Limitation of Infarct Size and No-Reflow by Intracoronary Adenosine Depends Critically on Dose and Duration

• Published in: JACC. Cardiovascular interventions 2015-12, Vol.8 (15), p.1990-1999
• Main Authors: Yetgin, Tuncay, MD, Uitterdijk, André, MSc, te Lintel Hekkert, Maaike, BASc, Merkus, Daphne, PhD, Krabbendam-Peters, Ilona, BASc, van Beusekom, Heleen M.M., PhD, Falotico, Robert, PhD, Serruys, Patrick W., MD, PhD, Manintveld, Olivier C., MD, PhD, van Geuns, Robert-Jan M., MD, PhD, Zijlstra, Felix, MD, PhD, Duncker, Dirk J., MD, PhD
• Format: Article
• Language: English
• Subjects: acute myocardial infarction; adenosine; Adenosine - administration & dosage; Animals; Cardiovascular; Coronary Circulation; Coronary Occlusion - physiopathology; Coronary Occlusion - therapy; Disease Models, Animal; Drug Administration Schedule; Female; Hemodynamics; Infusions, Parenteral; Male; Myocardial Infarction - etiology; Myocardial Infarction - pathology; Myocardial Infarction - physiopathology; Myocardial Infarction - prevention & control; Myocardial Reperfusion - adverse effects; Myocardial Reperfusion Injury - etiology; Myocardial Reperfusion Injury - pathology; Myocardial Reperfusion Injury - physiopathology; Myocardial Reperfusion Injury - prevention & control; Myocardium - pathology; no-reflow; No-Reflow Phenomenon - etiology; No-Reflow Phenomenon - pathology; No-Reflow Phenomenon - physiopathology; No-Reflow Phenomenon - prevention & control; reperfusion injury; Swine; Time Factors
• ISSN: 1936-8798; 1876-7605
• DOI: 10.1016/j.jcin.2015.08.033

Abstract Objectives 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.