EFFICACY OF RECOMBINANT HUMAN MANGANESE SUPEROXIDE-DISMUTASE COMPAREDTO ALLOPURINOL IN PROTECTION OF ISCHEMIC SKELETAL-MUSCLE AGAINST NO-REFLOW

A growing body of experimental data indicates that the ''no-reflow'' p henomenon is a type of reperfusion injury in skeletal muscle which may , in part, be mediated by oxygen free radicals, and thus may be attenu ated by using agents that scavenge or inhibit formation of these react ive oxygen metabolites. This study was undertaken to assess the effica cy of recombinant human manganese superoxide dismutase (rhMnSOD) in re ducing reperfusion injury in skeletal muscle. The specific advantage o f this agent over other SOD types is a much longer plasma half-life (5 to 7 hr), allowing better equilibration between extra- and intracellu lar compartments. The rat cremaster model was used to study ''no-reflo w'' in skeletal muscle. Reperfusion injury in the muscle was assessed by fluorescein dye perfusion, myocyte creatine phosphokinase (CPK) rel ease, and contractile function in response to electrical field stimula tion. Compared with untreated saline control animals, those treated wi th rhMnSOD after 5 hr of cremasteric ischemia, had a significantly hig her percentage area of blood reflow (78 percent +/- 6 percent of norma l), 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 baselin e CPK levels) (p <0.05). Untreated saline control CPK values were 60.9 percent higher than the prereperfusion level. Animals treated with al lopurinol also had a significantly higher percentage twitch contractio n (47 percent +/- 14 percent of normal) and a lower CPK release (11.1 percent of the prereperfusion value) 45 min after reperfusion than unt reated saline controls. These results indicate that both rhMnSOD and a llopurinol reduce the degree of ''no-reflow'' and the severity of repe rfusion injury in this post-ischemic skeletal muscle model and may hav e favorable clinical implications for prevention of ''no-reflow'' in m icrovascular surgery.