title: Regional and Systemic Platelet Function Is Altered by Myocardial Ischemia-Reperfusion.
abstract: Background: Myocardial reperfusion after short durations of ischemia causes prolonged contractile dysfunction (myocardial stunning). Recently it has also been suggested that ischemia-reperfusion results in impaired coronary endothelial function. Since platelet function is, in part, regulated by an intact functioning endothelium, platelet function could be expected to change during ischemia-reperfusion. However, the effect of ischemia and reperfusion on regional and systemic platelet function is unknown. The purpose of this study was to determine the effect of a brief period of myocardial ischemia followed by reperfusion on regional and systemic platelet function. Methods: Fourteen swine in an open-chest model underwent left anterior descending coronary artery (LAD) occlusion for 15 minutes followed by 120 minutes of reperfusion. Platelet aggregability in response to 5 µM ADP was determined simultaneously in the femoral (systemic; N = 14) and great cardiac (regional; N = 9) venous blood at baseline, during occlusion, and at 40 and 90 minutes after reperfusion. LAD blood flow and regional myocardial function were determined by standard methods. Results: Hemodynamics remained stable in all animals. During LAD occlusion platelet aggregability, increased only in the regional coronary circulation (126% of baseline, p =.0001). At 40 minutes of reperfusion systemic platelet aggregahility decreased (86% of baseline, p =.0001) and subsequently increased at 90 minutes at reperfusion in both the systemic (127% of baseline, p =.0001) and regional circula. tions (156% of baseline, p =.0001). Ischemia was evident by the absence ofdistal LAD flow during occlusion that returned during reperfusion and a typical response ofmyocardial stunning in each animal (stunning time = 47.7 +/- 5.2 minutes). Conclusions: This study demonstrates that platelet function is not static during ischemia-reperfusion. Instead, during ischemia regional platelet aggregability is increased. Systemic and regional platelet aggregability also increase during myocardial reperfusion. The mechanism of these responses is unknown but may be related to regional endathelial dysfunction created by ischernia. The response observed could also be explained by the release of proaggregatory mediators in the connary and/or systemic circulation during ischemia-reperfusion. The relative hyeraggregability observed following reperfusion may be relevant for further investigations of coronary artery reocclusion occurring after the relief of myocardial ischemia.
authors.affiliation: University of Maryland Medical Center, Division of Cardiology, Department of Medicine, Baltimore, MD.
authors.initials: PA
authors.lastname: Gurbel
authors.initials: VL
authors.lastname: Serebruany
authors.initials: SF
authors.lastname: Komjathy
authors.initials: ME
authors.lastname: Collins
authors.initials: DC
authors.lastname: Sane
authors.initials: HI
authors.lastname: Scott
authors.initials: ML
authors.lastname: Schlossberg
authors.initials: WR
authors.lastname: Herzog