Reflection of Cardioprotection by Remote Ischemic Perconditioning in Attenuated ST-Segment Elevation During Ongoing Coronary Occlusion in Pigs: Evidence for Cardioprotection From Ischemic Injury

Abstract

Rationale: Reduction of infarct size by remote ischemic perconditioning (perRIC) is evident only after several hours reperfusion.

Objective: To develop a potential real-time estimate of cardioprotection by perRIC, we have analyzed the time course of ST-segment elevation.

Methods and results: Anesthetized open-chest pigs were subjected to 60-minute coronary occlusion and 180-minute reperfusion (placebo; n=19). PerRIC (n=18; 4×5 min/5 min hindlimb occlusion/reperfusion) was induced 20 minutes after coronary occlusion. Regional myocardial blood flow was measured with microspheres, areas of no-reflow with thioflavin-S, area at risk with blue dye, and infarct size with triphenyl tetrazolium chloride staining. Phosphorylation of protein kinase B α/β/γ, extracellular signal-regulated kinase 1/2, and signal transducer and activator of transcription 3 was determined by Western blot. ST-segment elevation was analyzed in a V2-like ECG-lead at baseline, 5- and 55-minute coronary occlusion, and 10-, 30-, 60-, and 120-minute reperfusion. Transmural blood flow at 5-minute coronary occlusion was not different between perRIC (0.029±0.015 mL/min per gram; mean±SD) and placebo (0.024±0.018 mL/min per gram) as was area at risk (perRIC: 24±6% of the left ventricle; placebo: 21±4%). Areas of no-reflow tended to be smaller with perRIC (9±12% of area at risk versus 15±14% with placebo; P=0.13). Infarct size with perRIC was 23±12% of area at risk versus 40±11% with placebo (P<0.001). PerRIC increased phosphorylation of signal transducer and activator of transcription 3 at 120-minute reperfusion by 196±142% versus 109±120% with placebo (P=0.047). The time courses of ST-segment elevation in perRIC and placebo protocols, respectively, were different (P=0.017). With similar ST-segment elevation at 5-minute coronary occlusion (perRIC 282±34 µV; placebo 259±28 µV), partial recovery of ST-segment elevation between 5- and 55-minute coronary occlusion was more pronounced with perRIC than placebo (by 111±84 versus 15±94 µV; P=0.028).

Conclusion: Infarct size reduction by perRIC is reflected in the ST-segment elevation during coronary occlusion in pigs, supporting the notion of protection from ischemic injury.

Keywords: STAT3; coronary occlusion; electrocardiography; ischemic conditioning; myocardial infarction; reperfusion injury.