Effects of adenosine on extravascular lung water content in endotoxemic pigs.
OBJECTIVE
To investigate whether adenosine protects against endotoxin-induced increments in extravascular lung water content.


METHODS
Prospective, randomized, animal study.


METHODS
University research laboratory.


METHODS
Twenty-one anesthetized juvenile pigs.


METHODS
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.


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 (P(mv) [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 P(mv). 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.
Kutzsche
S
S
Institute of Clinical Medicine and Department of Anesthesiology, University of Tromsø, Tromsø, Norway.
Lyberg
T
T
Bjertnaes
L J
LJ
D000241:Adenosine / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D000704:Analysis of Variance; D000818:Animals; D001794:Blood Pressure; D002199:Capillary Permeability; D019332:Endothelin-1 / Q000097:blood; D019446:Endotoxemia / Q000188:drug therapy*; D004927:Escherichia coli Infections / Q000188:drug therapy*; D015633:Extravascular Lung Water / Q000187:drug effects* / Q000378:metabolism; D006439:Hemodynamics; D008168:Lung / Q000098:blood supply; D008833:Microcirculation; D011659:Pulmonary Gas Exchange; D011897:Random Allocation; D012128:Respiratory Distress Syndrome / Q000188:drug therapy; D013552:Swine; D014665:Vasodilator Agents / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use
D019332:Endothelin-1; D014665:Vasodilator Agents; D000241:Adenosine