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

J Nucl Cardiol. 2018 Feb;25(1):94-100. doi: 10.1007/s12350-017-1031-8. Epub 2017 Aug 24.

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.

Keywords: Molecular imaging; SPECT; acute coronary syndromes; apoptosis imaging; necrosis.

MeSH terms

  • Animals
  • Arsenicals
  • Cell Death
  • Disease Models, Animal
  • Glutathione / analogs & derivatives
  • Heart / diagnostic imaging
  • Heart / drug effects*
  • Indium Radioisotopes
  • Minocycline / administration & dosage*
  • Multimodal Imaging
  • Myocardial Ischemia / diagnostic imaging*
  • Myocardial Reperfusion Injury / diagnostic imaging*
  • Myocardium / pathology
  • Rabbits
  • Tomography, Emission-Computed, Single-Photon*
  • Tomography, X-Ray Computed

Substances

  • 4-(N-(S-glutathionylacetyl)amino)phenylarsenoxide
  • Arsenicals
  • Indium Radioisotopes
  • Indium-111
  • Minocycline
  • Glutathione