Abstract Sat201: Ribosome Profiling Uncovers Selective Translation in the Myocardium After Cardiac Arrest

Abstract

Background: Cardiac arrest (CA) affects over 600,000 Americans every year and remains a leading cause of death in the United States. After CA, myocardial dysfunction is a common occurrence leading to reduced cardiac output and cardiogenic shock. A broad milieu of molecular changes has been implicated in the post-arrest heart, including decreased ribosomal translation of nascent proteins. The translational changes in the post-arrest heart remain poorly understood. Methods: Male and female C57 mice (n=8-10/group) were subjected to 8-min of asystole by direct injection of potassium chloride and were revived by cardiopulmonary resuscitation or sham surgery (anesthesia only). Mice were monitored for 24 hours post-arrest through serial neurologic exam, temperature monitoring, and echocardiography. One day after arrest, left-ventricles from sham and CA mice were collected for transcriptomic analysis including bulk RNA sequencing and ribosome profiling (Ribo-seq; n=6/group). Ribo-seq allowed high-resolution quantification of ribosome-associated mRNA fragments, enabling analysis of translation efficiency independent of transcript abundance. Results: CA mice had reduced ejection fraction (48.9±4.1% in CA compared to ) compared to 60.9±2.7 in sham mice, p<0.05) as well as reduced neurologic score (7.0±0.5 in CA compared to 12.0±0.0 in sham, p<0.05) at one day after arrest. Ribosome profiling revealed widespread suppression of translation efficiency in cytosolic ribosomal genes following CA, including pronounced downregulation of core large subunit transcripts such as Rpl31 . In contrast, genes involved in mitochondrial translation and stress adaptation, such as Lars2 , Espn , and Cst6 , exhibited increased translation efficiency, suggesting a selective shift toward organelle-specific and protective protein synthesis. Conclusions: These findings demonstrate a post-arrest reprogramming of myocardial translation, marked by global cytosolic ribosomal suppression and targeted upregulation of mitochondrial and stress-responsive pathways. Ribosome profiling provides critical insight into translational regulation in the stunned heart and may identify novel targets to enhance myocardial recovery after cardiac arrest.