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Depletion of serum L-arginine in patients with acute pancreatitis
Linköping University, Department of Biomedicine and Surgery, Surgery. Linköping University, Faculty of Health Sciences.
Department of Surgery, Vrinnevi Hospital, Norrköping, Sweden.
Linköping University, Department of Molecular and Clinical Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
Department of Surgery, Vrinnevi Hospital, Norrköping, Sweden.
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2003 (English)In: Pancreas, ISSN 0885-3177, E-ISSN 1536-4828, Vol. 27, no 3, 261-266 p.Article in journal (Refereed) Published
Abstract [en]

Introduction: Acute pancreatitis may be initiated by interference with the pancreatic outflow to the duodenum. This flow is normally regulated by reflex relaxation of the sphincter of Oddi in which nitric oxide is an important mediator.

Aim: To test the hypothesis that acute pancreatitis involves a depletion in serum l-arginine resulting in impaired production of nitric oxide.

Methods: We measured serum l-arginine and l-citrulline and urinary nitrite/nitrate concentrations 1 to 3 days after the onset of symptoms in 11 patients with gallstone pancreatitis, 10 patients with alcoholic pancreatitis, and 6 patients with idiopathic pancreatitis. We compared their results with those from control groups of 13 healthy blood donors, 9 patients fasting before hernia operations, 8 patients with acute cholecystitis, and 9 alcoholic subjects but no pancreatitis. Serum arginine and citrulline concentrations were measured with high performance liquid chromatography, and urinary nitrite/nitrate spectrophotometrically.

Results: Patients with acute pancreatitis, of whatever cause, had lower serum l-arginine and l-citrulline concentrations than controls. Patients with gallstone and idiopathic pancreatitis also have reduced urinary concentrations of nitrite and nitrate but this was not seen in patients with alcoholic pancreatitis.

Conclusions: L-arginine and l-citrulline concentrations are depleted in the serum of patients with acute pancreatitis. Reduced urinary nitrite and nitrate in gallstone pancreatitis indicate that there is a defect formation of nitric oxide. This may cause a functional obstruction of the outflow of pancreatic juice to the duodenum and so may be involved in the pathophysiology of acute pancreatitis.

Place, publisher, year, edition, pages
2003. Vol. 27, no 3, 261-266 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-25345DOI: 10.1097/00006676-200310000-00012Local ID: 9787OAI: oai:DiVA.org:liu-25345DiVA: diva2:245674
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2012-10-26Bibliographically approved
In thesis
1. Nitric oxide, arginine and acute pancreatitis
Open this publication in new window or tab >>Nitric oxide, arginine and acute pancreatitis
2004 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Acute pancreatitis is a serious inflammatory condition which is managed symptomatically as there is no causal treatment to offer. The main background causes are alcohol abuse and gallstone disease. The inducing factors lead to a premature activation of pancreatic enzymes in the acinar cells and their subsequent release into the pancreatic tissue. This activates the inflammatory cascade leading to reduced pancreatic vascular perfusion, cellular necrosis and in some cases systemic disease. Nitric oxide (NO) and the by-product citrulline are synthesised from the amino acid L-arginine by NO-synthases (NOS), which exist in three isoforms. Two are constitutive, being necessary for relaxation of vascular myogenic cells (eN OS) or for the relaxation of the sphincter of Oddi, (nNOS). The third, iNOS, is activated mainly during inflammation, producing high concentrations of NO, which may be harmful.

We demonstrate that patients with acute pancreatitis, whatever the cause, have reduced sermn levels of arginine and citrulline, indicating a disturbed NO metabolism with possible negative effects on the outflow of pancreatic juice and on pancreatic blood perfusion. One possible reason for the reduced sermn levels could be an early high NO production via the iNOS route consuming L-arginine. Inhibition of iNOS may improve this imbalance and reduce the inflammation.

In experimental studies, low doses of selective iNOS inhibition do not interfere with blood pressure, pancreatic vascular perfusion or the sphincter of Oddi in vivo. However, in high doses both in vivo and in vitro, the inhibitor stimulates the sphincter muscle by interfering with nNOS, indicating that high doses are harmful.

The iNOS inhibitor was used in an experimental study of acute pancreatitis, and we showed that treatment with selective iNOS inhibition, two hours after induction, reduced inflammation in the pancreatic tissue and the need for fluid, stabilised blood pressure and improved the amino acid balance.

High doses of L-arginine cause necrotising acute pancreatitis in rats within 48 hours. Sermn arginine and citrulline increased at 8 hours, but fell below control levels, at 24 hours. An early increase in pancreatic ATP dropped to control level at 24 hours. The ATP production correlated with histological swelling of mitochondria, seen as vacuole formation, followed by an increased apoptotic activity. Cell proliferation decreased. Full amino acid analysis at 24 hours showed reduction in 14 out of 22 amino acids, including the glutamate family. The process with apoptosis and the reduction of ATP, cell proliferation and amino acids precedes the development of inflammation and necrosis.

Place, publisher, year, edition, pages
Linköping: Linköpings universitet, 2004. 75 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 866
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-24031 (URN)3587 (Local ID)91-7373-842-5 (ISBN)3587 (Archive number)3587 (OAI)
Public defence
2004-11-18, Elsa Brändströmsalen, Hälsouniversitetet, Linköpings, 09:00 (Swedish)
Opponent
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2012-10-26Bibliographically approved

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Sandström, PerSundqvist, TommySvanvik, Joar

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