Brain Death Impairs Pancreatic Microcirculation

Abstract

Brain death (BD) influences the quality of donor grafts in transplantation. To evaluate the impact of BD on pancreas grafts, we investigated the influence of BD on the microcirculation and histology of the pancreas in a rat model of explosive BD. A group of Wistar rats (n = = 7), rendered brain dead by inflating an intracranially inserted Fogarty catheter was compared with controls (CO) using intravital epifluorescence-microscopy over 4 h after BD induction; functional capillary density (FCD), leukocyte adherence (AL) in post-capillary venules, histology and pancreatic enzymes were investigated. Four hours after BD, FCD decreased (333 ± 11 vs. baseline 444 cm/cm 2 ± 5 SEM; p < 0.01) and showed lower values than CO (388 ± 9 p < 0.01). In BD, AL was increased (628 cells/mm 2 ± 110 SEM vs. baseline 123 ± 32, and vs. CO 180 ± 33; p < 0.001). BD caused increased histological damage (CO 1.6 scorepoints ± 0.7 SD vs. BD 8.3 ± 7.1; p < 0.05). Amylase was higher in BD (p < 0.05) but did not reach pathological values. We show for the first time that BD causes relevant changes in pancreatic microcirculation, histology and leukocyte endothelial interaction which might have a serious impact on the function of grafts. New strategies for preventing this damage are therefore highly desirable in order to improve the outcome of pancreas transplantation.

Paradoxical effects of brain death and associated trauma on rat mesenteric microcirculation: an intravital microscopic study

“…To evaluate the role of BD-associated trauma, matching sham-operated rats were assessed over time. As described previously, BD leads to an increase in the MAP followed by hypotension (6,10), both of which compromise organ perfusion (11). Our study demonstrates that BD-associated trauma did not influence hemodynamic and perfusion parameters, suggesting that all of the observed changes in MAP and mesenteric hypoperfusion were triggered by the BD itself.…”

“…Intravital microscopy has been used to assess microcirculation in experimental models, but few studies have used this technique following BD (11,12). In this study, intravital microscopy was used to evaluate mesenteric perfusion and leukocyte-endothelial interactions in post-capillary venules of BD and SH rats.…”

“…Decreased organ perfusion following BD has been previously demonstrated. Obermeier et al (11) described a decrease in the functional capillary density in the pancreatic microcirculation after BD induction in rats using intravital epifluorescence microscopy. In another study, BD induced the deterioration of the rat hepatic microcirculation, including a reduced sinusoidal perfusion rate and sinusoidal diameter (13).…”

“…Specific adhesion glycoproteins expressed on the surfaces of leukocytes and endothelial cells play important roles in leukocyte accumulation in a tissue (11,12). Members of the selectin family of cell adhesion molecules are thought to mediate leukocyte rolling along the walls of the microvasculature (18,19).…”

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

“…Meanwhile, one decade ago, only two experimental studies demonstrated that BD results in pathophysiological alterations in the pancreas, reflected by microcirculatory deterioration, elevated inflammatory tissue response and histological pancreas damage reducing islet yields and functionality 28, 29. In order to address the question whether donor BD accelerates IRI, we combined the experimental model of donor BD induction and a model of pancreas transplantation in the mouse.…”