Does iloprost mediate thromboxane activity and polymorphonuclear leukocyte sequestration in ischemic skeletal muscle?
Thromboxane is known to alter the endothelial cytoskeleton, thereby causing increased endothelial permeability and polymorphonuclear leukocyte (PMN) sequestration in the lungs. We investigated whether iloprost (a stable prostacyclin analog) can decrease thromboxane activity and consequently PMN sequestration because of its anti-platelet aggregation effect. This premise was investigated in a canine isolated gracilis muscle model using 18 animals. Six animals (group I) had the gracilis muscle subjected to 6 hours of complete ischemia followed by 48 hours of reperfusion. Group II (n = 6) received intravenous infusion of iloprost (0.45 micrograms/kg/hr) throughout the experiment (1 hour preischemia, 6 hours of ischemia and 1 hour of reperfusion) and boluses of 0.45 micrograms/kg 10 minutes before ischemia and reperfusion. Group III (n = 6) underwent a similar ischemic interval, but were given iloprost bolus of 0.45 micrograms/kg followed by intravenous infusion of 0.45 micrograms/kg/hr during 48 hours of reperfusion. Gracilis venous samples were obtained at preischemia (PI) and 1 hour of reperfusion (all 3 groups) and at 48 hours of reperfusion (groups I and III) to measure thromboxane (TXB2) levels. Muscle biopsies were taken at the same time to measure myeloperoxidase (MPO) activity, a marker of PMN infiltration. In group I, TXB2 level increased from a pre-ischemic value of 2983 +/- 1083 pg/ml to 9483 +/- 2218 pg/ml at 1 hour of reperfusion (p < 0.05) and then decreased to 2386 +/- 1533 pg/ml at 48 hours of reperfusion (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001706:Biopsy; D002199:Capillary Permeability / Q000187:drug effects; D004195:Disease Models, Animal; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D016285:Iloprost / Q000008:administration & dosage / Q000494:pharmacology*; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D007511:Ischemia / Q000188:drug therapy* / Q000473:pathology; D009132:Muscles / Q000098:blood supply*; D009336:Necrosis; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D009195:Peroxidase / Q000032:analysis; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology; D013929:Thromboxane B2 / Q000502:physiology*; D013997:Time Factors
D013929:Thromboxane B2; D009195:Peroxidase; D016285:Iloprost