Author(s): Kramer JH, Spurney CF, Iantorno M, Tziros C, Chmielinska JJ, , Kramer JH, Spurney CF, Iantorno M, Tziros C, Chmielinska JJ,
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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-β-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.
This article was published in Can J Physiol Pharmacol
and referenced in Journal of Blood Disorders & Transfusion