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.
METHODS AND RESULTS: 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.
CONCLUSIONS:
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.