Intestinal Conditioning After Cardiac Arrest: The Use of Normothermic Extracorporeal Membrane Oxygenation in the Non‐Heart‐Beating Animal Model

Abstract

The effect of normothermic extracorporeal membrane oxygenation (NECMO) on small bowel preservation in a clinically relevant large animal model of expected donation after cardiac death (eDCD) was evaluated. Thirty domestic crossbred donor pigs were divided into five groups. The first group served as the live donation (LD) group, the second group served as the donation after cardiac death (DCD) group, and the remaining were further assigned into three subgroups: E1 group (1 h NECMO support), E3 group (3 h NECMO support), and E5 group (5 h NECMO support). Pathology, electron microscopy, energy metabolism, cell apoptosis, and tight junction (TJ) protein expression level of intestinal mucosa and the level of plasma d‐lactic acid were evaluated in normal, cardiac death and at the end of extracorporeal support, respectively. The mean arterial pressure and PaO2 were maintained over 60 and 267 mm Hg during NECMO support, respectively. One hour of extracorporeal support could improve the energy status in intestines of the DCD group. Although the histologic damage and apoptosis of the E1 group had no significant difference with those of the LD and DCD groups (P > 0.05), the levels of intestinal mucosa TJ protein decreased (P < 0.05), and plasma d‐lactic acid increased progressively (P < 0.05). With the extension of extracorporeal support, the degree of intestinal mucosa damage and intestinal permeability gradually increased, as well as the content of adenosine triphosphate in intestinal mucosa. The normothermic extracorporeal support for 1 h in DCD is beneficial for improving the energy status and viability of the bowel. However, the integrity of intestinal mucosa was destroyed gradually as extracorporeal support time went by. And the activation of intestinal epithelial apoptosis and hyperoxia might be the factors that lead to intestinal mucosa injury.

Normothermic extracorporeal membrane oxygenation support: Improving the function of intestinal grafts obtained from cardiac death donors

“…In previous studies, ECMO technology was used in the field of DCD donor bowel preservation 4 . The analyses demonstrated that normothermic extracorporeal support for 1 hour in DCD was beneficial for improving the energy status and viability of the bowel.…”

“…Intestinal mucosal biopsy samples of the grafts were obtained for histologic examination, transmission electron microscopy, Western blotting of tight junction proteins, and cell apoptosis examination as described previously 4 . Histologic injury of the intestinal samples was quantitatively evaluated using the scoring system of Chiu et al in a blinded manner 6 .…”

“…The ECMO group: The abdominal aorta and external jugular vein of the donors were connected to the ECMO circuit using Bio-Medicus cannulas as previously described. 4 After 10 minutes of cardiac arrest, venoarterial perfusion was begun and run for 60 minutes, with the pump flow maintained at 1.5-1.8 L/min (>50 mL/kg/min). Oxygen (100%) was given at a flow rate equal to the blood flow rate with the temperature maintained at 38°C.…”

“…Intestinal mucosal biopsy samples of the grafts were obtained for histologic examination, transmission electron microscopy, Western blotting of tight junction proteins, and cell apoptosis examination as described previously. 4 Histologic injury of the intestinal samples was quantitatively evaluated using the scoring system of Chiu et al in a blinded manner. 6 The grades were as follows: 0, normal mucosa; 1, subepithelial Gruenhagen's space (edema) at the apex of villi; 2, extension of subepithelial space with moderate epithelial lifting; 3, large subepithelial space and extensive epithelial lifting with occasional denuded villi tips; 4, denuded villi with dilated capillaries; and 5, lamina propria disintegration, hemorrhage, and ulceration.…”

“…Regional perfusion by extracorporeal membrane oxygenation (ECMO) is an emerging technique of perfusing organs from DCD donors, which can reperfuse and reoxygenate abdominal organs after cardiac arrest 3 . Our previous research has shown that 1‐hour normothermic extracorporeal support is beneficial for improving the energy status and viability of bowel grafts although the integrity of the intestinal mucosa was destroyed gradually as the extracorporeal support time progressed 4 . However, the primary limitation of this study is that the absorptive ability and function of grafts after transplantation were not assessed.…”