Is pH of the contrast solution a determinant of post-ERCP panceatitis?

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Gut. Published Online First: 14 July 2008. doi:10.1136/gut.2008.148551

A pH-sensitive, neurogenic pathway mediates disease severity in a

model of post-ERCP pancreatitis.

Marc D Noble, le Romac, R Vigna and Rodger A Liddle *

Duke University Medical Center, United States

* To whom correspondence should be addressed. E-mail:

liddl001@....

Accepted 12 May 2008

Abstract

Background: Endoscopic retrograde cholangiopancreatography (ERCP) has

a high risk of pancreatitis although the underlying mechanisms are

unclear. Transient receptor potential vanilloid 1 (TRPV1) is a cation

channel expressed on C and A fibers of primary sensory neurons and is

activated by low pH. TRPV1 activation causes release of inflammatory

mediators that produce edema and neutrophil infiltration. We

previously demonstrated that neurogenic factors contribute to the

pathogenesis of pancreatitis. Resiniferatoxin (RTX) is a TRPV1

agonist that, in high doses, destroys C and A fibers. When we

discovered that the pH of radio-opaque contrast solutions used for

ERCP was 6.9, we hypothesized that low pH may contribute to the

development of contrast-induced pancreatitis via activation of TRPV1.

Methods: Rats underwent equal pressure pancreatic ductal injection of

contrast solutions at varying pH with or without RTX.

Results: Contrast solution (pH 6.9) injected into the pancreatic duct

caused a significant increase in pancreatic edema, serum amylase,

neutrophil infiltration, and histological damage. Solutions of pH 7.3

injected at equal pressure caused little damage. Pancreatitis

severity was significantly increased by injection of solutions at pH

6.0. To determine if the effects of low pH were mediated by TRPV1,

RTX was added to the contrast solutions. At pH levels of 6.0 and 6.9,

RTX significantly reduced pancreatitis severity.

Conclusions: Low pH contrast solutions contribute to the development

of pancreatitis through a TRPV1-dependent mechanism. It is possible

that increasing the pH of contrast solution and/or adding an agent

that inhibits primary sensory nerve activation may reduce the risk of

post-ERCP pancreatitis.

Dave

(father of (23); PSC 07/03; UC 08/03)