title: Changes in P-selectin expression on cardiac microvessels in blood-perfused rat hearts subjected to ischemia-reperfusion.
abstract: BACKGROUND
  During cardiac surgery involving cardiopulmonary bypass, activation of polymorphonuclear cells is believed to contribute to ischemia-reperfusion injury and subsequent myocardial impairment of function. The early tethering of polymorphonuclear cells to blood vessel walls depends upon recognition of the adhesion molecule P-selectin on endothelium. The purpose of this study was to define the kinetic changes in expression of P-selectin on myocardial vessels in a model of global ischemia-reperfusion injury.
  
  
  METHODS
  In a novel recirculating blood-based perfusion system, rat hearts were subjected to 30 minutes of aerobic perfusion, 60 minutes of global ischemia, and 60 minutes of reperfusion, or to 120 minutes of continuous aerobic blood perfusion (with or without leukocyte/platelet depletion). Heart function (left ventricular developed pressure), heart rate, and perfusion pressure were monitored throughout. Hearts were sampled at defined periods for microvascular expression of P-selectin, identified by immunohistochemistry.
  
  
  RESULTS
  In control (nonperfused) hearts and in hearts subjected to perfusion and ischemia, few cardiac vessels (8% to 16%) expressed P-selectin. After 15 minutes of reperfusion, P-selectin was present on the majority of vessels (77%; p < 0.05) but expression decreased subsequently throughout the remaining duration of reperfusion. Interestingly, upregulation of P-selectin also occurred when hearts were subjected to continuous perfusion alone (no ischemia), but this upregulation was less rapid. Depletion of leukocytes/platelets from the blood perfusate did not modify P-selectin expression.
  
  
  CONCLUSIONS
  The augmented expression of P-selectin on myocardial vessels during reperfusion of ischemic hearts probably reflects changes induced during global ischemia and by the duration of perfusion through the nonbiological tubing of the circuit. That is likely to mimic the effects initiated during cardiopulmonary bypass.
authors.affiliation: Cardiac Surgical Research/Cardiothoracic Surgery, Rayne Institute, Guy's and St. Thomas' NHS Trust, St. Thomas' Campus, London, United Kingdom.
authors.forename: Andrew O
authors.initials: AO
authors.lastname: Chukwuemeka
authors.forename: K Alun
authors.initials: KA
authors.lastname: Brown
authors.forename: Graham E
authors.initials: GE
authors.lastname: Venn
authors.forename: David J
authors.initials: DJ
authors.lastname: Chambers
mesh_terms: D000332:Aerobiosis; D000818:Animals; D001769:Blood; D002196:Capillaries / Q000378:metabolism; D002315:Cardiopulmonary Bypass; D002448:Cell Adhesion; D003331:Coronary Vessels / Q000378:metabolism*; D004867:Equipment Design; D047589:Leukocyte Reduction Procedures; D008297:Male; D017202:Myocardial Ischemia / Q000235:genetics / Q000378:metabolism*; D015425:Myocardial Reperfusion / Q000295:instrumentation / Q000379:methods; D015428:Myocardial Reperfusion Injury / Q000235:genetics / Q000378:metabolism*; D009504:Neutrophils / Q000502:physiology; D019007:P-Selectin / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D015854:Up-Regulation
chemical_list: D019007:P-Selectin