Hindlimb ischemia-reperfusion increases complement deposition and glycolysis

Michael S. Wong, Tirso M. Lara, Lester Kobzik, Jan D. Rounds, Malcolm K. Robinson, Danny O. Jacobs

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Background. Hindlimb ischemia-reperfusion (HIR) impairs cellular energy metabolism and causes local muscle injury possibly through free radical or complement-mediated mechanisms. Materials and methods. To determine the relationship among myocellular energetics, histopathological injury, and mediator activity, male Wistar rats underwent 4 h of Sham (n = 8), Unilateral (n = 8), or Bilateral (n = 8) hindlimb ischemia followed by 4 h of reperfusion. All rats underwent 31P magnetic resonance spectroscopy of their right gastrocnemius muscle to determine various high-energy phosphate ratios including ATP to P(i) (ATP/P(i), a measure of energy status) and phosphocreatine to P(i) (PCr/P(i), a measure of thermodynamic capacity). Gastrocnemius muscles were then harvested to determine muscle damage and complement membrane attack complex (MAC) deposition by immunohistochemical staining [grade 0 (none) to 3 (very severe)] and to measure glutathione (GSH), DNA, and enzyme activities: β-hydroxyacyl-CoA dehydrogenase, phosphofructokinase, and citrate synthetase. Results. HIR was associated with significant declines in ATP/P(i) and PCr/P(i) (P < 0.001). Progressively more severe HIR (Sham, Unilateral, Bilateral) was associated with greater MAC deposition (0.0 ± 0.0, 1.0 ± 0.3, 1.5 ± 0.4, P = 0.06, mean ± SEM) and histological damage (0.0 ± 0.0, 0.9 ± 0.3, 1.3 ± 0.4, P < 0.05). GSH levels, β-hydroxyacyl-CoA dehydrogenase, and citrate synthetase activities were not affected by HIR, but phosphofructokinase activity increased (24.09 ± 2.42, 35.16 ± 5.26, 59.29 ± 9.82 mmol/mg of DNA/min, P < 0.05). Although GSH levels were not significantly altered, complement deposition was closely associated with skeletal muscle injury and compensatory changes in glycolysis. Alterations in myocellular bioenergetics after HIR closely paralleled complement deposition rather than GSH depletion. Conclusions. Therapeutic strategies aimed at controlling complement activity and assessment techniques based on bioenergetics may allow more precise determinations of the effects of HIR injury.

Original languageEnglish
Pages (from-to)130-135
Number of pages6
JournalJournal of Surgical Research
Volume85
Issue number1
DOIs
StatePublished - Jul 1999
Externally publishedYes

Fingerprint

Glycolysis
Hindlimb
Reperfusion
Ischemia
Energy Metabolism
Complement Membrane Attack Complex
Phosphofructokinases
Skeletal Muscle
Adenosine Triphosphate
Coenzyme A
Ligases
Citric Acid
Oxidoreductases
Wounds and Injuries
Muscles
Phosphocreatine
DNA
Reperfusion Injury
Thermodynamics
Free Radicals

Keywords

  • Complement
  • Glycolysis
  • Ischemia-reperfusion injury
  • Magnetic resonance spectroscopy

ASJC Scopus subject areas

  • Surgery

Cite this

Wong, M. S., Lara, T. M., Kobzik, L., Rounds, J. D., Robinson, M. K., & Jacobs, D. O. (1999). Hindlimb ischemia-reperfusion increases complement deposition and glycolysis. Journal of Surgical Research, 85(1), 130-135. https://doi.org/10.1006/jsre.1999.5657

Hindlimb ischemia-reperfusion increases complement deposition and glycolysis. / Wong, Michael S.; Lara, Tirso M.; Kobzik, Lester; Rounds, Jan D.; Robinson, Malcolm K.; Jacobs, Danny O.

In: Journal of Surgical Research, Vol. 85, No. 1, 07.1999, p. 130-135.

