Improvement in early symptoms of shock by delayed intestinal protease inhibition.
OBJECTIVE
Recent findings indicate that intraintestinal pancreatic protease inhibition before superior mesentery artery occlusion (SMAO) attenuates inflammation and symptoms of shock. Herein we examine the effectiveness of delayed intestinal protease inhibition during reperfusion after SMAO.


METHODS
Three groups of male Wistar rats were studied: a nonshock sham group and 2 groups exposed to SMAO for 100 minutes and treated by delayed intestinal lavage starting 40 minutes after reperfusion with buffer (delayed-lavage group) or with the digestive protease inhibitor gabexate mesilate (FOY) (delayed FOY-lavage group).


RESULTS
Arterial pressure during reperfusion was significantly lower in the delayed-lavage animals compared with the sham group. Superior mesentery artery occlusion and reperfusion caused the formation of leukocyte activation factors in intestinal homogenates and in plasma, as well as intestinal injury. The delayed-lavage group had a significant increase in activated leukocytes in venules of cremaster muscle. In contrast, in the delayed FOY-lavage group, lavage 40 minutes after reperfusion led to a significant improvement of blood pressure and decreased formation of intestine-derived leukocyte activation factors and intestinal injury compared with the delayed-lavage group. In addition, the delayed FOY-lavage group exhibited fewer rolling leukocytes in venules and reduced apoptosis in the cremaster muscle microcirculation. Intestinal ischemia-induced endotoxemia was attenuated in the delayed FOY-lavage animals.


CONCLUSIONS
Delayed intestinal protease inhibition may improve experimental SMAO-induced shock by reducing intestinal injury, decreasing the level of cell activation in plasma and in the microcirculation, and restoring the blood pressure.
Fitzal
Florian
F
Microcirculation Laboratory, Department of Bioengineering, Whitaker Institute of Biomedical Engineering, University of California, San Diego, La Jolla, USA. florian.fitzal@akh-wien.ac.at
DeLano
Frank A
FA
Young
Corey
C
Schmid-Schönbein
Geert W
GW
D000009:Abdominal Muscles / Q000098:blood supply / Q000473:pathology; D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis; D001794:Blood Pressure; D010450:Endopeptidases / Q000378:metabolism*; D007249:Inflammation / Q000517:prevention & control*; D018836:Inflammation Mediators / Q000494:pharmacology*; D007422:Intestines / Q000098:blood supply; D007511:Ischemia / Q000150:complications / Q000378:metabolism; D008297:Male; D010179:Pancreas / Q000201:enzymology*; D011480:Protease Inhibitors / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012769:Shock / Q000503:physiopathology*; D018709:Statistics, Nonparametric
D018836:Inflammation Mediators; D011480:Protease Inhibitors; D010450:Endopeptidases