PMID- 31707811
OWN - NLM
STAT- MEDLINE
DCOM- 20200617
LR  - 20240229
IS  - 1942-0080 (Electronic)
IS  - 1941-9651 (Print)
IS  - 1941-9651 (Linking)
VI  - 12
IP  - 11
DP  - 2019 Nov
TI  - Application of Hybrid Matrix Metalloproteinase-Targeted and Dynamic (201)Tl 
      Single-Photon Emission Computed Tomography/Computed Tomography Imaging for 
      Evaluation of Early Post-Myocardial Infarction Remodeling.
PG  - e009055
LID - 10.1161/CIRCIMAGING.119.009055 [doi]
AB  - BACKGROUND: The induction of matrix metalloproteinases (MMPs) and reduction in 
      tissue inhibitors of MMPs (TIMPs) plays a role in ischemia/reperfusion (I/R) 
      injury post-myocardial infarction (MI) and subsequent left ventricular 
      remodeling. We developed a hybrid dual isotope single-photon emission computed 
      tomography/computed tomography approach for noninvasive evaluation of regional 
      myocardial MMP activation with (99m)Tc-RP805 and dynamic (201)Tl for 
      determination of myocardial blood flow, to quantify the effects of intracoronary 
      delivery of recombinant TIMP-3 (rTIMP-3) on I/R injury. METHODS: Studies were 
      performed in control pigs (n=5) and pigs following 90-minute balloon 
      occlusion-induced ischemia/reperfusion (I/R) of left anterior descending artery 
      (n=9). Before reperfusion, pigs with I/R were randomly assigned to intracoronary 
      infusion of rTIMP-3 (1.0 mg/kg; n=5) or saline (n=4). Three days post-I/R, dual 
      isotope imaging was performed with (99m)Tc-RP805 and (201)Tl along with contrast 
      cineCT to assess left ventricular function. RESULTS: The ischemic to nonischemic 
      ratio of (99m)Tc-RP805 was significantly increased following I/R in saline group 
      (4.03+/-1.40), and this ratio was significantly reduced with rTIMP-3 treatment 
      (2.22+/-0.57; P=0.03). This reduction in MMP activity in the MI-rTIMP-3 treatment 
      group was associated with an improvement in relative MI region myocardial blood 
      flow compared with the MI-saline group and improved myocardial strain in the MI 
      region. CONCLUSIONS: We have established a novel hybrid single-photon emission 
      computed tomography/computed tomography imaging approach for the quantitative 
      assessment of regional MMP activation, myocardial blood flow, and cardiac 
      function post-I/R that can be used to evaluate therapeutic interventions such as 
      intracoronary delivery of rTIMP-3 for reduction of I/R injury in the early phases 
      of post-MI remodeling.
FAU - Thorn, Stephanie L
AU  - Thorn SL
AD  - Section of Cardiovascular Medicine, Department of Internal Medicine (S.L.T., 
      A.F., M.R.S., A.J.S.), Yale University, School of Medicine, New Haven, CT.
AD  - Yale Translational Research Imaging Center, Department of Internal Medicine, New 
      Haven, CT (S.L.T., A.F., M.R.S., A.J.S.).
FAU - Barlow, Shayne C
AU  - Barlow SC
AD  - Department of Cell Biology and Anatomy, Surgery, Cardiovascular Translational 
      Research Center, WJB Dorn Veteran Affairs Medical Center, University of South 
      Carolina School of Medicine, Columbia (S.C.B., H.D., J.J., K.Z., F.G.S.).
FAU - Feher, Attila
AU  - Feher A
AD  - Section of Cardiovascular Medicine, Department of Internal Medicine (S.L.T., 
      A.F., M.R.S., A.J.S.), Yale University, School of Medicine, New Haven, CT.
AD  - Yale Translational Research Imaging Center, Department of Internal Medicine, New 
      Haven, CT (S.L.T., A.F., M.R.S., A.J.S.).
FAU - Stacy, Mitchel R
AU  - Stacy MR
AD  - Section of Cardiovascular Medicine, Department of Internal Medicine (S.L.T., 
      A.F., M.R.S., A.J.S.), Yale University, School of Medicine, New Haven, CT.
AD  - Yale Translational Research Imaging Center, Department of Internal Medicine, New 
      Haven, CT (S.L.T., A.F., M.R.S., A.J.S.).
FAU - Doviak, Heather
AU  - Doviak H
AD  - Department of Cell Biology and Anatomy, Surgery, Cardiovascular Translational 
      Research Center, WJB Dorn Veteran Affairs Medical Center, University of South 
      Carolina School of Medicine, Columbia (S.C.B., H.D., J.J., K.Z., F.G.S.).
