In Vivo Imaging of Human Pancreatic Microcirculation and Pancreatic Tissue Injury in Clinical Pancreas Transplantation

Abstract

Pancreatitis remains to be a major complication following clinical pancreas transplantation. We performed orthogonal polarized spectral (OPS) imaging for direct in vivo visualization and quantification of human pancreatic microcirculation in six healthy donors for living donor liver transplantation and 13 patients undergoing simultaneous pancreas-kidney transplantation. We further determined the impact of microvascular dysfunction during early reperfusion on pancreatic graft injury. Exocrine and endocrine pancreatic impairment was determined by analysis of serum lipase, amylase and C-peptide levels. Compared to normal pancreas in liver donors (homogeneous acinar perfusion) functional capillary density (FCD) and capillary red blood flow velocity of reperfused grafts were significantly decreased. Elevated CRP concentrations on day 2 post-transplant and serum lipase and amylase levels determined on days 4-5 significantly correlated with microvascular dysfunction during the first 30 min of graft reperfusion. Post-transplant serum C-peptide also correlated significantly with pancreatic capillary perfusion. OPS imaging allows to intra-operatively assess physiologic pancreatic microcirculation and to determine microcirculatory impairment during early graft reperfusion. This impairment correlated with the manifestation of post-transplant dysfunction of both exocrine and endocrine pancreatic tissue. OPS imaging may be used clinically to determine the efficacy of interventions, aiming at attenuating microcirculatory impairment during the acute post-transplant reperfusion phase.

Treatment With Tetrahydrobiopterin Overcomes Brain Death–Associated Injury in a Murine Model of Pancreas Transplantation

“…However, only serum lipase was significantly elevated following 2 h of reperfusion, showing a significant difference between BH4‐treated and nontreated grafts derived from BD donors (Figure 5B). We assume that the chosen time was too early to detect differences in terms of serum amylase, which is in line with observations showing indirect correlation between amylase levels in the serum and microcirculatory parameters 3 days following reperfusion 39. Moreover, the greater sensitivity and specificity of lipase over amylase make the former preferable for the diagnosis of pancreatitis in the clinical setting, as lipase remains unaltered in some nonpancreatic conditions whereas an increase in amylase may indicate macroamylasemia, parotitis, and some carcinomas 40, 41.…”

In vivo Visualization of Early Microcirculatory Changes following Ischemia/Reperfusion Injury in Human Kidney Transplantation

“…All hemodynamic parameters were within the range of healthy controls (data previously published [18] ). Only 2 patients developed postoperative complications, which were induced by problems of the pancreas graft (1 case of moderate pancreatitis with intra-abdominal enzyme release; 1 case of thrombosis of the external iliac artery successfully treated by embolectomy).…”

“…Linearly polarized light (wavelength 548 nm, which is within the absorption spectrum of hemoglobin) penetrates tissue with a depth of approximately 200-500 m, and the image area illuminated by the camera is approximately 1 mm To provide sterile conditions during the measurement, the OPS probe including the entire light cable was covered in sterile foil (OpMi-Drape TM , Zeiss, Oberkochen, Germany), and manually positioned on the kidney surface using physiological saline immersion solution. As validated for other visceral organs [17,18] , manual positioning of the OPS probe has been shown to provide the best image quality. Since factors such as organ movement (motion artifacts) and compression of the capillary bed with the probe (microvessel collapse) could influence OPS imaging, to reduce variability in our setting, all measurements were performed by the same method-experienced investigator.…”

Islets of Langerhans Are Protected from Inflammatory Cell Recruitment during Reperfusion of Rat Pancreas Grafts

“…In contrast to short-term ischemia, long-term hypothermic preservation of 18 h induced pronounced microcirculatory disturbances and tissue alterations to the exocrine pancreas already within the observation period of 2 h. Notably, in clinical PTx especially those initial microcirculatory alterations have been found to determine the degree of graft damage developing in the further postoperative course [12,26] . Leukocyte rolling peaked early after reperfusion and declined thereafter.…”