Recovery of regional contractile function and oxidative metabolism in stunned myocardium induced by 1-hour circumflex coronary artery stenosis in chronically instrumented dogs.

Abstract

Stunned myocardium produced by 1 hour of critical coronary artery stenosis was evaluated for alteration in regional mechanical function and overall oxidative and fatty acid metabolism by positron emission tomography (PET) in chronically instrumented dogs. Twenty-seven dogs, chronically instrumented for measurements of left ventricular pressure and regional myocardial wall thickening in normal and ischemic zones, were subjected to a 1-hour period of myocardial ischemia produced by graded left circumflex coronary artery stenosis, resulting in minimal residual flow. Mean transmural myocardial flow during 1-hour coronary stenosis decreased to 0.34±0.04 ml/min per gram in the ischemic zones (normal zone transmural flow, 0.96±0.10 ml/min per gram). Systolic wall thickening in the ischemic zone was almost completely abolished (-97±4%). On reperfusion, systolic wall thickening immediately resumed but remained depressed. Progressive recovery was noted with time. At 24 hours, systolic wall thickening was still depressed (-20+6%, p<0.01). At 1 week, wall thickening had completely recovered and was no longer significantly different from the control condition. In addition, the absence of necrosis at the site of wall thickness measurements was confirmed at autopsy in all dogs. No abnormalities were found by electron microscopy in four dogs undergoing myocardial biopsies at the time of PET studies. Dynamic PET studies using [1-`1C]acetate tracer (performed at 6 hours, 1 week, and 2 weeks after reperfusion) and [1-1'C]palmitic acid tracer (performed at 6 hours, 12 hours, 24 hours, 1 week, and 2 weeks after reperfusion) allowed the computation of regional tissue time-activity curves in different regions of interest at different times during follow-up. Despite full reperfusion, abnormal [1-11CJ acetate and [1-`1C]palmitic acid kinetics were observed in the posterior segments, previously subjected to ischemia, as evidenced by a significant decrease in the slope of the early`1C clearance curve component. Repeat PET studies revealed progressive normalization of overall oxidative metabolism and fatty acid metabolism, which paralleled the time course of recovery of mechanical function. Thus, myocardial ischemia, produced by 1-hour coronary artery stenosis, followed by full reperfusion is associated with a prolonged period of postischemic mechanical and metabolic dysfunction. This transient reduction in oxygen delivery induced a prolonged impairment in fatty acid beta-oxidation as well as a reduction in overall oxidative metabolism despite full reoxygenation. A similar time course for recovery of function and metabolism was observed. (Circulation Research 1993;72:901-913

Influence of .BETA.-Adrenoceptor Blockade on the Myocardial Accumulation of Fatty Acid Tracer and Its Intracellular Metabolism in the Heart After Ischemia-Reperfusion Injury

“…[2][3][4][5][6] Slow recovery of the tracer uptake after ischemic insult has been found in both clinical and experimental studies. [17][18][19] In the present study, the reduced tracer uptake by the IR seen in the early image after tracer injection was not present in the delayed image because of slow clearance of the tracer in the IR, a finding consistent with the previous study. 10 Beta-adrenoceptor blockers, including carvedilol, are frequently prescribed for patients with coronary heart disease and heart failure, so it is important to clarify their influence on the distribution and intracellular metabolism of FA tracers in the myocardium.…”

Carbon-11 acetate as a tracer of myocardial oxygen consumption

“…Weinheimer et al observed that preservation of 11 C-acetate clearance after 1 week and the recovery of wall motion after 4 weeks were significantly correlated in dogs after a 1-or 4-h occlusion of the LAD [63]. Similar observations were reported by Heyndrickx et al after a 1-h occlusion of the circumflex artery in dogs [64].…”

A Dynamic Change by ¹²³I-15-(p-Iodophenyl)-3-R,S-Methylpentadecanoic Acid Myocardial Single Photon Emission Computed Tomography in a 55-Year-Old Woman

“…Examination during the chronic stage, however, has disclosed the improvement of the decreased tracer uptake in the 123 I-BMIPP and 11 C-palmitic acid PET imaging, and that 18 F-FDG PET imaging showed a decreased tracer uptake. 14,15 These findings show that it is not aerobic glucose metabolism but fatty acid metabolism that mainly produces the energy during the chronic stage.…”

“…Examination of stunned myocardium in the subacute stage has revealed that 123 I-BMIPP myocardial imaging and 11 Cpalmitic acid with positron emission tomography (PET), which is considered to be an accurate agent for the quantification of regional fatty acid utilization, decreased the tracer uptake, and 18 F-fluorodeoxyglucose (FDG) PET imaging demonstrated an increased tracer uptake. 14,15 This indicates that it is not fatty acid metabolism but aerobic glucose metabolism that mainly produces the energy in the myocardium during the subacute stage. Examination during the chronic stage, however, has disclosed the improvement of the decreased tracer uptake in the 123 I-BMIPP and 11 C-palmitic acid PET imaging, and that 18 F-FDG PET imaging showed a decreased tracer uptake.…”