Defining the Role of a Tailored Luminal Solution for Small Bowel Preservation

Abstract

The mucosal layer is the initial site of small bowel (SB) graft injury sustained during cold storage. Vascular administration of preservation solutions alone is unable to prevent ischemic injury of this layer during clinically relevant storage periods. The SB is unique in that it possesses both a vascular and a luminal route by which preservation solutions can be administered. We hypothesized that addition of a luminal-delivered solution, formulated on amino acid requirements for energy-and non-energy-related reactions, would provide site-specific preservation of mucosal energetics, barrier function and morphology throughout an extended period of cold storage. Of the three luminal solutions containing amino acids which were tested (UWG, AA1, AA2), only the two groups (AA1, AA2), containing glutamine plus 18 other amino acids, ∫osmotic agent (lactobionate) and buffer (BES), exhibited significant improvements in energetics, barrier function, and histology compared to the clinical standard of isolated vascular University of Wisconsin (UW) solution. Although the AA1 and AA2 groups preserved barrier function and morphology up to 24 h better than all other solutions tested, AA2 proved to be the only luminal solution with values of permeability, conductance, and short-circuit current not significantly different from freshly isolated tissues. Furthermore, the greatest reduction in histologic injury was effected by AA2 treatment (median grade 2 compared to control, UW (v) , grade 8). This study documents that a luminaldelivered solution, formulated on physiologic SB requirements, provides targeted preservation of the SB mucosa.

Influence of PACAP on Oxidative Stress and Tissue Injury Following Small-Bowel Autotransplantation

“…Despite its overall acceptance as the first choice for solid organs, UW is unable to effective preserve the smallbowel grafts. Moreover, no consensus exists about optimal preservation solution for small-bowel grafts so far (Balaz et al 2007;Fraczek et al 2007;Fujimoto et al 2002).…”

Intestinal decontamination using povidone-iodine compromises small bowel storage quality

“…We believe one potential strategy is to develop a novel and effective preservation solution in conjunction with minimizing storage times. We have successfully formulated a nutrient-rich preservation solution (called amino-acid [AA] solution, denoting the high concentration of AAs) that preserves mucosal structure and barrier function when administered luminally (2). However, despite considerable improvements in overall graft quality, it is not possible at this stage to completely prevent all damage.…”

Different Ischemic Preconditioning Regimens Affecting Preservation Injury of Intestines

“…Strategies aiming to reduce the consequences of IR injury and thus to maintain mucosal morphology and function throughout clinically relevant storage periods may potentially have enormous impact on the success of ITx. To date, no solution can reliably prevent mucosal injury for prolonged storage periods [7,14,15], which encourages the application of different potentially protective factors in order to increase graft viability after preservation.…”

“…One of the serious problems stems from damage to the graft during ITx, which principally causes extreme susceptibility of the small intestine to mucosal ischemia [5,6,7]. ITx requires cold preservation and warm reperfusion of the graft, and results in certain degrees of ischemia-reperfusion (IR) injury [8].…”

“…With advancing storage duration (4–6 h), progressive compromise and eventual loss of the mucosa occurs, resulting in decreased barrier function and absorptive capacity (6–9 h) [9]. The intestinal graft simultaneously becomes susceptible to bacterial translocation and increased antigenic stimulus (>9 h) [7,10,11,12,13]. Strategies aiming to reduce the consequences of IR injury and thus to maintain mucosal morphology and function throughout clinically relevant storage periods may potentially have enormous impact on the success of ITx.…”