TNF but not IL-1 decreases pancreatic acinar cell survival without affecting exocrine function: a study in the perfused human pancreas.
Denham W. Yang J. Fink G. Denham D. Carter G. Bowers V. Norman J.
Department of Surgery, University of South Florida, Tampa 33612, USA.
Substantial quantities of interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) are produced within the pancreatic parenchyma during acute pancreatitis. Recent evidence suggests that IL-1 beta and TNF-alpha propagate acute pancreatitis and intensify the resulting pancreatic acinar cell death. This study examines the direct effect of IL-1 beta and TNF-alpha on pancreatic acinar cells. Human pancreata (n = 6), harvested during organ procurement, were perfused ex vivo through the splenic artery using a sterile, oxygenated colloid solution. Each pancreas was perfused with either recombinant human IL-1 beta or TNF-alpha for 2 h and subsequently with the cholecystokinin analogue caerulein (positive control). Venous effluent was collected continuously and amylase and lipase were determined at 15-min intervals. Pancreatic histology was graded at baseline and following cytokine and caerulein perfusion. To examine the long-term effects of these cytokines on acinar cell viability, additional in vitro studies utilized the AR42J acinar cell line which was exposed to either IL-1 beta or TNF-alpha with survival determined daily by MTT assay. Perfusion of the human pancreas with either IL-1 beta or TNF-alpha did not alter amylase, lipase, or histology. Caerulein did induce pancreatitis as measured by increased amylase, lipase, and pancreatic histology. Survival of pancreatic acinar cells decreased when they were incubated with TNF-alpha but not IL-1 beta. Although present in large amounts within the pancreas during acute pancreatitis, IL-1 beta and TNF-alpha have no direct effect on acinar cell viability or exocrine function acutely nor do they induce pancreatitis. When present for more than 24 h, however, TNF-alpha but not IL-1 beta has a dramatic effect on acinar cell survival.
Acute effects of bile acids on the pancreatic duct epithelium in vitro.
Alvarez C. Fasano A. Bass BL.
Surgical Service, Baltimore VAMC, Maryland 21201, USA.
BACKGROUND: Acute pancreatitis is associated with passage of gallstones, although the mechanism(s) linking the two processes remains undefined. Bile reflux into the pancreatic duct could play a role but the experimental conditions often employed to induce pancreatitis rarely develop clinically. Here we examined whether low concentrations of bile affect ductal electrophysiology as an indirect measure of ductal epithelial integrity and function in vitro. METHODS: The main duct was dissected out of freshly harvested bovine pancreata, cut into 1- x 2-cm sections, placed in tissue culture for 48-72 h, then placed in Ussing chambers. Changes in tissue resistance (Rt) and short-circuit current (Isc) were monitored. The responses to forskolin and bile (taurodeoxycholic acid, TDCA) were examined separately and together. RESULTS: Forskolin (10 microM) produced a decrease in the Isc without a significant change in Rt, suggesting a secretory response, followed by a return to baseline. TDCA caused a similarly reversible decrease in the Isc at low doses, but a persistent drop at higher concentrations. A concurrent drop in Rt was noted at all TDCA concentrations, the duration of which correlated with dosage and degree of histological damage. Prior exposure to low (0.5 mM) doses of TDCA significantly blunted the response to subsequent forskolin challenge. CONCLUSIONS: Acute exposure to TDCA in vitro causes epithelial damage at levels lower than those normally used to induce experimental pancreatitis. At the lower concentrations, Rt returns to baseline rapidly, suggesting recovery (restitution) from epithelial damage but with a persistent loss of the response to forskolin. Reflux of minute amounts of bile into the pancreatic duct could play a significant role in the pathogenesis of gallstone pancreatitis by uncoupling the normal stimulus-secretion apparatus of the ductal system and breaking down the epithelial barrier.
Immediate and long-term portal hemodynamic consequences of small-diameter H-graft portacaval shunt.
Zervos EE. Goode SE. Rosemurgy AS.
Department of Surgery, College of Medicine, University of South Florida, Tampa 33606, USA.
BACKGROUND: Effective hepatic blood flow is thought to play a critical role in outcome following portal decompressive procedures. We have shown previously that hepatic arterialization occurs soon after shunting, preserving nutrient flow, but the remote effects of shunting are unknown. The purpose of this study was to determine the effect of small-diameter prosthetic H-graft portacaval shunt (HGPCS) on effective hepatic blood flow (EHF) and portal pressures 1 year from shunt placement. METHODS: Patients undergoing 8-mm HGPCS had effective hepatic blood flow determined using low-dose galactose clearance preoperatively, postoperatively, and at 1 year postshunt. Portal blood flow, pressures, and portal vein/inferior vena cava pressure gradients were determined intraoperatively before and after shunt placement and at 1 year. RESULTS: Twenty patients undergoing shunting had flows measured. All patients had significant reductions in portal vein/inferior vena cava pressure gradients while effective hepatic flow was maintained immediately postoperatively. At 1 year following shunting, effective hepatic blood flow was significantly lower than both pre- and postoperative rates of flow while portal pressures and gradients were significantly increased. Albumin, cholesterol, and PT were improved at 1 year while total bilirubin was slightly worse. Nineteen of 20 patients are still alive with average follow-up of 26 +/- 10.3 months. Four patients were encephalopathic preop, 5 postop, and none chronically. CONCLUSIONS: Recollateralization of varices and progression of cirrhosis may account for the observed reductions in EHF at 1 year. Regardless of the cause, diminution of EHF at 1 year is well compensated as demonstrated by minimal encephalopathy and ascites, improved hepatic function reflected in blood chemistry profiles, and good survival.
Is tissue oxygen tension during esophagectomy a predictor of esophagogastric anastomotic healing?
Jacobi CA. Zieren HU. Zieren J. Muller JM.
Department of Surgery, University Hospital Charite, Humboldt University Berlin, Germany.
PURPOSE: The genesis of anastomotic leakage and late stenosis of esophagogastrostomy is still unknown, although minimal blood flow and tissue hypoxia of the gastric tube are discussed as main reasons. However, the changes in tissue oxygen tension (PtO2) on esophagogastric anastomoses have not yet been evaluated in the perioperative course. METHODS: Submucosal tissue oxygen tension (PtO2) was measured in 33 patients with cervical esophagogastrostomy during resection of esophageal carcinoma and reconstruction by a gastric tube. Measurements were taken close to the projected resection line and latter anastomosis using a Clark-type oxygen electrode. RESULTS: Mean baseline PtO2 was 55.1 +/- 10.4 mmHg. Following the ligature of the vasa gastricae brevis and the left gastroepiploic artery (46.1 +/- 9.7 mmHg), the left gastric artery (34.8 +/- 9.8 mmHg), and the pull up of the gastric tube, PtO2 decreased to 25.8 +/- 9.4 mmHg. Anastomotic leakage occurred in 6 patients and late stenosis in 10 patients. During the operation there was no significant evidence of decreased PtO2 levels in these two groups. Postoperative PtO2 levels showed a significant increase in patients with anastomotic leakage. CONCLUSION: A disorder in oxygen consumption may cause a significant increase of PtO2 in anastomotic tissue, which is associated with anastomotic leakage.