Accurate noninvasive diagnosis and quantification of early coronary artery disease in man would permit testing the hypothesis that coronary atherosclerosis is reversible in a tightly controlled study of relatively small numbers of patients randomized to treatment and non-treatment groups with progression or regression followed in each patient compared to pretreatment severity. Positron emission tomography (PET) of myocardial perfusion during pharmacologic coronary vasodilation identifies 47 percent diameter coronary narrowing in dogs. Improvements in imaging techniques and types of stress may now detect even milder coronary lesions, thereby providing a greater likelihood of regression since treatment may be started earlier. This project will test the hypotheses that (1) Myocardial perfusion in cc/min/gm can be accurately measured noninvasively in comparison to microspheres at up to six times baseline flow levels by PET, intravenous N-13 ammonia and our validated transport model suitable for any perfusion indicator. (2) Since first pass extraction is determined regionally in our model, flow measurements are accurate under all metabolic conditions altering myocardial uptake of N-13 ammonia such as ischemia, acidosis, alkalosis, catechols, insulin, digoxin and beta blockers as already validated for a comparable tracer, Rb-82 (3) Maximal coronary flows for purposes of diagnostic imaging are produced safely, reproducibly by combined pharmacologic and physical stress, such as iv dipyridamole with handgrip or oral dipyridamole with treadmill or supine bicycle exercise, the optimal combination to be determined by clinical trial (4) Early, mild CAD of 30 percent diameter narrowing by quantitative coronary arteriography can be noninvasively identified in humans with a sensitivity and specificity of 98 and 100 percent by PET of iv N-13 ammonia during maximal coronary vasodilation induced by combined pharmacologic and exercise stress (5) Severity of stenoses can be predicted and quantified physiologically from quantitative perfusion imaging with sufficient accuracy to follow changes in severity during reversal therapy.
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