Platelet glycoprotein IIb/IIIa receptor antagonist (abciximab) inhibited platelet activation and promoted skin flap survival after ischemia/reperfusion injury.
BACKGROUND
Evidence has shown that platelets play an important role in the pathogenesis of flap failure. Employing a rat inferior epigastric artery skin flap as a flap reperfusion injury model, we investigated whether platelet activation was involved in the skin flap failure and whether administration of abciximab (ReoPro, chimeric 7E3 Fab) could decrease platelet activation/aggregation and promote flap survival.


METHODS
Normal saline and abciximab (0.06 mg/kg; 0.2 mg/kg; 1 mg/kg) were injected intravenously into skin flaps 30 min before reperfusion and 1 h after reperfusion (each subgroup n = 6). Platelet activation as demonstrated by P-selectin (CD62P) was analyzed by flow cytometry. P-selectin expression on flap vessels was detected by immunohistochemical staining. Platelet aggregation was induced with adenosine diphosphate (ADP). Laser Doppler flowmetry monitored tissue perfusion. The surviving area was evaluated 7 days postoperatively.


RESULTS
CD62P progressively increased after reperfusion. The peak CD62P occurred after reperfusion for 12 h. Immunohistochemical staining showed CD62P significantly deposited on the endothelium after reperfusion. Administration of abciximab (1 mg/kg) effectively improved flap survival rate (P = 0.003), significantly decreased ADP-induced platelet aggregation (P < 0.001), and suppressed CD62P expression on blood platelets (P = 0.002) and its deposition on the flap vessels.


CONCLUSIONS
Abciximab promotion of skin flap survival is due to blocked platelet activation/aggregation and decreased activated-platelet deposition on the vascular endothelium. Thus, administration of a platelet glycoprotein IIb/IIIa receptor antagonist such as abciximab may save the skin flap from reperfusion injury after a long period of ischemia.
Kuo
Yur-Ren
YR
Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital at Kaohsiung, Taiwan.
Jeng
Seng-Feng
SF
Wang
Feng-Sheng
FS
Huang
Hui-Chen
HC
Wei
Fu-Chan
FC
Yang
Kuender D
KD
D000077284:Abciximab; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D007140:Immunoglobulin Fab Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D007511:Ischemia / Q000503:physiopathology; D008297:Male; D019007:P-Selectin / Q000378:metabolism; D015539:Platelet Activation / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects; D010976:Platelet Count; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D051381:Rats; D011917:Rats, Inbred Lew; D012039:Regional Blood Flow / Q000187:drug effects; D015427:Reperfusion Injury / Q000503:physiopathology; D012867:Skin / Q000098:blood supply; D013524:Surgical Flaps / Q000502:physiology*; D013997:Time Factors; D014022:Tissue Survival / Q000187:drug effects*
D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D019007:P-Selectin; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D000244:Adenosine Diphosphate; D000077284:Abciximab