enhancing coronary thrombolysis by streptokinase

Cited by 12 publications

References 32 publications

2022 Update of the Consensus on the Rational Use of Antithrombotics and Thrombolytics in Veterinary Critical Care (CURATIVE) Domain 6: Defining rational use of thrombolytics

2022 Update of the Consensus on the Rational Use of Antithrombotics and Thrombolytics in Veterinary Critical Care (CURATIVE) Domain 6: Defining rational use of thrombolytics

Emerging Therapeutic Approaches Multi-Targeting Receptor Tyrosine Kinases and G Protein-Coupled Receptors in Cardiovascular Disease

Effects of U-46619 on Pulmonary Hemodynamics Before and After Administration of BM-573, a Novel Thromboxane A2 Inhibitor

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