Pyruvate-enriched resuscitation protects hindlimb muscle from ischemia-reperfusion injury

Devin C. Flaherty, Besim Hoxha, Jie Sun, Hunaid Gurji, Jerry Simecka, Albert Yurvati, Robert T. Mallet

Research output: Contribution to journalArticleResearchpeer-review

4 Citations (Scopus)

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 languageEnglish
Pages (from-to)1020-1026
Number of pages7
JournalMilitary Medicine
Volume175
Issue number12
DOIs
StatePublished - 1 Jan 2010

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Hindlimb
Reperfusion Injury
Pyruvic Acid
Resuscitation
Muscles
Ischemia
Reperfusion
Tourniquets
Poly(ADP-ribose) Polymerases
NADPH Oxidase
Thigh
Goats
Reactive Oxygen Species
Arterial Pressure
Antioxidants
Ringer's lactate
Water
Wounds and Injuries
Proteins

Cite this

Flaherty, Devin C. ; Hoxha, Besim ; Sun, Jie ; Gurji, Hunaid ; Simecka, Jerry ; Yurvati, Albert ; Mallet, Robert T. / Pyruvate-enriched resuscitation protects hindlimb muscle from ischemia-reperfusion injury. In: Military Medicine. 2010 ; Vol. 175, No. 12. pp. 1020-1026.
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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.",
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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 journalArticleResearchpeer-review

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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.

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