Earliest cardiac toxicity induced by iron overload selectively inhibits electrical conduction.
Female guinea pigs were injected intraperitoneally with 0.083 g/kg iron dextran (Fe-D) to achieve progressively increasing levels of iron load; controls received dextran. Delayed and blocked cardiac conductivity at the Purkinje fiber-papillary muscle junction was initially observed with Fe-D loads of 0.33 g/kg. Serial magnetic resonance relaxation time measurements obtained from livers of live animals showed a decrease (8.1 +/- 0.86 vs. 14.8 +/- 1.03 ms in controls, P < 0.001) that was first observed in animals loaded with 0.25 g/kg Fe-D. Iron concentrations in hearts and livers were significantly increased (P < 0.001). Left ventricular pressure measurements on 1.5 g/kg Fe-D animals failed to demonstrate a defect in contractility, but 27% (9/33) (P < 0.050) of the animals died without warning signs. We conclude that 1) initial decreases in liver magnetic resonance-relaxation time occur in the same range of iron excess as the threshold of iron load that induces delay or blockade of cardiac conduction and 2) a high incidence of sudden death, presumably from cardiac arrhythmias, was observed with large doses of iron that did not decrease left ventricular contractility.
Department of Medicine, Michigan State University, East Lansing, Michigan 48824, USA. Schwart7@msu.edu
Kenneth A
KA
Schwartz
Zy
Z
Li
Dianne E
DE
Schwartz
Thomas G
TG
Cooper
W Emmett
WE
Braselton
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000503:physiopathology; D009202:Cardiomyopathies / Q000139:chemically induced / Q000503:physiopathology; D016757:Death, Sudden, Cardiac; D004553:Electric Conductivity; D005260:Female; D006168:Guinea Pigs; D006329:Heart Conduction System / Q000187:drug effects / Q000502:physiology*; D007501:Iron / Q000032:analysis / Q000633:toxicity*; D019190:Iron Overload / Q000503:physiopathology*; D008099:Liver / Q000737:chemistry / Q000503:physiopathology; D009682:Magnetic Resonance Spectroscopy; D009206:Myocardium / Q000737:chemistry; D016277:Ventricular Function, Left / Q000187:drug effects
D007501:Iron