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Effects of adenosine on extravascular lung water content in endotoxemic pigs

Kutzsche, Stefan MD; Lyberg, Torstein MD, PhD; Bjertnaes, Lars J. MD, PhD

LABORATORY INVESTIGATIONS
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Objective  To investigate whether adenosine protects against endotoxin-induced increments in extravascular lung water content.

Design  Prospective, randomized, animal study.

Setting  University research laboratory.

Subjects  Twenty-one anesthetized juvenile pigs.

Interventions  The animals were divided into two groups subjected to endotoxin infusion: Endotoxin alone (n = 7), or endotoxin combined with adenosine infusion (n = 7) administered during the whole experimental period. Two other groups were exposed to anesthesia alone (n = 4) or adenosine infusion alone (n = 3), respectively.

Measurements and Main Results  Central hemodynamic variables and extravascular lung water, as assessed by the thermal dye dilution double indicator technique, were monitored. Plasma endothelin-1 concentrations were measured hourly. Extravascular lung water increased significantly in response to endotoxemia (p < .001) along with an increase in pulmonary microvascular pressure (Pmv [p < .01]). Although the Pmv increased less in endotoxemic animals exposed to adenosine infusion, no intergroup difference was found. From 4 through 6 hrs, adenosine-treated pigs displayed only half of the extravascular lung water content of nontreated animals (p < .01). The latter did not differ from that of anesthetized controls receiving anesthesia or adenosine alone. Adenosine administered alone had no effect on Pmv. In pigs receiving adenosine alone, extravascular lung water content reached nadir after 3 hrs. In both endotoxin groups, plasma endothelin-1 concentration increased two-fold, peaking 4–6 hrs after the start of endotoxin infusion (p < .001).

Conclusions  The endotoxin-induced increase in lung extravascular water was hampered by intravenously infused adenosine in the presence of a nonsignificantly reduced microvascular pressure. This leaves reduced microvascular permeability the most likely reason for the beneficial effect of adenosine.

From the Institute of Clinical Medicine and Department of Anesthesiology, University of Tromsø, Tromsø, Norway (SK, LJB); and the Research Forum (TL) and Department of Anesthesiology (SK), Ulleval University Hospital, Oslo, Norway.

Supported, in part, by the Laerdal Foundation for Acute Medicine.

Address requests for reprints to: Stefan Kutzsche, MD, Department of Anesthesiology, Ulleval University Hospital, N-O407 Oslo, Norway.

The present study on anesthetized pigs demonstrates that systemically infused adenosine was associated with a reduction of enhanced extravascular lung water after endotoxin challenge.

© 2001 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins