Unusual effects of aspirin on ticlopidine induced thrombolysis

Rj, Gryglewski; Uracz, W; Swieş, J

doi:10.1136/thorax.55.suppl_2.s17

Cited by 8 publications

(6 citation statements)

References 18 publications

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“…ASA increases NO production by platelets (27), endothelial cells (28) and by neutrophils during endothelial damage (29). Thienopyridines cause similar increases in NO release in endothelial cells (30) and leucocytes (31). In addition to its known vasodilatory effects, dypiridamole appears to possess anti-inflammatory properties (32).…”

Section: Original Articlementioning

confidence: 99%

Pre Admission Antithrombotics are Associated with Improved Outcomes following Ischaemic Stroke: A Cohort from the Registry of the Canadian Stroke Network

Dowlatshahi

Hakim

Fang

et al. 2009

International Journal of Stroke

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Patients with acute ischaemic stroke taking antithrombotic medications at hospital admission have improved functional outcomes. No interaction is noted between use of these medications and outcome following thrombolysis. This large prospective cohort study is consistent with previous published reports, and supports the notion that pre admission antithrombotics may mitigate brain injury during acute stroke.

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Section: Original Articlementioning

confidence: 99%

Pre Admission Antithrombotics are Associated with Improved Outcomes following Ischaemic Stroke: A Cohort from the Registry of the Canadian Stroke Network

Dowlatshahi

Hakim

Fang

et al. 2009

International Journal of Stroke

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“…A collagen strip from the rabbit Achilles tendon was superfused with arterial blood at a rate of 1.5 ml/min −1 , and its weight was continuously monitored by an auxotonic Harvard transducer. During the initial 20 minutes of superfusion, the strip gained 80‐120 mg in weight23,24 because of the deposition of platelet‐rich thrombi,25 and this weight remained unchanged for the next 5 hours. In our assay system, intravenous injection of prostacyclin or iloprost (0.1‐1.0 μg/kg −1 ), glyceryl trinitrate (30‐100 μg/kg −1 ), metacholine hydrochloride (10 μg/kg −1 ), or kallikrein (100 units/kg −1 ) produced a transient loss in weight of thrombi described as the “thrombolytic response.” Streptokinase (3‐30 megaunits/kg −1 ) evoked a biphasic thrombogenic/thrombolytic response 23,24.…”

Section: Methodsmentioning

confidence: 99%

“…During the initial 20 minutes of superfusion, the strip gained 80‐120 mg in weight23,24 because of the deposition of platelet‐rich thrombi,25 and this weight remained unchanged for the next 5 hours. In our assay system, intravenous injection of prostacyclin or iloprost (0.1‐1.0 μg/kg −1 ), glyceryl trinitrate (30‐100 μg/kg −1 ), metacholine hydrochloride (10 μg/kg −1 ), or kallikrein (100 units/kg −1 ) produced a transient loss in weight of thrombi described as the “thrombolytic response.” Streptokinase (3‐30 megaunits/kg −1 ) evoked a biphasic thrombogenic/thrombolytic response 23,24. In the present study, the thrombolytic response to intravenously administered ACE‐Is or statins was complemented by a blood assay of 6‐keto‐PGF 1α and plasma assay of t‐PA antigen.…”

Section: Methodsmentioning

confidence: 99%

“…Streptokinase (3-30 megaunits/kg -1 ) evoked a biphasic thrombogenic/thrombolytic response. 23,24 In the present study, the thrombolytic response to intravenously administered ACE-Is or statins was complemented by a blood assay of 6-keto-PGF 1α and plasma assay of t-PA antigen. For this purpose, blood samples (500 µl) were collected in Eppendorff tubes with indomethacin to yield a final concentration of 10 µM.…”

Section: Assay Of Pgi 2 -Mediated Thrombolysis In Rats With Extracorpmentioning

confidence: 99%

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Comparison of Endothelial Pleiotropic Actions of Angiotensin Converting Enzyme Inhibitors and Statins

