Lipidomic remodeling in a porcine model of acute myocardial infarction–induced cardiogenic shock

Cardiogenic shock following acute myocardial infarction (AMI) is characterized by impaired forward flow and systemic hypoperfusion but remains incompletely understood from a metabolic perspective. While prior studies have focused predominantly on myocardial injury and recovery, the systemic lipidomic response to cardiogenic shock and its relationship to physiological severity remain poorly characterized. We aimed to define cardiac-enriched and systemic lipid remodeling during AMI-induced cardiogenic shock and identify lipid pathways associated with hemodynamic and metabolic dysfunction. Fifteen pigs underwent left anterior descending coronary artery balloon occlusion followed by reperfusion. Nine animals met pre-specified cardiogenic shock criteria (≥30% reduction in cardiac output and arterial lactate >2 mmol/L) and were included for analysis. Serial coronary sinus and mixed venous plasma sampling was performed throughout ischemia and reperfusion. High-throughput lipidomics profiling was integrated with contemporaneous physiological measurements related to cardiogenic shock, including cardiac output, stroke volume, heart rate, and arterial lactate. AMI-induced cardiogenic shock produced sustained reductions in cardiac output and stroke volume accompanied by progressive lactate accumulation. Multiple plasma lipid classes remodeled dynamically during ischemia-reperfusion, including increases in triglycerides, diglycerides, phosphatidylserines, and acylcarnitines. Lipid remodeling extended beyond cardiac-enriched coronary sinus sampling, with mixed venous plasma demonstrating substantial systemic metabolic adaptation to cardiac dysfunction. Lipid class and species-level analyses identified phosphatidylserines and acylcarnitines as the lipid classes most consistently associated with physiological severity. Phosphatidylserine species tracked worsening lactate accumulation and impaired stroke volume, while acylcarnitines demonstrated strong relationships with lactate and reduced cardiac output. Heart rate demonstrated broader lipidomic associations in coronary sinus plasma than mixed venous blood, supporting compartment-specific cardiac physiological sensitivity. AMI-induced cardiogenic shock is associated with coordinated cardiac-enriched and systemic lipid remodeling linked to impaired forward flow and tissue hypoperfusion. Phosphatidylserines and acylcarnitines emerged as candidate pathways associated with cardiogenic shock severity, identifying potential metabolic mechanisms and biomarker targets in acute cardiac failure.