Background The intestinal mucosa is the portion of the gut most susceptible
to impaired perfusion and oxygen delivery. The phosphodiesterase (PDE) inh
ibitor amrinone has been proposed to improve oxygen delivery and tissue per
fusion during sepsis. The objective of this study was to investigate the ef
fects of amrinone on arterial oxygenation (PaO2) and tissue oxygenation (Pt
iO(2)) of jejunal mucosa during endotoxemia.
Materials and methods. Forty anesthetized and ventilated rats were laparoto
mized and a jejunal portion was exteriorized and fixed on a plexiglass stag
e. The jejunum was punctured and a Clark-type microcatheter PO2 probe and a
microthermocouple were placed on the mucosa to measure PtiO(2). The animal
s were randomly assigned to receive one of the four treatments: infusion of
Escherichia coli lipopolysaccharides (LPS, 2 mg/kg/h) without amrinone pre
treatment (LPS group); infusion of LPS with amrinone pretreatment (40 mu g/
kg/min, start 30 min before LPS infusion, amrinone + LPS group); no treatme
nt with either amrinone or LPS (control group); treatment with amrinone wit
hout LPS infusion (amrinone group). Mean arterial pressure (MAP), heart rat
e (HR), PaO2, and PtiO(2) were measured 30 min before and 0, 60, and 120 mi
n after induction of endotoxemia.
Results. MAP remained stable in the control and LPS groups. In the amrinone
+ LPS group MAP decreased within the first 30 min of amrinone infusion and
decreased further during endotoxemia. PaO2 remained stable in the control
group and decreased in the LPS group. This endotoxin-induced decrease in Pa
O2 was attenuated in the amrinone + LPS group. The mucosal PtiO(2) decrease
d in the LPS group but remained stable in both the control and amrinone + L
PS groups.
Conclusions. Pretreatment with amrinone was able to diminish a decrease in
PaO2 during endotoxemia, indicating that pulmonary dysfunction was attenuat
ed. Endotoxin-induced tissue hypoxia of the intestinal mucosa, however, cou
ld be fully prevented, indicating that an additional improvement in comprom
ised tissue perfusion had occurred, (C) 2000 Academic Press.