Platelets activated by transient coronary occlusion exacerbate ischemia-reperfusion injury in rat hearts.
Platelets (Plt) accumulate in reperfused myocardium but their effect on myocardial necrosis has not been established. We tested the hypothesis that the effect of Plt depends on their activation status. Pig Plt were obtained before 48 min of coronary occlusion (pre-CO-Plt), 10 min after reperfusion (R-Plt), or after a 60-min sham operation (sham-Plt). Plt were infused into isolated rat hearts (n = 124) and subsequently submitted to 60 min of ischemia and 60 min of reperfusion. P-selectin expression was higher (P = 0.02) in R-Plt than in pre-CO-Plt or sham-Plt. Lactate dehydrogenase (LDH) release during reperfusion was similar in hearts receiving pre-CO-Plt, sham-Plt, or no Plt, but R-Plt increased LDH release by 60% (P = 0.004). Activation of pre-CO-Plt with thrombin increased P-selectin expression and LDH release (P < 0.001), and these results were unaffected by tirofiban. There was a close correlation between P-selectin expression and LDH release (r = 0.84; P < 0.001), and myocardial Plt accumulation (r = 0.85; P < 0.001). We conclude that the deleterious effect of Plt on reperfused myocardium depends on their activation status as represented by P-selectin expression, which is enhanced by ischemia-reperfusion.
Servicio de Cardiología, Hospital Universitari Vall d'Hebron, 08035 Barcelona, Spain.
Maribel
M
Mirabet
David
D
Garcia-Dorado
Javier
J
Inserte
José A
JA
Barrabés
Rosa-M
RM
Lidón
Bernat
B
Soriano
Marta
M
Azevedo
Ferran
F
Padilla
Luis
L
Agulló
Marisol
M
Ruiz-Meana
Anna
A
Massaguer
Pilar
P
Pizcueta
Jordi
J
Soler-Soler
D000818:Animals; D001792:Blood Platelets / Q000737:chemistry / Q000000981:diagnostic imaging / Q000502:physiology*; D003327:Coronary Disease / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D006490:Hemostatics / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000503:physiopathology*; D009336:Necrosis; D019007:P-Selectin / Q000032:analysis; D015539:Platelet Activation / Q000187:drug effects / Q000502:physiology; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals; D051381:Rats; D017207:Rats, Sprague-Dawley; D013552:Swine; D019690:Technetium Tc 99m Exametazime; D013917:Thrombin / Q000494:pharmacology
D006490:Hemostatics; D019007:P-Selectin; D019275:Radiopharmaceuticals; D019690:Technetium Tc 99m Exametazime; D013917:Thrombin