Oxygen persufflation of the human pancreas increases ATP levels and improves viable islet yields compared with the two-layer method

W.E. Scott III¹, M.D. Rizzari¹, S.A. Stein¹, E.S. Avgoustiniatos¹, T.M. Suszynski¹, B.P. Weegman¹, L.A. Tempelman², B.E. Hammer³, K.K. Papas^1
1 University of Minnesota, Department of Surgery, Minneapolis, MN, USA; ² Giner, Inc., Newton, MA, USA; ³ University of Minnesota, Department of Radiology, Minneapolis, MN, USA

Objective: Many human pancreata arrive at isolation centers after 8-12 hr cold-ischemia time (CIT), resulting in reduced islet yields. We have shown in a porcine model that persufflation (PSF) is a promising alternative to current methods of preservation due to its ability to oxygenate tissue throughout preservation. The objective of this study was to investigate whether PSF can extend human pancreas preservation to 24 hr while maintaining islet yield and quality.

Methods: Human pancreata underwent PSF or were divided into paired segments during procurement and preserved by the two-layer method (TLM) or PSF. PSF was performed by providing 20 cc/min of 40%-humidified oxygen gas via the vasculature utilizing an electrochemical oxygen concentrator (Giner, Inc.). Using a 1.5T magnet, MRI was performed to determine PSF homogeneity and³¹P-NMR spectroscopy was performed to measure ATP-to-inorganic phosphate ratio (ATP:Pi), an indicator of organ viability during PSF, from 8-24 hr CIT. Following 8-12 hr TLM or 24 hr PSF, islets were isolated from paired segments and cultured for further assessment.

Results: All tested pancreata demonstrated homogeneous PSF visualized by negative contrast on MRI due to the presence of gas in the vasculature. In 7 pancreata exposed to continuous PSF, ATP:Pi levels measured from 8-24 hr CIT were maintained at 79±9% of the initial measurement. When PSF was stopped from 8-12 hr CIT, ATP fell to undetectable levels. Upon restoration of PSF, 44% of previous ATP:Pi was recovered. Initial paired islet isolation outcomes following 8-12 hr TLM or 24 hr PSF demonstrated higher viable islet yields and favorable morphology from PSF segments.

Conclusion: PSF is capable of maintaining ATP levels in human pancreata with modest decay over 24 hr CIT. Isolation results show that PSF may improve viable islet yields and extend the effective duration of preservation, supporting our previous findings in a porcine model.

Disclosure: A patent application has been filed on the use of an electrochemical oxygen concentrator for organ persufflation (WES, MDR, TMS, LAT, KKP).