Activated platelets contribute importantly to myocardial reperfusion injury.
Platelets become activated during myocardial infarction (MI), but the direct contribution of activated platelets to myocardial reperfusion injury in vivo has yet to be reported. We tested the hypothesis that activated platelets contribute importantly to reperfusion injury during MI in mice. After 30 min of ischemia and 60 min of reperfusion, P-selectin knockout mice had a significantly smaller infarct size than that of wild-type mice (P < 0.05). Platelets were detected by P-selectin antibody in the previously ischemic region of wild-type mice as early as 2 min postreperfusion after 45 min, but not 20 min, of ischemia. The appearance of neutrophils in the heart was delayed when compared with platelets. Flow cytometry showed that the number of activated platelets more than doubled after 45 min of ischemia when compared with 20 min of ischemia or sham treatment (P < 0.05). Platelet-rich or platelet-poor plasma was then transfused from either sham-operated or infarcted mice after 45 and 10 min of ischemia-reperfusion to mice undergoing 20 and 60 min of ischemia-reperfusion. Infarct size was increased by threefold and platelet accumulation was remarkably enhanced in mice treated with wild-type, MI-activated platelet-rich plasma but not in mice receiving either platelet-poor plasma from wild types or MI-activated platelet-rich plasma from P-selectin knockout mice. In conclusion, circulating platelets become activated early during reperfusion and their activation depends on the duration of the preceding coronary occlusion and is proportional to the extent of myocardial injury. Activated platelets play an important role in the process of myocardial ischemia-reperfusion injury, and platelet-derived P-selectin is a critical mediator.
Xu
Yaqin
Y
Dept. of Biomedical Engineering, Univ. of Virginia Health System, Charlottesville, VA 22903, USA.
Huo
Yuqing
Y
Toufektsian
Marie-Claire
MC
Ramos
Susan I
SI
Ma
Yongguang
Y
Tejani
Ankit D
AD
French
Brent A
BA
Yang
Zequan
Z
D000818:Animals; D001792:Blood Platelets / Q000473:pathology; D003327:Coronary Disease / Q000150:complications; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009203:Myocardial Infarction / Q000209:etiology / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000097:blood* / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D009206:Myocardium / Q000473:pathology; D020556:Neutrophil Infiltration; D019007:P-Selectin / Q000378:metabolism; D015539:Platelet Activation; D013997:Time Factors
D019007:P-Selectin