J Reconstr Microsurg 1995; 11(3): 207-214
DOI: 10.1055/s-2007-1006534
ORIGINAL ARTICLE

© 1995 by Thieme Medical Publishers, Inc.

Efficacy of Recombinant Human Manganese Superoxide Dismutase Compared to Allopurinol in Protection of Ischemic Skeletal Muscle Against “No-Reflow”

Dermot O'Farrell, Long-En Chen, Anthony V. Seaber, George A. C. Murrell, James R. Urbaniak
  • Orthopaedic Research Laboratory, Duke University Medical Center, Durham, North Carolina
Further Information

Publication History

Accepted for publication 1994

Publication Date:
08 March 2008 (online)

ABSTRACT

A growing body of experimental data indicates that the “no-reflow” phenomenon is a type of reperfusion injury in skeletal muscle which may, in part, be mediated by oxygen free radicals, and thus may be attenuated by using agents that scavenge or inhibit formation of these reactive oxygen metabolites. This study was undertaken to assess the efficacy of recombinant human manganese superoxide dismutase (rhMnSOD) in reducing reperfusion injury in skeletal muscle. The specific advantage of this agent over other SOD types is a much longer plasma half-life (5 to 7 hr), allowing better equilibration between extra- and intracellular compartments. The rat cremaster model was used to study “no-reflow” in skeletal muscle. Reperfusion injury in the muscle was assessed by fluorescein dye perfusion, myocyte creatine phospho-kinase (CPK) release, and contractile function in response to electrical field stimulation. Compared with untreated saline control animals, those treated with rhMnSOD after 5 hr of cremasteric ischemia, had a significantly higher percentage area of blood reflow (78 percent + 6 percent of normal), a greater percentage tetanic (66 percent ± 9 percent of normal) and twitch (56 percent ± 9 percent of normal) contractile strength, and less CPK release (21.5 percent higher than pre-reperfusion baseline CPK levels) (p <0.05). Untreated saline control CPK values were 60.9 percent higher than the prereperfusion level. Animals treated with allopurinol also had a significantly higher percentage twitch contraction (47 percent ± 14 percent of normal) and a lower CPK release (11.1 percent of the prereperfusion value) 45 min after reperfusion than untreated saline controls. These results indicate that both rhMnSOD and allopurinol reduce the degree of “no-reflow” and the severity of reperfusion injury in this post-ischemic skeletal muscle model and may have favorable clinical implications for prevention of “no-reflow” in microvascular surgery.