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.
