International Circulation: So what is it about the animal models, does it have the same complexity?
《国际循环》:动物模型是否跟人体模型同样复杂?
Heusch: Well first of all, it is just a different species. In the evolutionary process, some proteins are very conserved in their function and structure, and others are not. Sometimes, a different isoform of a protein or a different molecule altogether is performing the same function in different species. The assumption of a straightforward transfer is probably even na?ve to begin with. Then again, most animals are being studied while they are young and healthy whereas human patients are old, sick, have had a multitude of diseases – hypertension, diabetes, hyperlipidemia, hypertriglyceridemia, hypercholestermia. This patient has these diseases over decades before eventually suffering a myocardial infarction. He has also received multiple treatments for all of these diseases, so you are dealing with an aged organism of a different species with comorbidities and co-medications. In retrospect, it was probably quite na?ve to assume to just take a molecule from an animal model and have it work in humans..
Heusch教授:首先,只是种属之间的区别。我的意思是存在进化过程。某些蛋白的功能和结构非常保守,其他蛋白则不是如此,有时候不同亚型的蛋白或化学、构成或结构不同的蛋白发挥同样的作用,在其他动物则由另一种蛋白发挥该作用。因此,假定可以把动物实验的结果直接推及到人体是天真的想法。另外,大多数实验动物是年轻且健康的,而患者年龄大且有疾病,通常有多种疾病,例如高血压、糖尿病、高脂血症、高甘油三酯血症、高胆固醇血症。在发生心梗之前,已经有上述病史几十年,也接受了多种药物治疗,因此我们面对的是老化的器官,有并存疾病,同时因为多种疾病接受了治疗。因此,我还想说的是,认为只是来自动物身上的一个分子会在人体发挥作用是一个天真的想法。
International Circulation: What are some of the predictive values for prognosis using MRI, SPECT and other techniques to evaluate myocardial ischemia and reperfusion?
《国际循环》:MRI、SPECT和其他技术评价心肌缺血和再灌注的预后的预测价值如何?
Heusch:That is a slightly different question. Once a patient comes in with the onset of an acute myocardial infarction, the biggest predictor of further prognosis is simply the size of the territory affected by it. The second most important factor, which is closely related to the first one, is the left ventricular function that results from the infarction. Those two parameters, infarct size and left ventricular dysfunction, largely determine the further fate of the patient and therefore it is good to reduce infarct size and to improve function quickly because that will have a prognostic impact.
Heusch教授:这是另外一个问题。我认为,一旦患者因急性心梗入院,我认为最佳的预后预测指标实际上是梗死区域的大小。第二个重要的预后指标与第一个指标紧密相关,即左室功能或相反的指标——心梗所导致的左室功能下降。梗死灶大小和左室功能障碍这两个指标在很大程度上决定了患者未来的命运,因此尽快缩小梗死体积和改善心室功能是正确的做法,因为这会对预后有影响。
International Circulation: So what is the relationship between ischemia reperfusion injury and the time interval between the infarct and the interventions?
《国际循环》:缺血再灌注损伤和梗死发病和干预时间间隔之间的关系是什么?
Heusch: Textbooks will explain that once a coronary artery is occluded, necrosis will start within twenty to forty minutes. We have now learned that this is not necessarily true. It can be true, but in some instances viable myocardium, even with a coronary artery occlusion, can be maintained for hours, up to twelve, or even longer, if there is a slight amount of residual blood flow. As such, a slight amount of residual blood flow in a patient is often present, because a patient who develops coronary artery diseases over a prolonged period of time develops a collateral blood flow, by-passing the actual site of the lesion, such that a little blood flow is maintained distal to the occlusion. That small amount of blood flow can go a long way to sustain residual viability in the myocardium. It is therefore that, even after ten hours or more , it maybe worth it to reopen the artery to rescue some of the myocardium, maybe not all of it, but at least a significant portion of it.
Heusch教授:通常来讲,即使是一些经典的教科书也指出,冠脉闭塞后20~40分钟心肌开始发生坏死。但是现在我们知道这不一定是正确的。可能是正确的。但是在某些情况下,即使冠脉闭塞了,如果有少量残存血流的话,心肌在几个小时内仍然是存活的,最长可达12小时。实际上,患者通常是有少量残存心肌,因为经过很长时间发生冠心病的患者有侧枝血流供应梗死灶的实际部位,使得闭塞部位远端有少量血流供应,这些血流可以维持残留心肌存活。因此,即使是梗死后10个小时,也值得再通动脉以挽救心肌,也许不会全部挽救,但是至少是一大部分心肌。