J Reconstr Microsurg 1999; 15(1): 37-45
DOI: 10.1055/s-2007-1000069
ORIGINAL ARTICLE

© 1999 by Thieme Medical Publishers, Inc.

Augmentation of cAMP Improves Muscle‐Flap Survival and Tissue Inflammation in Response to Ischemia/Reperfusion Injury

Sean Lille, Edward M. Boyle Jr. , Thomas Schoeller, Hans Suchy, Robert C. Russell
  • Institute of Plastic and Reconstructive Surgery, Southern Illinois University, Springfield, Illinois, and Department of Surgery, University of Washington, Seattle
Further Information

Publication History

Accepted for Publication 1998

Publication Date:
08 March 2008 (online)

ABSTRACT

The authors hypothesized that augmenting skeletal muscle adenosine 3′,5′-cyclic monophosphate (cAMP) levels could reduce tissue inflammation and improve muscle survival in response to ischemia/reperfusion (I/R) injury. Gracilis muscle flaps in male Wistar rats were subject to 4 hr of ischemia followed by 3 hr of reperfusion, to assess neutrophil accumulation and microvessel tone, or by 24 hr to evaluate percentage of muscle survival. Animals were grouped as follows: positive (saline) or negative (sham) control, or with infused cAMP elevating agents (8 Bromo-cAMP (8 Br-cAMP) or forskolin). Radioimmunoassay demonstrated significant increases in tissue cAMP levels throughout 3 hr of reperfusion with forskolin, while the 8 Br-cAMP-treated group showed only a temporary increase. Compared with vehicle-infused controls, forskolin administered 5 min prior to reperfusion and repeated as an infusion during the first 45 min of reperfusion, resulted in reduced neutrophil adherence and transmigration, and muscle edema with sustained vasodilatation. The percentage of muscle survival using nitro-blue tetrazolium staining demonstrated enhanced muscle-flap preservation with forskolin. There was no beneficial change in the presence of 8 Br-cAMP. These observations suggested that sustained elevation of the cAMP pathway may reduce ischemia-reperfusion injury by decreasing neutrophil-mediated injury and improving vessel tone. Elucidation of the cAMP pathway may provide novel opportunities to modulate ischemia/reperfusion injury.