1. Differential regulation of calcium regulatory proteins between sevoflurane postconditioning and delayed remote ischemic preconditioning in an isolated rat heart model Yang Yu, PhD Department of Anesthesiology Fuwai Hospital & National Center for Cardiovascular Diseases Chinese Academy of Medical Sciences Peking Union Medical College, Beijing, China

2. Fuwai Hospital & Cardiovascular Institute Background  Myocardial ischemia/reperfusion injury (MIRI) is a common phenomenon in clinical settings, which increases the morbidity and mortality of patients with coronary heart disease(CHD). Hausenloy DJ, et al. Atherosclerosis 2009, 204:334-341. Infarction DecreasedCardiacFunction MIRI Reperfusion Arrhythmia First hitSecond hit Reperfusion Ischemia

3. Fuwai Hospital & Cardiovascular Institute  Sevoflurane postconditioning  A commonly used volatile anesthetic  Favorable pharmacological profiles Entry point  Remote ischemic preconditioning(RIPC)  early phase (<4 hours)  delayed phase (24-72hours) DRIPC Background

4. Fuwai Hospital & Cardiovascular Institute Background Cardioprotective strategy  Sevoflurane postconditioning (SevoPoC)  Delayed remote ischemic preconditioning (DRIPC) Calcium regulatory proteins  L-type Ca 2+ channel (LTCCs)  Ryanodine receptor isoform 2 (RyR2)  Na + /Ca 2+ exchanger isoform 1 (NCX1)

5. Fuwai Hospital & Cardiovascular Institute Aim  Aim: To explore the effect of SevoPoC and DRIPC on the expression of three calcium regulatory proteins.  Animal: SD rats (250-300g)  Model: Langendorff perfusion

6. Fuwai Hospital & Cardiovascular Institute Protocol Anesthesia and Thoracotomy Heart excised DRIPC Langendorff Perfusion

7. Fuwai Hospital & Cardiovascular Institute Grouping TC=Time control; I/RI=ischemia/reperfusion; SevoPoC=sevoflurane postconditioning; DRIPC=delayed remote ischemic preconditioning  Hemodynamics  cTnI release and infarct size  Protein levels of calcium regulatory proteins  mRNA levels of calcium regulatory proteins

8. Fuwai Hospital & Cardiovascular Institute Hemodynamics LVEDP HR,LVDP

9. Fuwai Hospital & Cardiovascular Institute Infarct size

10. Fuwai Hospital & Cardiovascular Institute cTnI level † P < 0.001 vs I/RI group, # P < 0.001 vs SevoPoC group, ★ P < 0.001 vs DRIPC group.

11. Fuwai Hospital & Cardiovascular Institute Western blotting analysis

12. Fuwai Hospital & Cardiovascular Institute

13.  SevoPoC and DRIPC ▲ improved hemodynamics ▲ reduced infarct size ▲ decreased cTnI release  These results are similar with previous studies [1-3]  One innovation is the study on calcium regulatory proteins, which shows SevoPoC could provide more ability to regulate calcium regulatory proteins than DRIPC, especially in the deactivation of NCX1. Conclusion [1]. Chin Med J (Engl), 2009, 24(3): 133-141. [2]. MOL BIOL REP, 2010, 37(5):2439-46. [3]J Surg Res, 2014 19111): 51-57.

14. Fuwai Hospital & Cardiovascular Institute