Prolonged High-Dose Intracoronary Adenosine Shown to Limit Infarct Size

In a porcine model of acute myocardial infarction (AMI), intracoronary adenosine was shown to limit infarct size and no-reflow during reperfusion after prolonged high-dose infusion, according to research published in the JACC: Cardiovascular Interventions.

Timely reperfusion is the best treatment for AMI to improve residual ventricular function and clinical outcome, and adenosine has the potential to reduce reperfusion-mediated injury. However, prior studies examining adenosine at administration at reperfusion have produced inconsistent results in preclinical and clinical settings.

Researchers of the present study found that in a porcine model, intracoronary infusion of high-dose adenosine initiated before the onset of reperfusion for 2 hours of reperfusion period resulted in decreased infarct size and no-reflow.

“The beneficial effects observed in the current study with prolonged infusion of adenosine also suggest that maintaining a high therapeutic drug level in the coronary microcirculation is necessary to afford protection against reperfusion-mediated injury,” the authors wrote.

The swine had a 45-minute mid-left anterior descending artery occlusion and 2 hours of reperfusion. They were then divided into 2 groups. In protocol A, the swine had an intracoronary bolus of 3 mg adenosine injected over 1 minute (n=5) or saline (n=10) given at reperfusion. In protocol B, the intracoronary infusion was given at 50 µg/kg/min adenosine (n=15) or saline (n=21) starting 5 minutes before reperfusion and continued throughout the 2 hour period.

The area-at-risk was similar between adenosine and saline subgroups for both protocols. The researchers found that bolus injection of adenosine did not reduce infarct size (64 ± 4% vs 53 ± 3% in the saline swine; P=.07) or no-reflow (14 ± 4% vs 12 ± 3%, P=.74).

However, adenosine infusion during reperfusion notably decreased infarct size (46 ± 4% vs 59 ± 3% in the saline swine, P=.02) and in no-reflow (26 ± 6% vs 49 ± 6%, P=.03).

“Considering that there is currently no successful clinical pharmacological treatment for prevention of reperfusion injury, the findings in the present study warrant further clinical studies in patients with AMI, using prolonged high-dose intracoronary adenosine infusion,” the authors concluded.

Reference

Yetgin T, Uitterdijk A, Hekkert M, et al. Limitation of Infarct Size and No-Reflow by Intracoronary Adenosine Depends Critically on Dose and Duration. JACC: Cardiovasc Interv. 2015;8(15):1990-1999. doi: 10.1016/j.jcln.2015.08.033.