Importance of platelets in myocardial injury after reperfusion in the presence of residual coronary stenosis in dogs

Rousseau, Guy; Hebert, Daniel N.; Libersan, Danielle; Khalil, Ahmad; St-Jean, Gilles; Latour, Jean-Gilles

doi:10.1016/0002-8703(93)90740-z

Cited by 22 publications

(5 citation statements)

References 33 publications

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“…In addition to being involved in thrombus formation, aggregating platelets can initiate intense vasoconstriction after the activation and release of potent vasoactive mediators (Saldeen et al, 1993;Yao et al, 1993). Infarct size expansion is related to the extent of platelet accumulation in myocardium that has undergone reperfusion in the presence of a critical stenosis (Rousseau et al, 1993). The beneficial effect on the salvage of myocardial tissue, after inhibition of the GPIIb/IIIa receptor, may derive, in part, from the fact that coronary artery blood flow is maintained and not compromised by repetitive episodes of oscillatory blood flow commonly observed after thrombolysis in the absence of adjunctive anti-platelet therapy.…”

Section: Discussionmentioning

confidence: 99%

Prevention of thrombosis and rethrombosis and enhancement of the thrombolytic actions of recombinant tissue‐type plasminogen activator in the canine heart by DMP728, a glycoprotein IIb/IIIa antagonist

Lucchessi

Rote

Driscoll

et al. 1994

British J Pharmacology

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1 We studied DMP728, a non-peptide glycoprotein (GP) IIb/IIIa receptor antagonist, for prevention of coronary artery thrombosis or rethrombosis in a chronic canine model subjected to arterial injury. 2 In protocol I, DMP728 (1.0mg kg-', i.v., n = 8) or saline (n = 8) was administered and a 150 JA anodal current was applied to the intimal surface of the left circumflex coronary artery (LCX). Dogs were monitored for 6 h and again on each of 5 subsequent days. 3 Ex vivo platelet aggregation was inhibited but returned to baseline day after drug administration. Thrombus weight was reduced (saline, 20.7 ± 5.0 mg; DMP728 1.7 ± 0.4 mg; P < 0.05), as was infarct size [saline, 27.5 ± 4.3; DMP728, 1.6 ± 0.7 (per cent left ventricle); P<0.05]. All control animals died by day 3, while all but one of the treated dogs survived the entire protocol (P <0.05). 4 In protocol II, an LCX thrombus was induced and thrombolytic therapy was initiated 30 min later. DMP728 (1.0 mg kg-', i.v., n = 8) or saline (n = 8) was administered 5 min after recombinant tissue-type plasminogen activator infusion had begun. The incidence of reocclusion was reduced by DMP728 (saline, 4/8; DMP728, 1/8). One day after thrombolysis, 7/8 DMP728-treated animals were alive compared with 1/8 in the control group (P = 0.01). 5 DMP728 inhibited ex vivo platelet aggregation, prevented primary and secondary occlusive thrombus formation, reduced thrombus weight and infarct size and increased survival in a chronic canine model of coronary artery thrombus formation. DMP728 is an effective anti-platelet intervention when used as the singular adjunctive agent in association with thrombolytic therapy.

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Section: Discussionmentioning

confidence: 99%

Prevention of thrombosis and rethrombosis and enhancement of the thrombolytic actions of recombinant tissue‐type plasminogen activator in the canine heart by DMP728, a glycoprotein IIb/IIIa antagonist

Lucchessi

Rote

Driscoll

et al. 1994

British J Pharmacology

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“…The rabbit anti‐platelet serum (RAPS) was prepared as detailed previously (21,22). Briefly, washed platelets (3 × 10 9 ) were isolated from normal rats, homogenized with Freund’s complete adjuvant, and injected subcutaneously into rabbits.…”

Section: Methodsmentioning

confidence: 99%

Short-term induction of thrombocytopenia delays periodontal healing in rats with periodontal disease: participation of endostatin and vascular endothelial growth factor

Spolidório

Herrera

Coimbra

et al. 2010

Journal of Periodontal Research

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“…38,39 To evaluate the relevance of VASP for the regulation of platelet-vessel interactions under pathophysiologic conditions in vivo, we determined platelet adhesion within the microcirculation of an ischemic-reperfused segment of the jejunum using intravital video microscopy. Wild-type or VASP Ϫ/Ϫ mice were subjected to intestinal ischemia (60 minutes).…”

