99mTc-sestamibi kinetics predict myocardial viability in a perfused rat heart model |
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Authors: | Zhonglin Liu David R Okada Gerald Johnson III Sonia D Hocherman Delia Beju Robert D Okada |
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Institution: | (1) University of Tulsa and the University of Oklahoma Health Sciences Center, Tulsa, OK, USA;(2) University of Arizona, Tucson, AZ, USA;(3) Oklahoma State University School of Medicine, Tulsa, OK, USA;(4) Department of Biology, University of Tulsa, 6208 So. Oswego Ave., Tulsa, OK 74136, USA |
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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.
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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Keywords: | 99mTc-sestamibi Myocardium Viability Kinetics Ischemia Reperfusion |
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