Comparison of myocardial ATP, blood flow, and cytosolic adenosine in demand ischemia and coronary occlusion.

Abstract

To investigate the relationship between flow and energy metabolism during coronary underperfusion, regional myocardial ATP content, cytosolic adenosine concentrations, and blood flow were measured during segmental coronary artery occlusion (complete ligation, n = 10) and demand ischemia (catecholamines plus atrial pacing with subtotal stenosis, n = 6) in halothane anesthetized open-chest dogs. During coronary occlusion or demand ischemia, L-homocysteine thiolactone was infused for 20 min, after which left ventricular tissue was rapidly frozen and analyzed for regional blood flow (microspheres) and content of ATP and S-adenosylhomocysteine (SAH), an index of cytosolic adenosine. In nonischemic regions, ATP and SAH contents in both groups were the same as in unstimulated control animals with intact coronary circulation (n = 7), indicating that adrenergic stimulation during unrestricted flow had no effect on ATP or cytosolic adenosine. In the ischemic regions of both groups, there were decreases in regional flow, ATP content, and systolic wall thickening, and increases in SAH content. To compare the indexes of energy metabolism in tissue regions receiving equal blood flow, tissue samples were grouped into intervals of equal blood flow (ml.min-1.g-1). At every level of flow, ATP content in demand ischemia was 25-39% higher than in coronary occlusion. Estimates of cytosolic adenosine concentrations (using a mathematical model) in the lowest flow interval averaged 5 microM in demand ischemia, approximately twice as high as in coronary occlusion. It is concluded that in tissue regions receiving equal blood flow, ATP was better maintained and cytosolic adenosine was higher in demand ischemia than in coronary occlusion. The differences in ATP content and cytosolic adenosine were not due to different blood flows but rather to more favorable energy metabolism in demand ischemia.