The changes in myocardial high energy phosphates and pH during regional ischemia, and their potential role in mediating functional abnormalities, is unclear. To determine the degree of regional blood flow reduction required to induce changes in high energy phosphates and pH, and to correlate these metabolic changes with alterations hi blood flow,3IP nuclear magnetic resonance spectroscopy was employed in an in vivo porcine model of graded coronary stenosis. Simultaneous measurements of regional blood flow and phosphate compounds were made during various steady-state degrees of regional ischemia in which subendocardial blood flow was reduced by as much as 80percent;. ATP did not fall over the total range of graded ischemia, while phosphocreatine (PCr), inorganic phosphate (P,), and pH all changed progressively after blood flow was reduced below 50percent; of normal. The ratio of PCr/P, (a measure of the energy reserve of the myocardium) was strongly correlated to subendocardial blood flow (r=0.94) and declined by 25percent; when blood flow was reduced by only 21percent; below normal. These findings indicate that PCr/P, is a sensitive marker of ischemia and support the hypothesis that the in vivo energy status of the myocardium is closely coupled to myocardial blood flow.