Imaging assessment of cardioprotection mediated by a dodecafluoropentane oxygen-carrier administered during myocardial infarction

Zhonglin Liu, Christy Barber, Akash Gupta, Li Wan, Young Wook Won, Lars R Furenlid, Qin Chen, Ankit Desai, Ming Zhao, David A. Bull, Evan C Unger, Diego R Martin

Research output: Contribution to journalArticle

Abstract

Introduction: The objective of this study was to investigate the cardioprotective effects of a dodecafluoropentane (DDFP)-based perfluorocarbon emulsion (DDFPe) as an artificial carrier for oxygen delivery to ischemic myocardium, using 99m Tc-duramycin SPECT imaging. Methods: Rat hearts with Ischemia-reperfusion (I/R) was prepared by coronary ligation for 45-min followed by reperfusion. The feasibility of 99m Tc-duramycin in detecting myocardial I/R injury and its kinetic profile were first verified in the ischemic hearts with 2-h reperfusion (n = 6). DDFPe (0.6 mL/kg) was intravenously administered at 10 min after coronary ligation in fifteen rats and saline was given in thirteen rats as controls. 99m Tc-duramycin SPECT images were acquired in the DDFPe-treated hearts and saline controls at 2-h (DDFPe-2 h, n = 7 and Saline-2 h, n = 6) or 24-h (DDFPe-24 h, n = 8 and Saline-24 h, n = 7) of reperfusion. Results: SPECT images, showing “hot-spot” 99m Tc-duramycin uptake in the ischemic myocardium, exhibited significantly lower radioactive retention and smaller hot-spot size in the DDFPe-2 h and DDFPe-24 h hearts compared to controls. The infarcts in the Saline-24 h hearts extended significantly relative to measurements in the Saline-2 h. The extension of infarct size did not reach a statistical difference between the DDFPe-2 h and DDFPe-24 h hearts. Ex vivo measurement of 99m Tc-duramycin activity (%ID/g) was lower in the ischemic area of DDFPe-2 h and DDFPe-24 h than that of the Saline-2 h and Saline-24 h hearts (P < 0.05). The area of injured myocardium, delineated by the uptake of 99m Tc-duramycin, extended more substantially outside the infarct zone in the controls. Conclusions: Significant reduction in myocardial I/R injury, as assessed by 99m Tc-duramycin cell death imaging and histopathological analysis, was induced by DDFPe treatment after acute myocardial ischemia. 99m Tc-duramycin imaging can reveal myocardial cell death in ischemic hearts and may provide a tool for the non-invasive assessment of cardioprotective interventions.

Original languageEnglish (US)
JournalNuclear Medicine and Biology
DOIs
StatePublished - Jan 1 2019

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Fluorocarbons
Emulsions
Myocardial Infarction
Oxygen
Reperfusion
Single-Photon Emission-Computed Tomography
Myocardial Ischemia
Myocardial Reperfusion Injury
Myocardium
Reperfusion Injury
Ligation
perfluoropentane
Cell Death
duramycin
Ischemia

Keywords

  • Tc-Duramycin
  • Cell death imaging
  • Dodecafluoropentane perfluorocarbon emulsion
  • Myocardial ischemia-reperfusion
  • Phosphatidylethanolamine

