Recombinant soluble P-selectin glycoprotein ligand-Ig (rPSGL-Ig) attenuates infarct size and myeloperoxidase activity in a canine model of ischemia-reperfusion.
The role of P-selectin in the process of reperfusion injury was evaluated using a recombinant soluble P-selectin glycoprotein ligand-Ig (rPSGL-Ig) in a canine coronary artery balloon occlusion model. rPSGL-Ig (1 mg/kg) or saline was given as an intravenous bolus 15 min before balloon deflation. Balloon occlusion time was 90 min followed by either 120 min or 7 days reperfusion. Infarct size was significantly reduced in the treatment group when expressed either as percentage of the area at risk or as absolute infarct size. Histological analysis showed that extensive myocardial injury and neutrophil infiltration were reduced by rPSGL-Ig. Myeloperoxidase activity (MPO) was significantly reduced in the risk area in the rPSGL-Ig group. Left ventricular ejection fraction was significantly less impaired during the first 24 h after reperfusion in the rPSGL-Ig group, although there was no difference by 7-day follow-up. Thus, administration of rPSGL-Ig decreases myocardial injury and inflammatory response for at least 7 days after reperfusion of ischemic myocardium.
Wang
Kai
K
Department of Cardiovascular Medicine, The Cleveland Clinic Foundation, OH 44195, USA. wangk@ccf.org
Zhou
Xiaorong
X
Zhou
Zhongmin
Z
Tarakji
Khaldoun
K
Qin
Jian Xin
JX
Sitges
Marta
M
Shiota
Takahiro
T
Forudi
Farhad
F
Schaub
Robert G
RG
Kumar
Anjali
A
Penn
Marc S
MS
Topol
Eric J
EJ
Lincoff
A Michael
AM
D000818:Animals; D004195:Disease Models, Animal; D004285:Dogs; D005500:Follow-Up Studies; D008562:Membrane Glycoproteins / Q000008:administration & dosage / Q000494:pharmacology*; D009203:Myocardial Infarction / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control*; D019007:P-Selectin / Q000502:physiology; D009195:Peroxidase / Q000187:drug effects*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D015427:Reperfusion Injury / Q000188:drug therapy / Q000209:etiology / Q000517:prevention & control*; D013318:Stroke Volume; D013997:Time Factors
D008562:Membrane Glycoproteins; D019007:P-Selectin; C084882:P-selectin ligand protein; D011994:Recombinant Proteins; D009195:Peroxidase