Abstract
Myocardial ischemia/reperfusion (I/R) injury remains a major determinant of final infarct size and adverse outcomes in ST-segment elevation myocardial infarction (STEMI). Following our previous demonstration of CDP-choline-mediated cardioprotection in cultured cardiomyocytes and rodent models, the present study evaluated its efficacy in a clinically relevant closed-chest porcine model of myocardial I/R injury.
Sixteen Yorkshire pigs underwent 60 min of left anterior descending coronary artery occlusion followed by reperfusion and were randomized to intravenous CDP-choline (n = 8) or placebo (n = 8). CDP-choline (1,000 mg) was administered 30 min after coronary occlusion, followed by 500 mg every 12 h. The primary endpoint was infarct size assessed 24 h after reperfusion by cardiac magnetic resonance. Area at risk was quantified by T2-weighted imaging, whereas infarct size and myocardial salvage were assessed by late gadolinium enhancement.
Baseline characteristics and area at risk were comparable between groups. CDP-choline significantly reduced absolute infarct mass (10.34 ± 6.45 vs. 21.09 ± 10.36 g; P=0.026), increased myocardial salvage index (65.86 ± 18.72% vs. 40.42 ± 17.62%; PIn this proof-of-concept study, CDP-choline reduced infarct size, enhanced myocardial salvage, and attenuated myocardial injury in a clinically relevant porcine model of myocardial I/R. These findings support further mechanistic investigation and provide a rationale for future translational evaluation of CDP-choline as an adjunctive cardioprotective strategy during reperfusion in STEMI.