ASJC Scopus subject areas

  • Molecular Medicine
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

Cite this

@article{38221072017143d59c0c4c97b4c0e3e5,
title = "Imaging assessment of cardioprotection mediated by a dodecafluoropentane oxygen-carrier administered during myocardial infarction",
abstract = "Introduction: The objective of this study was to investigate the cardioprotective effects of a dodecafluoropentane (DDFP)-based perfluorocarbon emulsion (DDFPe) as an artificial carrier for oxygen delivery to ischemic myocardium, using 99m Tc-duramycin SPECT imaging. Methods: Rat hearts with Ischemia-reperfusion (I/R) was prepared by coronary ligation for 45-min followed by reperfusion. The feasibility of 99m Tc-duramycin in detecting myocardial I/R injury and its kinetic profile were first verified in the ischemic hearts with 2-h reperfusion (n = 6). DDFPe (0.6 mL/kg) was intravenously administered at 10 min after coronary ligation in fifteen rats and saline was given in thirteen rats as controls. 99m Tc-duramycin SPECT images were acquired in the DDFPe-treated hearts and saline controls at 2-h (DDFPe-2 h, n = 7 and Saline-2 h, n = 6) or 24-h (DDFPe-24 h, n = 8 and Saline-24 h, n = 7) of reperfusion. Results: SPECT images, showing “hot-spot” 99m Tc-duramycin uptake in the ischemic myocardium, exhibited significantly lower radioactive retention and smaller hot-spot size in the DDFPe-2 h and DDFPe-24 h hearts compared to controls. The infarcts in the Saline-24 h hearts extended significantly relative to measurements in the Saline-2 h. The extension of infarct size did not reach a statistical difference between the DDFPe-2 h and DDFPe-24 h hearts. Ex vivo measurement of 99m Tc-duramycin activity ({\%}ID/g) was lower in the ischemic area of DDFPe-2 h and DDFPe-24 h than that of the Saline-2 h and Saline-24 h hearts (P < 0.05). The area of injured myocardium, delineated by the uptake of 99m Tc-duramycin, extended more substantially outside the infarct zone in the controls. Conclusions: Significant reduction in myocardial I/R injury, as assessed by 99m Tc-duramycin cell death imaging and histopathological analysis, was induced by DDFPe treatment after acute myocardial ischemia. 99m Tc-duramycin imaging can reveal myocardial cell death in ischemic hearts and may provide a tool for the non-invasive assessment of cardioprotective interventions.",
keywords = "Tc-Duramycin, Cell death imaging, Dodecafluoropentane perfluorocarbon emulsion, Myocardial ischemia-reperfusion, Phosphatidylethanolamine",
author = "Zhonglin Liu and Christy Barber and Akash Gupta and Li Wan and Won, {Young Wook} and Furenlid, {Lars R} and Qin Chen and Ankit Desai and Ming Zhao and Bull, {David A.} and Unger, {Evan C} and Martin, {Diego R}",
year = "2019",
month = "1",
day = "1",
doi = "10.1016/j.nucmedbio.2019.01.004",
language = "English (US)",
journal = "Nuclear Medicine and Biology",
issn = "0969-8051",
publisher = "Elsevier Inc.",

}

TY - JOUR

T1 - Imaging assessment of cardioprotection mediated by a dodecafluoropentane oxygen-carrier administered during myocardial infarction

AU - Liu, Zhonglin

AU - Barber, Christy

AU - Gupta, Akash

AU - Wan, Li

AU - Won, Young Wook

AU - Furenlid, Lars R

AU - Chen, Qin

AU - Desai, Ankit

AU - Zhao, Ming

AU - Bull, David A.

