Background and Aims Intravenous iron therapies contain iron–carbohydrate complexes, designed to ensure iron becomes bioavailable via the intermediary of spleen and liver reticuloendothelial macrophages. How other tissues obtain and handle this iron remains unknown. This study addresses this question in the context of the heart. Methods A prospective observational study was conducted in 12 patients receiving ferric carboxymaltose (FCM) for iron deficiency. Myocardial, spleen, and liver magnetic resonance relaxation times and plasma iron markers were collected longitudinally. To examine the handling of iron taken up by the myocardium, intracellular labile iron pool (LIP) was imaged in FCM-treated mice and cells. Results In patients, myocardial relaxation time T1 dropped maximally 3 h post-FCM, remaining low 42 days later, while splenic T1 dropped maximally at 14 days, recovering by 42 days. In plasma, non-transferrin-bound iron (NTBI) peaked at 3 h, while ferritin peaked at 14 days. Changes in liver T1 diverged among patients. In mice, myocardial LIP rose 1 h and remained elevated 42 days after FCM. In cardiomyocytes, FCM exposure raised LIP rapidly. This was prevented by inhibitors of NTBI transporters T-type and L-type calcium channels and divalent metal transporter 1. Conclusions Intravenous iron therapy with FCM delivers iron to the myocardium rapidly through NTBI transporters, independently of reticuloendothelial macrophages. This iron remains labile for weeks, reflecting the myocardium’s limited iron storage capacity. These findings challenge current notions of how the heart obtains iron from these therapies and highlight the potential for long-term dosing to cause cumulative iron build-up in the heart.

中文翻译：

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静脉铁剂治疗通过一种新途径导致心肌铁含量快速持续上升


背景和目标静脉铁剂疗法含有铁-碳水化合物复合物，旨在确保铁通过脾脏和肝脏网状内皮巨噬细胞的中介变得可生物利用。其他组织如何获取和处理这种铁仍然未知。这项研究在心脏的背景下解决了这个问题。方法 对 12 名因缺铁而接受羧基麦芽糖铁 (FCM) 治疗的患者进行前瞻性观察研究。纵向收集心肌、脾脏和肝脏磁共振弛豫时间和血浆铁标记物。为了检查心肌吸收铁的处理情况，对 FCM 处理的小鼠和细胞中的细胞内不稳定铁池 (LIP) 进行成像。结果 在患者中，心肌舒张时间 T1 在 FCM 后 3 小时下降最大，并在 42 天后保持较低水平，而脾脏 T1 在 14 天时下降最大，并在 42 天恢复。在血浆中，非转铁蛋白结合铁 (NTBI) 在 3 小时达到峰值，而铁蛋白在 14 天达到峰值。患者之间肝脏 T1 的变化存在差异。在小鼠中，FCM 后心肌 LIP 上升 1 小时并保持升高状态 42 天。在心肌细胞中，FCM 暴露迅速升高 LIP。 NTBI 转运蛋白 T 型和 L 型钙通道以及二价金属转运蛋白的抑制剂可防止这种情况发生。 结论 FCM 静脉铁剂治疗可通过 NTBI 转运蛋白将铁快速输送至心肌，不依赖于网状内皮巨噬细胞。这种铁在数周内仍不稳定，反映出心肌的铁储存能力有限。这些发现挑战了目前关于心脏如何从这些疗法中获取铁的观念，并强调了长期给药可能导致心脏中铁累积的可能性。