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 oxyge n-derived free radicals catalyzed by low molecular weight iron (Imw Fe ), which is thought to accumulate during ischemia and reperfusion. We tested the hypothesis that functional preconditioning with transient i schemia in the rat heart may be due to decreasing the myocardial Imw F e pool, and consequently free radicals during ischemia or reperfusion. Hearts were preconditioned with two 5-min episodes of ischemia follow ed by 5 min of reperfusion, The Imw Fe pool of pre-ischemic hearts was 172 +/- 13 pmol/mg protein. After 40 min of prolonged ischemia, the I mw Fe contents were 176 +/- 25 and 127 +/- 13 pmol/mg for non-conditio ned and preconditioned hearts, respectively (P = N.S.). After 10 min o f reperfusion, the Imw Fe contents were 246 +/- 26 and 228 +/- 23 pmol /mg protein, respectively (P = N.S.). We next tested the ability of de feroxamine, 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-overloadin g by dietary enhancement and weekly iron injections would exacerbate p ostischemic contractile dysfunction and attenuate functional precondit ioning with ischemia, The total iron contents of the high iron and nor mal groups were 10.3 +/- 0.6 and 4.4 +/- 0.2 nmol/mg protein (P < 0.00 1). Percentage recoveries of heart rate x developed pressure were 36 /- 6 and 33 +/- 5 for non-conditioned hearts in the high iron and norm al iron groups, respectively (P = N.S.). Percentage recoveries of hear t rate x developed pressure were 58 +/- 5 and 68 +/- 6 for ischemicall y preconditioned hearts in the high and normal iron groups, repectivel y (P = N.S). The results suggest that functional preconditioning in th e rat heart is not due to attenuation Imw Fe accumulation. (C) 1997 Ac ademic Press Limited.