The long term objective of this application is to obtain a detailed quantitative description of the vascular supply in the myocardium and to determine whether dynamic exercise affects the structural basis for oxygen delivery within the heart and, thus may reduce the vulnerability of the myocardium to ischemic injury.
The specific aims are: (1) To evaluate morphometrically the responses of the whole coronary arterial vasculature and myocardial microvasculature to running and swimming in order to establish which of these two modalities of dynamic exercise is more effective in increasing the vascularity of the myocardium; and (2) To test the protective effects of running and swimming in a model of small vessel disease, hypertensive-diabetic cardiomyopathy. This disease model in rats produces myocardial lesions of replacement fibrosis and interstitial and perivascular fibrosis, similar to those found in human patients with hypertension and diabetes mellitus. Normal and hypertensive-diabetic rats will be subjected to running and swimming protocols of moderate and strenuous intensities for a training period of 10 weeks. Morphometric measurements will be made of the sizes of the left and right coronary arteries, the diameter and length distributions of all intermediate and small sized arteries and arterioles, and the volume, length and surface area of capillaries. The methodology for measuring arteries and arterioles is a new morphometric technique that solves the problem of measuring the total lengths of all vessels in the myocardium subdivided into size classes on the basis of diameter, cross sectional area or wall thickness. This information will be relevant to the analysis of collateral formation, coronary blood flow and vascular resistance. Electron microscopic morphometry will determine capillary volume for oxygen availability, capillary surface for oxygen transport, and the maximum distance from the capillary wall to myocyte mitochondria for oxygen diffusion. All vascular changes will be correlated with the changes in size and number of myocardial lesions in the hypertensive-diabetic rats. These effects will also be examined and comparisons made between male and female rats and between adult (7 month old) and aging (15 month old) rats, because of the influence of sex and age on the response of the myocardium to exercise.
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