Department of Cardiopulmonary Bypass, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, PR China.
Eur J Cardiothorac Surg. 2009 Dec;36(6):1018-23. doi: 10.1016/j.ejcts.2009.06.033. Epub 2009 Aug 15.
Although adenosine (ADO) has been shown to have beneficial effects against tissue injury after myocardial ischaemia, the controversy still remains regarding the optimal timing, dose, temperature, method of ADO administration and duration of exposure to the drug. This study investigates the cardioprotective effect of exogenous ADO pretreatment as an adjunct to 1 mmol l(-1) ADO cold (12 degrees C) blood cardioplegia during heart valve replacement surgery.
Thirty patients with rheumatic heart valve disease undergoing heart valve replacement operations were randomly assigned to two groups: group C (n=15) and group A (n=15). Patients in group C were the control group and received antegrade cold (12 degrees C) high-potassium ([K(+)]=20 mol l(-1)) institute blood cardioplegia. The patients in group A received 10-min 100 microgkg(-1)min(-1) ADO pretreatment before application of the aortic cross-clamp and antegrade 1 mmol l(-1) adenosine high-potassium ([K(+)]=20 mol l(-1)) cold (12 degrees C) blood cardioplegia. Clinical outcomes were observed before, during and after the operation. Plasma level markers of myocardial damage: cardiac Troponin I (cTnI), creatine kinase (CK-MB) and inflammatory factors (interleukin (IL)-6 and IL-8) were obtained from serial venous blood samples after induction, 5 min after cross-clamp of aorta, 10 min after clamp-off, 1h after return to ICU and postoperatively 24 h and 48 h. Right atrial samples were harvested before cross-clamp and after clamp-off.
Heart valve replacement was successful in all patients. There were no differences regarding operative parameters in the two groups. Time to arrest (during cardiolegia perfusion electrocardiography (ECG) change to a line) was shorter in group A compared to group C (19.9+/-4.6s vs 29.3+/-10.6s; p=0.03). Group A also had lower cTnI and IL-8 levels (p=0.03) at 10 min after aortic declamping, and lower IL-6 (p=0.04) at 24h postoperatively as well. Ultrastructural changes were slighter in group A than group C after clamp-off. Compared to group C, post-reperfusion biopsies in group A displayed only slight overall ultrastructural changes, and scored significantly better on mitochondrial damage (group A 2.23+/-0.65 vs group C 2.85+/-0.66) (p=0.04).
Compared with simple cold blood cardioplegia in heart valve replacement patients, ADO pretreatment as an adjunct to 1 mmol l(-1) ADO cold blood cardioplegia may reduce cTnI, IL-6 and IL-8 release, resulting in reduced myocardial injury in ultrastructure after surgery.
虽然腺嘌呤核苷（ADO）已被证明对心肌缺血后的组织损伤具有有益作用，但关于最佳时机、剂量、温度、ADO 给药方法和暴露于药物的持续时间，仍存在争议。本研究调查了外源性 ADO 预处理作为辅助 1mmol l(-1)ADO 冷（12°C）血心脏停搏液在心脏瓣膜置换术中的心脏保护作用。
30 例风湿性心脏瓣膜病患者行心脏瓣膜置换术，随机分为两组：C 组（n=15）和 A 组（n=15）。C 组为对照组，给予顺行冷（12°C）高钾（[K(+)]=20mol l(-1)) Institute 血心脏停搏液。A 组患者在应用主动脉钳夹前接受 10min100μgkg(-1)min(-1)ADO 预处理，并给予顺行 1mmol l(-1)ADO 高钾（[K(+)]=20mol l(-1))冷（12°C）血心脏停搏液。观察手术前后的临床转归。从诱导后、主动脉夹闭后 5min、夹闭后 10min、返回 ICU 后 1h 及术后 24h 和 48h 连续静脉血样中获得心肌损伤的血浆标志物：心肌肌钙蛋白 I（cTnI）、肌酸激酶（CK-MB）和炎症因子（白细胞介素（IL）-6 和 IL-8）。在夹闭前和夹闭后采集右心房样本。
所有患者的心脏瓣膜置换均成功。两组患者的手术参数无差异。与 C 组相比，A 组的停搏时间（在心脏停搏液灌注心电图（ECG）变为直线时）更短（19.9+/-4.6s 比 29.3+/-10.6s；p=0.03）。A 组主动脉开放后 10min 的 cTnI 和 IL-8 水平也较低（p=0.03），术后 24h 的 IL-6 水平也较低（p=0.04）。夹闭后 A 组的超微结构变化比 C 组更轻微。与 C 组相比，A 组再灌注活检仅显示轻微的整体超微结构变化，线粒体损伤评分明显更好（A 组 2.23+/-0.65 比 C 组 2.85+/-0.66）（p=0.04）。
与单纯冷血心脏停搏液相比，ADO 预处理作为 1mmol l(-1)ADO 冷血心脏停搏液的辅助手段，可能减少 cTnI、IL-6 和 IL-8 的释放，从而减少术后超微结构的心肌损伤。
