A Snapshot

Abstract

In this study deferoxamine (DF), a strong iron chelator, was administered either before storage or during reperfusion, in an attempt to inhibit the iron-dependent hydroxyl radical production and improve the functional recovery of the cold-stored/reperfused cardiac explant. Excised rat hearts were flushed with Krebs-Henseleit buffer (KHB), arrested with a cardioplegic solution, CP11-EB, with or without DF, and immersion stored in CP11-EB at 0°C for 16 hr. To assess function, the stored hearts were reperfused in the working mode with KHB for 30 min. Experimental groups included: (i) DF treatment during prestorage flush [CP11-EB + 0.01 mM (n = 5), 0.05 mM (n = 13), 0.1 mM (n = 5), 0.2 mM (n = 5), or 0.75 mM DF (n = 5)]; (ii) DF treatment during reperfusion [KHB + 0.3 mM (n = 5), 0.6 mM (n = 7), 0.75 mM (n = 11), 1.0 mM (n = 6), 1.5 mM (n = 4), or 2.5 mM DF (n = 7)]; and (iii) untreated group (n = 8) received no DF during flush or reperfusion. Function of unstored hearts (n = 7) including aortic flow (AF, 54.6 ± 2.6 ml/min); cardiac output (CO, 76.5 ± 3.3 ml/min), systolic pressure (SP, 135.7 ± 1 mm Hg), diastolic pressure (DP, 70.7 ± 3.8 mm Hg), and work (96.7 ± 6.4 g-meter/min) served as controls. Functional recovery of the untreated group was AF, 59%; CO, 58%; SP, 71%; DP, 73%; work, 41% of control values. DF treatment at any dose during the initial flush did not improve functional recovery. In contrast, DF treatment (0.75 and 1.0 mM) during 30 min reperfusion produced significantly better function compared to the untreated group (P < 0.05). The functional recovery of the 0.75 mM group was AF, 71%; CO, 67%; SP, 76%; work, 52% of control. The functional recovery of the 1.0 mM group was CO, 68%; SP, 79%; DP, 82%; work, 55% of control. Shorter treatment with 0.75 mM DF for the first 5 (n = 7) or 10 (n = 9) min of reperfusion did not elicit the beneficial effect of DF. These results suggest that hydroxyl radical production at reperfusion may play a role in injury to the cold-stored/reperfused rat heart. Furthermore, this production may affect function for a period longer than the first few minutes of reperfusion.