Intravenous iron sucrose reverses anemia-induced cardiac remodeling, prevents myocardial fibrosis, and improves cardiac function by attenuating oxidative/nitrosative stress and inflammation

- Intravenous (i.v.) iron sucrose (10 mg Fe/kg body weight) was administered to anemic rats in five weekly doses.
- Iron sucrose reversed anemia-induced cardiac remodeling, prevented myocardial fibrosis, and improved cardiac function.
- Anemia-induced inflammation was prevented by iron sucrose.
- Iron sucrose favorably modulated the levels of proinflammatory and repair process markers.
- Iron sucrose treatment reduced anemia-induced oxidative and nitrosative stress.
- The positive effects of iron sucrose treatment were evident in the heart even though anemia was not fully corrected.

BackgroundAccording to recent clinical trial data, correction of iron deficiency with intravenous (i.v.) iron has favorable outcomes on cardiac function. We evaluated whether i.v. iron treatment of anemic rats has favorable effect on the left ventricular (LV) performance and remodeling and the role of oxidative/nitrosative stress and inflammation in the process.MethodsAfter weaning, Sprague-Dawley rats were fed low iron diet for 16 weeks, after which the treatment group received five weekly doses of i.v. iron sucrose (10 mg Fe/kg body weight). Echocardiography of LV was performed and hematology parameters were assessed before treatment (baseline, day 0) and at the end of the study (day 29). On day 29, rats were sacrificed and extracellular expansion and fibrosis in LV and interventricular septum were evaluated together with oxidative/nitrosative stress, pro-inflammatory, and repair process markers.ResultsAlthough iron sucrose treatment did not fully correct the anemia, it reversed anemia-induced cardiac remodeling as indicated by echocardiographic and tissue Doppler parameters. Treatment with iron sucrose also prevented anemia-induced myocardial fibrosis as indicated by extracellular expansion and fibrosis markers. Anemia-induced inflammation was prevented by iron sucrose as indicated by the levels of proinflammatory (TNF-α, NF-κB65) and repair process markers (HSP27, HSP70). In addition, iron sucrose treatment significantly reduced (p < 0.01) anemia-induced oxidative and nitrosative stress.ConclusionIntravenous iron sucrose treatment reversed anemia-induced remodeling of LV, prevented myocardial fibrosis, and improved cardiac function by attenuating oxidative/nitrosative stress and inflammation in the heart.