Metabolic dysfunction and depletion of mitochondria in hearts of septic rats

J. A. Watts, Jeffrey Kline, L. R. Thornton, R. M. Grattan, S. S. Brar

Research output: Contribution to journalArticle

86 Citations (Scopus)

Abstract

Our previous studies indicate that hearts from septic rats have decreased work with oxygen wasting. The present studies test if there is energy deficit, changes in cardiac mitochondrial content and caspase activation during sepsis. Anesthetized, male Sprague-Dawley rats received no surgical treatment (control), laparotomy (sham), or laparotomy with cecal ligation and puncture (CLP) to induce polymicrobial septic shock. Hearts were isolated 12-14 h later. Cardiac work, oxygen consumption, substrate oxidation and energy stores were measured in perfused hearts. Normalized density of mitochondria was determined in ventricles without perfusion by morphometric analysis with electron microscopy. Citrate synthase activity was assessed in homogenates and isolated mitochondria. Cardiac work decreased significantly in CLP (47%), while oxygen consumption and glucose oxidation were unchanged compared with control or sham hearts (oxygen and substrate wasting). Tissue adenosine triphosphate, creatine phosphate and glycogen were lower in CLP hearts (energy deficit). Mitochondrial grid intersects decreased significantly from 151 ± 8 sham to 130 ± 4 CLP out of 361 possible intersects and autophagy was observed in CLP hearts. Total activity of citrate synthase decreased in homogenates (99 ± 8 μmol/min/g wet weight sham vs. 62 ± 7 CLP, P <0.05) and in the mitochondrial fraction (27 ± 1 μmol/min/g wet weight sham to 22 ± 1 CLP, P <0.05). Calculated mitochondrial content decreased from 63 ± 4 mg protein/g wet weight sham to 46 ± 5 CLP, P <0.05 (mitochondrial depletion). Caspase-3 activity doubled and tumor necrosis factor α content tripled in CLP hearts. Conclusions. - Oxygen and substrate wasting in CLP occurs with fewer mitochondria and energy deficit, processes that are coincident with caspase-3 activation.

Original languageEnglish (US)
Pages (from-to)141-150
Number of pages10
JournalJournal of Molecular and Cellular Cardiology
Volume36
Issue number1
DOIs
StatePublished - Jan 2004
Externally publishedYes

Fingerprint

Heart Mitochondria
Punctures
Ligation
Citrate (si)-Synthase
Mitochondria
Oxygen
Weights and Measures
Oxygen Consumption
Caspase 3
Laparotomy
Phosphocreatine
Autophagy
Septic Shock
Caspases
Glycogen
Sprague Dawley Rats
Sepsis
Electron Microscopy
Tumor Necrosis Factor-alpha
Perfusion

Keywords

  • Autophagy
  • Caspases
  • Cecal ligation and puncture
  • Myocardial efficiency
  • Myocardial work
  • Polymicrobial sepsis
  • Substrate oxidation
  • TNFα

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

Cite this

Metabolic dysfunction and depletion of mitochondria in hearts of septic rats. / Watts, J. A.; Kline, Jeffrey; Thornton, L. R.; Grattan, R. M.; Brar, S. S.

In: Journal of Molecular and Cellular Cardiology, Vol. 36, No. 1, 01.2004, p. 141-150.

Research output: Contribution to journalArticle

Watts, J. A. ; Kline, Jeffrey ; Thornton, L. R. ; Grattan, R. M. ; Brar, S. S. / Metabolic dysfunction and depletion of mitochondria in hearts of septic rats. In: Journal of Molecular and Cellular Cardiology. 2004 ; Vol. 36, No. 1. pp. 141-150.
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KW - Caspases

KW - Cecal ligation and puncture

KW - Myocardial efficiency

KW - Myocardial work

KW - Polymicrobial sepsis

KW - Substrate oxidation

KW - TNFα

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