In the myocardium, as in most mammalian tissues, the capillaries play a fundamental and necessary role in the delivery of oxygen and other nutrient substrate to tissue cells. The objective of this research is to test the hypothesis that the capillary system, as a distribution and exchange system, may act as a restraint on the ultimate size to which myocardial muscle cells may grow in the hypertrophy process. Myocardial hypertrophy is one cardinal feature of the varied compensatory mechanisms involved in maintaining normal circulatory homeostasis in response to a volume or pressure overload on the heart. From this it follows that the capillary bed may also be fundamentally involved in heart failure. To test this hypothesis, capillary flow will be measured using radioactive microspheres. Capillary exchange will be measured using the indicator diffusion technique. Such measurements will provide information on capillary surface area and capillary permeability. The indicator diffusion method can also be used to test for sarcolemmal membrane permeability when labeled water is used as a marker. The capillary data derived from the above studies will be contrasted and/or correlated with cellular changes (e.g., mitochondrial volume, fiber diameter, cell organelles, etc.) using electron microscopy and stereology (e.g., capillary counts) in an effort to more clearly define the relation between anatomic structure and physiologic function in the hypertrophy and failure process. The physiologic state of the animal will be carefully monitored and correlated with alterations in both capillary and anatomical parameters. Physiologic variables which will be measured include: dP/dt/P, myocardial oxygen consumption, diastolic pressure time index (DPTI), tension time index (TTI), left ventricular end diastolic pressure (LVEDP), stroke work, cardiac output and aortic and central venous pressures.
