Bimodal cardiac dysfunction in an animal model of iron overload.
Iron-overload cardiomyopathy is the most common cause of death in patients with thalassemia major, yet the associated changes in cardiac function have not been quantified. We studied the effects of iron overload on cardiac function in Mongolian gerbils, a species that responds to iron overload in the same manner as human beings. We injected iron-dextran or dextran alone at low subcutaneous doses (200 mg/kg/wk) for 20 to 60 weeks and at high doses (800 mg/kg/wk) for 6 to 20 weeks. At shorter durations for either dose, the mean values of cardiac work, coronary flow, left ventricular (dP/dt)(max) and left ventricular (dP/dt)(min) in isolated perfused hearts were significantly greater than control values; at longer durations, these values were significantly less than control values. Echocardiography in intact animals showed eccentric cardiac hypertrophy, increased cardiac output, and normal exercise tolerance at shorter durations of dosage. At longer durations, concentric cardiac hypertrophy developed, and cardiac output and exercise capacity were impaired. The response to iron overload in Mongolian gerbils progresses from an initial state of high cardiac output to a subsequent state of low-output failure similar to the course of cardiomyopathy that has been inferred in patients with transfusional iron overload.
Yang
Tianen
T
Rammelkamp Center for Education and Research, MetroHealth Campus, 2500 MetroHealth Drive R301, Cleveland, OH 44109-1998, USA.
Dong
Wei-Qiang
WQ
Kuryshev
Yuri A
YA
Obejero-Paz
Carlos
C
Levy
Matthew N
MN
Brittenham
Gary M
GM
Kiatchoosakun
Songsak
S
Kirkpatrick
Darryl
D
Hoit
Brian D
BD
Brown
Arthur M
AM
D000818:Animals; D002302:Cardiac Output; D009202:Cardiomyopathies / Q000000981:diagnostic imaging / Q000209:etiology* / Q000503:physiopathology*; D003326:Coronary Circulation; D004195:Disease Models, Animal; D004452:Echocardiography; D005260:Female; D005849:Gerbillinae; D006801:Humans; D007501:Iron / Q000008:administration & dosage; D019190:Iron Overload / Q000150:complications* / Q000503:physiopathology*; D009200:Myocardial Contraction; D017086:beta-Thalassemia / Q000150:complications / Q000503:physiopathology
D007501:Iron