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Extracorporeal circulation increases proliferation in the intestinal mucosa in a large animal model  Paula Rosalie Keschenau, MD, Stefanie Ribbe, Miriam.

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Presentation on theme: "Extracorporeal circulation increases proliferation in the intestinal mucosa in a large animal model  Paula Rosalie Keschenau, MD, Stefanie Ribbe, Miriam."— Presentation transcript:

1 Extracorporeal circulation increases proliferation in the intestinal mucosa in a large animal model 
Paula Rosalie Keschenau, MD, Stefanie Ribbe, Miriam Tamm, MSc, Sebastiaan J. Hanssen, MD, PhD, René Tolba, MD, PhD, Michael J. Jacobs, MD, PhD, Johannes Kalder, MD  Journal of Vascular Surgery  Volume 64, Issue 4, Pages (October 2016) DOI: /j.jvs Copyright © 2016 Society for Vascular Surgery Terms and Conditions

2 Fig 1 Timetable depicts the experimental protocol. There were three experimental phases (I: baseline measurement; II: main procedure, 1 hour; III: reperfusion, 2 hours) and four experimental cohorts (cohort I: sham operation; cohort II: 1 hour of thoracic aortic cross-clamping [TAC] at thoracal 7; cohort III: 1 hour of TAC at thoracal 7 and distal aortic perfusion [DAP] through the iliac vessels; cohort IV: 1 hour of TAC at thoracal 7 and DAP through the iliac vessels and selective visceral perfusion [SVP]).The duration of the three experimental phases was the same in all cohorts. Journal of Vascular Surgery  , DOI: ( /j.jvs ) Copyright © 2016 Society for Vascular Surgery Terms and Conditions

3 Fig 2 Experimental setup of (A) cohort II, with thoracic aortic cross-clamping (TAC) with distal aortic perfusion (DAP) via the iliac vessels, and (B) cohort IV, with TAC and DAP and selective visceral perfusion (SVP). ECC, Extracorporeal circulation. Journal of Vascular Surgery  , DOI: ( /j.jvs ) Copyright © 2016 Society for Vascular Surgery Terms and Conditions

4 Fig 3 Exemplary hematoxylin and eosin (H&E) staining (original magnification ×100) of mucosa specimens from (A) cohort I (sham operation), (B) cohort II (1 hour of thoracic aortic cross-clamping [TAC] at thoracal 7), (C) cohort III (1 hour of TAC at thoracal 7 and distal aortic perfusion [DAP] through the iliac vessels), and (D) cohort IV (1 hour of TAC at thoracal 7 and DAP through the iliac vessels and selective visceral perfusion [SVP]) at the end of the main procedure. Photomicrographs show extensive mucosal damage with ulceration only after TAC alone (cohort II). Journal of Vascular Surgery  , DOI: ( /j.jvs ) Copyright © 2016 Society for Vascular Surgery Terms and Conditions

5 Fig 4 Mean ± standard deviation of the relative count of cells positive for terminal deoxynucleotide transferase-mediated deoxy uridine triphosphate nick-end labeling (TUNEL) in the mucosa (missing data: n = 3). T2 is the moment before thoracic aortic cross-clamping (TAC) but after preparation of the vessels. T8 designates 2 hours after reperfusion. There is no significant difference between the groups. P values are given for log-transformed data. DAP, Distal aortic perfusion; SVP, selective visceral perfusion. Journal of Vascular Surgery  , DOI: ( /j.jvs ) Copyright © 2016 Society for Vascular Surgery Terms and Conditions

6 Fig 5 Mean ± standard deviation of the relative count of cells positive for proliferating cell nuclear antigen (PCNA) in the mucosa (missing data: n = 2). The values at T2 do not differ, proliferation increases in the distal aortic perfusion (DAP) group at T8, with a significant difference between groups in sensitivity analysis (P = .0157). P values are given for log-transformed data. SVP, Selective visceral perfusion; TAC, thoracic aortic cross-clamping. Journal of Vascular Surgery  , DOI: ( /j.jvs ) Copyright © 2016 Society for Vascular Surgery Terms and Conditions

7 Fig 6 Proliferating cell nuclear antigen (PCNA) staining of the ileal mucosa (original magnification ×100) reveals a change of proliferation in the experimental groups at different times during the experiment. There is no significant difference between the (A) distal aortic perfusion (DAP) group and (C) selective visceral perfusion (SVP) group at T2; however, at T8, there is a high increase of proliferation in the (B) DAP group compared with the (D) SVP group. Journal of Vascular Surgery  , DOI: ( /j.jvs ) Copyright © 2016 Society for Vascular Surgery Terms and Conditions

