title: Coronary microembolization does not induce acute preconditioning against infarction in pigs-the role of adenosine.
abstract: OBJECTIVE
  After coronary microembolization (ME) adenosine is released from ischemic areas of the microembolized myocardium. This adenosine dilates vessels in adjacent nonembolized myocardium and increases coronary blood flow. For ischemic preconditioning (IP) to protect the myocardium against infarction, an increase in the interstitial adenosine concentration (iADO) prior to the subsequent ischemia/reperfusion is necessary. We hypothesized that the adenosine release after ME is sufficient to increase iADO and protect the myocardium against infarction from subsequent ischemia/reperfusion. We have therefore compared myocardial protection by either coronary microembolization or ischemic preconditioning prior to ischemia/reperfusion.
  
  
  METHODS
  In anesthetized pigs, the left anterior descending (LAD) was cannulated and perfused from an extracorporeal circuit. In 11 pigs, sustained ischemia was induced by 85% inflow reduction for 90 min (controls). Two other groups of pigs were subjected either to IP (n = 8; 10-min ischemia/15-min reperfusion) or coronary ME (n = 9; i.c. microspheres; 42 microm Ø; 3000 x ml(-1) x min inflow) prior to sustained ischemia. Coronary venous adenosine concentration (vADO) and iADO (microdialysis) were measured. Infarct size was determined after 2-h reperfusion by triphenyl tetrazolium chloride staining.
  
  
  RESULTS
  In pigs subjected to IP, infarct size was reduced to 2.6 +/- 1.1% (mean +/- S.E.M.) vs. 17.0 +/- 3.2% in controls. iADO was increased from 2.4 +/- 1.3 to 13.1 +/- 5.8 micromol x l(-1) during the reperfusion following IP. In pigs subjected to ME, at 10 min after ME, coronary blood flow (38.6 +/- 3.6 to 53.6 +/- 4.3 ml x min(-1)) and vADO (0.25 +/- 0.04 to 0.48 +/- 0.07 micromol x l(-1)) were increased. However, iADO (2.0 +/- 0.5 at baseline vs. 2.3 +/- 0.6 micromol x l(-1) at 10 min after ME) did not increase. Infarct size induced by sustained ischemia following ME (22.5 +/- 5.2%) was above that of controls for any given subendocardial blood flow.
  
  
  CONCLUSIONS
  ME released adenosine into the vasculature and increased coronary blood flow. The failure of iADO to increase with ME possibly explains the lack of protection against infarction after ME.
authors.affiliation: Institut für Pathophysiologie, Zentrum für Innere Medizin, Universitätsklinikum Essen, Hufelandstrasse 55, 45122 Essen, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Skyschally
authors.forename: Rainer
authors.initials: R
authors.lastname: Schulz
authors.forename: Petra
authors.initials: P
authors.lastname: Gres
authors.forename: Ina
authors.initials: I
authors.lastname: Konietzka
authors.forename: Claus
authors.initials: C
authors.lastname: Martin
authors.forename: Michael
authors.initials: M
authors.lastname: Haude
authors.forename: Raimund
authors.initials: R
authors.lastname: Erbel
authors.forename: Gerd
authors.initials: G
authors.lastname: Heusch
mesh_terms: D000241:Adenosine / Q000378:metabolism*; D000818:Animals; D003326:Coronary Circulation; D023921:Coronary Stenosis / Q000378:metabolism*; D005260:Female; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D023421:Models, Animal; D009203:Myocardial Infarction / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D013552:Swine; D013556:Swine, Miniature; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D014409:Tumor Necrosis Factor-alpha; D000241:Adenosine