Increased nitric oxide excretion in patients with severe acute pancreatitis: evidence of an endotoxin mediated inflammatory response?
OBJECTIVE
Nitric oxide represents a potential key mediator of the local and systemic manifestations of acute pancreatitis (AP) in experimental models but its role in human disease is uncertain. We therefore sought to assess if systemic nitric oxide (NO) production is elevated in severe AP and determine whether this is a reflection of biochemical severity or endotoxin exposure.


METHODS
Patients were recruited within 72 hours of pain onset. NO derived nitrite excretion determined from a 24 hour sterile urine collection was correlated with intestinal macromolecular permeability (polyethylene glycol excretion ratio), markers of systemic endotoxin exposure (IgG:IgM endotoxin core antibody (EndoCAb) ratio), disease severity, and the magnitude of systemic inflammation (peak C reactive protein (CRP) and Acute Physiology and Chronic Health Evaluation score II (APACHE-II)).


RESULTS
In patients with a severe attack (n=20), nitrite excretion was increased significantly compared with patients with a mild attack (n=45, 20.6 micro g v 15.65 micro g; p<0.00) and the latter with healthy controls (n=20, p=0.004). Nitrite excretion correlated strongly with both intestinal permeability (r=0.7, p=0.006) and EndoCAb ratio (r=0.7, p<0.01) but not with CRP or APACHE-II scores (p>0.1).


CONCLUSIONS
Total urinary nitrite excretion is increased in patients with severe AP, and may not be simply a reflection of systemic inflammation, but potentially a consequence of endotoxin mediated upregulation of inducible NO synthase activity.
Rahman
S H
SH
Academic Unit of Surgery, the General Infirmary, Leeds, UK. zak-rahman@lineone.net
Ammori
B J
BJ
Larvin
M
M
McMahon
M J
MJ
D000208:Acute Disease; D000328:Adult; D000368:Aged; D018988:Bacterial Translocation / Q000502:physiology; D015415:Biomarkers / Q000652:urine; D002097:C-Reactive Protein / Q000032:analysis; D004731:Endotoxins / Q000378:metabolism; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis; D007075:Immunoglobulin M / Q000032:analysis; D007136:Immunoglobulins / Q000032:analysis; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009336:Necrosis; D009569:Nitric Oxide / Q000652:urine*; D009573:Nitrites / Q000652:urine*; D010195:Pancreatitis / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology
D015415:Biomarkers; D004731:Endotoxins; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007136:Immunoglobulins; D009573:Nitrites; C042866:antilipopolysaccharide antibodies; D009569:Nitric Oxide; D002097:C-Reactive Protein