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.
Schwartz
Kenneth A
KA
Department of Medicine, Michigan State University, East Lansing, Michigan 48824, USA. Schwart7@msu.edu
Li
Zy
Z
Schwartz
Dianne E
DE
Cooper
Thomas G
TG
Braselton
W Emmett
WE
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