Aya Matsushita

Xanthine oxidase inhibition improves left ventricular dysfunction in dilated cardiomyopathic hamsters.

BACKGROUND Oxidative stress is implicated in cardiac remodeling and failure. We tested whether xanthine oxidase (XO) inhibition could decrease myocardial oxidative stress and attenuate left ventricular (LV) remodeling and dysfunction in the TO-2 hamster model of dilated cardiomyopathy. METHODS AND RESULTS TO-2 hamsters were randomized to treatment with the XO inhibitor, allopurinol, or vehicle from 6 to 12 weeks of age. F1B hamsters served as controls. TO-2 hamsters treated with vehicle progressively developed severe LV systolic dysfunction and dilation between 6 and 12 weeks. Marked cardiac fibrosis was apparent in these hamsters at 12 weeks in comparison with F1B controls. The ratio of reduced to oxidized glutathione (GSH/GSSG) was decreased and malondialdehyde levels were increased in the hearts of vehicle-treated TO-2 hamsters. Treatment with allopurinol from 6 to 12 weeks attenuated LV dysfunction and dilation as well as myocardial fibrosis and the upregulation of a fetal-type cardiac gene. Allopurinol also inhibited both the decrease in GSH/GSSG ratio and the increase in malondialdehyde levels in the heart. CONCLUSIONS These results indicate that chronic XO inhibition with allopurinol attenuates LV remodeling and dysfunction as well as myocardial oxidative stress in this model of heart failure. Allopurinol may prove beneficial for the treatment of heart failure.

Changes in the chemical compositions of leaf litter in the canopy of a Japanese cedar plantation

ABSTRACT Canopy leaf litter is typically unevenly distributed due to interception by branches and epiphytes and/or due to attachment to branches and tree trunks. Japanese cedar (Cryptomeria japonica) trees hold a large amount of canopy litter that stays attached to foliage and branches for several years before litterfall. Litter retention in the canopy is predicted to affect the chemical composition of litterfall and throughfall. We analyzed the chemical compositions of water-soluble materials washed from the leaves and those of the leaf residues with different leaf litter ages to clarify the effect of leaf-litter retention in the canopy of Japanese cedar trees. Chemical components of the leaf litter after the washing procedure show temporal changes in total carbon, total nitrogen, and carbon/nitrogen ratio just after senescence and prior to litterfall. Higher inorganic ion concentrations in soluble materials from old dead leaves (ODL) dead for more than 2 years suggest the importance of ODL in leaching and catching chemical components in the canopy. Our results show that Japanese cedar canopies retain the various qualities of leaf litter, which are produced by senescence, leaching, and catching dry deposition, and that a large amount of dissolved components leach from dead leaves that are still attached to the canopy.

1106-185 Growth hormone-releasing peptide can suppress myocardial oxidative stress and ameliorate progressive left ventricular remodeling in cardiomyopathic hamsters

Background: Growth hormone-releasing peptide (GHRP) may act directly on the myocardium and improve left ventricular (LV) function, implicating a potential new approach to the treatment of cardiomyopathic hearts. We hypothesized that cardiac favorable effects of GHRPs might include the attenuation of myocardial oxidative stress. Methods and Results: Dilated cardiomyopathic TO-2 hamsters (6 weeks old) were injected with GHRP-2 (1mg/kg per day, n=8), or saline (n=8) for 6 weeks. F1B hamsters served as controls (n=8). LV functional and structural changes were evaluated by echocardiogram and the extents of myocardial oxidative stress were determined by myocardial 4-hydroxy-2-noneal (HNE) concentration as well as the tissue-reduced glutathion, oxidized glutathione, and the redox ratio (GSH/GSSG). LV fractional shortening (LVFS) decreased from 53.0 ± 1.4 to 25.1 ± 1.0 % and the LV end-diastolic dimension increased from 3.7 ± 0.1 to 5.0 ± 0.1 mm in untreated TO-2 hamsters between 6 and 12 weeks. Both LVFS and LV dimension were substantially improved by treatment with GHRP-2 (41.5 ± 1.5 %, 4.6 ± 0.1 mm, respectively). The ratio of LV dimension / LV wall thickness in untreated TO-2 hamsters was significantly greater than that in controls (6.42 ± 0.23 Versus 3.73 ± 0.13, p<0.001), and was substantially normalized by the treatment with GHRP-2 (4.78 ± 0.23). The extent of cardiac fibrosis in TO-2 hamsters with GHRP was significantly less than that in untreated TO-2 hamsters. The level of HNE in hearts of TO2 hamsters was greater than that in controls (1.63 ± 0.14 Versus 0.85 ± 0.08 pmol/mg protein ), and was normalized by the treatment of GHRP-2 (0.71 ± 0.07 pmol/mg protein). The redox ratio in hearts of untreated TO-2 hamsters was greater than that in controls (2.98 ± 0.08 Versus 1.95 ± 0.04, p<0.005) and it was improved by the treatment of GHRP-2 (2.36 ± 0.08). Myocardial glutathione peroxidase activity in untreated TO-2 hamsters was similar to that in F1B hamsters. Conclusion: GHRP can reduce myocardial oxidative stress during the initial development of LV dysfunction, leading to a favorable modification of progressive LV remodeling process in dilated cardiomyopathic hamsters.