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SUMMARY Intravenous iron preparations have shown benefit in patients with chronic heart failure (CHF) and iron deficiency. Iron isomaltoside 1000 (Monofer) is a novel intravenous iron compound with low immunological activity of the isomaltoside and low free‐iron‐related toxicity. The primary objective of this open‐label, non‐comparative, multicenter pilot study was to test the safety of iron isomaltoside 1000 in patients with CHF and anemia. In addition, its effect on markers of iron deficiency, anemia and on quality of life was assessed. Twenty patients with CHF and iron deficiency anemia attended six visits during the 8‐week study period. Iron isomaltoside 1000 was infused at baseline (mean dose 868 mg, range 650–1000 mg). No treatment‐related adverse reactions, no acute anaphylactic or delayed allergic reactions and no clinically significant changes in routine clinical laboratory safety tests or vital signs were observed. Markers of iron deficiency, anemia and quality of life improved from baseline with increase in mean value of 49% at 4 weeks in overall quality of life. Iron isomaltoside 1000 administered as a fast single infusion without a test dose to patients with CHF improved quality‐of‐life assessments and was well tolerated in this pilot safety study.

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The aim of the present study was to investigate the proliferative effects of Ang II in human cardiac fibroblasts. The effects of Ang II in human cardiac fibroblasts on the 3H-thymidine incorporation, the cell number, the 3H-leucine incorporation and the total protein content were measured. The expression of receptor mRNA was performed by reverse transcription-polymerase chain reaction (RT-PCR). Ang II increased 3H-leucine incorporation in a concentration-dependent manner but not 3H-thymidine incorporation in primary cultures of human cardiac fibroblasts. The maximum effect (24 +/- 3% over control) was obtained at a concentration of 10 nM. There were no significant alterations of cell number or total protein content, suggesting that Ang II stimulated protein synthesis but did not induce hypertrophy. The accumulation of 3H-leucine was blocked by the AT1 receptor antagonist candesartan but not by the AT2 receptor antagonist PD123319. By using RT-PCR, both AT1 and AT2 receptors mRNA were found to be expressed in human cardiac fibroblasts. The selective MAPKK inhibitor PD098059, the protein kinase C inhibitor K252a or the phospholipase C inhibitor U73122 did not significantly inhibit Ang II augmented 3H-leucine incorporation. However, this was significantly blocked by the Ca2+-dependent protein kinase C inhibitor GO6976, the non-selective protein kinase inhibitor staurosporine and the tyrosine kinase inhibitor tyrphostin 25. The effects of Ang II were unaffected by the Gi-protein blocker pertussis toxin, indicating a Gi-protein-independent pathway. Ang II was synergistic with insulin but showed no significant increase on 3H-leucine incorporation when combined with PDGF or EGF. In summary, Ang II stimulates protein synthesis through AT1 receptors in human cardiac fibroblasts, but has no hypertrophic or hyperplastic effect. The response is mediated by a MAPKK-independent and Ca2+-sensitive PKC-dependent pathway.