Document Type

Article

Publication Date

5-9-2025

Keywords

JMG, Animals, Myocardial Reperfusion Injury, Mice, Mice, Inbred C57BL, Echocardiography, Disease Models, Animal, Male, Ventricular Remodeling, Myocardial Infarction

JAX Source

Circ Res. 2025;136(10):1099-109.

ISSN

1524-4571

PMID

40207377

DOI

https://doi.org/10.1161/CIRCRESAHA.125.326156

Abstract

BACKGROUND: Mouse models of myocardial ischemia with subsequent heart failure are common approaches to examine heart failure pathology and possible treatment strategies. We sought to establish a high-throughput approach for echocardiography-guided induction of myocardial ischemia/reperfusion (IR) in mice.

METHODS: After visualization of the left coronary artery with high-resolution ultrasound imaging and echocardiographic definition of the level of coronary occlusion, the left anterior descending artery was temporarily occluded with 2 micromanipulator-controlled needles. Functional and molecular changes were assessed and compared with commonly performed surgical techniques.

RESULTS: Echocardiography-guided induction of myocardial IR enabled standardized induction of myocardial IR injury with subsequent left ventricular remodeling. Incorporation of various quality control measures throughout the procedure ensured a high success rate and the absence of relevant postinterventional mortality in experienced hands. Compared with surgical approaches, echocardiography-guided induction of myocardial IR showed a quicker recovery time and induced a less pronounced inflammatory response characterized by decreased local and systemic neutrophil counts. Notably, infarct size and subsequent post-myocardial infarction cardiac dysfunction were comparable between methods. The novel procedure was successfully implemented at different academic institutions with imaging expertise and demonstrated high interinstitutional reproducibility.

CONCLUSIONS: Echocardiography-guided induction of myocardial IR enables high-throughput induction of myocardial IR injury with precise echocardiographic definition of the occlusion level and immediate evaluation of cardiac function during ischemia. The method provides a more clinically relevant assessment of IR sequelae and offers notable animal welfare advantages by eliminating the need for ventilation and thoracotomy, thereby mitigating potential surgery-related confounders.

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