Pentoxifylline attenuates pulmonary macromolecular leakage after intestinal ischemia-reperfusion
M. B. Carter, M. A. Wilson, W. B. Wead and R. N. Garrison
Department of Surgery, School of Medicine, University of Louisville, Ky, USA.
OBJECTIVE: To assess the effects of pentoxifylline posttreatment on
hemodynamic variables and acute pulmonary injury in the rat intestinal
ischemia-reperfusion (I-R) model, using a recently developed method of
fluorescent intravital pulmonary videomicroscopy. DESIGN: Anesthetized male
Sprague-Dawley rats were cannulated for measurement of mean arterial
pressure, heart rate, cardiac output, arterial blood gas values, and
hematocrit. Rats underwent isolation of the superior mesenteric artery for
intestinal I-R (45 minutes of ischemia, 120 minutes of reperfusion) and
right lateral thoracotomy for pulmonary videomicroscopy. Epi-illumination
fluorescent videomicroscopy was used to quantitate leakage of intravascular
fluorescently labeled albumin into alveoli, while hemodynamic variables
were simultaneously recorded. In the treatment groups, pentoxifylline was
administered after 30 minutes of intestinal ischemia. Data (mean +/- SEM)
were recorded before and during intestinal ischemia and after reperfusion
at 30-minute intervals. MAIN OUTCOME MEASURE: The appearance of
fluorescently labeled albumin into alveolar airspaces was quantitated
off-line by computer and reported as the alveolar leak index. RESULTS:
Intestinal I-R caused alveolar macromolecular leakage, marked by a 300% +/-
48% increase from baseline (P < .05) in the alveolar leak index.
Intestinal I-R also produced systemic hemodynamic instability demonstrated
by a decrease in the mean arterial blood pressure (-36% +/- 5% vs baseline,
P < .05) and cardiac output (-42% +/- 6% vs baseline, P < .05),
metabolic acidosis (final arterial pH of 7.17, P < .05 vs initial pH),
and a 2.3-fold increase in the intravenous fluid requirement when compared
with that in sham animals (P < .05). Treatment with pentoxifylline 30
minutes after intestinal ischemia attenuated pulmonary macromolecular
leakage (P < .05 vs nontreated I-R) and reduced the decrease in cardiac
output (-15% +/- 7% vs baseline, not statistically significant).
Pentoxifylline treatment had no effect on the mean arterial blood pressure,
heart rate, metabolic acidosis, or intravenous fluid requirement.
CONCLUSIONS: Pentoxifylline reduces alveolar capillary membrane injury and
subsequent protein leakage and improves cardiac output when administered
after 30 minutes of intestinal ischemia. These data suggest that
pentoxifylline may be a possible candidate as a future therapy for acute
pulmonary dysfunction. Further studies in human patients are necessary.
