High-resolution structure-function mapping of intact hearts reveals altered sympathetic control of infarct border zones

Ching Zhu, Pradeep S. Rajendran, Peter Hanna, Igor R. Efimov, Guy Salama, Charless C. Fowlkes*, Kalyanam Shivkumar

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Remodeling of injured sympathetic nerves on the heart after myocardial infarction (MI) contributes to adverse outcomes such as sudden arrhythmic death, yet the underlying structural mechanisms are poorly understood. We sought to examine microstructural changes on the heart after MI and to directly link these changes with electrical dysfunction. We developed a high-resolution pipeline for anatomically precise alignment of electrical maps with structural myofiber and nerve-fiber maps created by customized computer vision algorithms. Using this integrative approach in a mouse model, we identified distinct structure-function correlates to objectively delineate the infarct border zone, a known source of arrhythmias after MI. During tyramine-induced sympathetic nerve activation, we demonstrated regional patterns of altered electrical conduction aligned directly with altered neuroeffector junction distribution, pointing to potential neural substrates for cardiac arrhythmia. This study establishes a synergistic framework for examining structure-function relationships after MI with microscopic precision that has potential to advance understanding of arrhythmogenic mechanisms.

Original languageEnglish (US)
Article numbere153913
JournalJCI Insight
Volume7
Issue number3
DOIs
StatePublished - Feb 8 2022
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)

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