Preconditioning effects of adenosine in patients with severe coronary artery disease but preserved coronary flow reserve

Abstract

Adenosine plays a key role in different protective and adaptive responses to ischemia and has been suggested to induce ischemic preconditioning. To investigate whether a low-dose adenosine infusion reduces the ischemic burden induced by pharmacological stress without affecting the coronary flow reserve (CFR). Myocardial ischemia was induced by dobutamine stress test and quantified by tissue Doppler echocardiography in 11 patients with advanced coronary artery disease. CFR was quantified during high-dose adenosine infusion by contrast echocardiography. Before the dobutamine stress test and contrast echocardiography, intravenous low-dose adenosine or placebo was infused over 15 min according to a randomized, double-blind, cross-over protocol. Echocardiographic left ventricular (LV) apical images and flow pattern of left anterior descending coronary artery (LAD) were obtained at baseline, during adenosine/placebo infusion, maximal, and recovery phases.Furthermore, the LV walls were categorized as ischemic or nonischemic according to a predefined ischemic threshold of at least 25% increment in peak systolic velocity (PSV)from baseline to maximal stress. CFR was measured as the ratio of peak/baseline of maximal diastolic velocity in the distal LAD. PSV increased both during placebo and adenosine infusions from baseline to maximal stress. However, in the ischemic walls, the PSV increased only during adenosine infusion, whereas no differences were observed in the nonischemic walls. There were no differences in blood pressure, heart rate, or regional CFR during placebo or adenosine infusion. Low-dose adenosine infusion improves regional LV systolic function in the ischemic walls, without any effect on CFR, suggesting that the observed improvement may be because of ischemic preconditioning.