Protective effects of bifunctional platelet GPIIIa49-66 ligand on myocardial ischemia-reperfusion injury in rats

Abstract

<p> <span style="font-size:10pt;font-family:Arial, sans-serif;"><span style="font-family:Verdana;">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 </span><span style="font-family:Verdana;">ligand (Single-chain antibody Linked first Kringle </span><span style="font-family:Verdana;">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 </span><span style="font-family:Verdana;">other arterial vascular beds associated with throm</span><span style="font-family:Verdana;">bosis to enhance fibrinolysis.</span></span> </p

Immune mechanisms of ischemia-reperfusion injury in transplantation

“…Interestingly, through its strong anti-inflammatory effect, nicotine has been shown to reduce tubular damage in experimental models of warm ischemia when administered before reperfusion [53]. As for myocardial ischemia-reperfusion injury, it was shown that the use of the bifunctional platelet GPIIIa49-66 ligand confers dosedependent protective effects in a rat model of acute myocardial ischemia [54].…”