Regulation of histamine and diamine oxidase in patients undergoing orthotopic liver transplantation

Abstract

increased concentrations of the vasodilator histamine have been observed in patients undergoing abdominal surgery. the role of histamine during orthotopic liver transplantation (oLt) has only been studied in animals. the aim of this study was to measure plasma concentrations of histamine and its degrading enzyme diamine oxidase (DAo) in patients undergoing orthotopic liver transplantation, and assess whether histamine or DAo correlate with intraoperative noradrenaline requirements. Histamine and DAO concentrations were measured in 22 adults undergoing liver transplantation and 22 healthy adults. Furthermore, norepinephrine requirements during liver transplantation were recorded. Baseline concentrations of histamine and DAo were greater in patients, who underwent liver transplantation, than in healthy individuals (Histamine: 6.4 nM, IQR[2.9-11.7] versus 4.3 nM, IQR[3.7-7.1], p = 0.029; DAO: 2.0 ng/mL, IQR[1.5-4.1] versus <0,5 ng/mL, IQR[<0.5-1.1], p < 0.001). During liver transplantation, histamine concentrations decreased to 1.8 nM, IQR[0.5-4.9] in the anhepatic phase (p < 0.0001 versus baseline), and to 1.5 nM, IQR[0.5-2.9] after reperfusion (p < 0.0001 versus baseline). In contrast, DAO concentrations increased to 35.5 ng/ml, IQR[20-50] in the anhepatic phase (p = 0.001 versus baseline) and to 39.5 ng/ml, IQR[23-64] after reperfusion (p = 0.001 versus baseline), correlating inversely with histamine. norepinephrine requirements during human liver transplantation correlated significantly with DAO concentrations in the anhepatic phase (r = 0.58, p = 0.011) and after reperfusion (r = 0.56; p = 0.022). In patients undergoing orthotopic liver transplantation, histamine concentrations decrease whereas DAo concentrations increase manifold. Diamine oxidase correlates with intraoperative norepinephrine requirements in patients undergoing oLt. Orthotopic liver transplantation (OLT) is the only curative procedure for end-stage liver disease (ESLD). Patients with ESLD usually present with a systemic hyperdynamic cardiovascular regulation, demonstrating an increased cardiac output, reduced systemic vascular resistance and impaired vascular responsiveness to stress. During OLT, patients are exposed to further major hemodynamic alterations primarily due to temporary caval clamping, blood loss and ischemia/reperfusion (I/R) injury. Temporary clamping of the inferior vena cava decreases cardiac output by approximately 50% due to a reduction in venous return to the heart 1,2 , while blood loss leads to hypovolemia. I/R injury, mainly characterized by oxidative damage and a severe inflammatory response, triggers the secretion of vasoactive mediators into the recipients' systemic circulation 3. Thus, OLT is frequently associated with hemodynamic instability of the recipient presenting clinically with hypotension, increased vasopressor support and cardiac arrhythmias.

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“…DAO is an intracellular enzyme that is mainly found in the cytoplasm of intestinal villous cells, while it is less abundant and less active in other tissues [20]. Once intestinal mucosal cells are damaged and the mucosal barrier is broken, DAO will be released into the blood or will enter the intestinal lumen with the shedding of intestinal mucosal cells, which will, in turn, cause an increase in blood and intestinal luminal DAO activity [20,48]. Since DAO activity is stable in peripheral blood, changes in DAO in peripheral blood are generally detected to reflect intestinal mucosal injury and repair [49].…”