Gryglewski

Uracz

Swieş

et al. 2001

Annals of the New York Academy of Sciences

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Two in vitro and one in vivo assay were performed to study the endothelial pleiotropic actions of “tissue type” angiotensin converting enzyme inhibitors (ACE‐Is) such as perindopril and quinapril, their active forms, that is, quinaprilat and peridoprilat, or of statins belonging to natural (lovastatin), semisynthetic (simvastatin), and synthetic enantiomeric (atorvastatin, cerivastatin) classes. Cytoplasmic [Ca2+]i levels in cultured bovine aortic endothelial cells and endothelium‐dependent nitric oxide‐mediated coronary vasodilatation in the Langendorff preparation of guinea pig heart constituted our in vitro assays. The in vivo assay consisted of study of PGI2‐mediated thrombolytic response in arterial blood of rats after intravenous administration of drugs. In this last assay, perindopril and quinapril proved to be, by two orders of magnitude, more potent PGI2‐dependent thrombolytics than the most potent statin (atorvastatin). However, in both in vitro assays we found a higher endothelial efficacy of statins as compared to ACE‐Is. In particular, those statins that contain the lactone ring in their molecules (lovastatin, simvastatin) were the most potent coronary vasodilators. In summary, the in vivo profile of action of ACE‐Is and statins contrasted with their reversed order of potency in vitro. We hypothesize that the endocrine‐like function of the pulmonary circulation [28‐31] may be responsible for the in vivo bradykinin‐triggered, PGI2‐mediated thrombolysis by ACE‐Is, whereas the pleiotropic action of statins, possibly involving inhibition of prenylation [14‐19], is diffused throughout many vascular beds.

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“…An in vivo model for studying thrombolysis in cats [29] was adopted to rats [30,31]. Brie£y, male Wistar rats (body weight 300^350 g) were anesthetized (thiopental 30 mg kg -1 ip) and unfractionated heparin at 800 units kg -1 iV was adminsitered.…”

Section: Thrombolytic Assay For Activation Of Entire Endothelial Systmentioning

confidence: 99%

Bradykinin as a Major Endogenous Regulator of Endothelial Function

Gryglewski

Uracz

Chłopicki

et al. 2002

Pediatric Pathology & Molecular Medicine

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Healthy vascular endothelium is a powerful generator of nitric oxide (NO), prostacyclin (PGI2), prostaglandin E2 (PGE2), and plasminogen activator (t-PA). These endothelial products protect vascular wall against aggression from activated blood platelets and leukocytes. In particular they protect against thrombosis, promote thrombolysis, maintain tissue perfusion, and inhibit remodeling of vascular and cardiac walls. Endothelial dysfunction appears on one hand as suppression in the release of the above mediators, and on the other as deleterious discharge of prostaglandin endoperoxides (PGH2, PGG2), superoxide anion O2-, peroxynitrite (ONOO-), and plasminogen activator inhibitor (PAI-1). Our data point to endothelial bradykinin (Bk) as a trigger for protective endothelial mechanisms. In cultured endothelial cells (CEC) Bk through kinin B2 receptors raised in a concentration-dependent manner (1pM-10 nM) free cytoplasmic calcium ions [Ca2+]i. This rise was accompanied by the release of NO as quantified by a porphyrinic sensor. Other endothelial agonists were weaker-stimulators of [Ca2+]i than Bk. In vivo we analyed the effects of exogenous Bk and of amplifiers of endogenous Bk, such as perindopril and quinapril ("tissue type" angiotensin converting enzyme inhibitors, ACE-I) on endothelial function using our original thrombolytic bioassay and EIA assays for 6-keto-PGF1alpha and t-PA antigen. A major difference found between exogenuous Bk and endogenous Bk (that rendered by "tissue ACE-I") was a) prolonged thrombolytic action (> 4h) of quinapril or perindopril. Moreover, only exogenous Bk evoked an immediate and profound hypotensive action. In vivo, Bk-induced thrombolysis was B2 kinin receptor-dependent, PGI2-mediated. The unexpected action of Bk came to light in CEC. Then appeared incubated for 4 h increased expression of mRNAs for haemoxygenase (HO-1), cyclooxygenase 2 (COX-2), prostaglandin E synthase (PGE-S), but hardly for nitric oxide synthase 2(NOS-2). We hypothesize that a network of interactions of Bk-induced enzymes may constitute a delayed phase of Bk effects in the endothelium, whereas the primary phase would be activation by BK of [Ca2+]i-dependent constitutive endothelial enzymes. In blood-perfused rat endotoxemic lungs, NO is the most eminent cytoprotective mediator. Summing up, in peripheral circulation endogenous Bk is the most efficient activator of protective endothelial function. Thrombolytic action of "tissue-type" ACE-Is relies on receptor B-2-mediated, [Ca2+]i-dependent release of PGI2. Bk also may act as a "microcytokine" by inducing mRNAs for HO-1, COX-2, or PGE-S. Activation of HO-1 may lead to a deficiency in intracellular heme required as a cofactor for both COX and NOS. This network of interactions triggered by Bk call for further studies.

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Unusual effects of aspirin on ticlopidine induced thrombolysis

Cited by 8 publications

References 18 publications

Pre Admission Antithrombotics are Associated with Improved Outcomes following Ischaemic Stroke: A Cohort from the Registry of the Canadian Stroke Network

Pre Admission Antithrombotics are Associated with Improved Outcomes following Ischaemic Stroke: A Cohort from the Registry of the Canadian Stroke Network

Comparison of Endothelial Pleiotropic Actions of Angiotensin Converting Enzyme Inhibitors and Statins

Bradykinin as a Major Endogenous Regulator of Endothelial Function

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