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Myocardial lactate deprivation is associated with decreased cardiovascular performance, decreased myocardial energetics, and early death in endotoxic shock

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Abstract

Objective

We examined whether lactate availability is a limiting factor for heart function during endotoxic shock, and whether lactate deprivation thus induces heart energy depletion, thereby altering cardiovascular performance. The study goals were to determine whether muscle lactate production is linked to β2-stimulation and to ascertain the effects of systemic lactate deprivation on hemodynamics, lactate metabolism, heart energetics, and outcome in a lethal model of rat's endotoxic shock.

Interventions

We modulated the adrenergic pathway in skeletal muscle using microdialysis with ICI-118551, a selective β2-blocker. Muscle lactate formation in endotoxic shock was further inhibited by intravenous infusion of ICI-118551 or dichloroacetate (DCA), an activator of pyruvate dehydrogenase (DCA) and their combination.

Results

Muscle lactate formation was decreased by ICI-118551. During endotoxic shock both ICI-118151 and DCA decreased circulating and heart lactate concentrations in parallel with a decrease in tissue ATP content. The combination ICI-118551-DCA resulted in early cardiovascular collapse and death. The addition of molar lactate to ICI-1185111 plus DCA blunted the effects of ICI-118551+DCA on hemodynamics. Survival was markedly less with ICI-118551 than with endotoxin alone.

Conclusion

Systemic lactate deprivation is detrimental to myocardial energetics, cardiovascular performance, and outcome.

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Authors and Affiliations

  1. Coordination Circulation UHP-INSERM, Groupe CHOC, Faculté de Médecine, Université Henri Poincaré Nancy 1, Nancy, France

    Bruno Levy, Arnauld Mansart, Chantal Montemont, Sebastien Gibot & Jean-Pierre Mallie

  2. Inserm U734, Faculté de Médecine, Université Henri Poincaré Nancy 1, Nancy, France

    Veronique Regnault & Thomas Lecompte

  3. Inserm U684, Faculté de Médecine, Université Henri Poincaré Nancy 1, Nancy, France

    Patrick Lacolley

Authors
  1. Bruno Levy
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  2. Arnauld Mansart
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  3. Chantal Montemont
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  4. Sebastien Gibot
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  5. Jean-Pierre Mallie
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  6. Veronique Regnault
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  7. Thomas Lecompte
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  8. Patrick Lacolley
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Correspondence to Bruno Levy.

Additional information

This article is discussed in the editorial available at: http://dx.doi.org/10.1007/s00134-006-0524-8

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Levy, B., Mansart, A., Montemont, C. et al. Myocardial lactate deprivation is associated with decreased cardiovascular performance, decreased myocardial energetics, and early death in endotoxic shock. Intensive Care Med 33, 495–502 (2007). https://doi.org/10.1007/s00134-006-0523-9

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  • DOI: https://doi.org/10.1007/s00134-006-0523-9

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