Ischemic preconditioning in the isolated rat heart is not due to attenuation of free iron accumulation during prolonged ischemia

Brief transient ischemia can protect the rat heart against a subsequent, prolonged period of ischemia (IS) . The cardio-protective mechanism of this phenomenon, known as ischémie preconditioning (IP), is unknown. Acid-stimulated release of bound iron during prolonged IS may produce free iron (FFe) which can catalyze the formation of potential1 y damaging hydroxyl radicals. Because IP is known to attenuate acidosis during prolonged IS, isolated rat hearts were used to test the following hypothesis: IP enhances the tolerance of the rat heart to T S by attenuating FFe accumulate on during 1S Control fC I hearts received 40 min of global ischemia 14 OIS) IF hearts were treated with 2 cycles of Smin ischemia/Smin reperfusion prior to 40IS. Myocardial pH was monitored with 3 mi c roe lee t rode inserted into the left, ventricular wall At the end of 4 OIS, the hearts were freeze - clamped, and the FFe contents of the homogenates were determined using a Fe- deferoxamine/HPLC assay Preischemic(Prel) FFe was determined in another group (n=6) which did not receive IS. After 401, myocardial pH was 5.96 £ O.ll and 6 39 ±0.12 for C (n = 6) and IP (n = 6) hearts, respectively (p < 0 05) Preischemic pH for both groups was approximately 7.2 FFe contents of Prel. C, and IP hearts were 13.6 ±1.0, 156 ±2.1; and 12.4 ±1.5 nmol /g. respectively {ANOVA, ns) . Therefore, IP is not due to attenuation of FFe accumulation. Also, myocardial injury resulting from prolonged IS does not appear to be due ischemia-induced accumulation of FFe in the rat heart rhi study was supported by NTH grant HL-50466.