title: Limitation of Infarct Size and No-Reflow by Intracoronary Adenosine Depends Critically on Dose and Duration.
abstract: OBJECTIVE
  In the absence of effective clinical pharmacotherapy for prevention of reperfusion-mediated injury, this study re-evaluated the effects of intracoronary adenosine on infarct size and no-reflow in a porcine model of acute myocardial infarction using clinical bolus and experimental high-dose infusion regimens.
  
  
  BACKGROUND
  Despite the clear cardioprotective effects of adenosine, when administered prior to ischemia, studies on cardioprotection by adenosine when administered at reperfusion have yielded contradictory results in both pre-clinical and clinical settings.
  
  
  METHODS
  Swine (54 ± 1 kg) were subjected to a 45-min mid-left anterior descending artery occlusion followed by 2 h of reperfusion. In protocol A, an intracoronary bolus of 3 mg adenosine injected over 1 min (n = 5) or saline (n = 10) was administered at reperfusion. In protocol B, an intracoronary infusion of 50 μg/kg/min adenosine (n = 15) or saline (n = 21) was administered starting 5 min prior to reperfusion and continued throughout the 2-h reperfusion period.
  
  
  RESULTS
  In protocol A, area-at-risk, infarct size, and no-reflow were similar between groups. In protocol B, risk zones were similar, but administration of adenosine resulted in significant reductions in infarct size from 59 ± 3% of the area-at-risk in control swine to 46 ± 4% (p = 0.02), and no-reflow from 49 ± 6% of the infarct area to 26 ± 6% (p = 0.03).
  
  
  CONCLUSIONS
  During reperfusion, intracoronary adenosine can limit infarct size and no-reflow in a porcine model of acute myocardial infarction. However, protection was only observed when adenosine was administered via prolonged high-dose infusion, and not via short-acting bolus injection. These findings warrant reconsideration of adenosine as an adjuvant therapy during early reperfusion.
authors.affiliation: Department of Cardiology, Thoraxcenter, Erasmus University Medical Center, Rotterdam, the Netherlands; Interuniversity Cardiology Institute of the Netherlands, Utrecht, the Netherlands.
authors.forename: Tuncay
authors.initials: T
authors.lastname: Yetgin
authors.affiliation: Department of Cardiology, Thoraxcenter, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: André
authors.initials: A
authors.lastname: Uitterdijk
authors.affiliation: Department of Cardiology, Thoraxcenter, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: Maaike
authors.initials: M
authors.lastname: Te Lintel Hekkert
authors.affiliation: Department of Cardiology, Thoraxcenter, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: Daphne
authors.initials: D
authors.lastname: Merkus
authors.affiliation: Department of Cardiology, Thoraxcenter, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: Ilona
authors.initials: I
authors.lastname: Krabbendam-Peters
authors.affiliation: Department of Cardiology, Thoraxcenter, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: Heleen M M
authors.initials: HMM
authors.lastname: van Beusekom
authors.affiliation: Cordis Corporation, Fremont, California.
authors.forename: Robert
authors.initials: R
authors.lastname: Falotico
authors.affiliation: Department of Cardiology, Thoraxcenter, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: Patrick W
authors.initials: PW
authors.lastname: Serruys
authors.affiliation: Department of Cardiology, Thoraxcenter, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: Olivier C
authors.initials: OC
authors.lastname: Manintveld
authors.affiliation: Department of Cardiology, Thoraxcenter, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: Robert-Jan M
authors.initials: RM
authors.lastname: van Geuns
authors.affiliation: Department of Cardiology, Thoraxcenter, Erasmus University Medical Center, Rotterdam, the Netherlands; Interuniversity Cardiology Institute of the Netherlands, Utrecht, the Netherlands.
authors.forename: Felix
authors.initials: F
authors.lastname: Zijlstra
authors.affiliation: Department of Cardiology, Thoraxcenter, Erasmus University Medical Center, Rotterdam, the Netherlands; Interuniversity Cardiology Institute of the Netherlands, Utrecht, the Netherlands. Electronic address: d.duncker@erasmusmc.nl.
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: Duncker
mesh_terms: D000241:Adenosine / Q000008:administration & dosage*; D000818:Animals; D003326:Coronary Circulation; D054059:Coronary Occlusion / Q000503:physiopathology / Q000628:therapy*; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D005260:Female; D006439:Hemodynamics; D007263:Infusions, Parenteral; D008297:Male; D009203:Myocardial Infarction / Q000209:etiology / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D015425:Myocardial Reperfusion / Q000009:adverse effects*; D015428:Myocardial Reperfusion Injury / Q000209:etiology / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D009206:Myocardium / Q000473:pathology*; D054318:No-Reflow Phenomenon / Q000209:etiology / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D013552:Swine; D013997:Time Factors
chemical_list: D000241:Adenosine
keywords: acute myocardial infarction; adenosine; no-reflow; reperfusion injury