Development of a computational Management system of hemodynamics in patients with acute myocardial infarction

我们研制了一种能同时控制体循环动脉压（AP）、心输出量（CO）和左心房压（P_2）的新型自动给药系统<LA>。该系统可自动使急性心肌梗死后心力衰竭患者的血流动力学恢复正常。我们进一步扩展了我们的系统，使该系统可以通过精确控制心率降低和心室收缩力来优化心脏氧代谢以及此类患者的血液动力学。在犬急性心力衰竭模型中，扩张系统能够改善心脏氧代谢，同时恢复正常的血流动力学状态。我们的系统所实现的心脏氧代谢的改善是否真的改善了心肌损伤仍有待评估。为了回答这个问题，我们开发了一种人工动脉制剂，将离体兔心脏连接到该制剂上。该制剂能连续监测家兔心脏氧代谢，同时将AP、CO和<LA>P_2控制在所需水平，电刺激迷走神经可有效降低心率。在兔心肌缺血再灌注损伤模型中，我们研究了电刺激迷走神经对心肌基质金属蛋白酶表达和激活的影响，该蛋白酶在急性心肌梗死后心力衰竭的进展中起着至关重要的作用。我们发现，刺激迷走神经的传出增加心脏基质金属蛋白酶的内源性抑制剂（TIMP-1）的mRNA和蛋白水平，并降低心脏基质金属蛋白酶的活性。这意味着迷走神经刺激不仅是降低心率的有效方法，而且是急性心力衰竭的有效心脏保护方法。

We have developed a novel automated drug delivery system for simultaneous control of systemic arterial pressue(AP) , cardiac output(CO) , and left atrial pressure(P_<LA>) . With this system, hemodynamics of heart failure patients after acute myocardial infarction can be automatically restored to normal condition. We further expanded our system so that the system can optimize cardiac oxygen metabolism as well as hemodynamics in such patients through precise control of heart rate reduction and ventricular inotropy. In a canine acute heart failure model, the expanded system was able to improve cardiac oxygen metabolism while restoring normal hemodynamic condition. Whether the improvement in cardiac oxygen metabolism as achieved by our system really ameliorates the myocardial damage remained to be evaluated. To answer this question, we developed an artificial arterial preparation, to which an isolated rabbit heart is connected. The preparation enables us to continuously monitor the oxygen metabolism of the rabbit heart while AP, CO, and P_<LA> are simultaneously controlled to a desired level.Electrical stimulation of vagal nerve can be an efficient method of heart rate reduction in our system. In a rabbit model of myocardial ischemia-reperfusion injury, we investigated the effects of electrical stimulation of efferent vagal nerve on myocaidial expression and activation of Cardiac Matrix Metalloproteinase, which is known to play crucial roles in the progression of heart failure after acute myocardial infarction. We disclosed that stimulation of the efferent vagal nerve increased mRNA and protein level of endogenous inhibitor of Cardiac Matrix Metalloproteinase(TIMP-1) , and reduced activity of Cardiac Matrix Metalloproteinase. This means that vagal stimulation can be not only an effective method of heart rate reduction, but also an effective method of cardio protection in acute heart failure.