Abstract 19210: Remote Ischemic Conditioning, Applied During Recurrent Coronary Thrombosis Mimicking Unstable Angina, Improves Coronary Patency

Abstract

Evidence from our group revealed that the benefits of preconditioning ischemia extend beyond infarct size reduction via up-regulation of cardioprotective signaling. We found that brief antecedent ischemia: i) attenuates molecular indices of platelet activation-aggregation (i.e., P-selectin expression, fibrinogen binding); and thus ii) improves arterial patency in models mimicking unstable angina. However, two issues limit potential translation of this endogenous anti-platelet effect: the conditioning stimulus was applied directly to the heart, as a pretreatment . Our current aim was to establish whether brief ischemia applied at a remote site (skeletal muscle), after the onset of recurrent coronary thrombosis, would improve subsequent coronary patency. Methods: Recurrent platelet-mediated coronary thrombosis was initiated in anesthetized dogs by application of a stenosis at a site of vessel injury. At 1 h after injury + stenosis, dogs received: i) remote ischemic conditioning (RIC: 4 5-min episodes of bilateral hindlimb ischemia); or ii) a time-matched sham-control period. Coronary blood flow was monitored throughout the 1 h before treatment and for 2 h after the RIC/sham stimulus. Primary endpoints were: i) area of the flow-time profile (index of coronary patency, expressed as % of baseline flow); and ii) % duration of total thrombotic occlusion (flow=0). Results: Both groups displayed poor coronary patency during the 1 h pretreat period: flow-time area averaged 31-32%, and duration of total thrombotic occlusion was 19-25%. Patency remained unchanged in controls throughout the protocol. In contrast, RIC evoked an immediate attenuation of recurrent thrombosis: flow-time area was increased to 63±10% (p<0.01) and duration of total occlusion was reduced to 4% (p=0.11). Conclusion: Remote ischemic conditioning, applied during episodes of recurrent platelet-mediated thrombosis mimicking unstable angina, improves subsequent coronary patency.