Department of Anesthesiology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China.
Chin Med J (Engl). 2009 Dec 20;122(24):3048-54.
There are few studies to assess whether propofol attenuates myocardial ischemia-reperfusion injury via a mechanism related to nitric oxide (NO) route, so we designed this randomized blinded experiment to observe the changes of NO contents, nitric oxide synthase (NOS) activity, NOS contents in the myocardium, and cardiac function in ischemic reperfused isolated rat hearts, and to assess the relation between myocardial NO system and cardioprotection of propofol.
The hearts of 30 Sprague-Dawley male rats were removed, mounted on a Langendorff apparatus, and randomly assigned to one of three groups (n = 10 each group) to be treated with the following treatments in a blinded manner: Group 1, control group, after perfusion with pure Krebs Henseleit bicarbonate (K-HBB) buffer solution for 15 minutes, hearts were subjected to 20 minutes global ischemia followed by 60 minutes reperfusion with pure K-HBB buffer; Group 2, after perfusion with K-HBB buffer solution containing propofol (10 microg/ml) for 15 minutes, the hearts underwent 20 minutes global ischemia followed by 60 minutes reperfusion with the same K-HBB buffer solution; Group 3, after perfusion with K-HBB buffer solution containing propofol (10 microg/ml) and L-NAME (100 micromol/L) for 15 minutes, the hearts underwent 20 minutes global ischemia followed by 60 minutes reperfusion with the same K-HBB buffer solution. The cardiac function was continuously monitored throughout the experiment. The coronary flow was also measured. An ISO-NO electrode was placed into the right atrium close to the coronary sinus to continuously measure NO concentration in the coronary effluent. The tissue samples from apex of hearts in Groups 1 and 2 were obtained to measure the NOS activity by spectrophotometry and the NOS contents by immunohistochemistry, respectively.
The cardiac function was significantly inhibited after ischemia and then gradually improved with reperfusion in all three groups. As compared with Group 1, the cardiac function variables and coronary flow at all the observed points were significantly improved in Group 2. The cardiac function variables and coronary flow were better in Group 3 than in Group 1, but were inferior in Group 3 than in Group 2. Both NO contents and NOS activity in the myocardium were significantly higher in Group 2 than in Group 1. However, NOS contents in the myocardium did not significantly differ between Groups 1 and 2.
In isolated rat hearts, propofol can improve cardiac functional recovery after ischemia-reperfusion by upregulating NOS activity in the myocardium. The NO system may play an important role in the preservation of myocardial ischemia-reperfusion injury produced by propofol.
目前仅有少数研究评估丙泊酚是否通过与一氧化氮（NO）途径相关的机制减轻心肌缺血再灌注损伤，因此我们设计了这项随机双盲实验，以观察缺血再灌注分离大鼠心脏中 NO 含量、一氧化氮合酶（NOS）活性、心肌 NOS 含量和心功能的变化，并评估心肌 NO 系统与丙泊酚的心脏保护作用之间的关系。
30 只雄性 Sprague-Dawley 大鼠的心脏被取出，安装在 Langendorff 仪器上，并以盲法方式随机分配至三组（每组 10 只）：组 1，对照组，在灌注纯 Krebs Henseleit 碳酸氢盐（K-HBB）缓冲液 15 分钟后，心脏经历 20 分钟的整体缺血，然后再用纯 K-HBB 缓冲液灌注 60 分钟；组 2，在灌注含有丙泊酚（10μg/ml）的 K-HBB 缓冲液 15 分钟后，心脏经历 20 分钟的整体缺血，然后再用相同的 K-HBB 缓冲液灌注 60 分钟；组 3，在灌注含有丙泊酚（10μg/ml）和 L-NAME（100μmol/L）的 K-HBB 缓冲液 15 分钟后，心脏经历 20 分钟的整体缺血，然后再用相同的 K-HBB 缓冲液灌注 60 分钟。整个实验过程中持续监测心功能。还测量冠状动脉流量。将一个 ISO-NO 电极放置在右心房靠近冠状窦处，以连续测量冠状动脉流出物中的 NO 浓度。从各组心脏的顶部获得组织样本，通过分光光度法测量 NOS 活性，通过免疫组织化学法测量 NOS 含量。
三组的心脏功能在缺血后明显受到抑制，然后在再灌注过程中逐渐改善。与组 1 相比，组 2 所有观察点的心功能变量和冠状动脉流量均显著改善。组 3 的心功能变量和冠状动脉流量优于组 1，但低于组 2。与组 1 相比，组 2 心肌中的 NO 含量和 NOS 活性均显著升高。然而，组 1 和组 2 之间的心肌 NOS 含量没有显著差异。
在分离的大鼠心脏中，丙泊酚通过上调心肌 NOS 活性来改善缺血再灌注后的心脏功能恢复。NO 系统可能在丙泊酚引起的心肌缺血再灌注损伤的保护中发挥重要作用。
