Demographic studies suggest that myocardial Mg, but not Ca, varies with dietary intake. Such studies also suggest that higher Mg intake (and hence higher myocardial Mg) protects against lethal myocardial infarction. Furthermore, Ca influx into injured tissue may be a determinant of irreversibility of injury, possibly through Ca-Mg competition. We propose to determine the effects of high and low dietary Mg on resistance to myocardial injury, as well as the mechanism of such effects. Dogs and hamsters will be provided diets high and low in Mg. Tissue levels of Ca and Mg will be measured in heart, liver, blood, skeletal muscle and aorta. Myocardial injury will be produced by one of three mechanisms: coronary occlusion, isoproterenol injection or freezing. The amount of necrosis will be determined by elementary morphometric techniques. In addition to steady-state tissue levels of Ca and Mg, we will study the change in these concentrations, as functions of time, during the early phase of necrosis. The studies will demonstrate whether tissue Mg levels influence the extent of injury after an insult, and if such an effect is related to altered Ca influx. In a later stage of this work, we will determine if Mg-loaded heart muscle responds differently from depleted muscle to the deleterious effect of Ca on energy metabolism. Respiration and ATP synthesis by muscle cells and mitochondria, isolated from the myocardium of Mg-loaded and Mg-depleted animals, will be studied with and without a Ca challenge in vitro. Collectively, these experiments will help determine the possible effects of dietary Mg on the pathogenesis of myocardial necrosis due to coronary occlusion, isoproterenol and freezing, and the mechanism of such effects. This may be of importance in determining the possible role of dietary Mg in human ischemic heart disease.
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