The pathophysiological sequelae of
myocardial infarction include neutrophil infiltration into the
infarct zone that contributes to additional damage to viable tissue and removal of cellular debris from necrosed tissue. Reactive chlorinating species produced by
myeloperoxidase 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 reactive chlorinating species that lead to the production of alpha-chloro fatty
aldehydes. Results herein demonstrate that the alpha-chloro
fatty aldehyde 2-chlorohexadecanal (2-ClHDA) accumulates in rat hearts subjected to left anterior descending coronary artery occlusion. Myocardia from rats subjected to surgical
infarction had increased 2-ClHDA and neutrophil infiltration levels compared with myocardia from rats subjected to
sham surgery. Additionally, infarcted myocardia from rats rendered neutropenic by treatments with an anti-neutrophil antibody had diminished 2-ClHDA and neutrophil infiltration levels compared with infarcted myocardia from normopenic rats; 2-ClHDA was shown to elicit myocardial damage as determined by
lactate dehydrogenase release in isolated perfused rat hearts. Additionally, 2-ClHDA treatment of hearts resulted in decreased heart rate and ventricular performance. Taken together, the present results demonstrate a novel neutrophil-dependent
myeloperoxidase-based mechanism that results in 2-ClHDA production in response to regional
myocardial infarction that may also contribute to cardiac dysfunction.