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      Myocardial clearance of technetium-99m-teboroxime in reperfused injured canine myocardium

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      1 , 2 , 3 , 2 , 3 ,
      EJNMMI Research
      Springer
      Teboroxime, Ischemia, Reperfusion, SPECT

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          Abstract

          Background

          Recent technical developments using solid-state technology have enabled rapid image acquisition with single photon emission computed tomography (SPECT) and have led to a renewed interest in technetium-99m-teboroxime (Tc-99m-teboroxime) as a myocardial imaging agent. Tc-99m-teboroxime has demonstrated high myocardial extraction, linear myocardial uptake relative to flow even at high flow rates, rapid uptake and clearance kinetics, and differential clearance in the setting of ischemia. However, the myocardial clearance kinetics of Tc-99m-teboroxime in a model of myocardial injury has not been previously reported. Thus, the purposes of this study were to use a canine model of ischemia-reperfusion to (1) compare Tc-99m-teboroxime clearance kinetics in normal and ischemic-reperfused myocardium and (2) assess the utility of Tc-99m-teboroxime clearance kinetics in determining the severity of injury following ischemia-reperfusion.

          Methods

          Thirteen dogs underwent left circumflex coronary artery (LCx) occlusion for either 30 min (IR30, n = 6) or 120 min (IR120, n = 7), followed by reperfusion, and finally Tc-99m-teboroxime administration 120 min after reperfusion. Microsphere blood flows were determined at baseline, during occlusion, after reperfusion, and before euthanasia. Post-mortem, area at risk was determined using Evans blue dye, and viability was determined using triphenytetrazolium chloride (TTC) staining. The hearts were then subdivided into 24 pieces and Tc-99m activity was measured in a well counter.

          Results

          TTC-determined infarct area as a percentage of total left ventricular myocardium was 1.1% ± 0.3% for the IR30 group and 7.5% ± 2.9% for the IR120 group ( p < 0.05). During coronary occlusion, both the IR30 and IR120 groups demonstrated decreases in percent wall thickening in the ischemia-reperfusion zone (IRZ) as compared with the normal zone (NZ). In the IR30 group, percent wall thickening in the IRZ recovered during the reperfusion phase as compared with the NZ. In the IR120 group, percent wall thickening in the IRZ remained depressed during the reperfusion phase and through the end of the experiment as compared with the NZ. Final Tc-99m-teboroxime myocardial IRZ/NZ activity ratio was 0.94 ± 0.01 for the IR30 group, compared to 0.80 ± 0.01 for the IR120 group ( p < 0.05).

          Conclusions

          Tc-99m-teboroxime demonstrates moderate differential clearance in a model of severe injury with 120 min of ischemia-reperfusion, but only minimal differential clearance in a model of mild injury with 30 min of ischemia-reperfusion. Thus, Tc-99m-teboroxime clearance kinetics may be helpful in differentiating normal and minimally injured from severely injured myocardium.

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          Most cited references30

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          Time course of endothelial dysfunction and myocardial injury during myocardial ischemia and reperfusion in the cat.

          Myocardial ischemia and reperfusion have been shown to impair coronary vasorelaxation to endothelium-dependent vasodilators. To examine the time course of this dysfunction, occlusion of the left anterior descending (LAD) coronary artery (90 minutes) was followed by reperfusion for 0, 2.5, 5, 20, 180, or 270 minutes. Coronary arterial rings from the ischemic LAD and control left circumflex (LCx) arteries were tested for responsiveness to the endothelium-dependent receptor-mediated vasodilator, acetylcholine (ACh), and the endothelium-dependent nonreceptor-mediated vasodilator, A23187, as well as the endothelium-independent vasodilator, NaNO2. ACh relaxation was not impaired after 90 minutes of ischemia without reperfusion. However, 2.5 minutes of reperfusion resulted in depressed ACh responses (36 +/- 10% of control) that was further reduced to 16 +/- 6% at 20 minutes, and remained comparably depressed at every time thereafter. A23187 vasodilator responses were also attenuated after reperfusion, although the reduced response occurred later (that is, at 20 minutes). There was no significant decrease in response to NaNO2 in the LAD at any time or to any vasodilator in LCx control rings. Treatment with recombinant human superoxide dismutase (hSOD, 5 mg/kg/hr, that is, 15,545 SOD units/kg/hr), starting 10 minutes before reperfusion, preserved the vasodilator response to ACh (82 +/- 6%) and A23187, but treatment with the hydroxyl ion scavenger N-(2-mercapto proprionyl)-glycine (MPG) (8 mg/kg/hr) only protected the A23187 response. No damage to the surface of the endothelium was observed by scanning electron microscopy at any time point. Myocardial cell damage increased with time of reperfusion as assessed by increasing plasma CK activities and amounts of necrotic tissue indexed to area at risk. Significant myocardial injury occurred at 3 hours after reperfusion. These findings suggest that endothelial dysfunction resulting in reduced endothelium-derived relaxing factor release occurs before the development of myocardial cell necrosis and may be due to oxygen-derived free radicals produced rapidly on reperfusion.
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            Solid-state SPECT technology: fast and furious.

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              Simultaneous assessment of cardiac perfusion and function using 5-dimensional imaging with Tc-99m teboroxime.

              Dynamic single photon emission computed tomography (SPECT) acquisition and reconstruction of early poststress technetium 99m teboroxime washout images has been shown to be useful in the detection of coronary disease. Assessment of poststress regional wall motion may offer additional use in assessing coronary disease. Our goal was to investigate the feasibility of simultaneously imaging myocardial ischemia and transient poststress akinesis using gated-dynamic SPECT. A gated-dynamic mathematical cardiac torso (MCAT) phantom was developed to model both teboroxime kinetics and cardiac regional wall motion. A lesion was simulated as having delayed poststress teboroxime washout together with a transient poststress wall motion abnormality. Gated projection data were created to represent a 3-headed SPECT system undergoing a total rotation of 480 degrees . The dynamic expectation-maximization reconstruction algorithm with postsmoothing across gating intervals by Wiener filtering, and the ordered-subset expectation maximization reconstruction algorithm with 3-point smoothing across gating intervals were compared. Compared with the ordered-subset expectation maximization with 3-point smoothing, the dynamic expectation-maximization algorithm with Wiener filtering was able to produce visually higher-quality images and more accurate left ventricular ejection fraction estimates. From simulations, we conclude that changing cardiac function and tracer localization possibly can be assessed by using a gated-dynamic acquisition protocol combined with a 5-dimensional reconstruction strategy.
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                Author and article information

                Contributors
                Journal
                EJNMMI Res
                EJNMMI Res
                EJNMMI Research
                Springer
                2191-219X
                2014
                1 August 2014
                : 4
                : 42
                Affiliations
                [1 ]Brigham and Women’s Hospital, Harvard Medical School, Boston 02446, MA, USA
                [2 ]University of Tulsa, Tulsa 74104, OK, USA
                [3 ]University of Oklahoma Health Sciences Center, 6208 S. Oswego Ave, Tulsa 74136, OK, USA
                Article
                s13550-014-0042-6
                10.1186/s13550-014-0042-6
                4233307
                25411652
                3d8efe9f-1d32-4c51-a3f2-5f2b58954423
                Copyright © 2014 Okada et al.; licensee Springer

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.

                History
                : 10 March 2014
                : 13 July 2014
                Categories
                Original Research

                Radiology & Imaging
                teboroxime,ischemia,reperfusion,spect
                Radiology & Imaging
                teboroxime, ischemia, reperfusion, spect

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