Prednisolone but not selenium and rtPA reduces edema and improves angiogenesis after burn in mice

Burns. 2016 Mar;42(2):375-83. doi: 10.1016/j.burns.2015.08.008. Epub 2016 Jan 15.

Abstract

Objective: Despite dramatic improvements in burn care, the major part of the therapy of thermal injuries remains symptomatical in nature. A targeted approach to accelerate angiogenesis and woundhealing and reduce edema formation remains to be found. We therefore aimed to investigate the impact of anti-inflammatory, anti-coagulative and thrombolytic agents on microcirculation after thermal injuries on the mentioned parameters.

Methods: Full thickness burns were inflicted on the ears of hairless mice (n=48). The effects of five intraperitoneal injections of either recombinant tissue plasminogen activator (rtPA), selenium, prednisolone or sodium chloride on microcirculation, edema formation, leukocytes and angiogenesis were investigated over a 13 day period using intravital fluorescent microscopy.

Results: Prednisolone slightly improved angiogenesis (100.0% day 0 vs. 91.4% non-perfused area on day 1 post burn, p<0.05) and reduced edema formation (93.3% vs. 123.1% control on day 3, p<0.05). The rtPA-group showed the highest number of sticking leukocytes up to day 7 post burn (233%, 265%, 254% on days 1, 3, and 7, p<0.05 compared to baseline). A post-traumatic expansion of the non perfused area could only be observed in the selenium group (100.0% day 0, 103.1% day 1 post burn). In addition, selenium caused an increase of rolling leukocytes over the complete observation time.

Conclusion: The often described positive influences of selenium for the treatment of burn patients could not be confirmed, on the contrary we found a post-traumatic expansion of the non perfused area and an increase of leukocytes in this group. The expectations to rtPA did not fulfill. Prednisolone improved angiogenesis and reduced the edema formation, both Parameters are essential for wound healing and survival of burned patients.

Keywords: Angiogenesis; Burns; Intravital fluorescent microscopy; Leukocytes; Prednisolone; Recombinant tissue plasminogen activator; Selenium; rtPA.

MeSH terms

  • Animals
  • Antioxidants / pharmacology*
  • Burns / diagnostic imaging
  • Burns / pathology*
  • Ear
  • Edema / diagnostic imaging
  • Edema / pathology
  • Fibrinolytic Agents / pharmacology*
  • Glucocorticoids / pharmacology*
  • Intravital Microscopy
  • Leukocytes / drug effects
  • Male
  • Mice
  • Mice, Hairless
  • Microcirculation / drug effects
  • Microscopy, Fluorescence
  • Neovascularization, Physiologic / drug effects*
  • Prednisolone / pharmacology*
  • Recombinant Proteins
  • Selenium / pharmacology*
  • Skin / diagnostic imaging
  • Skin / pathology
  • Tissue Plasminogen Activator / pharmacology*

Substances

  • Antioxidants
  • Fibrinolytic Agents
  • Glucocorticoids
  • Recombinant Proteins
  • Prednisolone
  • Tissue Plasminogen Activator
  • Selenium