Author + information
- Received July 20, 2015
- Accepted August 14, 2015
- Published online December 28, 2015.
- Tuncay Yetgin, MD∗,†,
- André Uitterdijk, MSc∗,
- Maaike te Lintel Hekkert, BASc∗,
- Daphne Merkus, PhD∗,
- Ilona Krabbendam-Peters, BASc∗,
- Heleen M.M. van Beusekom, PhD∗,
- Robert Falotico, PhD‡,
- Patrick W. Serruys, MD, PhD∗,
- Olivier C. Manintveld, MD, PhD∗,
- Robert-Jan M. van Geuns, MD, PhD∗,
- Felix Zijlstra, MD, PhD∗,† and
- Dirk J. Duncker, MD, PhD∗,†∗ ()
- ∗Department of Cardiology, Thoraxcenter, Erasmus University Medical Center, Rotterdam, the Netherlands
- †Interuniversity Cardiology Institute of the Netherlands, Utrecht, the Netherlands
- ‡Cordis Corporation, Fremont, California
- ↵∗Reprint requests and correspondence:
Dr. Dirk J. Duncker, Department of Cardiology, Thoraxcenter, Room Ee-2351 A, Erasmus University Medical Center, P.O. Box 2040, 3000 CA Rotterdam, the Netherlands.
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.
This work was supported by Cordis Corporation, a Johnson & Johnson Company. Dr. Falotico is an employee of Cordis Corporation, a Johnson & Johnson Company. Dr. van Geuns has received research grants and speakers honoraria from Abbott Vascular and Boston Scientific. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Drs. Yetgin and Uitterdijk contributed equally to this work.
- Received July 20, 2015.
- Accepted August 14, 2015.
- 2015 American College of Cardiology Foundation