Role of low molecular weight iron in functional preconditioning of the isolated rat heart

Post-ischemic contractile dysfunction in the heart may be due to oxygen-derived free radicals catalyzed by low molecular weight iron (lmw Fe), which is thought to accumulate during ischemia and reperfusion. We tested the hypothesis: that functional preconditioning with transient ischemia in the rat heart may be due to decreasing the myocardial lmw Fe pool, and consequently free radicals during ischemia or reperfusion. Hearts were preconditioned with two 5-min episodes of ischemia followed by 5 min of reperfusion. The lmw Fe pool of pre-ischemic hearts was 172 ± 13 pmol/mg protein. After 40 min of prolonged ischemia, the lmw Fe contents were 176 ± 25 and 127 ± 13 pmol/mg for non-conditioned and preconditioned hearts, respectively (P = N.S.). After 10 min of reperfusion, the lmw Fe contents were 246 ± 26 and 228 ± 23 pmol/mg protein, respectively (P = N.S.). We next tested the ability of deferoxamine, an iron chelator, to mimic functional preconditioning. The percentage recoveries of heart rate x developed pressure after 40 min of ischemia and 30 min of reperfusion were 38 ± 6 and 25 ± 5 for non-conditioned and deferoxamine-treated hearts, respectively (P = N.S.). We further tested the hypothesis by determining if iron-overloading by dietary enhancement and weekly iron injections would exacerbate post-ischemic contractile dysfunction and attenuate functional preconditioning with ischemia. The total iron contents of the high iron and normal groups were 10.3 ± 0.6 and 4.4 ± 0.2 nmol/mg protein (P < 0.001). Percentage recoveries of heart rate x developed pressure were 36 ± 6 and 33 ± 5 for non-conditioned hearts in the high iron and normal iron groups, respectively (P = N.S.). Percentage recoveries of heart rate x developed pressure were 58 ± 5 and 68 ± 6 for ischemically preconditioned hearts in the high and normal iron groups, repectively (P = N.S.). The results suggest that functional preconditioning in the rat heart is not due to attenuation lmw Fe accumulation.