Downregulation of Na^＋/Ca^2＋ Exchanger Isoform 1 Protects Isolated Hearts by Sevoflurane Postconditioning but Not by Delayed Remote Ischemic Preconditioning in Rats

Background：Calcium regulatory proteins-L-type Ca^2＋ channels （LTCCs）,ryanodine receptor 2 （RyR2）,and Na^＋/Ca^2＋ exchanger isoform 1 （NCX1） have been recognized as important protective mechanisms during myocardial ischemia-reperfusion injury （I/RI）.Both sevofturane 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 NCX 1 （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 ofNCX1 （r =0.505,P =0.023）.Conclusion：SevoPoC may be more effective in the cardioprotection than DRIPC partly due to the deactivation of NCX1.

心肺转流对冠状动脉旁路移植术后脑微栓子数量及认知功能障碍发生率的影响

背景手术后认知功能障碍（postoperative cognitive dysfunction，POCD）是冠状动脉旁路移植手术（CABG）后常见的并发症。心肺转流术（CPB）中的脑微栓子被认为是诱发POCD的一个重要原因。我们研究不使用体外循环的冠状动脉移植术能否减少中国人群CABG术后脑微栓子的数量及POCD发生率。方法227例患者参与了本次前瞻性队列研究。其中59例患者来自CPB组，另外168例加入非体外循环组。使用经颅多普勒超声持续测定双侧大脑中动脉内脑微栓子情况。分别在手术前、手术后1周及手术后3个月使用一套神经心理量表评估认知功能，该量表包括了7项测验，共9个小项。根据国际POCDl的研究定义来诊断POCD。结果CPB组和非体外循环组患者发生脑微栓子的平均数分别为430（155～2088）和2（0。66）（P〈0．001）。两组COPD的发生率在手术后I周及3个月均无明显差异，在第1周时CPB组发生率为55．2％（32／58，95％可信区间为41．5％-68．3％），非体外循环组发生率为47％（78/166，95％可信区间为39．2％～54．9％，P=0．283）；手术后3个月发生率分别为6．4％13／47，（1．3％～17．5％）]和13．1％[16／122，（7．7％-20．4％，P=0．214）]。年龄增长以及手术后住院天数缩短可能与手术后1周认知功能障碍独立相关。另外年龄增长以及糖尿病史则与手术后3个月认知功能障碍独立相关。CPB或者脑微栓子与POCD的发生率无显著相关性。结论在中国人群的CABG手术中，不使用CPB可明显减h脑微栓子数目，但并不降低手术后1周或手术后3个月时POCD的发生率。CPB或脑微栓子与POCD的发生率无明显相关性。