Department of Cardiology, Pulmonology and Vascular Medicine, Medical Faculty, Heinrich-Heine University, Moorenstr. 5, Düsseldorf, 40225, Germany.
Department of Nanomedicines, Vifor Pharma Management Ltd, Glattbrugg, Switzerland.
ESC Heart Fail. 2021 Dec;8(6):5445-5455. doi: 10.1002/ehf2.13639. Epub 2021 Oct 11.
Iron deficiency is frequently observed in patients with acute coronary syndrome and associates with poor prognosis after acute myocardial infarction (AMI). Anaemia is linked to dysregulation of iron metabolism, red blood cell dysfunction, and increased reactive oxygen species generation. Iron supplementation in chronic heart failure is safe and improves cardiac exercise capacity. Increases in iron during ischaemia or immediately after reperfusion are associated with detrimental effects on left ventricular (LV) function. The safety and applicability of iron during or immediately after reperfusion of AMI in anaemia are not known. We aimed to study the safety and efficacy of iron supplementation within 1 h or deferred to 24 h after reperfusion of AMI by analysing LV function and infarct size.
In a mouse model of moderate blood loss anaemia (n = 6-8 mice/group), the effects of iron supplementation (20 mg iron as ferric carboxymaltose per kg body weight) within 1 h and deferred to 24 h after ischaemia/reperfusion were assessed. Cardiac function was analysed in vivo by echocardiography at baseline (Day 3) with and without anaemia, after AMI (24 h), and after administration of intravenous iron. Anaemia was characterized by iron deficiency and a trend towards increased haemolysis, which was supported by increased plasma free-haemoglobin [sham vs. anaemia (n = 8/group): P < 0.05]. Anaemia increased heart rate, LV end-diastolic volume, stroke volume, and cardiac output, while LV end-systolic volume remained unchanged at baseline. Superimposition of AMI deteriorated global LV function, whereas infarct sizes remained unaffected [sham vs. anaemia (n = 6/group): P = 0.9]. Deferred iron supplementation 24 h after ischaemia/reperfusion resulted in reversal of end-systolic volume increase and reduced infarct size [% of area at risk: sham vs. anaemia + iron after 24 h; (n = 6/group); 48 ± 7 vs. 38 ± 7; P < 0.05], whereas administration within 1 h after reperfusion was neutral [sham vs. anaemia + iron; (n = 6/group); 48 ± 7 vs. 42 ± 8; P = 0.56]. Moreover, iron application after reperfused AMI showed unaltered mortality compared with sham.
Iron supplementation 24 h after reperfusion of AMI is safe and reversed enlargement of end-systolic volume after AMI resulting in increased stroke volume and cardiac output. This highlights its potential as adjunctive treatment in anaemia with ID after reperfused AMI. Time point of iron application after reperfusion appears critical.
急性冠状动脉综合征患者常伴有缺铁，且与急性心肌梗死（AMI）后预后不良相关。贫血与铁代谢失调、红细胞功能障碍和活性氧生成增加有关。在慢性心力衰竭中补充铁是安全的，并能改善心脏运动能力。缺血或再灌注后铁的增加与左心室（LV）功能的有害影响有关。在 AMI 贫血患者再灌注期间或之后立即补充铁的安全性和适用性尚不清楚。我们旨在通过分析 LV 功能和梗死面积来研究 AMI 再灌注后 1 小时内或延迟至 24 小时内补充铁的安全性和疗效。
在中度失血性贫血的小鼠模型中（每组 6-8 只小鼠），评估了缺血/再灌注后 1 小时内和 24 小时内补充铁（每公斤体重 20 毫克铁作为羧基麦芽糖铁）的效果。通过超声心动图在基础状态（第 3 天），有无贫血，AMI 后（24 小时）以及静脉内铁剂给药后，在体内分析心功能。贫血的特征是缺铁和溶血趋势增加，这得到了血浆游离血红蛋白增加的支持[假手术 vs. 贫血（每组 8 只）：P<0.05]。贫血增加心率、LV 舒张末期容积、每搏输出量和心输出量，而 LV 收缩末期容积在基础状态下保持不变。再灌注 AMI 的叠加使整体 LV 功能恶化，而梗死面积保持不变[假手术 vs. 贫血（每组 6 只）：P=0.9]。缺血/再灌注后 24 小时延迟铁补充导致收缩末期容积增加逆转，并减少梗死面积[梗死面积占危险区域的百分比：假手术+贫血后 24 小时（每组 6 只）：（48±7）%比（38±7）%；P<0.05]，而在再灌注后 1 小时内给药则无影响[假手术+贫血（每组 6 只）：（48±7）%比（42±8）%；P=0.56]。此外，与假手术相比，AMI 再灌注后的铁应用并未增加死亡率。
AMI 再灌注后 24 小时补充铁是安全的，并逆转 AMI 后收缩末期容积增大，导致每搏输出量和心输出量增加。这突出了其在 AMI 再灌注后 ID 合并贫血中的辅助治疗潜力。再灌注后铁应用的时间点似乎至关重要。
