<International Circulation>: I have a question about why there are so few drugs out there. Is it because the human model is vastly more complicated?
Prof. Heusch:First of all， apparently the species translating is big problem. That is one issue. The second issue is that the signal transduction as far as we can schematize is very complex so maybe the expectation to just hit a single signaling button and assume that this will work was na?ve to begin with. So that is why the mechanical intervention that recruits the entire signaling scheme works in humans but just taking and picking out one single signal and adding that as an exogenous drug did not work so far. The only drug trial that has worked so far is the one using Cyclosporin A and again considering the complexity of the signaling scheme， there is an explanation for that because in that signaling scheme， cyclosporine A hits a target very far downstream where all the signals converges which is on the mitochondria and that is basically the only signal that is working also in humans. So it is both. It is the complexity of the signal transduction scheme and the translations from animal preparations to the humans and those two issues have complicated matters.
《国际循环》：现在新药很少，这是因为人体模型过于复杂吗？
Heusch教授 ：首先，显然药物由一个种属应用到另一个种属是个大问题。其次，我们目前所了解到的信号转导通路非常复杂，因此只针对单一信号分子并认为这样会有效是个天真的想法。因此，机械上干预整个信号通路对人体有作用，但是只针对一个信号分子的药物是无效的，到目前来讲还是如此。目前唯一一个被临床试验证实有效的此类药物是环孢素A。同样地，考虑到信号通路的复杂性，对此也有解释，因为在该信号通路中，环孢素A针对的是一个非常下游的靶点，该靶点是所有信号交汇之处，该靶点位于线粒体上，该信号是唯一一个在人体和动物都发挥作用的信号。因此，是信号转导通路的复杂性以及将动物研究的结果推及到人体这两方面使得新药的研发变得复杂化。
<International Circulation>: So what is it about the animal models， does it have the same complexity?
Prof. Heusch:Well first of all， it is just species. I mean there is an evolutionary process. Some proteins are very conserved in their function and structure and others are not so sometimes a different isoform or a different chemical or composition or structure is doing the same function that in another animal is done by another one. So the assumption of the straightforward transfer is probably even na?ve to begin with. Then again， most animals are being studied while they are young and while they are healthy whereas the patient is old and is sick， has had diseases， usually a multitude – hypertension， diabetes， hyperlipidemia， hypertriglyceridemia， hypercholestermia so say a few only. And he has these over decades before he eventually suffers a myocardial infarction and then he has also received multiple treatments for all of these diseases so you are dealing with an aged organism with comorbidities， co-medications of a different species. So again， in retrospect it is probably quite na?ve to assume to just take a molecule from an animal and it will work.
《国际循环》：动物模型是否跟人体模型同样复杂？
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?
Prof. Heusch:That is a slightly different question. I think that once a patient comes in with the onset of an acute myocardial infarction， I think the biggest predictor of further prognosis is actually simply the size of the territory that is effected by it. The second most important factor which is closely related to the first one is the left ventricular function or visa versa， the function that results from the infarction. Those two parameters， infarct size and left ventricular dysfunction resulting from the table， 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.
《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。
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