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d-Propranolol protects against oxidative stress and progressive cardiac dysfunction in iron overloaded rats.

by Spurney, Christopher F; Iantorno, Micaela.

Citation: Canadian Journal of Physiology & Pharmacology. 90(9):1257-68, 2012 Sep..Journal: Canadian journal of physiology and pharmacology.ISSN: 0008-4212.Full author list: Kramer JH; Spurney CF; Iantorno M; Tziros C; Chmielinska JJ; Mak IT; Weglicki WB.UI/PMID: 22913465.Subject(s): Acetylglucosaminidase/bl [Blood] | Adrenergic beta-Antagonists/ad [Administration & Dosage] | Adrenergic beta-Antagonists/ch [Chemistry] | *Adrenergic beta-Antagonists/tu [Therapeutic Use] | Animals | Cardiac Output/de [Drug Effects] | Disease Progression | Dose-Response Relationship, Drug | Echocardiography | Erythrocytes/de [Drug Effects] | Erythrocytes/me [Metabolism] | Glutathione | Heart Diseases/bl [Blood] | Heart Diseases/et [Etiology] | Heart Diseases/me [Metabolism] | *Heart Diseases/pc [Prevention & Control] | Iron Overload/bl [Blood] | Iron Overload/co [Complications] | *Iron Overload/dt [Drug Therapy] | Iron Overload/me [Metabolism] | Male | Myocardium/me [Metabolism] | Neutrophils/de [Drug Effects] | Neutrophils/en [Enzymology] | *Oxidative Stress/de [Drug Effects] | Perfusion | Propranolol/ad [Administration & Dosage] | Propranolol/ch [Chemistry] | *Propranolol/tu [Therapeutic Use] | Rats | Rats, Sprague-Dawley | Stereoisomerism | Superoxide Dismutase/me [Metabolism] | Treatment OutcomeInstitution(s): MedStar Washington Hospital Center | MedStar Heart & Vascular InstituteDepartment(s): Neonatology and PediatricsActivity type: Journal Article.Medline article type(s): Journal Article | Research Support, Non-U.S. Gov't | Research Support, U.S. Gov't, P.H.SOnline resources: Click here to access online Digital Object Identifier: http://dx.doi.org/10.1139/y2012-091 (Click here) Abbreviated citation: Can J Physiol Pharmacol. 90(9):1257-68, 2012 Sep.Abstract: 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.

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