Why So Few New Cardiovascular Drugs Translate to the Clinics.
Why So Few New Cardiovascular Drugs Translate to the Clinics.
复制标题
为什么很少有新的心血管药物转化为临床。
DOI：
10.1161/circresaha.116.309512
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发表时间：
2016
影响因子：
20.1
通讯作者：
Vatner,StephenF
中科院分区：
文献类型：
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作者：
Vatner,StephenF
绝大多数的心血管研究都是在急性制备或麻醉的动物模型中进行的，尽管麻醉对心血管功能有深远的直接影响，但更重要的是，麻醉改变了心血管的自主控制，其次改变了对常见干预措施（如药物）的反应。因此，不难想象麻醉是如何改变结果的，也不难理解药物的作用，并将其转化为临床。最近的一个例子是，一种新药可以增加心脏肌节收缩，这是一种改善心脏功能的新机制。对长期使用仪器的心衰有意识动物的研究发现，这种药物优于拟交感神经胺，因为它在不增加心肌耗氧量（MVO2）的情况下改善心肌功能。在麻醉的动物中报告了不同的结果，药物不再具有保护MVO2的有益作用，这是任何肌力药物在心力衰竭患者中成功的最关键因素。
The overwhelming number of cardiovascular research studies performed are in acutely prepared or anesthetized animal models, despite the fact that there are profound direct effects of anesthesia on cardiovascular function, but more importantly, anesthesia alters autonomic cardiovascular control and secondarily alters responses to common interventions, such as drugs. 4 Thus, it is not difficult to imagine how anesthesia may modify results and also in understanding the effects of drugs for translation to the clinics. A recent example occurred with a new drug that increases sarcomere contraction in the heart, a novel mechanism to improve cardiac performance. 5 Studies in chronically instrumented, conscious animals with heart failure found that this drug was superior to sympathomimetic amines because it improved myocardial function without an increase in myocardial oxygen consumption (MVO2). 6 Different results were reported in anesthetized animals, where the drug no longer had the salutary action on protecting MVO2, 6 which is most critical for success of any inotropic agents in patients with heart failure.