Inflammation, Proinflammatory Mediators and Myocardial Ischemia–reperfusion Injury
Section snippets
The Pathophysiology of Myocardial Ischemia—Reperfusion Injury
In 2002, there were over 3,480,000 heart attacks in the United States alone. There were 1,121,000 angioplasties performed in the United States; this number is estimated to increase to 2.4 million in 2004 to 2005. Angioplasty is the primary approach to achieving reperfusion and is the definitive treatment for coronary occlusive disease to reduce the extent of myocardial infarction. Without reperfusion, the entire area at risk involved in a coronary occlusion will become necrotic.
In the 1970s,
Attenuating Reperfusion Injury in Acute Myocardial Ischemia with Reperfusion Therapeutics: Going Beyond Restoring Blood Flow
The questions must be asked: (1) whether infarct size and other manifestations of postischemic damage can be reduced by therapies applied at reperfusion, and (2) is it important to limit infarct size in the setting of percutaneous coronary intervention or cardiac surgery? Acute myocardial ischemia is used here instead of acute myocardial infarction because reperfusion contributes to the ultimate infarct size (and other injuries), and therefore there is the potential for infarction depending on
Nitric Oxide Therapy
Numerous experimental studies have tested agents with anti-inflammatory properties delivered at the time of reperfusion as a therapeutic approach. Nitric oxide [130], nitric oxide donor agents [131], and the physiologic precursor l-arginine [132], [133] have been effective at reducing postischemic injury by reducing neutrophil activation, accumulation, superoxide anion generation, and endothelial cell activation. Nitric oxide has also been used in cardioplegia solutions to protect hearts from
Summary
Although ischemic myocardium must be reperfused to survive, there is a cost to reperfusion that offsets the intended clinical benefits of minimizing infarct size, postischemic blood flow defects, and contractile dysfunction. There is a multiplicity of contributors to reperfusion injury. Proinflammatory mediators and inflammatory cells play an integral part by not only triggering deleterious responses but also by amplifying ongoing responses to build a cascade of injury. This cascade may be
Acknowledgments
The authors thank the Carlyle Fraser Heart Center Foundation for their continued support of the research effort.
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This study was supported in part by a grant from the National Heart Lung and Blood Institute of the National Institutes of Health to JV-J (HL069487).