Effect of flow-independent reduction of metabolism on regional myocardial clearance of 11C-palmitate.

Abstract

Recent studies with sequential positron emission tomography demonstrated that early clearance of activity from myocardium after i.v. 11C-palmitate is decreased in regions of ischemia. To determine whether the reduced clearance is a reflection of decreased washout of labeled substrate or its metabolites, or a reflection of decreased metabolism labeled fatty acid, the effects of restricted O2 supply on regional 11C clearance rates in vivo were characterized under 2 conditions: hypoxia without concomitant reduction of flow and hypoxia induced by reduction of flow (ischemia). In 21 open-chest dogs, the left anterior descending coronary artery (LAD) was cannulated and perfused by an extracorporal bypass system. In each dog, 2 regional time-activity curves (90 min apart) were recorded with a .beta.-detector probe after intracoronary injection of 11C-palmitate. In control dogs, no intervention was imposed between the 2 studies. In the experimental dogs, O2 supply was reduced 15 min before the 2nd injection of 11C-palmitate by either reducing LAD flow by an average of 76% or by perfusing the LAD bed at normal flow rate with venous blood, resulting in an average reduction in O2 content of 66%. Myocardial blood flow in the LAD-perfused region determined based on washout of H215O did not change in either the control or hypoxia group, but decreased by an average of 64% (P < 0.025) in the ischemia group. Similarly, 11C clearance rates did not change from the 1st to the 2nd study in control dogs. The 11C clearance rate was reduced by an average of 52% with hypoxia despite maintenance of flow (P < 0.02) as well as by ischemia itself (61%, P < 0.005). Clearance of 11C-activity after extraction of 11C-palmitate by myocardium is consistently reduced in regions rendered hypoxic despite persistence of perfusion, supporting the hypothesis that the metabolic attenuation induced by hypoxia or ischemia per se can be detected in patients based on sequential and quantitative analysis of regional time-activity curves obtained by positron-emission tomography.