8 Fig 7 Mean ± standard deviation of the relative count of cells positive for annexin-V in the mucosa (missing data: n = 9). There is a significant decrease in all groups at the end of the experiment (T8). P values are given for log-transformed data. DAP, Distal aortic perfusion; SVP, selective visceral perfusion; TAC, thoracic aortic cross-clamping. Journal of Vascular Surgery  , DOI: ( /j.jvs ) Copyright © 2016 Society for Vascular Surgery Terms and Conditions

9 Fig 8 Annexin-V-stained smooth muscle cells of the ileum. The photomicrographs (original magnification ×100) shows the difference between (A) 1 hour (T5) of ischemia or extracorporeal circulation (ECC) and (B) 2 hours (T8) after reperfusion. In the early phase, there is a higher rate of cells in the early and reversible state of apoptosis than at the end of surgery after reperfusion. Journal of Vascular Surgery  , DOI: ( /j.jvs ) Copyright © 2016 Society for Vascular Surgery Terms and Conditions

10 Fig 9 Mean ± standard deviation of the relative count of cells positive for caspase-3 in the mucosa (missing data: n = 12). T4 is the moment of the beginning of thoracic aortic cross-clamping (TAC), and T5 describes the situation after 1 hour of ischemia. There is no significant difference among the four groups. P values are given for log-transformed data. DAP, Distal aortic perfusion; SVP, selective visceral perfusion. Journal of Vascular Surgery  , DOI: ( /j.jvs ) Copyright © 2016 Society for Vascular Surgery Terms and Conditions

11 Fig 10 Mean ± standard deviation of the quotient of annexin-V and proliferating cell nuclear antigen (PCNA)-positive cell proportions in the mucosa (missing data: n = 5). The trend in the distal aortic perfusion (DAP) group is similar to the control group, whereas the progression in the selective visceral perfusion (SVP) group is similar to the thoracic aortic cross-clamping (TAC) group. P values are given for log-transformed data. Journal of Vascular Surgery  , DOI: ( /j.jvs ) Copyright © 2016 Society for Vascular Surgery Terms and Conditions

12 Fig 11 Mean ± standard deviation of the quotient of caspase-3 and annexin-V-positive cell proportions in the mucosa (missing data: n = 13). It shows a significant increase in all groups at the end of surgery. P values are given for log-transformed data. DAP, Distal aortic perfusion; SVP, selective visceral perfusion; TAC, thoracic aortic cross-clamping. Journal of Vascular Surgery  , DOI: ( /j.jvs ) Copyright © 2016 Society for Vascular Surgery Terms and Conditions

13 Fig 12 Mean ± standard deviation of the relative count of smooth muscle cells positive for terminal deoxynucleotide transferase-mediated deoxy uridine triphosphate nick-end labeling (TUNEL) in the ileum (data missing: n = 7). There is no significant difference between the groups. P values are given for log-transformed data. DAP, Distal aortic perfusion; SVP, selective visceral perfusion; TAC, thoracic aortic cross-clamping. Journal of Vascular Surgery  , DOI: ( /j.jvs ) Copyright © 2016 Society for Vascular Surgery Terms and Conditions

14 Fig 13 Mean ± standard deviation of the relative count of proliferating cell nuclear antigen (PCNA)-positive smooth muscle cells in the ileum (data missing: n = 3). There is no significant difference among the four groups. P values are given for log-transformed data. DAP, Distal aortic perfusion; SVP, selective visceral perfusion; TAC, thoracic aortic cross-clamping. Journal of Vascular Surgery  , DOI: ( /j.jvs ) Copyright © 2016 Society for Vascular Surgery Terms and Conditions

15 Fig 14 Mean ± standard deviation of the relative count of annexin-V-positive smooth muscle cells of the ileum (missing data: n = 13). In elapsed time there is a significant decrease of annexin-V 2 hours after reperfusion in all groups. DAP, Distal aortic perfusion; SVP, selective visceral perfusion; TAC, thoracic aortic cross-clamping. Journal of Vascular Surgery  , DOI: ( /j.jvs ) Copyright © 2016 Society for Vascular Surgery Terms and Conditions

16 Fig 15 Mean ± standard deviation of the relative count of caspase-3-positive smooth muscle cells of the ileum (missing data: n = 16). Compared with the control group, there is a significant decrease of positive cells at the end of the ischemia-phase in the thoracic aortic cross-clamping (TAC) group (T4). At T5, there is a significant difference between cohort II and cohort IV, but neither group differs from the control cohort (I). P values are given for log-transformed data. DAP, Distal aortic perfusion; SVP, selective visceral perfusion. Journal of Vascular Surgery  , DOI: ( /j.jvs ) Copyright © 2016 Society for Vascular Surgery Terms and Conditions

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