Ductal injection does not increase the islet yield or function after cold storage in a vascular perfusion model

PLoS One. 2012;7(8):e42319. doi: 10.1371/journal.pone.0042319. Epub 2012 Aug 10.

Abstract

Several studies have reported that pancreatic ductal preservation greatly improved the islet yield and function after cold storage. However, these studies were devoid of appropriate controls, such as vascular perfusion, which is routinely performed to preserve organs in the clinical setting. In this study, we created a vascular perfusion model using inbred rats, and investigated the effect of ductal injection on the islet yield and function after cold storage. Rat pancreases after 10 h cold ischemia were classified as follows: without ductal/vascular perfusion; with ductal injection; with vascular perfusion; and with ductal/vascular perfusion. The islet yield, function, viability, release of inflammatory mediators, and pathological changes in the exocrine tissues were assessed in the Hanks' Balanced Salt Solution (HBSS) model. The islet yield was also assesed by introducing University of Wisconsin Solution (UWS) and Histidine-Tryptophan-Ketoglutarate solution (HTK), which are the standard clinical preservation solutions. In the HBSS model, ductal injection and vascular perfusion significantly improved the islet yield compared with the control group. However, ductal injection showed no additional effects on the islet yield, function, viability and suppressing the release of inflammatory mediators when vascular perfusion was performed. Although ductal injection significantly decreased the apoptosis of exocrine cells, no beneficial effect on vacuolation was observed. In contrast, vascular perfusion significantly suppressed vacuolation in the exocrine tissues. Likewise, in the UWS and HTK model, ductal injection and vascular perfusion improved the islet yield compared with the control group. Nevertheless, the combination group showed no additional effects. These data suggest that ductal injection has no additional effect on islet yield and function after cold storage in a vascular perfusion model. We propose that ductal injection can be an effective and simple alternative for vascular perfusion prior to pancreas harvest, but is not necessary in most cases, since vascular perfusion is routinely performed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / administration & dosage
  • Allopurinol / administration & dosage
  • Animals
  • Cell Survival
  • Cold Ischemia
  • Glucose / administration & dosage
  • Glutathione / administration & dosage
  • Inflammation Mediators / metabolism
  • Injections
  • Insulin / administration & dosage
  • Islets of Langerhans / cytology*
  • Islets of Langerhans / metabolism
  • Islets of Langerhans / pathology
  • Male
  • Mannitol / administration & dosage
  • Organ Preservation / methods*
  • Organ Preservation Solutions / administration & dosage
  • Pancreas / blood supply*
  • Pancreas / metabolism
  • Pancreas / pathology
  • Pancreas, Exocrine / metabolism
  • Pancreas, Exocrine / pathology
  • Pancreatic Ducts*
  • Perfusion / methods*
  • Potassium Chloride / administration & dosage
  • Procaine / administration & dosage
  • Raffinose / administration & dosage
  • Rats
  • Rats, Inbred Lew
  • Stress, Physiological

Substances

  • Bretschneider cardioplegic solution
  • Inflammation Mediators
  • Insulin
  • Organ Preservation Solutions
  • University of Wisconsin-lactobionate solution
  • Mannitol
  • Procaine
  • Allopurinol
  • Potassium Chloride
  • Glutathione
  • Glucose
  • Adenosine
  • Raffinose

Grants and funding

This study was supported by grants from Innovation Plaza Miyagi of Japan Science and Technology Agency (JST), the Japanese Grant-in-Aid for Scientific Research (B), the Mochida Memorial Foundation for Medical and Pharmaceutical Research and the Takeda Science Foundation. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.