In Vivo Mapping of Myocardial Injury Outside the Infarct Zone: Tissue at an Intermediate Pathological State

Overview

Journal J Am Heart Assoc

Specialty Cardiology & Vascular Diseases

Date 2024 Apr 19

PMID 38639350

Authors

Kaixi Ren

Songwang Hou

Steven E Johnson

Jon Lomasney

Chad R Haney

Jungwha Lee

Zhi-Dong Ge

Daniel C Lee

Jeffrey J Goldberger

Rishi Arora

Ming Zhao

Affiliations

Soon will be listed here.

Abstract

Background: The goal was to determine the feasibility of mapping the injured-but-not-infarcted myocardium using Tc-duramycin in the postischemic heart, with spatial information for its characterization as a pathophysiologically intermediate tissue, which is neither normal nor infarcted.

Methods And Results: Coronary occlusion was conducted in Sprague Dawley rats with preconditioning and 30-minute ligation. In vivo single-photon emission computed tomography was acquired after 3 hours (n=6) using Tc-duramycin, a phosphatidylethanolamine-specific radiopharmaceutical. The Tc-duramycin areas were compared with infarct and area-at-risk (n=8). Cardiomyocytes and endothelial cells were isolated for gene expression profiling. Cardiac function was measured with echocardiography (n=6) at 4 weeks. In vivo imaging with Tc-duramycin identified the infarct (3.9±2.4% of the left ventricle and an extensive area 23.7±2.2% of the left ventricle) with diffuse signal outside the infarct, which is pathologically between normal and infarcted (apoptosis 1.8±1.6, 8.9±4.2, 13.6±3.8%; VCAM-1 [vascular cell adhesion molecule 1] 3.2±0.8, 9.8±4.1, 15.9±4.2/mm; tyrosine hydroxylase 14.9±2.8, 8.6±4.4, 5.6±2.2/mm), with heterogeneous changes including scattered micronecrosis, wavy myofibrils, hydropic change, and glycogen accumulation. The Tc-duramycin tissue is quantitatively smaller than the area-at-risk (26.7% versus 34.4% of the left ventricle, =0.008). Compared with infarct, gene expression in the Tc-duramycin-noninfarct tissue indicated a greater prosurvival ratio (BCL2/BAX [B-cell lymphoma 2/BCL2-associated X] 7.8 versus 5.7 [cardiomyocytes], 3.7 versus 3.2 [endothelial]), and an upregulation of ion channels in electrophysiology. There was decreased contractility at 4 weeks (regional fractional shortening -8.6%, <0.05; circumferential strain -52.9%, <0.05).

Conclusions: The injured-but-not-infarcted tissue, being an intermediate zone between normal and infarct, is mapped in vivo using phosphatidylethanolamine-based imaging. The intermediate zone contributes significantly to cardiac dysfunction.

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