Multimodal Transgastric Local Pancreatic Hypothermia Reduces Severity of Acute Pancreatitis in Rats and Increases Survival

Cristiane de Oliveira, Biswajit Khatua, Arup Bag, Bara El-Kurdi, Krutika Patel, Vivek Mishra, Sarah Navina, Vijay Prem Singh

Research output: Contribution to journalArticle

Abstract

Background & Aims: Acute pancreatitis (AP) of different etiologies is associated with the activation of different signaling pathways in pancreatic cells, posing challenges to the development of targeted therapies. We investigated whether local pancreatic hypothermia, without systemic hypothermia, could lessen the severity of AP induced by different methods in rats. Methods: A urethane balloon with 2 polyurethane tubes was placed inside the stomach of rats. AP was induced in Wistar rats by the administration of cerulein or glyceryl tri-linoleate (GTL). Then, cold water was infused into the balloon to cool the pancreas. Pancreatic temperatures were selected based on those found to decrease acinar cell injury. An un-perfused balloon was used as a control. Pancreatic and rectal temperatures were monitored, and an infrared lamp or heating pad was used to avoid generalized hypothermia. We collected blood, pancreas, kidney, and lung tissues and analyzed them by histology, immunofluorescence, immunoblot, cytokine and chemokine magnetic bead, and DNA damage assays. The effect of hypothermia on signaling pathways initiated by cerulein and GTL was studied in acinar cells. Results: Rats with pancreatic cooling developed less severe GTL-induced AP compared with rats that received the control balloon. In acinar cells, cooling decreased the lipolysis induced by GTL, increased the micellar form of its fatty acid, lowered the increase in cytosolic calcium, prevented the loss of mitochondrial membrane potential (by 70%–80%), and resulted in a 40%–50% decrease in the uptake of a fatty acid tracer. In rats with AP, cooling decreased pancreatic necrosis by 48%, decreased serum levels of cytokines and markers of cell damage, and decreased markers of lung and renal damage. Pancreatic cooling increased the proportions of rats surviving 6 hours after induction of AP (to 90%, from <10% of rats that received the control balloon). In rats with cerulein-induced AP, pancreatic cooling decreased pancreatic markers of apoptosis and inflammation. Conclusions: In rats with AP, transgastric local pancreatic hypothermia decreases pancreatic necrosis, apoptosis, inflammation, and markers of pancreatitis severity and increases survival.

Original languageEnglish (US)
Pages (from-to)735-747.e10
JournalGastroenterology
Volume156
Issue number3
DOIs
StatePublished - Feb 1 2019

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Hypothermia
Pancreatitis
Linoleic Acid
Ceruletide
Acinar Cells
Pancreas
Necrosis
Fatty Acids
Apoptosis
Cytokines
Inflammation
Kidney
Lung
Temperature
Polyurethanes
Mitochondrial Membrane Potential
Lipolysis
Urethane
Chemokines
Heating

Keywords

  • Animal Model
  • Death-Associated Molecular Pattern
  • Exocrine Pancreas
  • Glucose

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

Cite this

Multimodal Transgastric Local Pancreatic Hypothermia Reduces Severity of Acute Pancreatitis in Rats and Increases Survival. / de Oliveira, Cristiane; Khatua, Biswajit; Bag, Arup; El-Kurdi, Bara; Patel, Krutika; Mishra, Vivek; Navina, Sarah; Singh, Vijay Prem.

In: Gastroenterology, Vol. 156, No. 3, 01.02.2019, p. 735-747.e10.

Research output: Contribution to journalArticle

de Oliveira, Cristiane ; Khatua, Biswajit ; Bag, Arup ; El-Kurdi, Bara ; Patel, Krutika ; Mishra, Vivek ; Navina, Sarah ; Singh, Vijay Prem. / Multimodal Transgastric Local Pancreatic Hypothermia Reduces Severity of Acute Pancreatitis in Rats and Increases Survival. In: Gastroenterology. 2019 ; Vol. 156, No. 3. pp. 735-747.e10.
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AU - El-Kurdi, Bara

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AU - Navina, Sarah

AU - Singh, Vijay Prem

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