972-102 Suppression of ICAM-1 and P-Selectin Adhesion Molecule Expression by Bolus IV Liposomal PGE1 (TLC-C53) Immediately Prior to Reperfusion in a Two Hour Canine Infarct/Reperfusion Model

Bolus administration of 2 μ/kg Liposomal PGE l (TLC-C53) after 2 hrs of ischemia inhibits WBC accumulation into ischemic tissue and significantly reduces infarct size upon reperfusion. To test the hypothesis that inhibition of adhesion molecule expression was the mechanism of this observation we studied 11 dogs subjected to 2 hrs of ischemia followed by 3 hrs of reperfusion, Animals were randomly assigned to receive either placebo or 2 μ/kg TLC-C53 just prior to reperfusion, Samples obtained from the coronary sinus at baseline and at various intervals throughoutthe experiment were analyzed for expression of L-Selectin (CL2) and C011 b (MY 904) on WBC using indirect immunofluorescence and flow cytometry. After sacrifice, tissue samples obtained from the infarct, border, risk and control regions were analyzed for WBC infiltration (myeloperoxidase) and expression of ICAM-1 (CL18) and PSelectin (MD3) on the endothelium using immuno-histochemistry, Intensity of staining was graded from (no stain I to 31 intense stain). Results No differences in WBC mean channel fluorescence between the treatment and control groups could be detected for either L-Selectin or C011 b. Risk region expression of ICAM-l was reduced from 2.6 ± 0.6 to 0.9 ± 0.6 (p l 0.001) and P-Selectin from 1.6 ± 0.6 to 0.9 ± 0.8 (p l 0.01), In farct zone myeloperoxidase was reduced from 0.28 ± 0.1 to 0.1 ± 0.1 U/l00 mg (p = 0.03) Conclusion Bolus IV administration of TLC-C53 at reperfusion suppresses expression of ICAM-l and P-Selectin on ischemic but viable endothelium and prevents secondary (presumably lethal) WBC myocardial infiltration, The effect of TLC-C53 on WBC adhesion molecule expression may be less marked, We propose that inhibition of adhesion molecules in ischemic myocardium is the principle mechanism of infarct salvage by TLC-C53.