Mitochondrial Protective Agents for Ischemia/Reperfusion Injury
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- heart failure
- percutaneous coronary intervention
- renal artery obstruction
- ST elevation myocardial infarction
Ischemia of organs, including that of the heart, kidney, and brain, account for major morbidity and mortality in the United States. When an organ is ischemic, the logical approach is to relieve the ischemia by re-establishing blood flow as is accomplished by percutaneous interventions, such as angioplasty and placing a stent in an occluded coronary artery or occluded renal artery. However, even after establishing patency of the large obstructed blood vessel, a degree of organ damage may persist because of reperfusion injury.1 In the heart, this may manifest as reperfusion arrhythmias, stunned myocardium (postischemic left ventricular dysfunction), and no reflow or microvascular obstruction. Whether reperfusion actually kills myocardial cells remains debatable. In the kidneys, reperfusion injury may manifest as microvascular damage, loss of glomerular filtration, and damage because of reactive oxygen species that includes loss of cortical structure. It has been postulated that abrupt reperfusion results in reactive oxygen species production by the mitochondria, opening of the mitochondrial permeability transition pore, an influx of calcium into the mitochondria, release of cytochrome C, and peroxidation of cardiolipin in the inner mitochondrial membrane.2 Certainly, angioplasty/stenting for renal artery stenosis alone for the treatment of hypertension has been disappointing in its effect on major adverse clinical outcomes.3 Most patients need to remain on medical therapies, and there is limited evidence of preservation of renal function. One potential explanation is that reperfusion injury has contributed to the disappointing outcomes.
See Article by Saad et al
Numerous therapies have been tested in preclinical models to try to reduce ischemia/reperfusion injury.4 In the setting of clinical ST-elevation–myocardial infarction (STEMI), various adjunctive agents have been tried along with reperfusion to further reduce myocardial infarct size and limit ischemia/reperfusion injury. Although many of these therapies showed promise in preclinical studies, most did not work …