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Pentoxifylline improves reoxygenation-induced contractile<br />

recovery through a nitric oxide dependent mechanism in rat<br />

papillary muscles<br />

Dehpour AR, Ebrahimi F, Hajrasouliha AR , S Tavakoli, Sadeghipour H, Ghasemi<br />

M, Ahmadi SH and Ziabakhsh Sh<br />

Mazandaran Heart Center, Sari, Iran.<br />

Tehran Heart Center, Medical Sciences/University of Tehran, Tehran, Iran<br />

Abstarct<br />

Background: In this study, the protective effect of pentoxifylline against hypoxiareoxygenation<br />

injury and the possible involvement of nitric oxide (NO)-mediated<br />

pathways in this protection were investigated in isolated rat papillary muscles.<br />

Methods: Papillary muscles were excised and isolated in Krebs-Henseleit solution<br />

aerated with 95% O2 and 5% CO2. Hypoxia was simulated by substituting O2 with<br />

argon. Three sets of experiments, testing 30, 60, and 90 min of hypoxia, were performed.<br />

The effects of different pentoxifylline concentrations on papillary muscle contractile<br />

parameters and responsiveness to isoproterenol were assessed. To investigate the role of<br />

NO, N(omega)-nitro-L-arginine methyl ester was added before pentoxifylline treatment.<br />

Results: Pentoxifylline did not show any inotropic effect on papillary muscles. Hypoxia<br />

caused a profound depression of contractile parameters, which was not affected by<br />

pentoxifylline treatment. Reoxygenation resulted in significant partial recovery of<br />

contractile parameters after 30 and 60 but not 90 min of hypoxia. In experiments with 30<br />

and 60 min of hypoxia, reoxygenation-induced contractile recovery and responsiveness to<br />

isoproterenol were improved by pentoxifylline in a concentration-dependent fashion.<br />

These functional improvements were completely blocked by N(omega)-nitro-L-arginine<br />

methyl ester pretreatment. No improvement was observed in 90-min hypoxia experiment.<br />

Conclusion: In conclusion, pentoxifylline improved contractile recovery during<br />

reoxygenation and postreoxygenation responsiveness to beta-adrenergic stimulation<br />

through the NO-dependent mechanism.<br />

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