Deferoxamine Given at Reperfusion Improves Function of the Cold-Stored Rat Heart

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 m M ( n = 5), 0.05 m M ( n = 13), 0.1 m M ( n = 5), 0.2 m M ( n = 5), or 0.75 m M DF ( n = 5)]; (ii) DF treatment during reperfusion [KHB + 0.3 m M ( n = 5), 0.6 m M ( n = 7), 0.75 m M ( n = 11), 1.0 m M ( n = 6), 1.5 m M ( n = 4), or 2.5 m M 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 m M ) during 30 min reperfusion produced significantly better function compared to the untreated group (P M group was AF, 71%; CO, 67%; SP, 76%; work, 52% of control. The functional recovery of the 1.0 m M group was CO, 68%; SP, 79%; DP, 82%; work, 55% of control. Shorter treatment with 0.75 m M 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.