This research is designed to evaluate quantitatively specific factors influencing the recovery potential of myocardium to compensate for tissue loss sustained after infarction. A favorable prognosis for long-term survival among patients with myocardial infarction depends on the efficient reconstitution of myocardium with usable microcirculatory and cellular reserves. Since myocardial regeneration ultimately relies on increasing its cellular mass, this project uses a new morphometric methodology for the direct measurement of cellular hypertrophy and hyperplasia, supplemented by autoradiography with 3H-L-leucine and 3H-thymidine as a parallel indicator of dynamic cell growth and multiplication. The capacity of each of these methods to measure localized in situ parameters will allow the detection of transmural and periinfarct gradients of response, particularly those in the currently controversial """"""""border zone"""""""" of an infarct. Local changes in capillary reserve will be measured with horseradish peroxidase vascular tracer. This quantitative test system will be used to evaluate the influence of absolute infarct size, measured by the numerical loss of myocyte nuclei, on the ability of surviving myocardium to realize a full regenerative response. The possibilities for augmenting the regenerative capacity of the surviving myocardium by program of physical exercise training will be tested by measuring the rate and extent of myocardial recovery after the induction of infarcts of comparable size in sedentary, moderately exercised and strenously exercised rats. The response of the myocardium to infarction will also be measured in animals whose regenerative capacity has been partially utilized by a preexisting cardiac hypertrophy. These 4 modalities of preconditioning are relevant to their human counterparts as symbolized by the sedentary office worker, the recreational jogger, the professional athlete, and the patient with a pathologically enlarged heart.
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