Depression of contractility in isolated rabbit myocardium following exposure to iron: role of free radicals.
The mechanism of acute iron cardiotoxicity was investigated in isometrically contracting left atrial strips and right ventricular papillary muscles isolated from rabbit hearts. A 90-min exposure to iron (1.8 mM; as ferrous sulfate) reduced the peak-developed tension and the maximal rate of tension development. The presence of either N-acetylcysteine (20 mM), superoxide dismutase (2000 units/ml), or mannitol (5 mM) prevented this depression of contractility. Catalase (30,000 units/ml) was not protective against the effects of iron. Iron did not decrease myocardial adenosine triphosphate or creatine phosphate contents. The force-frequency relationship (positive staircase phenomenon) was examined in the absence and presence of iron. Iron did not reduce the positive inotropic response evoked by increasing the stimulation frequency, but at higher frequencies iron prolonged the time from peak tension to 90% relaxation. We conclude that acute iron cardiotoxicity may be mediated by free radical generation and does not involve impairment of myocardial high energy phosphate production.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D004558:Electric Stimulation; D005260:Female; D005609:Free Radicals; D066298:In Vitro Techniques; D007501:Iron / Q000633:toxicity*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009200:Myocardial Contraction / Q000187:drug effects*; D010210:Papillary Muscles / Q000187:drug effects; D010725:Phosphocreatine / Q000378:metabolism; D011817:Rabbits
D005609:Free Radicals; D010725:Phosphocreatine; D000255:Adenosine Triphosphate; D007501:Iron