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

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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.