Research output: Contribution to journalArticle

Wong, MS, Lara, TM, Kobzik, L, Rounds, JD, Robinson, MK & Jacobs, DO 1999, 'Hindlimb ischemia-reperfusion increases complement deposition and glycolysis', Journal of Surgical Research, vol. 85, no. 1, pp. 130-135. https://doi.org/10.1006/jsre.1999.5657
Wong, Michael S. ; Lara, Tirso M. ; Kobzik, Lester ; Rounds, Jan D. ; Robinson, Malcolm K. ; Jacobs, Danny O. / Hindlimb ischemia-reperfusion increases complement deposition and glycolysis. In: Journal of Surgical Research. 1999 ; Vol. 85, No. 1. pp. 130-135.
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abstract = "Background. Hindlimb ischemia-reperfusion (HIR) impairs cellular energy metabolism and causes local muscle injury possibly through free radical or complement-mediated mechanisms. Materials and methods. To determine the relationship among myocellular energetics, histopathological injury, and mediator activity, male Wistar rats underwent 4 h of Sham (n = 8), Unilateral (n = 8), or Bilateral (n = 8) hindlimb ischemia followed by 4 h of reperfusion. All rats underwent 31P magnetic resonance spectroscopy of their right gastrocnemius muscle to determine various high-energy phosphate ratios including ATP to P(i) (ATP/P(i), a measure of energy status) and phosphocreatine to P(i) (PCr/P(i), a measure of thermodynamic capacity). Gastrocnemius muscles were then harvested to determine muscle damage and complement membrane attack complex (MAC) deposition by immunohistochemical staining [grade 0 (none) to 3 (very severe)] and to measure glutathione (GSH), DNA, and enzyme activities: β-hydroxyacyl-CoA dehydrogenase, phosphofructokinase, and citrate synthetase. Results. HIR was associated with significant declines in ATP/P(i) and PCr/P(i) (P < 0.001). Progressively more severe HIR (Sham, Unilateral, Bilateral) was associated with greater MAC deposition (0.0 ± 0.0, 1.0 ± 0.3, 1.5 ± 0.4, P = 0.06, mean ± SEM) and histological damage (0.0 ± 0.0, 0.9 ± 0.3, 1.3 ± 0.4, P < 0.05). GSH levels, β-hydroxyacyl-CoA dehydrogenase, and citrate synthetase activities were not affected by HIR, but phosphofructokinase activity increased (24.09 ± 2.42, 35.16 ± 5.26, 59.29 ± 9.82 mmol/mg of DNA/min, P < 0.05). Although GSH levels were not significantly altered, complement deposition was closely associated with skeletal muscle injury and compensatory changes in glycolysis. Alterations in myocellular bioenergetics after HIR closely paralleled complement deposition rather than GSH depletion. Conclusions. Therapeutic strategies aimed at controlling complement activity and assessment techniques based on bioenergetics may allow more precise determinations of the effects of HIR injury.",
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AU - Jacobs, Danny O.

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N2 - Background. Hindlimb ischemia-reperfusion (HIR) impairs cellular energy metabolism and causes local muscle injury possibly through free radical or complement-mediated mechanisms. Materials and methods. To determine the relationship among myocellular energetics, histopathological injury, and mediator activity, male Wistar rats underwent 4 h of Sham (n = 8), Unilateral (n = 8), or Bilateral (n = 8) hindlimb ischemia followed by 4 h of reperfusion. All rats underwent 31P magnetic resonance spectroscopy of their right gastrocnemius muscle to determine various high-energy phosphate ratios including ATP to P(i) (ATP/P(i), a measure of energy status) and phosphocreatine to P(i) (PCr/P(i), a measure of thermodynamic capacity). Gastrocnemius muscles were then harvested to determine muscle damage and complement membrane attack complex (MAC) deposition by immunohistochemical staining [grade 0 (none) to 3 (very severe)] and to measure glutathione (GSH), DNA, and enzyme activities: β-hydroxyacyl-CoA dehydrogenase, phosphofructokinase, and citrate synthetase. Results. HIR was associated with significant declines in ATP/P(i) and PCr/P(i) (P < 0.001). Progressively more severe HIR (Sham, Unilateral, Bilateral) was associated with greater MAC deposition (0.0 ± 0.0, 1.0 ± 0.3, 1.5 ± 0.4, P = 0.06, mean ± SEM) and histological damage (0.0 ± 0.0, 0.9 ± 0.3, 1.3 ± 0.4, P < 0.05). GSH levels, β-hydroxyacyl-CoA dehydrogenase, and citrate synthetase activities were not affected by HIR, but phosphofructokinase activity increased (24.09 ± 2.42, 35.16 ± 5.26, 59.29 ± 9.82 mmol/mg of DNA/min, P < 0.05). Although GSH levels were not significantly altered, complement deposition was closely associated with skeletal muscle injury and compensatory changes in glycolysis. Alterations in myocellular bioenergetics after HIR closely paralleled complement deposition rather than GSH depletion. Conclusions. Therapeutic strategies aimed at controlling complement activity and assessment techniques based on bioenergetics may allow more precise determinations of the effects of HIR injury.

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