The pathophysiological sequelae of myocardial infarction include neutrophil infiltration into the infarct zone. Neutrophil infiltration into the infarct region contributes both to additional damage to viable tissue and the removal of cellular debris from necrosed tissue. Reactive chlorinating species (RCS) produced by myeloperoxidase (MPO) amplify the oxidant capacity of activated neutrophils. Plasmalogens are a major phospholipid subclass of both endothelial cells and cardiac myocytes. Recent studies have shown that plasmalogens are targeted by neutrophil-derived RCS leading to the production of -chloro fatty aldehydes. Results, herein, demonstrate that the -chloro fatty aldehyde, 2-chlorohexadecanal (2-ClHDA), accumulates in rat hearts subjected to left anterior descending coronary artery (LAD) occlusion. Myocardium from rats subjected to surgical infarction had increased 2-ClHDA levels and neutrophil infiltration in comparison to myocardium from rats subjected to sham surgery. Additionally, infarcted myocardium from rats rendered neutropenic by treatments with an anti-neutrophil antibody had both diminished 2-ClHDA levels and neutrophil infiltration compared to infarcted myocardium from normopenic rats. Utilizing isolated perfused rat hearts, 2-ClHDA was shown to elicit myocardial damage as determined by lactate dehydrogenase (LDH) release. Additionally, 2-ClHDA treatment of hearts resulted in decreased heart rate and ventricular performance. Taken together, the present results demonstrate a novel neutrophil-dependent MPO-based mechanism resulting in the production of 2-ClHDA in response to regional myocardial infarction that may also contribute to cardiac dysfunction.