Brief antecedent ischemia attenuates platelet-mediated thrombosis in damaged and stenotic canine coronary arteries: Role of adenosine

K. Hata, P. Whittaker, R. A. Kloner, K. Przyklenk

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58 Scopus citations

Abstract

Background - Recent studies suggest that patients with angina before myocardial infarction exhibit improved recovery of coronary perfusion after thrombolysis by an as-yet-unknown mechanism. We therefore proposed that brief antecedent ischemia/reperfusion may, via release of adenosine, improve vessel patency in damaged and stenotic coronary arteries. Methods and Results - Anesthetized dogs underwent coronary injury+stenosis, resulting in repeated cyclic variations in coronary blood flow (CFVs) caused by the formation/dislodgment of platelet-rich thrombi. Vessel patency was assessed for 3 hours after stenosis by quantification of the nadir of the CFVs, duration of total thrombotic occlusion (flow= 0), and area of the flow-time profile (expressed as percent of baseline flow X 180 minutes). In protocol 1, dogs received 10 minutes of coronary occlusion+ 10 minutes of reflow or a comparable 20-minute control period before injury+stenosis. The median nadir of the CFVs was higher (4.0 versus 0.3 mL/min), median zero flow duration per 30-minute time interval was shorter (0.4 versus 15.1 minutes), and mean percent flow-time area was greater (54±8% versus 28±9%) in dogs that received antecedent ischemia versus controls (P<.05). These benefits of antecedent ischemia/reperfusion were largely mimicked by a 10-minute intracoronary adenosine infusion (400 μg/min) in lieu of brief ischemia (protocol 2) and were abolished by administration of the adenosine A1/A2 receptor antagonist PD 115,199 (3 mg/kg IV) before brief antecedent coronary occlusion (protocol 3). Conclusions - Brief antecedent ischemia attenuates subsequent platelet-mediated thrombosis in damaged and stenotic canine coronary arteries, due, in large part, to an adenosine-mediated mechanism.

Original languageEnglish
Pages (from-to)692-702
Number of pages11
JournalCirculation
Volume97
Issue number7
DOIs
StatePublished - Feb 24 1998

Keywords

  • Adenosine
  • Ischemia
  • Platelets
  • Stenosis
  • Thrombosis

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