Temporal profiling of myocardial inflammation and recovery in a murine model of cardiac arrest and adrenaline exposure.

Background: Myocardial dysfunction after cardiac arrest (CA) is a major contributor to poor outcomes, yet the underlying inflammatory mechanisms within cardiac tissue remain incompletely defined. We sought to delineate the temporal evolution of myocardial inflammation following CA, distinguishing the effects of ischemia-reperfusion injury from those of adrenaline exposure alone. Methods and Results: Using a murine model of CA and resuscitation, we profiled transcriptomic, immunologic, and functional cardiac changes in mice exposed to either CA followed by resuscitation with adrenaline (Arrest group), adrenaline alone (Adr group), or anesthesia alone (Naïve group). Animals were assessed at 0.5-, 1-, 3-, and 7-days via echocardiography, RNA-sequencing, flow cytometry, immunohistochemistry, and multiplex cytokine analysis. CA elicited a robust, early myocardial inflammatory response characterized by neutrophil infiltration, systemic cytokine surges (IL-6, TNF-α, IL-1β), and downregulation of mitochondrial and metabolic pathways. This immune activation peaked at 0.5 days and resolved by day 7, coinciding with transient myocardial dysfunction and recovery of ejection fraction. In contrast, adrenaline alone induced a delayed, attenuated response peaking at 1 day. Transcriptomic and immunophenotypic signatures distinguished ischemia-driven injury from catecholaminergic effects. Conclusions: CA induces a distinct, self-limited myocardial inflammatory cascade that parallels functional cardiac recovery. These findings identify a narrow therapeutic window for immunomodulatory interventions and provide a mechanistic foundation for targeted therapies to mitigate cardiac injury after resuscitation.