目的:临床研究表明,钙增敏剂左西孟旦对心脏手术患者的临床结局有轻微的有益影响。这里,在Langendorff模型中灌注的大鼠心脏中检查了心脏骤停前24小时给予左西孟旦对心肌功能的影响。
方法:在将切除的心脏安装在Langendorff装置上24小时之前,通过饮用水对53只大鼠施用左西孟旦(Levo组)或NaCl(对照组)。两组均诱发有或没有心脏停搏液的心脏骤停;连续灌注另一组心脏。在36°C的90分钟再灌注期间,测量功能参数并将其归一化为基线值.肌钙蛋白I在冠状窦流出物中被定量,并研究了分离心肌细胞的功能。
结果:口服左西孟旦显示疗效。除了冠状动脉流量外,Levo和NaCl组的基线值相似。缺血再灌注后,左心未恢复优于NaCl心脏{左心室衍生压:63[标准偏差(SD):36.2]vs基线46(SD:41.8)%;P=0.386},在暴露于心脏停搏液的心脏中,Levo组和NaCl组的功能恢复仅略有差异[左心室衍生压:69.96(SD:12.7)对51.89(SD:28.1)%基线;P=0.09].从暴露于缺血或灌注的心脏中分离的心肌细胞的细胞缩短在Levo组中更好[细胞缩短:7.65(SD:1.95)%;7.8(SD:1.79)%vs6.28(SD:1.67)%;6.5(SD:1.87)%,P<0.001];在心脏停搏液治疗的心脏中没有这种益处。
结论:在缺血/再灌注前口服左西孟旦可改善功能恢复,但是当包括心脏停搏液时,这种效果只有中等。暴露于心脏停搏液或全身缺血的心脏之间的差异可能表明为什么左西孟旦相关的有益作用不能直接转化为更好的临床结果。
OBJECTIVE: Clinical studies have indicated minor beneficial effects of the calcium sensitizer levosimendan on clinical outcomes in patients undergoing cardiac surgery. Here, the influence of levosimendan administered 24 h before cardiac arrest on myocardial function was examined in rat hearts perfused in a Langendorff model.
METHODS: Levosimendan (Levo group) or NaCl (control group) was administered to 53 rats via drinking water 24 h prior to mounting excised hearts on a Langendorff apparatus. Cardiac arrest with or without cardioplegia was induced in both groups; another set of hearts was perfused continuously. During 90-min reperfusion at 36°C, functional parameters were measured and normalized to baseline values. Troponin I was quantified in coronary sinus effluent, and the functionality of isolated cardiomyocytes was studied.
RESULTS: Oral application of levosimendan showed therapeutic efficacy. Baseline values were similar in the Levo and NaCl groups except for coronary flow. After ischaemia and reperfusion, Levo hearts did not recover better than NaCl hearts {left ventricular derived pressure: 63 [standard deviation (SD): 36.2] vs 46 (SD: 41.8)% baseline; P = 0.386}, In hearts exposed to cardioplegia, functional recovery only slightly differed in the Levo and NaCl groups [left ventricular derived pressure: 69.96 (SD: 12.7) vs 51.89 (SD: 28.1)% baseline; P = 0.09]. Cell shortening of cardiomyocytes isolated from hearts exposed to ischaemia or perfusion was better in Levo groups [cell shortening: 7.65 (SD: 1.95) %; 7.8 (SD: 1.79)% vs 6.28 (SD: 1.67)%; 6.5 (SD: 1.87)%, P < 0.001]; this benefit was absent in cardioplegia-treated hearts.
CONCLUSIONS: Levosimendan applied orally before ischaemia/reperfusion improves functional recovery, but this effect is only moderate when cardioplegia is included. Differences between hearts exposed to cardioplegia or to global ischaemia may indicate why levosimendan-related beneficial effects do not directly translate into better clinical outcome.