This renewal proposal will extend the use of magnetic resonance imaging and spectroscopy for the evaluation of ischemic heart disease. The initial three years of this project defined to the overall goal of investigating the use of MRI and MRS to evaluate reperfusion after ischemic insults of various severity. Determination of reperfusion of a jeopardized region will be done using contrast enhanced MRI employing the paramagnetic contrast media, manganese polyphosphonate, while the status of the myocardium will be assessed by phosphorus 31 (31P) and sodium 23 (23Na) spectroscopy and multiphasic ECG gated MRI. Three experimental models will be used: intact murine heart with acute regional myocardial ischemia; intact feline heart with regional myocardial ischemia; isolated murine heart with global ischemia. Isolated murine hearts with pre-existing left ventricular hypertrophy and dilation and alcohol induced cardiomyopathy will also be studied in order to assess the influence of these diseases on the response to ischemia and reperfusion. The size of jeopardy area and severity of ischemia will be verified using histochemical staining and microsphere distribution. The 31P MRS peaks will be verified and correlated with biochemical measurements of phosphorus compounds using high pressure liquid chromotography (HPLC). We will attempt in the isolated heart to define a relationship between the change in 31P MRS peaks in the isolated heart during ischemic events and the total concentration of these phosphorus compounds as measured by HPLC. Such studies are intended to verify the isolated murine heart with regional ischemia and reperfusion as a model for initial assay of therapeutic agents. Beneficial therapeutic agents will then be assessed in the canine model of ischemia - reperfusion. The long-term objective is to define the capability of MRI and MRS to provide comprehensive assessment of the myocardium after reperfusion of ischemic injury using contrast enhanced MRI (perfusion, 31P and 23Na MRS (metabolism), and multiphasic ECG gated MRI (regional function).
