Effect of flow-independent reduction of metabolism on regional myocardial clearance of 11C-palmitate.
Authors: R A Lerch, S R Bergmann, H D Ambos, M J Welch, M M Ter-Pogossian, B E Sobel
Journal: Circulation (1982)

Recent studies with sequential positron-emission tomography have demonstrated that early clearance of activity from myocardium after i.v.carbon-11 ("C)-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, we characterized the effects of restricted oxygen supply on regional '1C clearance rates in vivo u'nder two 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 two regional time-activity curves (90 minutes apart) were recorded with a d-detector probe after intracoronary injection of "IC-palmitate.'Incontrol dogs (n = 7), no intervention was imposed between'the two studies.In the experimental dogs, oxygen supply was reduced 15 minutes before the second i'njection of "C- palmitate by either reducing LAD flow by an average of 76% (ischemia group, n = 7) or by perfusing the LAD bed at normal flow rate with venous blood, resulting in an average reduction in oxygen content of 66% (hypoxia group, n = 7).Myocardial blood flow in the LAD-perfused region determined based on washout of H210 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, "C clearance rates did not change from the first to the second study in control dogs.However, the, "C 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).Thus, clearance of "C-activity after extraction of "C-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.DECREASED OXIDATIVE METABOLISM of fatty acids 'is an early consequence of ischemia.1'6Since palmitate labeled with the positron-emitting isotope carbon-li ("IC) has the same biochemical properties as its physiologic counterpart and since positron-emission tomography permits quantitative determination of regional myocardial uptake and release of positron-emitting isotopes noninvasively, positron-emission tomography with "IC-palmitate has been' suggested as an approach for delineation of ischemic myocardium based on its altered fatty acid metabolism.6-9However, Schelbert et al.'0 suggested that results would be distorted because of altered residence time or that altered washout would mask detection of impaired metabolism induced by hypoxia.We showed that viable but ischemic myocardium supplied by -vessels with critical coronary stenosis in dogs extracts "IC-palmitate.9In ischemic zones, the monoexponential decline of activity 5-15 minutes after administration of tracer has a lower rate constant than that in normal regions.9At least two factors