Pancreatic proteases and inflammatory mediators in peritoneal fluid during splanchnic arterial occlusion and reperfusion.
Pancreatic enzymes in the ischemic intestine are involved in the production of in vivo inflammatory mediators. These mediators stimulate cells in the cardiovascular system during shock and initiate multiorgan failure. An important aspect that controls the extent of the inflammation is the dispersion of these mediators from the ischemic intestine. In the past, two pathways for dispersion of these inflammatory mediators have been identified, absorption into the intestinal venous circulation and uptake into the lymphatics. We hypothesize here that the inflammatory mediators produced by pancreatic digestive enzymes in the lumen of the intestine may also be released directly into the peritoneal space. To assess the presence of inflammatory mediators in the peritoneal cavity in response to splanchnic arterial occlusion (90 min) and reperfusion (SAO shock), we measured the ability of fluid collected from this cavity to activate naive donor granulocytes. After SAO in control rats, peritoneal lavage fluid caused activation of naive donor granulocytes when tested in vitro. In contrast, when the lumen of the small intestine was flushed with a broad-acting pancreatic enzyme inhibitor (6-amidino-2-naphtyl p-guanidinobenzoate dimethanesulfate), the fluid no longer caused leukocyte activation. Reduction of the levels of inflammatory mediators in the peritoneal fluid was associated with an attenuation in the fall of blood pressure after SAO shock. These results indicate that the inflammatory mediators, which are produced by pancreatic digestive enzymes, can be absorbed directly into the systemic circulation via a transperitoneal route and play a part in the development of multiorgan failure.
Ishimaru
Kei
K
Second Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Mitsuoka
Hiroshi
H
Unno
Naoki
N
Inuzuka
Kazunori
K
Nakamura
Satoshi
S
Schmid-Schönbein
Geert W
GW
D000818:Animals; D001158:Arteries / Q000473:pathology; D001550:Benzamidines; D001794:Blood Pressure; D002319:Cardiovascular System; D010450:Endopeptidases / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D006098:Granulocytes / Q000166:cytology; D006146:Guanidines / Q000494:pharmacology; D007249:Inflammation; D007413:Intestinal Mucosa / Q000378:metabolism; D007421:Intestine, Small / Q000378:metabolism; D007511:Ischemia; D007962:Leukocytes / Q000166:cytology / Q000378:metabolism; D008213:Lymphocyte Activation; D008297:Male; D008833:Microcirculation; D009102:Multiple Organ Failure; D010179:Pancreas / Q000201:enzymology*; D010533:Peritoneal Lavage; D011480:Protease Inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015424:Reperfusion; D015427:Reperfusion Injury; D012769:Shock; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014652:Vascular Diseases / Q000473:pathology
D001550:Benzamidines; D004791:Enzyme Inhibitors; D006146:Guanidines; D011480:Protease Inhibitors; D014409:Tumor Necrosis Factor-alpha; D010450:Endopeptidases; C032855:nafamostat