TY  - BOOK
AU  - Iantorno, Micaela
AU  - Spurney, Christopher F
TI  - d-Propranolol protects against oxidative stress and progressive cardiac dysfunction in iron overloaded rats
SN  - 0008-4212
PY  - 2012///
KW  - *Adrenergic beta-Antagonists/tu [Therapeutic Use]
KW  - *Heart Diseases/pc [Prevention & Control]
KW  - *Iron Overload/dt [Drug Therapy]
KW  - *Oxidative Stress/de [Drug Effects]
KW  - *Propranolol/tu [Therapeutic Use]
KW  - Acetylglucosaminidase/bl [Blood]
KW  - Adrenergic beta-Antagonists/ad [Administration & Dosage]
KW  - Adrenergic beta-Antagonists/ch [Chemistry]
KW  - Animals
KW  - Cardiac Output/de [Drug Effects]
KW  - Disease Progression
KW  - Dose-Response Relationship, Drug
KW  - Echocardiography
KW  - Erythrocytes/de [Drug Effects]
KW  - Erythrocytes/me [Metabolism]
KW  - Glutathione
KW  - Heart Diseases/bl [Blood]
KW  - Heart Diseases/et [Etiology]
KW  - Heart Diseases/me [Metabolism]
KW  - Iron Overload/bl [Blood]
KW  - Iron Overload/co [Complications]
KW  - Iron Overload/me [Metabolism]
KW  - Male
KW  - Myocardium/me [Metabolism]
KW  - Neutrophils/de [Drug Effects]
KW  - Neutrophils/en [Enzymology]
KW  - Perfusion
KW  - Propranolol/ad [Administration & Dosage]
KW  - Propranolol/ch [Chemistry]
KW  - Rats
KW  - Rats, Sprague-Dawley
KW  - Stereoisomerism
KW  - Superoxide Dismutase/me [Metabolism]
KW  - Treatment Outcome
KW  - MedStar Heart & Vascular Institute
KW  - MedStar Washington Hospital Center
KW  - Neonatology and Pediatrics
KW  - Journal Article
KW  - Research Support, Non-U.S. Gov't
KW  - Research Support, U.S. Gov't, P.H.S
N2  - d-Propranolol (d-Pro: 2-8 mg.(kg body mass)(-1).day(-1)) protected against cardiac dysfunction and oxidative stress during 3-5 weeks of iron overload (2 mg Fe-dextran.(g body mass)(-1).week(-1)) in Sprague-Dawley rats. At 3 weeks, hearts were perfused in working mode to obtain baseline function; red blood cell glutathione, plasma 8-isoprostane, neutrophil basal superoxide production, lysosomal-derived plasma N-acetyl--galactosaminidase (NAGA) activity, ventricular iron content, and cardiac iron deposition were assessed. Hearts from the Fe-treated group of rats exhibited lower cardiac work (26%) and output (CO, 24%); end-diastolic pressure rose 1.8-fold. Further, glutathione levels increased 2-fold, isoprostane levels increased 2.5-fold, neutrophil superoxide increased 3-fold, NAGA increased 4-fold, ventricular Fe increased 4.9-fold; and substantial atrial and ventricular Fe-deposition occurred. d-Pro (8 mg) restored heart function to the control levels, protected against oxidative stress, and decreased cardiac Fe levels. After 5 weeks of Fe treatment, echocardiography revealed that the following were depressed: percent fractional shortening (%FS, 31% lower); left ventricular (LV) ejection fraction (LVEF, 17%), CO (25%); and aortic pressure maximum (P(max), 24%). Mitral valve E/A declined by 18%, indicating diastolic dysfunction. Cardiac CD11b+ infiltrates were elevated. Low d-Pro (2 mg) provided modest protection, whereas 4-8 mg greatly improved LVEF (54%-75%), %FS (51%-81%), CO (43%-78%), P(max) (56%-100%), and E/A >100%; 8 mg decreased cardiac inflammation. Since d-Pro is an antioxidant and reduces cardiac Fe uptake as well as inflammation, these properties may preserve cardiac function during Fe overload
UR  - http://dx.doi.org/10.1139/y2012-091
ER  -