J G Kingma1, S Plante, P Bogaty. 1. Department of Medicine, Faculty of Medicine, Laval University, Sainte-Foy, Quebec, Canada. john.kingma@med.ulaval.ca
Abstract
OBJECTIVES: We studied the effects of N-acetyl-cys-asn-(5,5-dimethyl-4-thiazolidine-carbonyl)-4-amino-methyl-phe-gly-asp-cys, monoacetate (MK-0852) (platelet GPIIb/IIIa receptor blocker) on peak reactive hyperemia, distribution of blood flow, regional contractile function and infarct size in a canine model of acute ischemia-reperfusion injury. BACKGROUND: Platelet activation and formation of platelet microaggregates in coronary vessels could contribute to ischemia-induced myocyte injury. Inhibition of platelet aggregation could reduce ischemia-reperfusion injury. METHODS: Three groups of dogs (n = 10/group) were studied; group 1--heparin (HEP) (100 U/kg/h intravenously), group 2--MK-0852 (300 microg/kg intravenous bolus followed by 3 microg/kg/min for 3 h) and group 3--MK-0852 plus HEP. Infarct size after 60 min regional ischemia and 3 h reperfusion was evaluated by tetrazolium staining and normalized to risk area (Monastral blue dye). RESULTS: Infarct size in HEP-treated controls was 32.4+/-2.8%; in MK-0852 without or with HEP groups, infarct size was 17.4+/-1.9% (p = 0.001) and 23.4+/-3.0% (p = 0.04), respectively. Cardiac hemodynamics and rate-pressure product were comparable between groups. Multivariate analysis using collateral blood flow as the independent variable confirmed the cytoprotective actions of MK-0852. Postischemic peak reactive hyperemia in the infarct-related artery was depressed in all groups; during reperfusion, transmural distribution of myocardial blood flow returned to near control levels, but severe regional hypokinesia persisted. CONCLUSIONS: Diminished infarct size with MK-0852 treatment suggests an additional mechanism of benefit for GPIIb/IIIa blockers beyond stabilization of a "culprit" acute coronary lesion. This cytoprotective effect was unrelated to preservation of coronary vasoreactivity (assessed by reactive hyperemia), restoration of blood flow across the myocardium or acute improvement in contractility.
OBJECTIVES: We studied the effects of N-acetyl-cys-asn-(5,5-dimethyl-4-thiazolidine-carbonyl)-4-amino-methyl-phe-gly-asp-cys, monoacetate (MK-0852) (platelet GPIIb/IIIa receptor blocker) on peak reactive hyperemia, distribution of blood flow, regional contractile function and infarct size in a canine model of acute ischemia-reperfusion injury. BACKGROUND: Platelet activation and formation of platelet microaggregates in coronary vessels could contribute to ischemia-induced myocyte injury. Inhibition of platelet aggregation could reduce ischemia-reperfusion injury. METHODS: Three groups of dogs (n = 10/group) were studied; group 1--heparin (HEP) (100 U/kg/h intravenously), group 2--MK-0852 (300 microg/kg intravenous bolus followed by 3 microg/kg/min for 3 h) and group 3--MK-0852 plus HEP. Infarct size after 60 min regional ischemia and 3 h reperfusion was evaluated by tetrazolium staining and normalized to risk area (Monastral blue dye). RESULTS:Infarct size in HEP-treated controls was 32.4+/-2.8%; in MK-0852 without or with HEP groups, infarct size was 17.4+/-1.9% (p = 0.001) and 23.4+/-3.0% (p = 0.04), respectively. Cardiac hemodynamics and rate-pressure product were comparable between groups. Multivariate analysis using collateral blood flow as the independent variable confirmed the cytoprotective actions of MK-0852. Postischemic peak reactive hyperemia in the infarct-related artery was depressed in all groups; during reperfusion, transmural distribution of myocardial blood flow returned to near control levels, but severe regional hypokinesia persisted. CONCLUSIONS: Diminished infarct size with MK-0852 treatment suggests an additional mechanism of benefit for GPIIb/IIIa blockers beyond stabilization of a "culprit" acute coronary lesion. This cytoprotective effect was unrelated to preservation of coronary vasoreactivity (assessed by reactive hyperemia), restoration of blood flow across the myocardium or acute improvement in contractility.
Authors: Amy H Kao; Christine A McBurney; Abdus Sattar; Apinya Lertratanakul; Nicole L Wilson; Sarah Rutman; Barbara Paul; Jeannine S Navratil; Andrea Scioscia; Joseph M Ahearn; Susan Manzi Journal: Transl Stroke Res Date: 2013-10-27 Impact factor: 6.829
Authors: Mehran Ghasemzadeh; Zane S Kaplan; Imala Alwis; Simone M Schoenwaelder; Katrina J Ashworth; Erik Westein; Ehteramolsadat Hosseini; Hatem H Salem; Robyn Slattery; Shaun R McColl; Michael J Hickey; Zaverio M Ruggeri; Yuping Yuan; Shaun P Jackson Journal: Blood Date: 2013-04-02 Impact factor: 22.113