Earliest cardiac toxicity induced by iron overload selectively inhibits electrical conduction

Schwartz, Kenneth A.; Zy, Li; Schwartz, Dianne E.; Cooper, Tim F.; Braselton, W. Emmett

doi:10.1152/japplphysiol.01144.2001

Cited by 42 publications

(39 citation statements)

References 31 publications

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“…The effects of iron overload on mortality are consistent with observations showing that free radical-mediated lipid peroxidation alters cardiomyocyte electrophysiology 42,50 and Ca 2ϩ handling 20,43 and blockade of electrical conduction and sudden death in iron-overloaded guinea pigs. 51 Our strategy was to increase myocardial taurine levels to protect the cardiovascular system and prevent iron overloadinduced cardiovascular dysfunction, even though myocardial taurine levels were not affected by iron overload. This rationale is based on the observation that in the setting of increased oxidative stress, there appears to be an increased (conditioned) demand for taurine.…”

Section: Discussionmentioning

confidence: 99%

Taurine Supplementation Reduces Oxidative Stress and Improves Cardiovascular Function in an Iron-Overload Murine Model

et al. 2004

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Background-Iron overload has an increasing worldwide prevalence and is associated with significant cardiovascular morbidity and mortality. Elevated iron levels in the myocardium lead to impaired systolic and diastolic function and elevated oxidative stress. Taurine accounts for 25% to 50% of the amino acid pool in myocardium, possesses antioxidant properties, and can inhibit L-type Ca 2ϩ channels. Thus, we hypothesized that this agent would reduce the cardiovascular effects of iron overload. Methods and Results-Iron-overloaded mice were generated by intraperitoneal injection of iron either chronically (5 days per week for 13 weeks) or subacutely (5 days per week for 4 weeks). Iron overload causes increased mortality, elevated oxidative stress, systolic and diastolic dysfunction, hypotension, and bradycardia. Taurine supplementation increased myocardial taurine levels by 45% and led to reductions in mortality and improved cardiac function, heart rate, and blood pressure in iron-overloaded mice. Histological examination of the myocardium revealed reduced apoptosis and interstitial fibrosis in iron-overloaded mice supplemented with taurine. Taurine mediated reduced oxidative stress in iron-overloaded mice along with attenuation of myocardial lipid peroxidation and protection of reduced glutathione level. Conclusions-These results demonstrate that treatment with taurine reduces iron-mediated myocardial oxidative stress, preserves cardiovascular function, and improves survival in iron-overloaded mice. The role of taurine in protecting reduced glutathione levels provides an important mechanism by which oxidative stress-induced myocardial damage can be curtailed. Taurine, as a dietary supplement, represents a potential new therapeutic agent to reduce the cardiovascular burden from iron-overload conditions.

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Section: Discussionmentioning

confidence: 99%

Taurine Supplementation Reduces Oxidative Stress and Improves Cardiovascular Function in an Iron-Overload Murine Model

et al. 2004

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“…In a similar way, increased QTc dispersion may also be an indicator of higher risk for arrhythmia and sudden death in thalassaemia major patients. In vitro and in vivo studies have shown that a myocardial iron might change electrical conduction of the cardiomyocytes and lead to sudden death in the patients with iron overload [21,22]. The mechanism of arrhythmia induced by iron accumulation might be due to the loss of functional Na + channels and enhance Na channel inactivation, resulting in a reduced overshoot of cardiac action potential.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of QT dispersion in β thalassaemia major patients

et al. 2006

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Cardiac complications are considered to be the primary cause of death in patients with b thalassaemia major. QT dispersion is a marker variability of ventricular repolarization and is elevated in various high risk groups of patients. This study was carried out in patients with b thalassaemia major to evaluate QT dispersion and to investigate the relationship between QT dispersion and body iron load. Sixty-two b thalassaemia major patients were enrolled into the study. The average serum ferritin levels and liver iron concentration was assessed. For each patient, QTQTc intervals and QT-QTc dispersions were calculated and V1S and V5R were measured. All the subjects underwent two-dimensional M mode echocardiogram and Doppler study. LVMI was found higher in thalassaemia major patients compared to control group. b thalassaemia major patients showed significantly higher mean QT, QTc, QTd, and QTcd values compared to the control group. The mean V5R and V1S amplitudes were also higher in b thalassaemia major patients. There was a positive correlation between LVMI and QTc, QTd and QTcd. However, there was no significant correlation between QT dispersion and serum ferritin and liver iron concentration. Prospective longitudinal studies are needed to assess the prognostic significance of these findings. Am. J. Hematol. 81:901-906, 2006. V V C 2006 Wiley-Liss, Inc.

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“…MR-T2* seems to be superlative (but costly) in terms of noninvasiveness, earliness (sensitivity) and accuracy (specificity), due to its ability to simultaneously assess both cardiac iron and structure, as well as cardiac function. Although cardiac dysfunction is more clinically obvious than conduction disturbance or arrhythmias in iron-overloaded patients, the pathogenesis of arrhythmias may start at the same time, with, or even earlier, than contractile dysfunction (39). It has been shown that when patients have symptoms of arrhythmias, the mortality rate is potentially high (12).…”

Section: Assessment For the Development Of Iron Overload Cardiomyopathymentioning

confidence: 99%

“…In ex vivo guinea pig hearts, delayed and blocked electrical conduction has been demonstrated to occur earlier in iron-loaded cardiac toxicity than impaired contractility (39). An optical mapping study of ironloaded Mongolian gerbils (77) also exhibited pertinent results of slow conduction and impulse block, with evidence of re-entry, which may lead to cardiac arrhythmias.…”

Section: Mechanisms Of Electrical Disturbance In Iron Overload Cardiomentioning

confidence: 99%

Iron overload thalassemic cardiomyopathy: Iron status assessment and mechanisms of mechanical and electrical disturbance due to iron toxicity

Lekawanvijit

Chattipakorn

2009

Canadian Journal of Cardiology

106

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Earliest cardiac toxicity induced by iron overload selectively inhibits electrical conduction

Abstract: Earliest cardiac toxicity induced by iron overload selectively inhibits electrical conduction.

Cited by 42 publications

References 31 publications

Taurine Supplementation Reduces Oxidative Stress and Improves Cardiovascular Function in an Iron-Overload Murine Model

Taurine Supplementation Reduces Oxidative Stress and Improves Cardiovascular Function in an Iron-Overload Murine Model

Evaluation of QT dispersion in β thalassaemia major patients

Iron overload thalassemic cardiomyopathy: Iron status assessment and mechanisms of mechanical and electrical disturbance due to iron toxicity

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