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Effects of epinephrine and norepinephrine on hemodynamics, oxidative metabolism, and organ energetics in endotoxemic rats

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Abstract

Objective

To determine whether epinephrine increases lactate concentration in sepsis through hypoxia or through a particular thermogenic or metabolic pathway.

Design

Prospective, controlled experimental study in rats.

Setting

Experimental laboratory in a university teaching hospital.

Interventions

Three groups of anesthetized, mechanically ventilated male Wistar rats received an intravenous infusion of 15 mg/kg Escherichia coli O127:B8 endotoxin. Rats were treated after 90 min by epinephrine (n=14), norepinephrine (n=14), or hydroxyethyl starch (n=14). Three groups of six rats served as time-matched control groups and received saline, epinephrine, or norepinephrine from 90 to 180°min. Mean arterial pressure, aortic, renal, mesenteric and femoral blood flow, arterial blood gases, lactate, pyruvate, and nitrate were measured at baseline and 90 and 180 min after endotoxin challenge. At the end of experiments biopsy samples were taken from the liver, heart, muscle, kidney, and small intestine for tissue adenine nucleotide and lactate/pyruvate measurements.

Measurements and results

Endotoxin induced a decrease in mean arterial pressure and in aortic, mesenteric, and renal blood flow. Plasmatic and tissue lactate increased with a high lactate/pyruvate (L/P) ratio. ATP decreased in liver, kidney, and heart. The ATP/ADP ratio did not change, and phosphocreatinine decreased in all organs. Epinephrine and norepinephrine increased mean arterial pressure to baseline values. Epinephrine increased aortic blood flow while renal blood low decreased with both drugs. Plasmatic lactate increased with a stable L/P ratio with epinephrine and did not change with norepinephrine compared to endotoxin values. Nevertheless epinephrine and norepinephrine when compared to endotoxin values did not change tissue L/P ratios or ATP concentration in muscle, heart, gut, or liver. In kidney both drugs decreased ATP concentration.

Conclusions

Our data demonstrate in a rat model of endotoxemia that epinephrine-induced hyperlactatemia is not related to cellular hypoxia.

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Acknowledgements

The authors thanks Pr. O. Lesur (Sherbrooke, Québec, Canada) and Pr. R. Nevière (Lille, France) for their helpful comments. This work was carried out in the Laboratoire d'Exploration Fonctionnelle Rénale, Faculté de Médecine, Vandoeuvre-les-Nancy, France. The study was supported in part by a grant from Nestle-Perrier France.

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Authors and Affiliations

  1. Réanimation Médicale, Hôpital Central, 54035, Nancy Cedex, France

    Bruno Levy & Pierre-Edouard Bollaert

  2. Laboratoire d'Exploration Fonctionnelle Rénale, Faculté de Médecine, 54000, Vandoeuvre-les-Nancy, France

    Bruno Levy, Arnaud Mansart, Pierre-Edouard Bollaert & Jean-Pierre Mallie

  3. Laboratoire de Biochimie, Hôpital Central, 54035, Nancy Cedex, France

    Patricia Franck

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  1. Bruno Levy
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  2. Arnaud Mansart
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  3. Pierre-Edouard Bollaert
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  4. Patricia Franck
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  5. Jean-Pierre Mallie
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Correspondence to Bruno Levy.

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An editorial regarding this article can be found in the same issue (http://dx.doi.org/10.1007/s00134-002-1596-8)

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Levy, B., Mansart, A., Bollaert, PE. et al. Effects of epinephrine and norepinephrine on hemodynamics, oxidative metabolism, and organ energetics in endotoxemic rats. Intensive Care Med 29, 292–300 (2003). https://doi.org/10.1007/s00134-002-1611-0

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  • DOI: https://doi.org/10.1007/s00134-002-1611-0

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