Ex vivo normothermic porcine pancreas: A physiological model for preservation and transplant study.

INTRODUCTION: An ex vivo normothermic porcine pancreas perfusion (ENPPP) model was established to investigate effects of machine perfusion pressures on graft preservation. METHODOLOGY: Nine porcine pancreata were perfused with autologous blood at 50 mmHg (control) pressure. Graft viability was compared against four ex-vivo porcine pancreata perfused at 20 mmHg ('low') pressure. Arterio-venous oxygen gas differentials, biochemistry, and graft insulin responses to glucose stimulation were compared. Immunohistochemistry stains compared the cellular viability. RESULTS: Control pancreata were perfused for a median of 3 h (range 2-4 h) with a mean pressure 50 mmHg and graft flow 141 mL min-1. In comparison, all of the 'low' pressure models were perfused for 4 h, with mean perfusion pressure 20 mmHg and graft flow 40 mL.min-1. All pancreata demonstrated cellular viability with evidence of oxygen consumption with preserved endocrine and exocrine function. However, following statistical analysis, the 'low' pressure perfusion of porcine pancreata compared favourably in important biochemical and immunohistochemistry cellular profiles; potentially arguing for an improved method for graft preservation. CONCLUSION: ENPPP will facilitate whole organ preservation to be studied in further detail and avoids use of expensive live animals. ENPPP is reproducible and mimics a "donation after circulatory death" scenario.

A Study of Normothermic Hemoperfusion of the Porcine Pancreas and Kidney.

Normothermic machine perfusion has enormous potential to improve organ preservation and expand the organ donor pool. It is well established in other organs but not the pancreas, which has especially strict organ acceptance criteria. We established a model of normothermic hemoperfusion of the porcine pancreas with and without addition of the kidney as a dialysis organ. Four pancreases were harvested and perfused for 120 min with autologous whole blood at body temperature, two with parallel perfusion of the kidney and two without. The organs and perfusion circuit were evaluated for gross appearance, pH, histology and perfusion parameters. The organs maintained steadily increasing flow rate and perfusion pressure. Gross appearance of the organs was stable but appeared grossly ischemic toward the end of the perfusion period. Histology demonstrated necrosis centered in acinar tissue but islet cells were preserved. pH was significantly alkalotic toward the end of the perfusion, likely due to pancreatic tissue damage. Addition of the kidney did not result in significant improvement of the acid-base environment in this small series. In conclusion, normothermic perfusion of the pancreas is still in the experimental stages but holds great potential. Further studies to optimize perfusion parameters will significantly improve results. Parallel perfusion of the kidney may facilitate improvement in the acid-base environment.

Extracorporeal machine perfusion of the pancreas: technical aspects and its clinical implications--a systematic review of experimental models.

Pancreas or pancreatic islet transplantation is an important treatment option for insulin-dependent diabetes and its complications. However, as the pancreas is particularly susceptible to ischaemic-reperfusion injury, the criteria for pancreas and islet donation are especially strict. With a chronic shortage of donors, one critical challenge is to maximise organ availability and expand the donor pool. To achieve that, continuous improvement in organ preservation is required, with the aims of reducing ischaemia-reperfusion injury, prolong preservation time and improve graft function. Static cold storage, the only method used in clinical pancreas and islet cell transplant currently, has likely reached its plateau. Machine perfusion, hypothermic or normothermic, could hold the key to improving donor pancreas quality as well as quantity available for transplant. This article reviews the literature on experimental models of pancreas machine perfusion, examines the benefits of machine perfusion, the technical aspects and their clinical implications.

Gut symptoms in diabetics correlate with components of the rectoanal inhibitory reflex, but not with pudendal nerve motor latencies or systemic autonomic neuropathy.

OBJECTIVE: Fecal incontinence (FI) occurs in up to 20% of diabetes mellitus (DM) patients. Rectoanal inhibitory reflex (RAIR) is an enteric anorectal reflex that reflects the integrity of mechanisms in the physiology of FI. We aimed to investigate whether diabetic patients with FI, not constipation, had prolongation of RAIR and altered gut-specific autonomic tone. METHODS: In this prospective case-matched study 31 type I DM (19 FI and 12 constipation) and 42 type II DM (26 FI and 16 constipation). Another 21 participants were included as controls. Patients underwent the following assessments: cardiovagal autonomic tone (Modified Mayo Clinic composite autonomic severity score), rectal mucosal blood flow (RMBF) (assessment of gut-specific autonomic tone) and RAIR. Three phases of RAIR and the amplitude of maximal reflex relaxation were compared between groups. All participants completed symptom scores for FI and constipation. RESULTS: RAIR recovery time back to resting pressure was slower in diabetic patients with FI than controls (8.7 s vs 3.6 s, P < 0.05) and was an independent variable correlating with symptoms of FI (P < 0.05). RAIR recovery time was correlated with RMBF (r = 0.58, P = 0.04). CONCLUSION: RAIR is correlated with anorectal symptoms of FI and was associated with gut-specific autonomic neuropathy.