TITLE:
Protective effects of bifunctional platelet GPIIIa49-66 ligand on myocardial ischemia-reperfusion injury in rats
AUTHORS:
Jing Fan, Fang Jing, Suying Dang, Wei Zhang
KEYWORDS:
Thrombus; Antiplatelet Drugs; Ischemia-Reperfusion Injury
JOURNAL NAME:
Health,
Vol.5 No.7C,
July
18,
2013
ABSTRACT:
Current antiplatelet drugs mainly focus on prevention
rather than the more clinically relevant issue of clearance of an existing
thrombus. We recently described a novel and effective therapeutic strategy for
dissolution of preexisting platelet thrombus in a murine ischemic stroke model
with a bifunctional platelet GPIIIa49-66 ligand
(Single-chain antibody Linked first Kringle 1 of plasminogen, named
SLK), which homes to newly deposited fibrin strands tangled of platelet
thrombus and induces aggregated platelet fragmentation. In this study, we
perform in-depth analysis of the effect of SLK on myocardial ischemia-reperfusion
(IR) injury in rats. We show that SLK dose-dependently reduces lactate dehydrogenase
(LDH) release as well as mean infarction size of left ventricle. Histological
observation demonstrates that the arterial thrombi in coronary arteries of
rat almost disappear after SLK injection. Optimal dose of SLK (37.5 μg/ individual)
provides the myocardial protection at 2 hours post-infusion. However, there are
no significant protective effects if SLK was given at 4 or 8 hours
post-infusion. The combined application of SLK and urokinase (UK) demonstrates
greater myocardial protection than UK alone at 2 hours post-infusion. Thus, SLK
could be used as a thrombolytic alternative in other arterial vascular beds associated with thrombosis to
enhance fibrinolysis.