Apoptosis in the ischemic reperfused myocardium.
Recovery of the myocardium from an ischemic event depends on the reperfusion of the ischemic area. Resumed blood flow to the tissue restores the metabolic substrates necessary for energy production and cell survival. Paradoxically, ischemic reperfusion (I/R) can result in further damage to the myocardium (I/R injury) through an acute inflammatory response mediated by cytokines, neutrophils, macrophages, and reactive oxygen species. These events can trigger cardiomyocyte death through either necrosis or apoptosis. This report will focus on the apoptosis process, which is an organized, active, and gene-directed process of cell self-destruction that can be initiated by intracellular genetic programs, or second messenger pathways inside the cell upon extracellular stimulation by signaling molecules or stress. Awareness of the apoptotic process in cardiomyocytes and endothelial cells is relevant to myocardial preservation during cardiopulmonary bypass compared with off-pump cornary artery bypass procedures. Pharmacological interventions of the signaling pathways that control apoptosis provide an opportunity for new therapeutic approaches to reduce I/R injury in the heart. This review of apoptosis will introduce the perfusionist to apoptosis in the I/R heart, discuss some of the metabolic pathways that initiate it, and report on developing strategies to prevent it.
Holleyman
C R
CR
Sarver Heart Center, University Medical Center, Tucson, Arizona 85724, USA.
Larson
D F
DF
D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology; D006801:Humans; D017202:Myocardial Ischemia / Q000473:pathology; D015425:Myocardial Reperfusion / Q000009:adverse effects; D015428:Myocardial Reperfusion Injury / Q000209:etiology / Q000473:pathology* / Q000517:prevention & control*
D000975:Antioxidants; D016207:Cytokines