Top

Published in:

01-02-2018 | Brief Report

Cardioprotection by minocycline in a rabbit model of ischemia/reperfusion injury: Detection of cell death by in vivo ¹¹¹In-GSAO SPECT

Authors: Takayoshi Yamaki, MD, PhD, Hans J. de Haas, MD, Nobuhiro Tahara, MD, PhD, Artiom Petrov, PhD, Dilbahar Mohar, MD, Nezam Haider, PhD, Jun Zhou, MD, Atsuko Tahara, MD, Yasuchika Takeishi, MD, PhD, Hendrikus H. Boersma, PharmD, PhD, Tiziano Scarabelli, MD, PhD, Annapoorna Kini, MD, MRCP, H. William Strauss, MD, Jagat Narula, MD, PhD

Published in: Journal of Nuclear Cardiology | Issue 1/2018

Abstract

Background

Preclinical studies indicate that minocycline protects against myocardial ischemia/reperfusion injury. In these studies, minocycline was administered before ischemia, which can rarely occur in clinical practice. The current study aimed to evaluate cardioprotection by minocycline treatment upon reperfusion.

Methods

Rabbits were subjected to myocardial ischemia/reperfusion injury and received either intravenous minocycline (n = 8) or saline (n = 8) upon reperfusion. Cardiac cell death was assessed by in vivo micro-SPECT/CT after injection of Indium-111-labeled 4-(N-(S-glutathionylacetyl)amino) phenylarsonous acid (¹¹¹In-GSAO). Thereafter, hearts were explanted for ex vivo imaging, γ-counting, and histopathological characterization.

Results

Myocardial damage was visualized by micro-SPECT/CT imaging. Quantitative GSAO uptake (expressed as percent injected dose per gram, %ID/g) in the area at risk was lower in minocycline-treated animals than that in saline-treated control animals (0.32 ± 0.13% vs 0.48 ± 0.15%, P = 0.04). TUNEL staining confirmed the reduction of cell death in minocycline-treated animals.

Conclusions

This study demonstrates cardioprotection by minocycline in a clinically translatable protocol.

Available only for authorised users

Narula J, Strauss HW. Invited commentary: P.S.* I love you: Implications of phosphatidyl serine (PS) reversal in acute ischemic syndromes. J Nucl Med. 2003;44:397-9.PubMed

Liao TV, C Forehand C, C Hess D, C Fagan S. Minocycline repurposing in critical illness: Focus on stroke. Curr Top Med Chem. 2013;13:2283-90.CrossRefPubMed

Scarabelli TM, Stephanou A, Pasini E, Gitti G, Townsend P, Lawrence K, et al. Minocycline inhibits caspase activation and reactivation, increases the ratio of XIAP to smac/DIABLO, and reduces the mitochondrial leakage of cytochrome C and smac/DIABLO. J Am Coll Cardiol. 2004;43:865-74.CrossRefPubMed

Romero-Perez D, Fricovsky E, Yamasaki KG, Griffin M, Barraza-Hidalgo M, Dillmann W, et al. Cardiac uptake of minocycline and mechanisms for in vivo cardioprotection. J Am Coll Cardiol. 2008;52:1086-94.CrossRefPubMedPubMedCentral

Hu X, Zhou X, He B, Xu C, Wu L, Cui B, et al. Minocycline protects against myocardial ischemia and reperfusion injury by inhibiting high mobility group box 1 protein in rats. Eur J Pharmacol. 2010;638:84-9.CrossRefPubMed

Park D, Don AS, Massamiri T, Karwa A, Warner B, MacDonald J, et al. Noninvasive imaging of cell death using an Hsp90 ligand. J Am Chem Soc. 2011;133:2832-5.CrossRefPubMed

Xie B, Park D, Van Beek E, Blankevoort V, Orabi Y, Que I, et al. Optical imaging of cell death in traumatic brain injury using a heat shock protein-90 alkylator. Cell Death Dis. 2013;4:e473.CrossRefPubMedPubMedCentral

Tahara N, Zandbergen HR, de Haas HJ, Petrov A, Pandurangi R, Yamaki T, et al. Noninvasive molecular imaging of cell death in myocardial infarction using 111In-GSAO. Sci Rep. 2014;4:6826.CrossRefPubMedPubMedCentral

Donoghue N, Yam PT, Jiang XM, Hogg PJ. Presence of closely spaced protein thiols on the surface of mammalian cells. Protein Sci. 2000;9:2436-45.CrossRefPubMedPubMedCentral

10.

