Background: Tourniquets impose ischemia on distal musculature. Resuscitation with pyruvate, an energy substrate and antioxidant, may ameliorate muscle ischemia-reperfusion injury. Methods: After goats were exsanguinated to lower mean arterial pressure to 48 mmHg, femoral vessels were occluded for 90 minutes to impose hindlimb ischemia. Lactate Ringer's (LR) or pyruvate Ringer's (PR) solution was infused from 30 minutes ischemia until 30 minutes reperfusion. Pro-and antiapoptotic proteins and injury markers were measured in gastrocnemius at 4 hours reperfusion. Results: Pro-oxidant NADPH oxidase activity and nitrotyrosine content, a footprint of nitrosative stress, doubled, and poly(ADP-ribose) polymerase cleavage, an early apoptotic event, increased 80% in LR-resuscitated vs. sham muscle, but PR prevented these increases. Antiapoptotic Bcl-X L content fell in LR-treated vs. sham and PR-treated muscle. Water content increased in LR-but not PR-resuscitated muscle. Conclusions: LR resuscitation imposed oxido-nitrosative stress and initiated proapoptotic mechanisms, while PR blunted these harmful consequences of muscle ischemia-reperfusion.