Small intestinal ischemia/reperfusion injury prediction during the subnormothermic machine perfusion focusing on the electrogastroenterogram
Satoshi Muto1, Hiromichi Obara1, Daisuke Ishii2, Yuga Okazawa1, Mio Takashima1, Taiki Mori1, Masafumi Furukawa1, Tomoki Abe1, Hiroki Kaneko3,4, Shohei Ishizawa5, Shotaro Iino5, Seisuke Sakamoto3, Naoto Matsuno1,3.
1Tokyo Metropolitan University, Hino, Tokyo, Japan; 2Asahikawa Medical University, Asahikawa, Hokkaido, Japan; 3National Center for Child Health and Development, Setagaya, Tokyo, Japan; 4Azabu University Veterinary Teaching Hospital, Sagamihara, Kanagawa, Japan; 5Nippon Veterinary and Life Science University, Musashino, Tokyo, Japan
Objective: Intestinal transplantation (IT) is performed as a definitive treatment for irreversible intestinal failure. However, patient survival is the lowest among thoracic and abdominal organs. While preclinical studies of normothermic machine perfusion (NMP) and hypothermic machine perfusion (HMP) have been conducted as strategies to improve IT outcomes, the possibility of subnormothermic machine perfusion (SNMP) has not been discussed. Here, we perform SNMP on small intestines with warm ischemia and examine its effectiveness.
Methods: Pig small intestines were used in the experiment. We performed three hours of cold storage (CS) with a warm ischemia time (WIT) of 45 minutes and three hours of SNMP with a WIT45 (N=3). HTK solution was selected as the organ preservation solution. During SNMP, small intestinal serosa voltage (SISV) was measured to quantify the electrical activity of the ex vivo small intestine. Subsequently, during 120 min of ex vivo blood reperfusion (Rep) using diluted autologous blood, plasma enzymes were measured to evaluate ischemia/reperfusion injury (IRI).
Results: LDH at Rep-60 min was CS: 786±145; SNMP: 437±130 (IU/L), and at Rep-120 min was CS: 1470±589; SNMP: 775±108 (IU/L). The SNMP group at Rep-60 min had significantly lower values than the CS group (P<0.05). CPK at Rep-60min was CS: 1277±235; SNMP: 610±212 (IU/L), and at Rep-120min was CS: 2272±1364; SNMP: 1127±127 (IU/L), showing a tendency to decrease in the SNMP group. The periodicity rmax of SISV, filtered to 1-3 Hz, measured during SNMP, tended to correlate negatively with LDH and CPK at Rep120min (r = -0.59, r = -0.88).
Discussion: It has been reported that small intestinal electrical activities in the range of 1-3 Hz contribute to the induction of excitatory postsynaptic potentials (EPSPs). The rmax during SNMP quantified as the periodicity of SISV correlated with plasma LDH and CPK during reperfusion, suggesting the possibility of predicting small intestinal function before transplantation using SISV.
Conclusion: SNMP is effective in suppressing small intestinal IRI. In addition, quantification of small intestinal electrical activity during SNMP predicts small intestinal function after transplantation.
[1] Intestinal Transplantation
[2] Subnormothermic Machine Perfusion
[3] Ischemia/Reperfusion Injury