This project has two basic purposes: (1) To study the functional and structural changes in the small blood vessels (microcirculation) when blood flow is reduced or abolished (ischemia), and (2) To compare, under the conditions just mentioned, changes in the microcirculation of non-diabetic versus diabetic animals. Previous studies on ischemia have concentrated almost exclusively on the effects of the extravascular cells (muscle fibers, etc.); whereas little is known about the effects of reduced blood flow on the vessels themselves. Models of diabetes will be: spontaneously diabetic Wistar rats, rats with streptozotocin-induced diabetes, and spontaneously diabetic Chinese hamsters. The overall approach will be to correlate, wherever possible, (a) The study of living vessels under the microscope, (b) Light and electron microscopic study of the same vessels after fixation, and (c) Functional studies of various kinds, including tests on blood (such as clotting time and microhematocrit). Special attention will be given to the conditions of reflow after the ischemic period because there is evidence that - in some organs -reflow after ischemia is impaired (a phenomenon that could have important implications for stroke and myocardial infarction in man). Organs and tissues submitted to ischemia will be: striated muscle, mesentery, gut and brain. Because shock is a condition of low blood flow (and thus related to ischemia, which represents no flow), the project will include a study of shock (which is also a common complication of myocardial infarction in diabetics). Shock will be induced in rats by bleeding and with tourniquets. The effects of shock will be studied, with the electron microscope, on the microcirculation of several fields (including muscle, gut and heart) and compared in diabetic and non-diabetic animals. The effect of shock on the inflammatory process will also be explored, and related to the pathogenesis of shock. Another condition of low-flow will be studied, namely chronic passive congestion, a common complication of heart disease in man.