Sustained regional abnormalities in cardiac metabolism after transient ischemia in the chronic dog model

Abstract

Positron emission tomography allows noninvasive assessment of myocardial blood flow and metabolism, and may aid in defining the extent and severity of an ischemic injury. This hypothesis was tested by studying, in chronically instrumented dogs, regional blood flow and metabolism during and after a 3 hour balloon occlusion of the left anterior descending coronary artery. The metabolic findings after ischemia were compared with the recovery of regional function over a 4 week period. N-13 ammonia was used as a blood flow tracer, and C-11 palmitic acid and F-18 deoxyglucose as tracers of fatty acid and glucose metabolism, respectively. Regional myocardial function was monitored with ultrasonic crystals implanted subendocardially. Regional function improved most between 24 hours and 1 week after reperfusion, but was still attenuated at 4 weeks. The slow functional recovery was paralleled by sustained metabolic abnormalities, reflected by segmentally delayed clearance of C-11 activity from myocardium and increased uptake of F-18 deoxyglucose. Absence of blood flow and C-11 palmitic acid uptake at 24 hours of reperfusion correlated with extensive necrosis as evidenced by histologic examination. Conversely, uptake of C-11 palmitic acid with delayed C-11 clearance and increased F-18 deoxyglucose accumulation identified reversibly injured tissue that subsequently recovered functionally and revealed little necrosis. Thus, recovery of metabolism after 3 hours of ischemia is slow in canine myocardium and paralleled by slow recovery of function. Metabolic indexes by positron tomography early after reperfusion can identify necrotic and reversibly injured tissue. Positron tomography may therefore aid in defining the extent and prognosis of an ischemic injury in patients undergoing reperfusion during evolving myocardial infarction.

Early Positive Biomarker in Relation to Myocardial Necrosis and Impaired Fatty Acid Metabolism in Patients Presenting With Acute Chest Pain at an Emergency Room

“…In this study, myocardial metabolic injury was also evaluated by fatty acid imaging with BMIPP because myocardial fatty acid metabolism is more susceptible to ischemia and could be a better marker of myocardial injury than myocardial perfusion abnormality. [21][22][23][24] Cardiac fatty acid metabolism is impaired even in the myocardium that survives after an acute ischemic event, and impaired BMIPP uptake is closely related to intracellular high-energy phosphate depletion due to ischemia 22 and to regional wall motion abnormality. 23,24 The present study showed that the first single-point troponin data on arrival can reflect injured myocardial mass, although the accuracy is limited and peak values of biomarkers more closely correlated with scintigraphically assessed injured mass than did the first singlepoint data.…”

Quantitative assessment of prolonged metabolic abnormalities in reperfused canine myocardium.

“…Results with positron emission tomography (PET) and [1-"'C]palmitate, based on analysis of tissue time-activity curves, have been interpreted to indicate decreased oxidation and increased esterification of fatty acid in postischemic myocardium both acutely13 and in chronic preparations. 2 Lopaschuk et a17 found increased esterification of labeled fatty acid in postischemic myocardium, but oxidation, although tending to be decreased, was not significantly depressed. Liedtke et al10 found normal or increased fatty acid oxidation in acutely reperfused myocardium but decreased fatty acid oxidation 4 days after reperfusion in chronically instrumented pigs.14 Thus, the time course of changes in fatty acid utilization after reperfusion remains unclear.…”

Discrepancy between myocardial perfusion and fatty acid metabolism following acute myocardial infarction for evaluating the dysfunctional viable myocardium

“…25,26 To prevent these events, the lipid pool in cardiac muscle cells expands, and incorporates excess free fatty acids. 27,28 Among various clinical, angiographic, and radionuclide indices, discrepant BMIPP uptake was the best predictor of future cardiac events. 29 It has been shown that the additional information provided by BMIPP substantially increases the accuracy of perfusion tracer uptake alone or dobutamine echocardiography alone to predict functional outcome early after AMI.…”