AU - Unger, Evan C

AU - Martin, Diego R

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Introduction: The objective of this study was to investigate the cardioprotective effects of a dodecafluoropentane (DDFP)-based perfluorocarbon emulsion (DDFPe) as an artificial carrier for oxygen delivery to ischemic myocardium, using 99m Tc-duramycin SPECT imaging. Methods: Rat hearts with Ischemia-reperfusion (I/R) was prepared by coronary ligation for 45-min followed by reperfusion. The feasibility of 99m Tc-duramycin in detecting myocardial I/R injury and its kinetic profile were first verified in the ischemic hearts with 2-h reperfusion (n = 6). DDFPe (0.6 mL/kg) was intravenously administered at 10 min after coronary ligation in fifteen rats and saline was given in thirteen rats as controls. 99m Tc-duramycin SPECT images were acquired in the DDFPe-treated hearts and saline controls at 2-h (DDFPe-2 h, n = 7 and Saline-2 h, n = 6) or 24-h (DDFPe-24 h, n = 8 and Saline-24 h, n = 7) of reperfusion. Results: SPECT images, showing “hot-spot” 99m Tc-duramycin uptake in the ischemic myocardium, exhibited significantly lower radioactive retention and smaller hot-spot size in the DDFPe-2 h and DDFPe-24 h hearts compared to controls. The infarcts in the Saline-24 h hearts extended significantly relative to measurements in the Saline-2 h. The extension of infarct size did not reach a statistical difference between the DDFPe-2 h and DDFPe-24 h hearts. Ex vivo measurement of 99m Tc-duramycin activity (%ID/g) was lower in the ischemic area of DDFPe-2 h and DDFPe-24 h than that of the Saline-2 h and Saline-24 h hearts (P < 0.05). The area of injured myocardium, delineated by the uptake of 99m Tc-duramycin, extended more substantially outside the infarct zone in the controls. Conclusions: Significant reduction in myocardial I/R injury, as assessed by 99m Tc-duramycin cell death imaging and histopathological analysis, was induced by DDFPe treatment after acute myocardial ischemia. 99m Tc-duramycin imaging can reveal myocardial cell death in ischemic hearts and may provide a tool for the non-invasive assessment of cardioprotective interventions.

AB - Introduction: The objective of this study was to investigate the cardioprotective effects of a dodecafluoropentane (DDFP)-based perfluorocarbon emulsion (DDFPe) as an artificial carrier for oxygen delivery to ischemic myocardium, using 99m Tc-duramycin SPECT imaging. Methods: Rat hearts with Ischemia-reperfusion (I/R) was prepared by coronary ligation for 45-min followed by reperfusion. The feasibility of 99m Tc-duramycin in detecting myocardial I/R injury and its kinetic profile were first verified in the ischemic hearts with 2-h reperfusion (n = 6). DDFPe (0.6 mL/kg) was intravenously administered at 10 min after coronary ligation in fifteen rats and saline was given in thirteen rats as controls. 99m Tc-duramycin SPECT images were acquired in the DDFPe-treated hearts and saline controls at 2-h (DDFPe-2 h, n = 7 and Saline-2 h, n = 6) or 24-h (DDFPe-24 h, n = 8 and Saline-24 h, n = 7) of reperfusion. Results: SPECT images, showing “hot-spot” 99m Tc-duramycin uptake in the ischemic myocardium, exhibited significantly lower radioactive retention and smaller hot-spot size in the DDFPe-2 h and DDFPe-24 h hearts compared to controls. The infarcts in the Saline-24 h hearts extended significantly relative to measurements in the Saline-2 h. The extension of infarct size did not reach a statistical difference between the DDFPe-2 h and DDFPe-24 h hearts. Ex vivo measurement of 99m Tc-duramycin activity (%ID/g) was lower in the ischemic area of DDFPe-2 h and DDFPe-24 h than that of the Saline-2 h and Saline-24 h hearts (P < 0.05). The area of injured myocardium, delineated by the uptake of 99m Tc-duramycin, extended more substantially outside the infarct zone in the controls. Conclusions: Significant reduction in myocardial I/R injury, as assessed by 99m Tc-duramycin cell death imaging and histopathological analysis, was induced by DDFPe treatment after acute myocardial ischemia. 99m Tc-duramycin imaging can reveal myocardial cell death in ischemic hearts and may provide a tool for the non-invasive assessment of cardioprotective interventions.

KW - Tc-Duramycin

KW - Cell death imaging

KW - Dodecafluoropentane perfluorocarbon emulsion

KW - Myocardial ischemia-reperfusion

KW - Phosphatidylethanolamine

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U2 - 10.1016/j.nucmedbio.2019.01.004

DO - 10.1016/j.nucmedbio.2019.01.004

M3 - Article

JO - Nuclear Medicine and Biology

JF - Nuclear Medicine and Biology

SN - 0969-8051

ER -