Heusch教授:在过去的20年中,通过基础研究我们了解到有一些机械干预手段实际上能够保护心肌,即缺血预适应、缺血后处理和远隔预适应,三者都包括罪犯血管短暂的缺血和再灌注。
<International Circulation>: Could you please discuss some of the new myocardial protection therapies for treatment of acute myocardial infarction.
Prof. Heusch:From the experimental side we have learned over the last 20 years that there are a number of mechanical interventions that can actually protect the myocardium, which is pre-conditioning, post conditioning, and remote conditioning and they all contain a brief period of ischemia and reperfusion in conjunction with the culprit infarction. So preconditioning is a brief cycle of myocardial ischemia to precede that culprit lesion, post conditioning is something afterwards, and remote is an ischemia cycle that is in a distant organ of the heart itself. It can be the arm, the liver, the kidney, whatever. And all of these interventions actually protect the myocardium in the sense that eventually, the resulting infarction is reduced. Now what can we use for the patient? Preconditioning has a problem that you do not know when a patient undergoes an infarction so it can only be utilized in elective interventions. So for instance if you plan an intervention such as cardiac surgery, you can utilize preconditioning to attenuate the eventual damage.
《国际循环》:能否介绍下急性心梗的新型心肌保护治疗手段?
Heusch教授:在过去的20年中,通过基础研究我们了解到有一些机械干预手段实际上能够保护心肌,即缺血预适应、缺血后处理和远隔预适应,三者都包括罪犯血管短暂的缺血和再灌注。因此预适应是在罪犯血管闭塞之前短暂的心肌缺血再灌注的循环,而缺血后处理则是在罪犯血管闭塞之后,远隔预适应则是在心脏以外远隔器官的缺血再灌注循环。可以是双臂、肝脏和肾脏等。这些干预手段实际上能够保护心肌,最终缩小梗死体积。哪些可以用在患者身上呢?缺血预适应有一个问题,就是你不知道患者何时会发生心梗,因此只能用在择期PCI的情况下。例如计划心脏外科手术等干预时可以利用缺血预适应来减少最终的损害。
<International Circulation>: How far in advance would the preconditioning need to be?
Prof. Heusch: There are two time windows. One is briefly before, which is the acute preconditioning, one to two hours before and then there one which is late form of protection which is a little weaker but more sustained and that is about twenty-four hours before. I think one of the more practical relevance is post conditioning, considering you do not know when you undergo an infarction. The patient who comes in with an infarction can still undergo post conditioning. At least once the artery has been opened you can use a few cycles of ischemia reperfusion, so to call a “stuttering reperfusion” if you wish to say. And that will attenuate the resulting infarct and that is quite useful and most proof of concept studies has shown that this is effective. And also the remote conditioning, just by inflating a blood pressure cuff around the arms several cycles will eventually protect the myocardium and will reduce infarction.
《国际循环》:预适应的时机是什么?
Heusch教授:有两个时间窗。一个是在干预之前1~2小时,即急性预适应。另一个是在干预之前24小时,虽然作用弱一些,但是作用更为持久。我想更为实用的是缺血后处理,因为我们不知道患者何时会发生心梗。已经发生心梗的患者还可以接受缺血后处理。至少在动脉一旦开通时,可以进行几个缺血再灌注循环,也就是所谓的“stuttering reperfusion”。这有助于缩小梗死体积,很有帮助,众多研究证实了它的有效性。远隔预适应即在手臂用袖带进行充气放气几个循环,最终有助于保护心肌和缩小梗死体积。
<International Circulation>: Do we know of any other mechanisms?
Prof. Heusch:That is the major problem. We know hundreds of mechanisms from thousands of studies, literally. But they are all in isolated cells, isolated sub-cellular systems, they are in experimental animals ranging from far away zebrafish to eventually monkeys or pigs or dogs. But there is very little transfer in all these single transduction mechanisms that we have pinpointed in animals in various preparations to human hearts. Very little is actually known for the human heart and this is in my view the explanation by the mechanical interventions that work preconditioning, post conditioning, and remote conditioning but the translation into drugs and into chemicals has been largely failing so far and this is probably because people have then focused on individual signaling molecules that have certain importance in the reductionist model but they are not explaining the full picture of the entire complex signals transduction cascade and therefore when we are translating it to the human being, it will be failed.
《国际循环》:还有其他机制吗?
Heusch教授:这是主要的问题。实际上通过大量的研究,我们了解到了成千上万个机制。但是,这些机制来自于单个细胞、分离的亚细胞器,来自于形形色色的试验动物,从斑马鱼到猴子、猪和狗。但是,来自动物制备物的单一信号转导机制转化到人体心脏的还非常少。对于人体心脏,我们的了解还非常有限,我认为这就是缺血预适应、缺血后处理和远隔适应虽然有效,但是转化为药物的努力大部分失败的原因所在。可能是由于人们关注了动物模型中有一定重要性的单个信号分子但是没有解释清楚整个复杂的信号转导级联反应的整体图像,因此当应用于人体时,就会失败。