Effect of ischemic preconditioning in whole liver transplantation from deceased donors. A pilot study

Abstract

The effect of ischemic preconditioning (IPC) in orthotopic liver transplantation (OLT) has not yet been clarified. We performed a pilot study to evaluate the effects of IPC in OLT by comparing the outcomes of recipients of grafts from deceased donors randomly assigned to receive (IPCϩ group, n ϭ 23) or not (IPCϪ group, n ϭ 24) IPC (10-min ischemia ϩ 15-min reperfusion). In 10 cases in the IPCϩ group and in 12 in the IPCϪ group, the expression of inducible nitric oxide synthase (iNOS), neutrophil infiltration, and hepatocellular apoptosis were tested by immunohistochemistry in prereperfusion and postreperfusion biopsies. Median aspartate aminotransferase (AST) levels were lower in the IPCϩ group vs. the IPCϪ group on postoperative days 1 and 2 (398 vs. 1,234 U/L, P ϭ 0.002; and 283 vs. 685 U/L, P ϭ 0.009). Alanine aminotransferases were lower in the IPCϩ vs. the IPCϪ group on postoperative days 1, 2, and 3 (333 vs. 934 U/L, P ϭ 0.016; 492 vs. 1,040 U/L, P ϭ 0.008; and 386 vs. 735 U/L, P ϭ 0.022). Bilirubin levels and prothrombin activity throughout the first 3 postoperative weeks, incidence of graft nonfunction and graft and patient survival rates were similar between groups. Prereperfusion and postreperfusion immunohistochemical parameters did not differ between groups. iNOS was higher postreperfusion vs. prereperfusion in the IPCϪ group (P ϭ 0.008). Neutrophil infiltration was higher postreperfusion vs. prereperfusion in both groups (IPCϩ, P ϭ 0.007; IPCϪ, P ϭ 0.003). Prereperfusion and postreperfusion apoptosis was minimal in both groups. In conclusion, IPC reduced ischemia/reperfusion injury through a decrease of hepatocellular necrosis, but it showed no clinical benefits. Liver Transpl 12: 628-635, 2006.

The Ischemic Preconditioning Paradox in Deceased Donor Liver Transplantation—Evidence from a Prospective Randomized Single Blind Clinical Trial

“…In the third trial, a pilot study of 47 liver recipients, Cescon et al showed that 10 min IPC decreased biochemical RP injury. However, clinical outcomes including initial poor function, graft nonfunction and graft and patient survival were similar between the IPC and No IPC groups (19).…”

“…We concluded that longer periods of IPC might be more effective (17). Two other groups published conflicting results of prospective randomized studies of 10 min of IPC in DDLT (18,19).…”

“…Previously, three prospective randomized trials of IPC have been reported in DDLT (17)(18)(19). In the first report of 91 patients, Azoulay et al showed that 10 min of hilar clamping followed by 10 min of RP led to a significant decrease in serum AST/ALT in the early posttransplant period (18).…”

Ischemic preconditioning of the liver: A few perspectives from the bench to bedside translation

“…67,68 The fact that liver IPC in deceased donors reduces RP injury in some studies shows that IPC is inducible in the presence of brain death. 27 Additional studies of IPC of the liver and other organs in brain-dead animals are needed to fill the knowledge gaps. A summary of the potential reasons for the observed disparity between the bench and bedside is provided in Table 4.…”

Role of ischaemic preconditioning in liver regeneration following major liver resection and transplantation

“…Azoulay et al [212] found that although IPC protected cadaveric liver grafts against IRI, this beneficial effect was counter-balanced by decreased early graft function. Cescon and colleagues demonstrated similar protective effects against IRI, but IPC showed no clinical benefit (primary graft function and survival rates) in liver transplantation from deceased donors [213] . Although gaining popularity, the incongruous evidence of the clinical effects of IPC has precluded its widespread adoption in liver transplantation units.…”