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Intensive Care Medicine
Published in: Intensive Care Medicine 4/2011

Open Access 01-04-2011 | Experimental

The effects of levosimendan and glibenclamide on circulatory and metabolic variables in a canine model of acute hypoxia

Authors: Lothar A. Schwarte, Ingo Schwartges, Kai Thomas, Patrick Schober, Olaf Picker

Published in: Intensive Care Medicine | Issue 4/2011

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Abstract

Purpose

To study the effects of pretreatment with levosimendan (LEVO, a Ca2+-sensitizer and K ATP + channel opener) and/or the K ATP + channel antagonist glibenclamide (GLIB) on systemic hemodynamics, metabolism, and regional gastromucosal oxygenation during hypoxic hypoxemia.

Methods

Chronically instrumented, healthy dogs (24–32 kg, n = 6 per group, randomized cross-over design) were repeatedly sedated, mechanically ventilated (FiO2 ~0.3) and subjected to the following interventions: no pretreatment, LEVO pretreatment, GLIB pretreatment, or combined LEVO + GLIB pretreatment, each followed by hypoxic hypoxemia (FiO2 ~0.1). We measured cardiac output (CO, ultrasonic flow probes), oxygen consumption (VO2, indirect calorimetry), and gastromucosal microvascular hemoglobin oxygenation (μHbO2, spectrophotometry). Statistics: data are presented as mean ± SEM and compared by one-way ANOVA (direct drug effects within group) and two-way ANOVA (between all hypoxic conditions) both with Bonferroni corrections; p < 0.05.

Results

In LEVO-pretreated hypoxemia, CO was significantly higher compared to unpretreated hypoxemia. The increased CO was neither associated with an increased VO2 nor with markers of aggravated anaerobiosis (pH, BE, lactate). In addition, LEVO pretreatment did not further compromise gastromucosal μHbO2 in hypoxemia. After combined LEVO + GLIB pretreatment, systemic effects of GLIB were apparent, however, CO was significantly higher than during unpretreated and GLIB-pretreated hypoxemia, but equal to LEVO-pretreated hypoxemia, indicating that GLIB did not prevent the increased CO in LEVO-pretreated hypoxia.

Conclusions

LEVO pretreatment resulted in improved systemic circulation (CO) during hypoxemia without fueling systemic VO2, without aggravating systemic anaerobiosis markers, and without further compromising microvascular gastromucosal oxygenation. Thus, LEVO pretreatment may be an option to support the systemic circulation during hypoxia.
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Metadata
Title
The effects of levosimendan and glibenclamide on circulatory and metabolic variables in a canine model of acute hypoxia
Authors
Lothar A. Schwarte
Ingo Schwartges
Kai Thomas
Patrick Schober
Olaf Picker
Publication date
01-04-2011
Publisher
Springer-Verlag
Published in
Intensive Care Medicine / Issue 4/2011
Print ISSN: 0342-4642
Electronic ISSN: 1432-1238
DOI
https://doi.org/10.1007/s00134-011-2144-1

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