期刊
CIRCULATION RESEARCH
卷 122, 期 8, 页码 1102-+出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/CIRCRESAHA.118.312784
关键词
coronary occlusion; electrocardiography; ischemic conditioning; myocardial infarction; reperfusion injury; STAT3
资金
- German Research Foundation [He 1320/18-3, SFB 1116 B08]
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; 4x5 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 alpha/beta/gamma, 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 mu V; placebo 259 +/- 28 mu V), 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 mu V; 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.
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