Myocardial release of non-transferrin-bound iron during cardio-pulmonary bypass surgery

Abstract

Myocardium reperfusion following coronary artery bypass grafting (CABG) may result in "reperfusion injury" by free radical generations. Since desferrioxamine administration attenuates this syndrome, non-transferrin-bound-iron (NTBI) released into the perfusing medium during CABG was implicated as a catalyst for oxygen radical formation. From 13 patients with "redo" CABG, specimens were collected from the coronary sinus (influx) and the aortic vent (efflux) after each distal coronary anastomosis. Specimens were subjected to sieving chromatography, and fractions were analyzed for total iron and NTBI using atomic absorption spectrometry (AAS). A statistically significant increase in NTBI was measured in influx (p = 0.002) and efflux samples (p = 0.023) collected after each graft. The combined amount of NTBI measured in these specimen was proportional to the CK-MB increase measured in the patients' sera on the day of surgery and the subsequent day. NTBI which accumulated in the circulatory bypass fluid during CABG may catalyze the generation of free radicals in the myocardium when body temperature is restored. This may aggravate myocardial damage as reflected by a post-surgical increase in CK-MB concentrations. Studies are in progress to develop new methods for the removal of NTBI during cardiac surgery. Tissue injury occurs with reperfusion during ischemia. This has been attributed to oxygen-derived free radicals that are generated by substances released from hypoxic areas (Kloner, Przyklenk et al., 1989; McCord, 1998). Reperfusion injury, i.e. the "reperfusion syndrome," occurs after coronary artery bypass grafting (CABG) when the ischemic myocardium is again provided with a supply of blood. Its most serious manifestations are arrhythmia and myocardial stunning (Ar"Rajab, Dawidson et al., 1996; Ferrari, Ceconi et al, 1996). The role of iron in reperfusion injury has been implicated by indirect evidence: during the reperfusion syndrome, the binding of iron with the chelator desferrioxamine (Ambrosio, Zweier et al., 1987; Bel, Martinod et al., 1996), or the administration of exogenous apo-transferrin, improved cardiac contractility and delayed manifestations of cardiac injury (Tiede, Sareen et al., 1990). Iron, as a transition metal, is able to catalyze free radical formation when released into the circulation from endogenous stores as non-transferrin-bound-iron (NTBI). This iron may be bound to small proteins or inorganic ligands (Halliwell and Gutteridge, 1984; Pollock and Campana, 1980; Zweier, 1992). A method for the measurement of NTBI was recently developed (Ambrus, Stadler et al., 1999). The purpose of this study was to explore whether a correlation exists among (a) the amount of NTBI released during CABG surgery, (b) the length of time of myocardial ischemia, and (c) the myocardial damage that occurs during cardiopulmonary bypass.