TY - JOUR
T1 - Reperfusion injury in ST-segment elevation myocardial infarction
T2 - The final frontier
AU - Ndrepepa, Gjin
AU - Colleran, Roisin
AU - Kastrati, Adnan
N1 - Publisher Copyright:
© 2017 Wolters Kluwer Health, Inc. All rights reserved.
PY - 2017
Y1 - 2017
N2 - ST-segment elevation myocardial infarction is a major cause of morbidity and mortality worldwide. Reperfusion injury (RI) following the opening of an occluded coronary artery mitigates the effect of reperfusion by further accentuating ischemic damage and increasing infarct size. Experimental studies have shown that nearly 50% of final infarct size is attributable to RI, an elusive phenomenon that remains resistant to treatment. This review proposes a hypothesis to explain the failure of strategies that have been used in an attempt to prevent RI. This hypothesis suggests that, after a certain duration of myocardial ischemia in the affected myocardium, three phases of myocardial damage occur: reversible ischemia, irreversible ischemia, and necrosis. In the reversible ischemia phase, cellular adaptive responses remain functional, and cellular repair and thus recovery of cellular functions is possible, whereas in the irreversible ischemia phase protective maneuvers fail to confer cytoprotection. Preventive therapies for RI fail because they cannot prevent cell death once cells have entered the irreversible ischemia phase, although they may succeed in postponing cell death. Failure to salvage myocardium with irreversible ischemia in addition to postponement and change in the mode of cell death (mainly from necrosis to apoptosis) by various RI preventive strategies may be the key to understanding the failure of these strategies in the clinical setting, despite their success in the reduction of infarct size in the experimental setting. Early reperfusion before large amounts of myocardium at risk reach the stage of irreversible ischemia is the best strategy for reduction of RI-related myocardial damage.
AB - ST-segment elevation myocardial infarction is a major cause of morbidity and mortality worldwide. Reperfusion injury (RI) following the opening of an occluded coronary artery mitigates the effect of reperfusion by further accentuating ischemic damage and increasing infarct size. Experimental studies have shown that nearly 50% of final infarct size is attributable to RI, an elusive phenomenon that remains resistant to treatment. This review proposes a hypothesis to explain the failure of strategies that have been used in an attempt to prevent RI. This hypothesis suggests that, after a certain duration of myocardial ischemia in the affected myocardium, three phases of myocardial damage occur: reversible ischemia, irreversible ischemia, and necrosis. In the reversible ischemia phase, cellular adaptive responses remain functional, and cellular repair and thus recovery of cellular functions is possible, whereas in the irreversible ischemia phase protective maneuvers fail to confer cytoprotection. Preventive therapies for RI fail because they cannot prevent cell death once cells have entered the irreversible ischemia phase, although they may succeed in postponing cell death. Failure to salvage myocardium with irreversible ischemia in addition to postponement and change in the mode of cell death (mainly from necrosis to apoptosis) by various RI preventive strategies may be the key to understanding the failure of these strategies in the clinical setting, despite their success in the reduction of infarct size in the experimental setting. Early reperfusion before large amounts of myocardium at risk reach the stage of irreversible ischemia is the best strategy for reduction of RI-related myocardial damage.
KW - acute myocardial infarction
KW - apoptosis
KW - myocardial ischemia
KW - necrosis
KW - reperfusion injury
UR - http://www.scopus.com/inward/record.url?scp=85009212535&partnerID=8YFLogxK
U2 - 10.1097/MCA.0000000000000468
DO - 10.1097/MCA.0000000000000468
M3 - Review article
C2 - 28072597
AN - SCOPUS:85009212535
SN - 0954-6928
VL - 28
SP - 253
EP - 262
JO - Coronary Artery Disease
JF - Coronary Artery Disease
IS - 3
ER -