Intracoronary infusion of adenosine reduces infarct size and no-reflow in ST-segment elevation myocardial infarction

Purpose: Adenosine exerts a variety of actions that may attenuate many of the proposed mechanisms of reperfusion-mediated injury, including inhibition of neutrophil-mediated microvascular obstruction. Yet, attempts to achieve cardioprotection with administration of adenosine at reperfusion have yielded conflicting results in both pre-clinical and clinical settings. We sought to determine the effects of adenosine on infarct size (IS) and no-reflow in an appropriate translational porcine model, taking into account the predicted terms for efficacious intervention (i.e., prolonged intracoronary infusion starting just prior to reperfusion). Methods: Thirty-six open-chest swine of either sex were subjected to a 45-min left anterior descending coronary artery occlusion followed by 2 h of reperfusion. Animals received either intracoronary adenosine (50 μg/kg/min; n=15) infused for 2 h starting 5 min prior to reperfusion or an equal volume of saline (controls; n=21). The area-at-risk was delineated with Evans Blue, IS was determined histochemically with triphenyltetrazolium staining and no-reflow measured with thioflavin S staining. Results: Adenosine infusion significantly increased coronary blood flow throughout the 2-h reperfusion period compared with controls (p<0.001), with a maximum fourfold increase relative to baseline at 30 min of reperfusion (397±62% vs. 217±18% in controls; p<0.001). In contrast, adenosine did not affect systemic hemodynamic variables. Area-at-risk was similar between groups (p=NS). Administration of adenosine resulted in a significant reduction in IS (% area-at-risk; 46±4%) compared with controls (59±3%; p=0.02). Likewise, no-reflow (% IS) was significantly reduced in the adenosine-treated group (26±6%) compared to controls (49±6%; p=0.03). Conclusion: High and prolonged intracoronary adenosine infusion during early reperfusion limits infarct size and no-reflow in a porcine preparation of ST-segment elevation myocardial infarction. Further studies are warranted to confirm this effect, especially, when considering that there is no successful clinical pharmacological treatment for prevention of reperfusion-mediated injury at present.