The Effect Of Alprostadil On Ischemic Skeletal Muscle Cultures. Comparative Proteomic Study With Healthy Muscle

Introduction: Alprostadil has vasodilator properties and inhibits platelet aggregation. Its effectson endothelial wall have been widely studied, but there is no knowledge about possible skeletalmuscle effects, and differences with ischemic muscle.Objective: To determine the effects of alprostadil on skeletal muscle metabolism, and to investigate possible differences with ischemic muscle.Methods: Samples were obtained in 10 patients with leg above-knee amputation due to severeirreversible ischemia, of ischemic muscle (extensor digitorum brevis, group I), and healthy muscle (quadriceps femoris, amputation edge, group S). Muscle segments were incubated withalprostadil 5 ng, or without it (baseline). Proteomic analysis of metabolic enzymes was performed: Triose-phosphate isomerase (TPI), malate dehydrogenase (MDH), lactate dehydrogenase(LDH) and pyruvate carboxylase (PC). Lactate and pyruvate was also determined.Results: A decrease in malate dehydrogenase was observed in group I in the baseline samples( 2196 +/- 348 group S vs 644 +/- 192 group I, P < .05). PC was increased in both samples in group I( baseline: 1.80 +/- 1.27 vs 3.16 +/- 2.25; alprostadil: 6.72 +/- 2.13 vs 8.16 +/- 3.63, group S vs group I, respectively, P < .05). No changes were observed in pyruvate and lactate.Discussion: Decreased MDH in ischemic muscle suggests a Krebs cycle reduction. Alprostadilstimulates the expression of PC, which leads to oxaloacetate production. This product is insertedin Krebs cycle, improving energy obtaining. In this manner, Krebs cycle can work partially inischemic muscle. (C) 2013 SEACV. Published by Elsevier Espana, S. L. All rights reserved.