Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 1020-1026 |
| Number of pages | 7 |
| Journal | Military Medicine |
| Volume | 175 |
| Issue number | 12 |
| DOIs | |
| State | Published - 1 Jan 2010 |
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Pyruvate-enriched resuscitation protects hindlimb muscle from ischemia-reperfusion injury. / Flaherty, Devin C.; Hoxha, Besim; Sun, Jie; Gurji, Hunaid; Simecka, Jerry; Yurvati, Albert; Mallet, Robert T.
In: Military Medicine, Vol. 175, No. 12, 01.01.2010, p. 1020-1026.Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - Pyruvate-enriched resuscitation protects hindlimb muscle from ischemia-reperfusion injury
AU - Flaherty, Devin C.
AU - Hoxha, Besim
AU - Sun, Jie
AU - Gurji, Hunaid
AU - Simecka, Jerry
AU - Yurvati, Albert
AU - Mallet, Robert T.
PY - 2010/1/1
Y1 - 2010/1/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=78650331958&partnerID=8YFLogxK
U2 - 10.7205/MILMED-D-10-00097
DO - 10.7205/MILMED-D-10-00097
M3 - Article
VL - 175
SP - 1020
EP - 1026
JO - Military Medicine
JF - Military Medicine
SN - 0026-4075
IS - 12
ER -