ABSTRACT
This study examined whether ischemia-reperfusion injury to skeletal muscle could be
reduced by post-ischemic infusion of phosphoenolpyruvate (PEP) and adenosine triphosphate
(ATP). The rectus femoris muscle of 54 rabbits was rendered ischemic for 3.5 hr. Eighteen
rabbits received no further treatment. Thirty-six were infused intra-arterially at
the end of ischemia, 18 with vehicle alone, and 18 with a mixture of PEP (80 (μmol/kg)
and ATP (2.6 μmol/kg). Six rabbits from each group were explored after 24 hr reperfusion
and the muscles assessed for viability (by nitro blue tetrazolium), ATP (by luciferin-luciferase
chemiluminescence), malonyldialdehyde (MDA) (thiobarbituric acid method), and water
content. The remaining muscles in each group were examined histologically after either
1 hr or 4 days of reperfusion. At 24 hr the viability of the PEP/ ATP infused muscles
(78.9 ± 15.4 percent) was significantly greater than that of untreated (41.4 ± 27.3
percent) or vehicle-infused groups (34.0 ± 32.7 percent). ATP stores were significantly
higher and MDA (indicative of free radical activity) and water content significantly
lower in the PEP/ATP treated group. At 24 hr and 4 days, muscles infused with PEP/ATP
showed less necrosis and fewer infiltrating neutrophils than the untreated groups.
Studies with isolated rabbit neutrophils showed that ATP alone significantly inhibited
superoxide anion production by stimulated neutrophils. However, when combined with
PEP at concentrations similar to those achieved in vivo, ATP did not significantly affect superoxide production. The findings indicate that
post-ischemic infusion of PEP/ATP significantly reduces ischemia-reperfusion injury
in rabbit skeletal muscle. The protective effect of PEP/ATP is more likely to be due
to supplementation of intracellular ATP stores than to the inhibition of superoxide
production by infiltrating neutrophils.
