Adjunctive selectin blockade successfully reduces @entity1188 size beyond thrombolysis in the electrolytic XXXX coronary artery model.

@entity20402 @entity63 @entity235 @entity1188 @entity73259 @entity583 @entity943
BACKGROUND: An adjunctive pharmacological strategy to thrombolytic therapy that is tailored to limit reperfusion injury after thrombolysis could further maximize the unquestioned benefit of restoring flow to @entity63 . @entity63 -reperfusion injury exhibits features characteristic of an acute inflammatory response, including the rapid activation and infiltration of neutrophils. The initial process of neutrophil migration from the circulation to injured tissue is modulated by a group of adhesion molecules called selectins. The purpose of the present study was to assess the efficacy of a selectin blocker ( @entity73259 ) given as an adjunct to thrombolytic therapy to interfere with the inflammatory response after @entity63 -reperfusion and subsequently reduce @entity583 size in the electrolytic @entity235 model. METHODS AND RESULTS: A fully occlusive thrombus was formed in the left circumflex coronary artery by electrolytic injury in 20 anesthetized open-chest @entity235 . After occlusion, an infusion of 1 mg/kg recombinant tissue-type plasminogen activator (rTPA) was administered over 20 minutes with either a bolus of placebo or the selectin blocker @entity73259 (40 mg/kg). At the onset of reperfusion, 20 micrograms/kg per minute rTPA was administered for 1 hour to prevent reocclusion. After 1 hour of reperfusion, @entity1188 size, myocardial @entity20402 activity, and reperfusion @entity943 were measured. In @entity73259 -treated @entity235 , there was a significant 69% reduction in @entity1188 size when expressed as a percentage of the area at risk (6.7 +/- 8.4% versus 21.8 +/- 13.6%; P = .008) and a marked reduction in @entity20402 activity (0.014 +/- 0.009 versus 0.0370 +/- 0.025 U/min per gram; P = .02) compared with the placebo group. There was no difference between the groups in the occurrence of reperfusion @entity943 . CONCLUSIONS: Selectin blockade as an adjunct to rTPA-mediated thrombolysis significantly reduces @entity1188 size and myocardial neutrophil infiltration well beyond thrombolysis alone in the electrolytic @entity235 model. These data suggest that selectin blockade is extremely effective at reducing @entity63 -reperfusion injury and @entity583 size in this model and that the neutrophil is a potent mediator of @entity63 -reperfusion injury.
