Three hours continuous injection of adenosine improved left ventricular function and infarct size in patients with ST-segment elevation myocardial infarction

Background  The definitive treatment for myocardial ischemia is reperfusion. However, reperfusion injury has the potential to cause additional reversible and irreversible damage to the myocardium. One likely candidate for a cardioprotection is adenosine. The present study aimed at investigating the effect of intravenous adenosine on clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). 

Methods  Patients with STEMI within 12 hours from the onset of symptoms were randomized by 1:1:1 ratio to receive either adenosine 50 µg∙kg^-1∙min^-1 (low-dose group, n=31), or 70 µg∙kg^-1∙min^-1 (high-dose group, n=32), or saline 1 ml/min (control group, n=27) for three hours. Drugs were given to the patients immediately after the guide wire crossed the culprit lesion. Recurrence of no-reflow, TIMI flow grade (TFG) and TIMI myocardial perfusion grade (TMPG), and collateral circulation were recorded. The postoperative and preoperative ST segment elevation sum of 18-lead electrocardiogram (ECG) and their ratio (STsum-post/STsum-pre) were recorded, as well as the peak time and peak value of CK-MB enzyme. Serial cardiac echo and myocardial perfusion imaging were performed at 24 hours and 6 months post-stenting. The primary endpoint was left ventricular function, and infarct size. The secondary end-point was the occurrence of cardiac and non-cardiac death, non-fatal myocardial infarction, and heart failure.

Results  A total of 90 STEMI patients were studied. No-reflow immediately after stent procedure was seen in 11 (35.5%) patients in the control group, significantly different from 6.3% in the low-dose group or 3.7% in the high-dose group (both P=0.001). STsum-post/STsum-pre in the low-dose and high-dose groups was significantly different from the control group (low-dose group vs. control group, P=0.003 and high-dose group vs. control group, P=0.001), without a dose-dependent pattern (P=0.238). The peak value of CK-MB enzyme was significantly reduced in the high-dose group compared to the control group (P=0.024). Compared to the left ventricular ejection fraction (LVEF) in control group, LVEF in the low-dose group increased by 5.8% at 24 hours (P=0.012) and by 10.9% at 6 months (P=0.007), LVEF in the high-dose group increased by 9.5% at 24 hours (P=0.001) and by 10.0% at 6 months (P=0.001), respectively. Significant reduction of infarct size by 24.2% was detected in the high-dose group vs. low-dose or control groups (P=0.008). There was no significant difference regarding secondary endpoints at 6 months among the treated groups. Cardiac function by NYHA classification in both the low-dose and the high-dose groups was improved significantly (P=0.013, P=0.016).

Conclusion  Intravenous adenosine administration might significantly reduce the recurrence of no-reflow, with resultant improved left ventricular systolic function. High-dose adenosine was further associated with significant reduction of infarct size.