The cellular injury that results from irreversible
ischemia leads to the alteration of tissue function responsible for the phenomenon that we call
left ventricular remodeling. Oxidative stress and
inflammation are key elements of this process; in mice as in humans, elevation of markers of
inflammation at the time of
myocardial infarction (MI) is a predictor of the development of ischemic
myopathy and of adverse clinical outcomes. Several leukocyte-derived
enzyme systems are responsible for the release of
oxidizing agents into the myocardium after ischemic injury and provide a means of better understanding MI. By identifying the oxidation products present after
inflammation, the responsible leukocyte-generating
oxidant systems can be elucidated. Interestingly, a key leukocyte-derived marker,
myeloperoxidase (MPO), was formerly measured routinely by older-generation hematology analyzers. Patients with lower levels of MPO were noted to be at lower risk for untoward cardiovascular events, suggesting that humans are more genomically "hardwired" than previously thought. Studies with genetic knockout mice confirm the importance of these leukocyte-generated
oxidants in the pathophysiologic consequences of
ischemia. This clearly affects the anatomic extent of damage, the hemodynamic consequences, and ultimately, the clinical correlates and potential outcomes. An understanding of these oxidative processes and their relation to
inflammation will be extremely useful in the development and understanding of potential therapeutic agents.