The effects of aminophylline and pentoxifylline on multiple organ damage after Escherichia coli sepsis.
We studied the effects of the methylxanthines, aminophylline (AMPH) and pentoxifylline (PTXF), on multiple organ damage following Escherichia coli sepsis in guinea pigs. To assess multiple organ damage, 125I-labeled albumin accumulation was measured in bronchoalveolar lavage (BAL) fluid, lung, kidneys, liver, heart, adrenal glands, and spleen and expressed as a ratio of BAL fluid or tissue to 125I-labeled albumin plasma (albumin index: Al). Wet-to-dry lung weight (W/D) ratios were also measured. The methylxanthines were administered by a bolus injection followed by a continuous infusion. The seven experimental groups included: saline-control, AMPH-control, PTXF-control, E. coli septic-control, E. coli septic-AMPH high dose, E coli septic-AMPH low dose, and E. coli septic-PTXF. The AI of the BAL fluid and all examined organs significantly increased in the septic-control group compared to those in the saline-, AMPH-, and PTXF-control groups, In all septic-methylxanthine groups, the AI of the BAL fluid and all organs, except for the spleen, were significantly lower than those of the septic-control group. Compared to the saline-, AMPH-, and PTXF-control groups, the septic-control group revealed a significant increase in lung W/D ratios, whereas the septic-AMPH high and low dose groups and the septic-PTXF group did not. Of importance, the septic-PTXF group did not cause a significant decrease in mean arterial pressure (MAP) as compared to the control groups, whereas the septic-AMPH groups did cause a significant decrease in MAP compared to the septic-control group. Therefore, the data from this experiment demonstrate that both AMPH and PTXF attenuate the multiple organ albumin leak seen in septic guinea pigs. However, PTXF exerted this protective effect with no discernible effect on the MAP whereas the MAP of AMPH-treated guinea pigs was significantly decreased.
Harada
H
H
Department of Medicine, Stanford University Medical Center, CA 94305-5204.
Ishizaka
A
A
Yonemaru
M
M
Mallick
A A
AA
Hatherill
J R
JR
Zheng
H
H
Lilly
C M
CM
O'Hanley
P T
PT
Raffin
T A
TA
D000418:Albumins / Q000032:analysis; D000628:Aminophylline / Q000627:therapeutic use*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001992:Bronchoalveolar Lavage Fluid / Q000032:analysis; D004487:Edema / Q000473:pathology; D004927:Escherichia coli Infections / Q000097:blood / Q000378:metabolism; D006168:Guinea Pigs; D007958:Leukocyte Count; D009102:Multiple Organ Failure / Q000188:drug therapy* / Q000378:metabolism; D009929:Organ Size; D010431:Pentoxifylline / Q000627:therapeutic use*; D013047:Specific Pathogen-Free Organisms; D013805:Theobromine / Q000031:analogs & derivatives*; D014018:Tissue Distribution
D000418:Albumins; D000628:Aminophylline; D013805:Theobromine; D010431:Pentoxifylline