Ischemic Preconditioning and Iloprost Reduces Ischemia-Reperfusion Injury in Jejunal Flaps: An Animal Model

Plast Reconstr Surg. 2019 Jul;144(1):124-133. doi: 10.1097/PRS.0000000000005708.

Abstract

Background: Free jejunal flaps are among the most commonly used flaps for esophageal reconstruction. However, ischemia-reperfusion injury caused by warm ischemia seen during transfer limits their use. Iloprost, a prostacyclin analogue, has been shown to reduce ischemia-reperfusion injury in various organs. The authors investigated tissue damage in jejunal flaps with iloprost and ischemic preconditioning and compared the effectiveness of these two modalities.

Methods: Thirty-four Sprague-Dawley rats were randomized into five groups: sham, ischemia-reperfusion (control), ischemic preconditioning, iloprost, and ischemic preconditioning plus iloprost. All flaps, except those in the sham group, underwent ischemia for 60 minutes and reperfusion for 2 hours. Flap perfusion was assessed by laser Doppler perfusion monitoring. Histologic sections were scored using the Chiu scoring system. Superoxide dismutase and myeloperoxidase levels were measured spectrophotometrically.

Results: Animals that were administered iloprost and/or underwent ischemic preconditioning had better postischemic recovery of mesenteric perfusion (ischemic preconditioning, 78 percent; iloprost, 83 percent; ischemic preconditioning plus iloprost, 90 percent; versus ischemia-reperfusion, 50 percent; p < 0.05). All intervention groups showed improved histology of jejunal flaps following ischemia-reperfusion injury (ischemic preconditioning, 3; iloprost, 2.3; ischemic preconditioning plus iloprost, 3.2; versus ischemia-reperfusion, 4.7; p < 0.01, p < 0.001, and p < 0.05, respectively). Superoxide dismutase levels were higher in ischemic preconditioning, iloprost plus ischemic preconditioning, and iloprost groups (ischemic preconditioning, 2.7 ± 0.2; ischemic preconditioning plus iloprost, 2.5 ± 0.3; versus ischemia-reperfusion, 1.2 ± 0.1; p < 0.01; iloprost, 2.4 ± 1.1; versus ischemia-reperfusion, 1.2 ± 0.1; p < 0.05). Myeloperoxidase, a marker for neutrophil infiltration, was lower in the iloprost group (iloprost, 222 ± 5; versus ischemia-reperfusion, 291 ± 25; p < 0.05).

Conclusions: This study showed that both iloprost and ischemic preconditioning reduced reperfusion injury in jejunal flaps. Based on histologic results, iloprost may be a novel treatment alternative to ischemic preconditioning.

MeSH terms

  • Animals
  • Antioxidants / metabolism
  • Biomarkers / metabolism
  • Disease Models, Animal
  • Esophagus / surgery
  • Free Tissue Flaps*
  • Iloprost / pharmacology*
  • Ischemic Preconditioning / methods*
  • Jejunum / transplantation*
  • Laser-Doppler Flowmetry / methods
  • Male
  • Neutrophil Infiltration / drug effects
  • Peroxidase / metabolism
  • Platelet Aggregation Inhibitors / pharmacology*
  • Random Allocation
  • Rats, Sprague-Dawley
  • Reperfusion Injury / prevention & control*
  • Superoxide Dismutase / metabolism

Substances

  • Antioxidants
  • Biomarkers
  • Platelet Aggregation Inhibitors
  • Peroxidase
  • Superoxide Dismutase
  • Iloprost