Narula J, Petrov A, Pak KY, Lister BC, Khaw BA. Very early noninvasive detection of acute experimental nonreperfused myocardial infarction with 99mTc-labeled glucarate. Circulation. 1997;95:1577-84.CrossRefPubMed

11.

Sarai M, Hartung D, Petrov A, Zhou J, Narula N, Hofstra L, et al. Broad and specific caspase inhibitor-induced acute repression of apoptosis in atherosclerotic lesions evaluated by radiolabeled annexin A5 imaging. J Am Coll Cardiol. 2007;50:2305-12.CrossRefPubMed

12.

Cohen J. Statistical power analysis for the behavioral sciences. Hillsdale: Lawrence Earlbaum Associates; 1988. p. 20-6.

13.

Boersma HH, Kietselaer BL, Stolk LM, Bennaghmouch A, Hofstra L, Narula J, et al. Past, present, and future of annexin A5: From protein discovery to clinical applications. J Nucl Med. 2005;46:2035-50.PubMed

14.

Kenis H, Zandbergen HR, Hofstra L, Petrov AD, Dumont EA, Blankenberg FD, et al. Annexin A5 uptake in ischemic myocardium: Demonstration of reversible phosphatidylserine externalization and feasibility of radionuclide imaging. J Nucl Med. 2010;51:259-67.CrossRefPubMed

15.

Thimister PW, Hofstra L, Liem IH, Boersma HH, Kemerink G, Reutelingsperger CP, et al. In vivo detection of cell death in the area at risk in acute myocardial infarction. J Nucl Med. 2003;44:391-6.PubMed

16.

De Saint-Hubert M, Prinsen K, Mortelmans L, Verbruggen A, Mottaghy FM. Molecular imaging of cell death. Methods. 2009;48:178-87.CrossRefPubMed

Title: Cardioprotection by minocycline in a rabbit model of ischemia/reperfusion injury: Detection of cell death by in vivo 111In-GSAO SPECT
Authors: Takayoshi Yamaki, MD, PhD
Hans J. de Haas, MD
Nobuhiro Tahara, MD, PhD
Artiom Petrov, PhD
Dilbahar Mohar, MD
Nezam Haider, PhD
Jun Zhou, MD
Atsuko Tahara, MD
Yasuchika Takeishi, MD, PhD
Hendrikus H. Boersma, PharmD, PhD
Tiziano Scarabelli, MD, PhD
Annapoorna Kini, MD, MRCP
H. William Strauss, MD
Jagat Narula, MD, PhD
Publication date: 01-02-2018
Publisher: Springer US
Published in: Journal of Nuclear Cardiology / Issue 1/2018
Print ISSN: 1071-3581
Electronic ISSN: 1532-6551
DOI: https://doi.org/10.1007/s12350-017-1031-8

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Cardioprotection by minocycline in a rabbit model of ischemia/reperfusion injury: Detection of cell death by in vivo ¹¹¹In-GSAO SPECT

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2018

The very hungry caterpillar and the ongoing effort to reduce radiation in myocardial perfusion scintigraphy: Have we become the beautiful butterfly?

Measurement of MBF by PET is ready for prime time as an integral part of clinical reports in diagnosis and risk assessment of patients with known or suspected CAD-PRO

More important than the impact factor

Prediction of 14-year cardiovascular outcomes by dobutamine stress 99mTc-tetrofosmin myocardial perfusion SPECT in elderly patients unable to perform exercise testing

Announcement: New initiative ‘case presentation corner’

Stress myocardial perfusion imaging in the elderly