This study will analyze the sequence of structural changes, including ultrastructure, occurring in animal heart subjected to chronic pressure or volume work-overload that produces cardiac hypertrophy. It will also correlate these changes with alterations in regional distribution of myocardial blood flow and regional myocardial function. Pressure-overload will be induced by aortic banding with a cuff and volume-overload will be induced by arterio-venous fistula regulated by a cuff. These workloads will be induced in chronically instrumented animals. Regional myocardial blood flows will be measured using radiolabelled tracer microspheres. We will study these animals at different stages of developing cardiac hypertrophy. Postmortem studies will be undertaken, including morphometric measurements, to determine the extend of vessel wall lesions in the hypertrophied heart that may be responsible for altering regional myocardial blood flow and regional myocardial function. We will also administer several cardiovascular drugs continously before and during chronic work overload to evaluate their effects on regional myocardial blood flow distribution and function and on structural changes. We will attempt to define the factors that characterize early reverse ability of cardiac hypertrophy. Better quantitative definitions may be clinically useful in judging which patients with hypertrophic heart disease may benefit from appropriate intervention to restore normal myocardial function.