Belhomme D, Peynet J, Florens E, Tibourtine O, Kitakaze M, Menasché P
Department of Cardiovascular Surgery, Hôpital Bichat, Paris, France.
Ann Thorac Surg. 2000 Aug;70(2):590-4. doi: 10.1016/s0003-4975(00)01502-2.
The large number of experimental studies showing that adenosine "turns on" the protein kinase C (PKC)-mediated pathway that accounts for the cardioprotection conferred by ischemic preconditioning contrasts with the scarcity of clinical data documenting the preconditioning-like protective effect of adenosine during cardiac operations on humans.
Forty-five patients undergoing coronary artery bypass were randomized to receive, after the onset of cardiopulmonary bypass, a 5-minute infusion of adenosine (140 microg x kg(-1) x min(-1)) followed by 10 minutes of washout before cardioplegic arrest (n = 23) or an equivalent period (15 minutes) of prearrest drug-free bypass (controls, n = 22). Outcome measurements included troponin I release over the first 48 postoperative hours and activity of ecto-5'-nucleotidase, an admitted reporter of PKC activation, as assessed on right atrial biopsies taken before bypass and at the end of the preconditioning protocol (or after 15 minutes of bypass in control patients).
Aortic cross-clamping times were not different between the two groups. Likewise, prebypass values of ecto-5'-nucleotidase (nanomoles/mg protein per minute) were similar in control (3.14+/-1.02) and adenosine-treated (2.66+/-1.08) patients. They subsequently remained unchanged in control patients (3.87+/-1.65) whereas they significantly increased after adenosine preconditioning (4.47+/-1.96, p<0.001 versus base line values). However, peak postoperative values of troponin I (microg/L) were not significantly different between control (4.8+/-2.8) and adenosine-preconditioned patients (5.9+/-6.6) nor were the areas under the curve. There were no adverse effects related to adenosine.
Adenosine, given at a clinically safe dose, can turn on the PKC-mediated signaling pathway involved in preconditioning but this biochemical event does not translate into reduced cell necrosis after coronary artery surgery, suggesting that a preconditioning-like protocol may not be the best suited for exploiting the otherwise well-documented cardioprotective effetcs of adenosine.
大量实验研究表明，腺苷可“开启”蛋白激酶C（PKC）介导的通路，该通路介导了缺血预处理所赋予的心脏保护作用。然而，关于腺苷在心脏手术期间对人类产生类似预处理保护作用的临床数据却很匮乏，这两者形成了鲜明对比。
45例行冠状动脉搭桥术的患者在体外循环开始后被随机分组，其中23例在心脏停搏前接受5分钟的腺苷输注（140μg·kg⁻¹·min⁻¹），随后冲洗10分钟；另外22例为对照组，接受相当于15分钟的停搏前无药物体外循环。观察指标包括术后48小时内肌钙蛋白I的释放量，以及在体外循环前和预处理方案结束时（对照组患者为体外循环15分钟后）从右心房活检组织中评估的ecto-5'-核苷酸酶活性，该酶被认为是PKC激活的报告分子。
两组患者的主动脉阻断时间无差异。同样，对照组（3.14±1.02）和腺苷治疗组（2.66±1.08）患者体外循环前ecto-5'-核苷酸酶（纳摩尔/毫克蛋白每分钟）的值相似。对照组患者该值随后保持不变（3.87±1.65），而腺苷预处理后该值显著升高（4.47±1.96，与基线值相比p<0.001）。然而，对照组（4.8±2.8）和腺苷预处理组患者术后肌钙蛋白I的峰值（μg/L）以及曲线下面积均无显著差异。未发现与腺苷相关的不良反应。
给予临床安全剂量的腺苷可开启预处理中涉及的PKC介导的信号通路，但这一生化事件并未转化为冠状动脉手术后细胞坏死的减少，这表明类似预处理的方案可能并非最适合发挥腺苷其他已充分证明的心脏保护作用。
