Abstract:
:Tumor necrosis factor-alpha (TNF alpha) has been implicated as one of the numerous likely mediators of the systemic complications of acute pancreatitis. Recent suggestions that calcium (Ca2+) acts as a signal not only for TNF alpha release but also for TNF alpha action at distant sites led us to hypothesize that the calcium channel blocker diltiazem could inhibit TNF alpha release in acute pancreatitis, ameliorating the severity of the disease and improving overall survival. A rat model of acute pancreatitis induced by retrograde ductal infusion of bile was used for two experiments (n = 120). Experiment 1 was designed to determine the effects of calcium channel blockade using diltiazem on the severity of pancreatitis as measured by changes in biochemistry, pathology, and serum TNF alpha levels. In experiment 2, effects of calcium channel blockade on animal survival were measured over 72 h. Calcium channel blockade was associated with a significant reduction in serum TNF alpha levels as well as amelioration of pancreatitis by biochemical and pathological criteria. Overall survival from bile-induced pancreatitis was dramatically improved in rats pretreated with diltiazem (80%) compared to untreated animals (40%). Our data suggest that calcium channel blockade is associated with TNF alpha inhibition and improved outcome in a rat model of acute pancreatitis.
journal_name
Pancreasjournal_title
Pancreasauthors
Hughes CB,el-Din AB,Kotb M,Gaber LW,Gaber AOdoi
10.1097/00006676-199607000-00003subject
Has Abstractpub_date
1996-07-01 00:00:00pages
22-8issue
1eissn
0885-3177issn
1536-4828journal_volume
13pub_type
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