Remote Ischemic Conditioning Modulates Myocardial Perfusion and Coronary Vascular Resistance in Ischemic and Non-ischemic Myocardial Territories in Humans

Purpose: Remote ischemic conditioning (RIC) confers protection against myocardial ischemia-reperfusion injury through cellular protective pathways but may also involve modulation of the myocardial perfusion (MP). We investigated whether RIC modulates MP and coronary vascular resistance (CVR) in ischemic and non-ischemic myocardial territories in humans. Methods: In a prospective, single blinded study, we studied 49 patients with suspected stable coronary artery disease. MP was quantified by 82 Rb-PET before and after RIC, and CVR was calculated as mean arterial pressure divided by MP. RIC was conducted as 4 cycles of 5 min upper arm ischemia followed by 5 min of reperfusion. A subsequent adenosine 82 Rb-PET stress scanning identified non-ischemic, reversibly and irreversibly ischemic myocardial segments by summed difference scores, and quantified coronary flow reserve (CFR). Results: Stress 82 Rb-PET data were available for 47 patients and identified 682 non-ischemic, 38 reversibly ischemic, and 37 irreversibly ischemic myocardial segments. Mean CFR was decreased in reversibly ischemic myocardial segments. Global MP and CVR were not affected by RIC (p=0.64 and p=0.53). RIC decreased MP and increased CVR in reversibly ischemic myocardial segments but not in non-ischemic or irreversibly ischemic myocardial segments (Table). Overall, CFR correlated with a change in MP and CVR by RIC (r 2 =0.08, p<0.001 and r 2 =0.10, p<0.001), and allowed identification of a cut-off of CFR<2.3 for a decrease in MP by RIC. Conclusion: RIC modulated MP and CVR dependent on the ischemic status of the myocardium and the vasodilatative capacity of the microcirculation. These findings support the assumption that gentle perfusion may be involved in the cardioprotective mechanisms underlying RIC.