TY - JOUR
T1 - 99mTc-sestamibi kinetics predict myocardial viability in a perfused rat heart model
AU - Liu, Zhonglin
AU - Okada, David R.
AU - Johnson, Gerald
AU - Hocherman, Sonia D.
AU - Beju, Delia
AU - Okada, Robert D.
N1 - Funding Information:
This work was supported by the American Heart Association, the Anne and Henry Zarrow Foundation, and the William K. Warren Medical Research Foundation. D.R.Okada.G.JohnsonIII.S.D.Hocherman.R.D.Okada University of Tulsa and the University of Oklahoma Health Sciences Center, Tulsa, OK, USA
PY - 2008/3
Y1 - 2008/3
N2 - 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.
AB - 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.
KW - Ischemia
KW - Kinetics
KW - Myocardium
KW - Reperfusion
KW - Tc-sestamibi
KW - Viability
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U2 - 10.1007/s00259-007-0549-4
DO - 10.1007/s00259-007-0549-4
M3 - Article
C2 - 17952434
AN - SCOPUS:43349088834
SN - 1619-7070
VL - 35
SP - 570
EP - 578
JO - European Journal of Nuclear Medicine and Molecular Imaging
JF - European Journal of Nuclear Medicine and Molecular Imaging
IS - 3
ER -