99mTc-glucarate kinetics differentiate normal, stunned, hibernating, and nonviable myocardium in a perfused rat heart model

Eur J Nucl Med Mol Imaging. 2010 Oct;37(10):1909-17. doi: 10.1007/s00259-010-1495-0. Epub 2010 Jul 24.

Abstract

Purpose: (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).

Conclusion: (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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Transport
  • Creatine Kinase / metabolism
  • Glucaric Acid / analogs & derivatives*
  • Glucaric Acid / metabolism
  • Heart* / physiology
  • Heart* / physiopathology
  • Hemodynamics
  • Kinetics
  • Male
  • Microscopy, Electron, Transmission
  • Models, Animal
  • Myocardial Infarction / complications
  • Myocardial Stunning / metabolism*
  • Myocardial Stunning / pathology
  • Myocardial Stunning / physiopathology
  • Myocardium / enzymology
  • Myocardium / metabolism*
  • Myocardium / pathology
  • Myocardium / ultrastructure
  • Organotechnetium Compounds / metabolism*
  • Perfusion*
  • Rats
  • Rats, Sprague-Dawley
  • Tetrazolium Salts / chemistry
  • Tissue Survival*

Substances

  • Organotechnetium Compounds
  • Tetrazolium Salts
  • technetium Tc 99m glucarate
  • triphenyltetrazolium
  • Creatine Kinase
  • Glucaric Acid