Endotoksemik sıçan torasik aortasındaki damar yanıtları üzerine pentoksifilin'in etkileri
Küçük Resim Yok
Tarih
2009
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Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Amaç: Endotoksin ve benzeri diğer bakteri ürünleri, mantar ve viruslar tarafından başlatılan olaylar dizisi olan septik şokta TNF-? ve NO başlıca rol oynayan medyatörlerdir. Çalışmada deneysel endotoksik şok modelinde, hücre içi gen transkripsiyonunu inhibe eden, fosfodiesteraz cAMP düzeyini artırarak TNF-? inhibitörü olan pentoksifilin'in sepsiste bozulmuş olan damar yanıtları üzerine olan etkileri araştırıldı. Yöntem ve Gereç: Sıçanlarda endotoksik şok oluşturmak üzere 5 mg/kg LPS (E.coli, serotip 055:B5) intraperitoneal yolla verildi. LPS injeksiyonundan 1 saat sonra pentoksifilin (12.5 ve 25 mg/kg) intraperitoneal yolla uygulandı. LPS injeksiyonundan 18 saat sonra izole edilen torasik aort halkalarında kasılma (fenilefrin, KCl) ve gevşeme (asetilkolin ve sodyum nitroprussid) yanıtları değerlendirildi. Bulgular: Sepsiste hem kasıcı yanıtların hem de endotel bağımlı, reseptör aracılı gevşeme yanıtlarının bozulduğunu göstermektedir. Sepsisteki damar yanıtlarındaki bu olumsuz değişikliklerde LPS'nin ve TNF-? gibi sitokinlerin neden olduğu iNOS indüksiyonu sonucu aşırı NO yapımının başlıca rol oynadığını göstermektedir. Pentoksifilin 12.5 mg/kg verilen sepsisli gruptaki bozulmuş fenilefrin kontraktil yanıtlarını düzeltti (p<0.05). Sepsis grubunda azalmış olan asetilkolin yanıtları pentoksifilin (12.5, 25 mg/kg) verilmesiyle düzeldi (p<0.05). Direkt düz kas gevşetici ajan olan sodyum nitroprussid yanıtlarında gruplar arasında farklılık gözlenmedi. Sonuç: Pentoksifilin ile elde ettiğimiz sonuçlar, bu ajanın önemli bir mortalite nedeni olan septik şokun tedavisinde umut verici olduğunu düşündürmektedir.
Aim: Tumor necrosis factor alpha (TNF-&#945;) and nitric oxide (NO) are important mediators playing key roles in septic shock, a situation which is trigerred by endotoxin and other bacterial products. In this study we investigated the effects of a phosphodiesterase inhibitor, pentoxifylline on the impaired vascular responses in septic shock, since the agent is known to inhibit TNF- &#945; gene expression by increasing intracellular cAMP levels. Material and Methods: Rats were injected intraperitoneally with 5 mg/kg LPS (E.Coli, serotype 055:B5) to induce endotoxic shock. 1 hour after LPS administration pentoxifylline (12.5, 25 mg/kg) was given by the same route. Contractile responses to phenylephrine, potassium chloride-KCl) and relaxant responses to acetylcholine-ACh and sodium nitroprusside- SNP were studied in the thoracic aortas 18 hours after LPS injection. Results: The contractile responses were decreased in septic shock as well as the endothelium-dependent, receptor-mediated vasorelaxant responses. These results show that excessive NO production via iNOS induction caused by LPS and cytokines such as TNF-&#945; play a key role in the vascular responsiveness seen in septic shock. Pentoxifylline (12.5 mg/kg) reversed the contractile responses (p<0.05) in the sepsis group, whereas it increased the ACh responses in both doses (12.5, 25 mg/kg)(p<0.05), which were decreased in the endotoxaemic animals. No differences were found between the groups in terms of the responses to the direct smooth muscle relaxant, sodium nitroprussid. Conclusion: These data obtained from the study consider that pentoxifylline administration might be a useful maneuver in the therapy of septic shock, which is a common cause of mortality.
Aim: Tumor necrosis factor alpha (TNF-&#945;) and nitric oxide (NO) are important mediators playing key roles in septic shock, a situation which is trigerred by endotoxin and other bacterial products. In this study we investigated the effects of a phosphodiesterase inhibitor, pentoxifylline on the impaired vascular responses in septic shock, since the agent is known to inhibit TNF- &#945; gene expression by increasing intracellular cAMP levels. Material and Methods: Rats were injected intraperitoneally with 5 mg/kg LPS (E.Coli, serotype 055:B5) to induce endotoxic shock. 1 hour after LPS administration pentoxifylline (12.5, 25 mg/kg) was given by the same route. Contractile responses to phenylephrine, potassium chloride-KCl) and relaxant responses to acetylcholine-ACh and sodium nitroprusside- SNP were studied in the thoracic aortas 18 hours after LPS injection. Results: The contractile responses were decreased in septic shock as well as the endothelium-dependent, receptor-mediated vasorelaxant responses. These results show that excessive NO production via iNOS induction caused by LPS and cytokines such as TNF-&#945; play a key role in the vascular responsiveness seen in septic shock. Pentoxifylline (12.5 mg/kg) reversed the contractile responses (p<0.05) in the sepsis group, whereas it increased the ACh responses in both doses (12.5, 25 mg/kg)(p<0.05), which were decreased in the endotoxaemic animals. No differences were found between the groups in terms of the responses to the direct smooth muscle relaxant, sodium nitroprussid. Conclusion: These data obtained from the study consider that pentoxifylline administration might be a useful maneuver in the therapy of septic shock, which is a common cause of mortality.
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48
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3