Section: Vasp Attenuates Platelet Adhesion To the Postischemic Microvmentioning

confidence: 99%

Enhanced in vivo platelet adhesion in vasodilator-stimulated phosphoprotein (VASP)–deficient mice

Maßberg

Grüner

Konrad

et al. 2004

Blood

122

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Platelet adhesion and activation at the vascular wall are the initial steps leading to arterial thrombosis and vascular occlusion. Prostacyclin and nitric oxide inhibit platelet adhesion, acting via cyclic adenosine monophosphate (cAMP)-and cyclic guanosine monophosphate (cGMP)-dependent protein kinases. A major downstream target for both cAMP-and cGMPdependent protein kinases is the vasodilator-stimulated phosphoprotein (VASP). To test the significance of VASP for the regulation of platelet adhesion in vivo, we studied platelet-vessel wall interactions using VASP-deficient (VASP ؊/؊ ) mice. Under physiologic conditions, platelet adhesion to endothelial cells was significantly enhanced in VASP null mutants when compared with wild-type mice (P < .05). Platelet recruitment in VASP null mice involved P-selectin and the fibrinogen receptor glycoprotein IIb-IIIa (GPIIb-IIIa). Under pathophysiologic conditions, the loss of VASP increased platelet adhesion to the postischemic intestinal microvasculature, to the atherosclerotic endothelium of ApoE-deficient mice, and to the subendothelial matrix following endothelial denudation (P < .05 vs wild type). Importantly, platelet adhesion in VASP null mutants was unresponsive to nitric oxide. These data show for the first time in vivo that VASP is involved in down-regulation of platelet adhesion to the vascular wall under both physiologic and pathophysiologic conditions. ( IntroductionThe adhesion of platelets to the vascular wall is central to the pathogenesis of atherogenesis and arterial thrombosis. 1,2 Nitric oxide (NO) and prostacyclin are of major importance for the regulation of platelet-vessel wall interactions. They activate soluble guanylyl cyclase and adenylate cyclase, respectively, initiating a subsequent rise in platelet cyclic guanosine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP). [3][4][5] Cyclic GMPdependent protein kinase I (cGKI) and cAMP-dependent protein kinase (cAK) are thought to be the major downstream targets of the NO/cGMP and prostacyclin/cAMP signaling cascades in platelets. 3,6,7 A common substrate of both cAK and cGK is the vasodilatorstimulated phosphoprotein (VASP). [8][9][10] VASP was isolated initially from human platelets but it is also expressed in a wide variety of other cells and tissues. 11 VASP is the founding member of a family of proline-rich proteins designated the Ena/VASP protein family, which comprises VASP, Drosophila Enabled (Ena), a substrate of the Abelson tyrosine kinase (Abl), the mammalian Ena homolog Mena, and the Ena-VASP-like protein Evl. 12-14 These proteins share highly homologous N-terminal and C-terminal domains (Ena-VASP homology domains 1 and 2, designated EVH1 and EVH2) and proline-rich central domains. 12-14 VASP has been found to be associated with focal adhesions, stress fibers, cell-cell contacts, and highly dynamic membrane regions in platelets, smooth muscle cells, endothelial cells, and fibroblasts. 11,15 VASP directly binds to profilin, zyxin, and to the focal adhesion and cell-cell cont...

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Importance of platelets in myocardial injury after reperfusion in the presence of residual coronary stenosis in dogs

Cited by 22 publications

References 33 publications

Prevention of thrombosis and rethrombosis and enhancement of the thrombolytic actions of recombinant tissue‐type plasminogen activator in the canine heart by DMP728, a glycoprotein IIb/IIIa antagonist

Prevention of thrombosis and rethrombosis and enhancement of the thrombolytic actions of recombinant tissue‐type plasminogen activator in the canine heart by DMP728, a glycoprotein IIb/IIIa antagonist

Short-term induction of thrombocytopenia delays periodontal healing in rats with periodontal disease: participation of endostatin and vascular endothelial growth factor

Enhanced in vivo platelet adhesion in vasodilator-stimulated phosphoprotein (VASP)–deficient mice

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