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99mTc-sestamibi kinetics predict myocardial viability in a perfused rat heart model

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Introduction

99mTc-sestamibi has been proposed as a viability imaging agent. The purposes of this study were: (1) to determine the relationship between myocardial viability and 99mTc-sestamibi kinetics using perfused rat heart models across a full spectrum of viability, (2) to do so under conditions where myocardial flow was controlled and held constant, and (3) to do so using multiple quantitative methods to assess myocardial viability.

Methods

Twenty-three isolated rat hearts were perfused retrogradely with a modified Krebs-Henseleit (KH) solution. Four groups were studied: controls (C, n = 6), stunned (S, n = 6), ischemic-reperfused (IR, n = 6), and calcium injured (CAL, n = 5). Following a 20-min baseline and subsequent treatment phase, 99mTc-sestamibi was infused over 60 min (uptake) followed by 60 min clearance. Treatment phases consisted of 20 min no flow for S, 60 min no flow followed by 60 min reflow for IR, and 10 min infusion of KH solution without calcium followed by 20 min infusion of KH solution with 2 times normal calcium for CAL hearts. Creatine kinase (CK) assay, triphenyltetrazolium chloride (TTC) staining, and transmission electron microscopic (TEM) analysis were used to determine tissue viability.

Results

Myocardial peak 99mTc-sestamibi uptake (%id) was significantly decreased in IR (4.11 ± 0.22 SEM; p < 0.05) and CAL (1.07 ± 0.13; p < 0.05), but not in S (4.88 ± 0.17) as compared with C (5.99 ± 0.50). One hour fractional retention was 79.3 ± 1.9% for C, 80.3 ± 1.3% for S (p = n.s.), 79.1 ± 1.8% for IR (p = n.s.), and 14.9 ± 4.3% for CAL (p < 0.05 compared to all other groups). 99mTc-sestamibi absolute retention (%id) 1 h after the end of tracer administration was significantly decreased in IR (3.26 ± 0.23) and CAL (0.15 ± 0.02) as compared with both S (3.92 ± 0.16) and C (4.52 ± 0.32) (p < 0.05). CK increased significantly from baseline in the IR and CAL hearts. TTC determined percent viability was 100 ± 0% for C, 98.3 ± 1.1% for S, 82.8 ± 2.6% for IR, and 0.0 ± 0% for CAL. TEM analysis supported these findings. End tracer activity was significantly correlated with TTC determined percentage viable myocardium (r = 0.93, p < 0.05) and CK leak (r = −0.90, p < 0.05).

Conclusion

99mTc-sestamibi myocardial activity is significantly reduced in areas of nonviability after 1 h of tracer uptake and 1 h of tracer clearance. There is a linear correlation between myocardial viability, as determined by three independent methods, and tracer activity.

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Acknowledgements

The authors wish to thank the American Heart Association for supporting this project. This study is dedicated to Mr. Henry Zarrow and family, and to William K. Warren and family for their continuing support of medical research, without which these experiments would not have been possible.

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Authors and Affiliations

  1. University of Tulsa and the University of Oklahoma Health Sciences Center, Tulsa, OK, USA

    David R. Okada, Gerald Johnson III, Sonia D. Hocherman & Robert D. Okada

  2. University of Arizona, Tucson, AZ, USA

    Zhonglin Liu

  3. Oklahoma State University School of Medicine, Tulsa, OK, USA

    Delia Beju

  4. Department of Biology, University of Tulsa, 6208 So. Oswego Ave., Tulsa, OK, 74136, USA

    Robert D. Okada

Authors
  1. Zhonglin Liu
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  2. David R. Okada
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  3. Gerald Johnson III
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Correspondence to Robert D. Okada.

Additional information

This work was supported by the American Heart Association, the Anne and Henry Zarrow Foundation, and the William K. Warren Medical Research Foundation.

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Liu, Z., Okada, D.R., Johnson, G. et al. 99mTc-sestamibi kinetics predict myocardial viability in a perfused rat heart model. Eur J Nucl Med Mol Imaging 35, 570–578 (2008). https://doi.org/10.1007/s00259-007-0549-4

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  • DOI: https://doi.org/10.1007/s00259-007-0549-4

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