title: 99mTc-glucarate kinetics differentiate normal, stunned, hibernating, and nonviable myocardium in a perfused rat heart model.
abstract: OBJECTIVE
  (99m)Tc-glucarate is an infarct-avid imaging agent. However, patients may have mixtures of normal, irreversibly injured, stunned, and hibernating myocardium. The purposes were to determine (99m)Tc-glucarate uptake and clearance kinetics in these four conditions, and its ability to determine the extent of injury.
  
  
  METHODS
  Twenty-two perfused rat hearts were studied: controls (n = 5), stunned (n = 5; 20-min no-flow followed by 5-min reflow), hibernating (n = 6; 120-min low flow at 4 ml/min), and ischemic-reperfused (n = 6; 120-min no-flow followed by reflow). (99m)Tc-glucarate was then infused. Tracer activity was monitored using a NaI scintillation detector and a multichannel analyzer. Creatine kinase, electron microscopy, and triphenyltetrazolium chloride determined viability.
  
  
  RESULTS
  (99m)Tc-glucarate 10-min myocardial uptake was significantly greater in ischemic-reperfused (2.50 +/- 0.09) (cpm, SEM) than in control (1.74 +/- 0.07), stunned (1.68 +/- 0.11), and hibernating (1.59 +/- 0.11) (p < 0.05). Tracer retention curves for ischemic-reperfused were elevated at all time points as compared with the other groups. (99m)Tc-glucarate 60-min myocardial uptake was significantly greater in ischemic-reperfused (7.60 +/- 0.63) than in control (1.98 +/- 0.15), stunned (1.79 +/- 0.08), and hibernating (2.33 +/- 0.15) (p < 0.05). The 60-min well-counted tracer activity ratio of ischemic-reperfused to control was 9:1 and corroborated the NaI detector results. Creatine kinase, triphenyltetrazolium chloride, and electron microscopy all demonstrated significantly greater injury in ischemic-reperfused compared to the other groups. An excellent correlation was observed between viability markers and tracer activity (r = 0.99 triphenyltetrazolium chloride; r = 0.90 creatine kinase).
  
  
  CONCLUSIONS
  (99m)Tc-glucarate activity continually and progressively increased in irreversibly injured myocardium. (99m)Tc-glucarate uptake was strongly correlated with myocardial necrosis as determined by three independent assessments of viability. There were minimal and similar (99m)Tc-glucarate uptakes in control, stunned, and hibernating myocardium.
authors.affiliation: University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
authors.forename: David R
authors.initials: DR
authors.lastname: Okada
authors.forename: Zhonglin
authors.initials: Z
authors.lastname: Liu
authors.forename: Gerald
authors.initials: G
authors.lastname: Johnson
authors.forename: Delia
authors.initials: D
authors.lastname: Beju
authors.forename: Ban An
authors.initials: BA
authors.lastname: Khaw
authors.forename: Robert D
authors.initials: RD
authors.lastname: Okada
mesh_terms: D000818:Animals; D001692:Biological Transport; D003402:Creatine Kinase / Q000378:metabolism; D005937:Glucaric Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D006321:Heart / Q000502:physiology / Q000503:physiopathology; D006439:Hemodynamics; D007700:Kinetics; D008297:Male; D046529:Microscopy, Electron, Transmission; D023421:Models, Animal; D009203:Myocardial Infarction / Q000150:complications; D017682:Myocardial Stunning / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D015609:Organotechnetium Compounds / Q000378:metabolism*; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D013778:Tetrazolium Salts / Q000737:chemistry; D014022:Tissue Survival
chemical_list: D015609:Organotechnetium Compounds; D013778:Tetrazolium Salts; C067171:technetium Tc 99m glucarate; C009591:triphenyltetrazolium; D003402:Creatine Kinase; D005937:Glucaric Acid