FAU - Jacobs, Julia
AU  - Jacobs J
AD  - Department of Cell Biology and Anatomy, Surgery, Cardiovascular Translational 
      Research Center, WJB Dorn Veteran Affairs Medical Center, University of South 
      Carolina School of Medicine, Columbia (S.C.B., H.D., J.J., K.Z., F.G.S.).
FAU - Zellars, Kia
AU  - Zellars K
AD  - Department of Cell Biology and Anatomy, Surgery, Cardiovascular Translational 
      Research Center, WJB Dorn Veteran Affairs Medical Center, University of South 
      Carolina School of Medicine, Columbia (S.C.B., H.D., J.J., K.Z., F.G.S.).
FAU - Renaud, Jennifer M
AU  - Renaud JM
AD  - Division of Cardiology, University of Ottawa Heart Institute, ON, Canada (J.M.R., 
      R.K., R.dK.).
FAU - Klein, Ran
AU  - Klein R
AD  - Division of Cardiology, University of Ottawa Heart Institute, ON, Canada (J.M.R., 
      R.K., R.dK.).
FAU - deKemp, Robert A
AU  - deKemp RA
AD  - Division of Cardiology, University of Ottawa Heart Institute, ON, Canada (J.M.R., 
      R.K., R.dK.).
FAU - Khakoo, Aarif Y
AU  - Khakoo AY
AD  - Amgen, CardioMetabolic Disorders, South San Francisco, CA (A.Y.K., T.W.).
FAU - Lee, TaeWeon
AU  - Lee T
AD  - Amgen, CardioMetabolic Disorders, South San Francisco, CA (A.Y.K., T.W.).
FAU - Spinale, Francis G
AU  - Spinale FG
AD  - Department of Cell Biology and Anatomy, Surgery, Cardiovascular Translational 
      Research Center, WJB Dorn Veteran Affairs Medical Center, University of South 
      Carolina School of Medicine, Columbia (S.C.B., H.D., J.J., K.Z., F.G.S.).
FAU - Sinusas, Albert J
AU  - Sinusas AJ
AD  - Section of Cardiovascular Medicine, Department of Internal Medicine (S.L.T., 
      A.F., M.R.S., A.J.S.), Yale University, School of Medicine, New Haven, CT.
AD  - Department of Radiology and Biomedical Imaging (A.J.S.), Yale University, School 
      of Medicine, New Haven, CT.
AD  - Yale Translational Research Imaging Center, Department of Internal Medicine, New 
      Haven, CT (S.L.T., A.F., M.R.S., A.J.S.).
LA  - eng
GR  - R42 HL131280/HL/NHLBI NIH HHS/United States
GR  - R01 HL113352/HL/NHLBI NIH HHS/United States
GR  - R01 HL137365/HL/NHLBI NIH HHS/United States
GR  - I01 BX000168/BX/BLRD VA/United States
GR  - R01 HL078650/HL/NHLBI NIH HHS/United States
GR  - R01 HL130972/HL/NHLBI NIH HHS/United States
GR  - T32 HL098069/HL/NHLBI NIH HHS/United States
GR  - S10 RR025555/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20191111
PL  - United States
TA  - Circ Cardiovasc Imaging
JT  - Circulation. Cardiovascular imaging
JID - 101479935
RN  - EC 3.4.24.- (Matrix Metalloproteinases)
SB  - IM
CIN - Circ Cardiovasc Imaging. 2019 Nov;12(11):e009915. PMID: 31707812
MH  - Animals
MH  - Male
MH  - Coronary Circulation/physiology
MH  - Disease Models, Animal
MH  - *Heart Ventricles/growth & development/metabolism/physiopathology
MH  - *Matrix Metalloproteinases/metabolism
MH  - *Myocardial Infarction/diagnosis/metabolism/physiopathology
MH  - *Myocardium/metabolism
MH  - *Single Photon Emission Computed Tomography Computed Tomography/methods
MH  - Swine
MH  - *Ventricular Function, Left/physiology
MH  - *Ventricular Remodeling/physiology
PMC - PMC7250243
MID - NIHMS1548954
OTO - NOTNLM
OT  - balloon occlusion
OT  - matrix metalloproteinases
OT  - myocardial infarction
OT  - reperfusion injury
OT  - ventricular remodeling
EDAT- 2019/11/12 06:00
MHDA- 2020/06/17 06:00
PMCR- 2020/11/11
CRDT- 2019/11/12 06:00
PHST- 2019/11/12 06:00 [entrez]
PHST- 2019/11/12 06:00 [pubmed]
PHST- 2020/06/17 06:00 [medline]
PHST- 2020/11/11 00:00 [pmc-release]
AID - 10.1161/CIRCIMAGING.119.009055 [doi]
PST - ppublish
SO  - Circ Cardiovasc Imaging. 2019 Nov;12(11):e009055. doi: 
      10.1161/CIRCIMAGING.119.009055. Epub 2019 Nov 11.