Redistribution of labile plasma zinc during mild surgical stress in the rat

Zinc is an essential trace element and cofactor for many cellular processes. Uptake of ionized divalent zinc (Zn²⁺) in peripheral tissues depends on its total content in the circulation and on mechanisms facilitating delivery to tissues in its labile form. Understanding mechanisms of Zn²⁺ delivery has been hindered by the absence of techniques to detect labile Zn²⁺ in the circulation. In this study, we report the use of the fluorescent zinc-binding dye (ZnAF-2) to detect changes in labile Zn²⁺ in the circulating plasma of the rat under standardized conditions, including exogenous infusions to increase plasma Zn²⁺ and an infusion of the chelator, citrate, to decrease labile Zn²⁺ in the plasma without altering total Zn²⁺ content. In a model of mild surgical stress (unilateral femoral arterial ligation), plasma levels of total and labile Zn²⁺ decreased significantly 24 h after the operation. Ultrafiltration of plasma into high- and low-molecular weight macromolecule fractionations indicated that binding capacity of zinc in the high-molecular weight fraction is impaired for the entire 24-h interval after induction of mild surgical stress. Affinity of the filtrate fraction was rapidly and reversibly responsive to anesthesia alone, decreasing significantly at 4 h and recovering at 24 h; in animals subjected to moderate surgical stress, this responsiveness was lost. These findings are the first reported measurements of labile Zn ²⁺ in the circulation in any form of mild systemic stress. Zinc undergoes substantial redistribution in the plasma as a response to surgical stress, leading to increased availability in lower molecular weight fractions and in its labile form.