Downregulation of Na+/Ca2+ Exchanger Isoform 1 Protects Isolated Hearts by Sevoflurane Postconditioning but Not by Delayed Remote Ischemic Preconditioning in Rats

• Published in: Chinese medical journal 2017-09, Vol.130 (18), p.2226-2233
• Main Authors: Yu, Yang, Zhou, Cheng-Hui, Yao, Yun-Tai, Li, Li-Huan
• Format: Article
• Language: English
• Subjects: Anesthesiology; Calcium Regulatory Protein; Delayed Remote Ischemic Preconditioning; Ischemia-reperfusion Injury; Na+/Ca2+ Exchanger; Sevoflurane Postconditioning; Cardiovascular disease; Heart; Ischemia; Kinases; Laboratory animals; Original; Proteins; Rodents; Studies
• ISSN: 0366-6999; 2542-5641
• DOI: 10.4103/0366-6999.213967

Background: Calcium regulatory proteins-L-type Ca2+ channels (LTCCs), ryanodine receptor 2 (RyR2), and Na+ /Ca2+ exchanger isoform 1 (NCX1) have been recognized as important protective mechanisms during myocardial ischemia-reperfusion injury (I/RI). Both sevoflurane postconditioning (SevoPoC) and delayed remote ischemic preconditioning (DRIPC) have been shown to protect the heart against I/RI. In this study, we aimed to compare the effects of SevoPoC and DRIPC on the expression of the three calcium regulatory proteins in an isolated rat heart model. Methods: After 30-min balanced perfusion, isolated hearts from rats were subjected to 30-min ischemia followed by 60-min reperfusion. Totally 40 isolated hearts were randomly assigned to four groups (n = 10/group): time control group, I/RI group, SevoPoC group, and DRIPC group. The effect of SevoPoC (3% v/v) and DRIPC were observed. Myocardial infarct size (IS), cardiac troponin I level, and heart function were measured. The protein and messenger RNA levels of LTCCs, RyR2, and NCX1 were determined. Results: Both SevoPoC and DRIPC improved the recovery of myocardial function, and reduced cardiac troponin I release after I/RI. The decrease in IS was more significant in the SevoPoC group than that in the DRIPC group (16.50% +- 4.54% in the SevoPoC group [P = 0.0006], and 22.34% +- 4.02% in the DRIPC group [P = 0.0007] vs. 35.00% +- 5.24% in the I/RI group, respectively). SevoPoC, but not DRIPC significantly inhibited the activity of NCX1 (0.59 +- 0.09 in the I/RI group vs. 0.32 +- 0.16 in the SevoPoC group, P = 0.006; vs. 0.57 +- 0.14 in the DRIPC group, P = 0.072). No statistical significant differences were observed in the expression of LTCCs and RyR2 between SevoPoC and DRIPC. In addition, subsequent correlation analysis showed a significantly positive relationship between the cardiac troponin I level and the protein expression of NCX1 (r = 0.505, P = 0.023). Conclusion: SevoPoC may be more effective in the cardioprotection than DRIPC partly due to the deactivation of NCX1.