d-Propranolol protects against oxidative stress and progressive cardiac dysfunction in iron overloaded rats.
d-Propranolol protects against oxidative stress and progressive cardiac dysfunction in iron overloaded rats.
- 2012
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.
English
0008-4212
*Adrenergic beta-Antagonists/tu [Therapeutic Use]
*Heart Diseases/pc [Prevention & Control]
*Iron Overload/dt [Drug Therapy]
*Oxidative Stress/de [Drug Effects]
*Propranolol/tu [Therapeutic Use]
Acetylglucosaminidase/bl [Blood]
Adrenergic beta-Antagonists/ad [Administration & Dosage]
Adrenergic beta-Antagonists/ch [Chemistry]
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]
Iron Overload/bl [Blood]
Iron Overload/co [Complications]
Iron Overload/me [Metabolism]
Male
Myocardium/me [Metabolism]
Neutrophils/de [Drug Effects]
Neutrophils/en [Enzymology]
Perfusion
Propranolol/ad [Administration & Dosage]
Propranolol/ch [Chemistry]
Rats
Rats, Sprague-Dawley
Stereoisomerism
Superoxide Dismutase/me [Metabolism]
Treatment Outcome
MedStar Heart & Vascular Institute
MedStar Washington Hospital Center
Neonatology and Pediatrics
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
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.
English
0008-4212
*Adrenergic beta-Antagonists/tu [Therapeutic Use]
*Heart Diseases/pc [Prevention & Control]
*Iron Overload/dt [Drug Therapy]
*Oxidative Stress/de [Drug Effects]
*Propranolol/tu [Therapeutic Use]
Acetylglucosaminidase/bl [Blood]
Adrenergic beta-Antagonists/ad [Administration & Dosage]
Adrenergic beta-Antagonists/ch [Chemistry]
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]
Iron Overload/bl [Blood]
Iron Overload/co [Complications]
Iron Overload/me [Metabolism]
Male
Myocardium/me [Metabolism]
Neutrophils/de [Drug Effects]
Neutrophils/en [Enzymology]
Perfusion
Propranolol/ad [Administration & Dosage]
Propranolol/ch [Chemistry]
Rats
Rats, Sprague-Dawley
Stereoisomerism
Superoxide Dismutase/me [Metabolism]
Treatment Outcome
MedStar Heart & Vascular Institute
MedStar Washington Hospital Center
Neonatology and Pediatrics
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.