Release of cytokines and hemodynamic instability during the reperfusion of a liver graft

Abstract

The objectives of this prospective, observational study were (1) to determine whether a transplanted liver graft releases proinflammatory cytokines into the systemic circulation upon reperfusion and (2) to determine whether they contribute to any subsequent hemodynamic instability observed after graft reperfusion (if this release occurs). Blood samples from 17 consecutive patients undergoing liver transplantation were analyzed for cytokines, including tumor necrosis factor a (TNFa), interleukin-1b (IL-1b), IL-2, IL-6, and IL-8. Blood samples were obtained from the radial artery, portal vein, and flush blood (a sample taken from a catheter placed above the infrahepatic inferior vena cava clamp). The amount of catecholamines necessary to maintain a mean arterial pressure between 65 and 75 mm Hg during graft reperfusion was compared with the level of cytokines. A statistical analysis was performed with the least squares method, Kendall's tau-b test, and regression analysis. We demonstrated that flush blood from the liver grafts contained a significant amount and variety of cytokines. Most of these were removed by graft irrigation. The concentration of TNF-a in samples obtained from flush blood at the end of liver irrigation was significantly higher than the concentration in samples obtained from the radial artery (P ¼ 0.0067) or portal vein (P ¼ 0.0003) before reperfusion. This correlated directly with the amount of catecholamines used to treat hemodynamic instability. Although there were increased levels of IL-1b, IL-2, and IL-8 in the flush blood, there was no statistically significant correlation between the levels of these cytokines and the amount of catecholamines used. Liver

Hepatic ischemia/reperfusion injury associates with acute kidney injury in liver transplantation: Prospective cohort study

“…Activated neutrophils release enzymes and cytokines into the subendothelial space, directly causing kidney injury and the recruitment of monocytes and macrophages . Cytokine release from the liver after cold storage has been shown by Bezinover et al, and additional analysis revealed that the levels of cytokines were higher in grafts from higher‐risk donors . In a pig model, we showed that cytokine release and Kupffer cell activation was also higher in DCD livers exposed to increased warm ischemia times, resulting in increased HIRI and PNF .…”

Intrarenal resistance index for the assessment of acute renal injury in a rat liver transplantation model

“…During LT, on the reperfusion of the implanted liver, the graft itself can release substances such as proinflammatory cytokines [3,30,31] and nitric oxide [32], which can lead to the imbalance between vasoconstrictive and vasodilative factors and subsequently disturbance the adapt capacity of vascular resistance and renal vascular dilates [31,33]. Furthermore, this reduction of tone within renal might overwhelm the elevated renal RI values related to leukocyte activation and infiltration, renal tubular injury and renal edema.…”

Early cytokine signatures of ischemia/reperfusion injury in human orthotopic liver transplantation

“…In transplant, a unique situation occurs in which the cytokine profile of the donor allograft combines with that of the recipient, as cytokines produced in the donor allograft are likely to be flushed into the patient's circulating blood during reperfusion. It has been shown that donor-derived cytokines contribute to hemodynamic instability during reperfusion (29), which could affect IRI severity. To determine the contribution of the donor organ to cytokine release and patient IRI status, we directly compared blood samples obtained from the recipient's portal blood before or after reperfusing the donor organ as well as characterizing cytokine profiles of systemic blood samples obtained from recipients after transplant.…”