Liver transplantation. The inflammatory and hemodynamic response during reperfusion

Abstract

Transient, profound cardiovascular insufficiency often occurs following reperfusion of the grafted liver in liver transplantation. Postreperfusion syndrome (PRS) describes a decrease in mean arterial pressure of a least 30% within 5 minutes of reperfusion of the grafted liver. The hemodynamic response is similar to the hyperdynamic circulation seen in sepsis. The aim of this thesis was to evaluate the inflammatory and hemodynamic response following reperfusion of the grafted liver in human orthotopic liver transplantation.Methods: Fifty-three patients with end-stage liver disease undergoing liver transplantation were studied. Blood samples for the analyses of complement factors, markers for neutrophil and macrophage activation, cytokines and prostaglandin E2 were drawn during the operative procedures. Hemodynamic profiles were obtained simultaneously. Neutrophil and macrophage activation was determined as PMN-elastase and neopterin release. Complement activation as well as TNF-alpha, IL-6 and prostaglandin E2 release were evaluated in relation to the postreperfusion syndrome. Influence of the duration of cold ischemia on activation of complement and the release of neopterin and interleukin 6 and 8 was studied.Results: The plasma concentrations of C1INH, C3, C4, and C5 decreased and the anaphylatoxin C3a and the terminal C5b-9 complement complex (TCC) increased after the start of reperfusion of the grafted liver. C5a levels remained statistically unchanged compared to the preoperative levels. The levels of C3a in the portal vein were higher compared to the levels in the simultaneously obtained samples from the radial artery. There were significantly higher PMN-elastase and C3a anaphylatoxin concentrations in patients suffering from PRS. The hemodynamic profiles showed hyperdynamic circulation with low systemic vascular resistance and high cardiac index before surgery, with aggravated vasodilatation and increased cardiac filling pressures and cardiac performance, upon reperfusion. The patients with PRS increased stroke volume less than those without PRS. They also had higher plasma concentrations of PMN-elastase, TNF-alpha and IL-6. In patients receiving a liver with a cold ischemia time longer than 12 hours, the concentration of IL-8 was higher compared to those receiving a liver with a cold ischemia time shorter than 12 hours.Conclusions: The studies show activation of complement and of neutrophils and macrophages during reperfusion of the grafted liver in human transplantation. Release of inflammatory mediators may be one explanation for the circulatory instability often seen in patients undergoing orthotopic liver transplantation. The studies indicate that PRS is mainly caused by a depressed myocardial performance due to systolic and/or diastolic dysfunction, and not only an exaggerated system vasodilatation as previously suggested.