Induction of Anaerobic Glucose Metabolism During the Development of Acute Pancreatitis

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Abstract

Objective

Studies were performed with the ex vivo perfused canine pancreas preparation to characterize acinar cell metabolism during the development of acute pancreatitis.

Summary Background Data

Acute pancreatitis can be initiated in the ex vivo perfused canine pancreas preparation by five different stimuli as follows: (1) the infusion of oleic acid (FFA), (2) partial obstruction of the pancreatic duct and secretin stimulation (POSS), (3) a 2-hour ischemic period before perfusion (ISCH 2), (4) a 1 -hour ischemto period followed by acetaldehyde infusion (ISCH1 + AA), and (5) supramaximal stimulation by cerulein (CER-HIGH). In each model, weight gain, edema formation, and hyperamylasemia occur, signifying the development of pancreatitis. Previously, the authors demonstrated that intracellular adenosine triphosphate (ATP) levels decline during the development of pancreatitis in the FFA model but not in the other four models.

Methods

The ex vivo perfused canine pancreas preparation was used to study five different stimuli that result in the initiation of acute pancreatitis, as manifested by weight gain, edema formation, and hyperamylasemia during a 4-hour perfusion period. Glucose metabolism (using 13C-labeled glucose) and intracellular pH and ATP levels were monitored by magnetic resonance spectroscopy. Oxygen consumption and pancreatic secretion were measured directly.

Results

In control preparations, a glucose signal appeared in the 13C-labeled spectra within 15 minutes, and a signal from glycogen appeared at the end of the 4-hour perfusion. In the preparations with an ischemic period (ISCH 2 and ISCH 1 + AA), a lactate signal appeared during the ischemia, disappeared during the early perfusion, and appeared again later during the perfusion as the physiologic injury response of pancreatitis developed. Similarly, in the POSS and CER-HIGH pancreatitis preparations, lactate accumulated in the pancreas during the perfusion period. In these four preparations, the intracellular pH did not differ significantly during the perfusion from that of the control preparations. Oxygen consumption was unchanged during the perfusion in the ISCH 2 and ISCH 1 + AA preparations and increased in the POSS and CER-HIGH preparations. In the FFA pancreatitis preparations, only a trace of glycogen was observed, and the metabolites of glucose were not detected. Intracellular pH and oxygen consumption both dropped significantly during the perfusion.

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