Mechanisms involved in the in vitro contractile dysfunction induced by different concentrations of ferrous iron in the rat myocardium

- In vitro high Fe2 + concentrations acutely impair myocardial contractility.
- Both myosin ATPase activity and myofibrillar sensitivity to Ca2 + are reduced.
- Iron toxicity is, at least in part, mediated by local production of OH
- and H2O2.
- Milimolar Fe2 + depressed force also by impairing the participation of Ca2 + influx.
- Regardless the oxidative stress, Fe2 + probably competes with Ca2 + for its channels.

Iron intoxication is related to reactive oxygen species (ROS) production and organic damage including the cardiovascular system, and is a leading cause of poisoning deaths in children. In this study we examined whether a range of ferrous iron (Fe(2 +)) concentrations can interfere differently on the myocardial mechanics, investigating the ROS-mediated effects. Developed force of isolated rat papillary muscles was depressed with a concentration- and time-dependency by Fe(2 +) 100-1000 μM. The contractile response to Ca(2 +) was reduced, but it was partially reversed by co-incubation with catalase and DMSO, but not TEMPOL. In agreement, in situ detection of OH was increased by Fe(2 +) whereas O2− was unchanged. The myosin-ATPase activity was significantly decreased. Contractions dependent on the sarcolemal Ca(2 +) influx were impaired only by Fe(2 +) 1000 μM, and antioxidants had no effect. In skinned fibers, Fe(2 +) reduced the pCa-force relationship, and pCa50 was right-shifted by 0.55. In conclusion, iron overload can acutely impair myocardial contractility by reducing myosin-ATPase activity and myofibrillar Ca(2 +) sensitivity. These effects are mediated by local production of OH and H2O2. Nevertheless, in a such high concentration as 1000 μM, Fe(2 +) appears to depress force also by reducing Ca(2 +) influx, probably due to a competition at Ca(2 +) channels.