Abstract
High risk ST segment elevation myocardial infarction (STEMI) patients undergoing reperfusion therapy continue to exhibit significant morbidity and mortality due in part to myocardial reperfusion injury. Importantly, preclinical studies demonstrate that progressive microcirculatory failure (the “no‐reflow” phenomenon) contributes significantly to myocardial reperfusion injury. Diagnostic techniques to measure tissue perfusion have validated this concept in humans, and it is now clear that abnormal tissue perfusion occurs frequently in STEMI patients undergoing reperfusion therapy. Moreover, because tissue perfusion correlates poorly with epicardial blood flow (TIMI flow grade), clinical studies show that tissue perfusion is an independent predictor of early and late mortality in STEMI patients and is associated with infarct size, ventricular function, CHF and ventricular arrhythmias. The mechanisms responsible for abnormal tissue perfusion are multifactorial and include both mechanical obstruction and vasoconstrictor humoral factors. Adenosine, an endogenous nucleoside, maintains microcirculatory flow following reperfusion by activating four well‐characterized extracellular receptors. Because activation of adenosine receptors attenuates the mechanical and functional mechanisms leading to the “no reflow” phenomenon and activates other cardioprotective pathways as well, it is not surprising that both experimental and clinical studies show striking myocardial salvage with intravenous infusions of adenosine administered in the peri‐reperfusion period. For example, a post hoc analysis of the AMISTAD II trial indicates a significant reduction in 1 and 6‐month mortality in STEMI patients undergoing reperfusion therapy who are treated with adenosine within 3 hours of symptoms. In conclusion, adenosine's numerous cardioprotective effects, including attenuation of the “no‐reflow” phenomenon, support its use in high risk STEMI undergoing reperfusion. Copyright © 2007 Wiley Periodicals, Inc.
Keywords: tissue perfusion, myocardial infarction, reperfusion, adenosine
Full Text
The Full Text of this article is available as a PDF (223.2 KB).
References
- 1. Gibson CM, Schömig A: Coronary and myocardial angiography. Angiographic assessment of both epicardial and myocardial perfusion. Circulation 2004; 109: 3096–3105. [DOI] [PubMed] [Google Scholar]
- 2. Forman MB, Stone GW, Jackson EK: Role of adenosine in acute myocardial infarction. Cardiovasc Drug Rev 2006; 24: 116–147. [DOI] [PubMed] [Google Scholar]
- 3. Brosh D, Assali AR, Mayer A, Porter A, Hasdai D, et al.: Effect of no‐reflow during primary percutaneous coronary intervention for acute myocardial infarction on six‐month mortality. Am J Cardiol 2007; 99: 442–445. [DOI] [PubMed] [Google Scholar]
- 4. Wong GC, Morrow DA, Murphy S, Kraimer N, Pai R, et al.: Elevations in troponin T and I are associated with abnormal tissue level perfusion. A TACTICS‐TIMI 18 substudy. Circulation 2002; 106: 202–207. [DOI] [PubMed] [Google Scholar]
- 5. Gibson CM, Murphy SA, Morrow DA, Arvesty JM, Gibbons RJ, et al.: Angiographic perfusion score: an angiographic variable that integrates both epicardial and tissue level perfusion before and after facilitated percutaneous coronary intervention in acute myocardial infarction. Am Heart J 2004; 148: 336–340. [DOI] [PubMed] [Google Scholar]
- 6. Kerins DM, Roy L, Fitzegerald GA, Fitzgerald DJ: Platelet and vascular function during thrombolysis with tissue–type plasminogen activator. Circulation 1989; 80: 1718–1725. [DOI] [PubMed] [Google Scholar]
- 7. Lesoco D, Fineschi M, Pierli C, Fiaschi A, Ferrara N, et al.: Intracoronary serotonin release after high‐pressure coronary stenting. Am J Cardiol 1999; 84: 1317–1322. [DOI] [PubMed] [Google Scholar]
- 8. Taylor AJ, Bobik A, Richards M, Kaye D, Raines G, et al.: Myocardial endothelin‐1 release and indices of inflammation during angioplasty for acute myocardial infarction and stable coronary artery disease. Am Heart J 2004; 148: e10. [DOI] [PubMed] [Google Scholar]
- 9. Kloner RA, Forman MB, Gibbons RJ, Ross AM, Alexander RW, et al.: Impact of time to therapy and reperfusion modality on the efficacy of adenosine in acute myocardial infarction: the AMISTAD ‐2 trial. Eur Heart J 2006; 27: 2400–2405. [DOI] [PubMed] [Google Scholar]