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Post-mortem CMR in a model of sudden death due to myocardial ischemia: validation with connexin-43

  • Cardiac
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Abstract

Objectives

We sought to evaluate the effectiveness of post-mortem cardiac magnetic resonance (PM-CMR) for the identification of myocardial ischemia as cause of sudden cardiac death (SCD) when the time interval between the onset of ischemia and SCD is ≤ 90 min.

Methods

PM-CMR was performed in 8 hearts explanted from pigs with spontaneous death caused by occlusion of the left anterior descending coronary artery: 4 with SCD after ≤ 40 min of coronary occlusion and 4 between 40 and 90 min. PM-CMR included conventional T1 and T2-weighted image and T1, T2, and T2* mapping techniques. Imaging data were compared and validated with immunohistochemical evaluation of the altered proportion and redistribution of phosphorylated versus non-phosphorylated connexin 43 (CX43 and npCX43, respectively), an established molecular marker of myocardial ischemia.

Results

At T2-weighted images, the ischemic core was hypointense (core/remote ratio 0.67 ± 0.11) and surrounded by and hyperintense border zone. Compared to remote myocardium, the ischemic core had higher T1 (p = 0.0008), and lower T2 (p = 0.007) and T2* (p = 0.002). Cytoplasmatic npX43 and the npCX43/CX43 ratio were significantly higher in animals deceased > 40 min than in others.

Conclusion

PM-CMR can reliably detect early signs of myocardial damage induced by ischemia, based on conventional pulse sequences complemented by a novel ad hoc application of quantitative mapping techniques.

Key Points

• Post-mortem MRI may help to understand cause of sudden cardiac death.

• Post-mortem MRI allows detection of signs of myocardial ischemia as cause of sudden cardiac death within 90 and 40 min following coronary occlusion as demonstrated in a pig model of myocardial ischemia.

• Signs of myocardial ischemia using conventional and mapping MRI technique are associated with the immunohistochemical changes of phosphorylated and dephosphorylated connexin-43 which is an established molecular marker of myocardial ischemia.

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Abbreviations

AMI:

Acute myocardial infarction

CP:

Cytoplasm

CX43:

Phosphorylated connexin-43

FSE:

Fast spin echo

ID:

Intercalated disk

LCB:

Lateral cellular border

LV:

Left ventricle

MOLLI:

Modified Lock-Locker

npCX43:

Dephosphorylated connexin-43

PM-MRI:

Post-mortem cardiac magnetic resonance

SCD:

Sudden cardiac death

SSFP:

Steady-state free precession

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Funding

This study has received funding by the Italian Ministry of Health grant RF-2011-02348164 “CardioRigen” (FAR).

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Author notes

  1. Giovanni Donato Aquaro and Marco Di Paolo contributed equally to this work.

Authors and Affiliations

  1. Fondazione Toscana G. Monasterio, Via Giuseppe Moruzzi, 1, 56124, Pisa, Italy

    Giovanni Donato Aquaro, Silvia Burchielli, Michele Emdin & Fabio A. Recchia

  2. UO Medicina legale, University of Pisa, Pisa, Italy

    Marco Di Paolo & Emanuela Turillazzi

  3. Clinical and Translational Science Research Department, University of Pisa, Pisa, Italy

    Benedetta Guidi, Giacomo Aringheri, Musetti Veronica, Enrica Chiti & Davide Caramella

  4. Institute of Life Sciences, Scuola Superiore Sant’Anna, Pisa, Italy

    Khatia Ghabisonia, Nikoloz Gorgodze, Michele Emdin & Fabio A. Recchia

  5. Azienda Ospedaliero Universitaria Pisana, Pisa, Italy

    Angela Pucci

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  1. Giovanni Donato Aquaro
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  2. Marco Di Paolo
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Corresponding author

Correspondence to Giovanni Donato Aquaro.

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Guarantor

The scientific guarantor of this publication is Giovanni Donato Aquaro.

Conflict of interest

The authors of this manuscript declare no relationships with any companies whose products or services may be related to the subject matter of the article.

Statistics and biometry

Giovanni Donato Aquaro kindly provided statistical advice for this manuscript.

Informed consent

Approval from the institutional animal care committee was obtained.

Ethical approval

Institutional Review Board approval was obtained.

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• performed at one institution

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Aquaro, G.D., Di Paolo, M., Guidi, B. et al. Post-mortem CMR in a model of sudden death due to myocardial ischemia: validation with connexin-43. Eur Radiol 31, 8098–8107 (2021). https://doi.org/10.1007/s00330-021-07890-1

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  • DOI: https://doi.org/10.1007/s00330-021-07890-1

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