ROLE OF CYCLOSPORINE A ON ORGAN INJURY SEEN AFTER HEMORRHAGIC SHOCK AND REPERFUSION IN RATS

Neutrophils are an important factor in the organ injury associated with ischemia and reperfusion (I-R). In experimental conditions, besides many chemicals, immunosuppressive agents like cyclosporineA (CsA) and FK 506 were also used to prevent I-R injury. But effect of immunosuppressives on neutrophils still remains unclear. We designed an experimental study to investigate the role of CsA in organ injury after hemorrhagic shock and reperfusion in rats. Forty Wistar albino rats were divided into 4 groups. G 1: Control, G2: Shock, G3: Shock + Reperfusion, G4: CsA. Shock was induced by with drawing of 2,5 ml blood viafemoralvein. The shed blood was then reinfused after 20 min in reperfusion groups. In G4, CsA (20 mg/kg) was given by a single IV injection just before (5 min) the perfusion. Rats were sacrified24 hours after operation. Plasma malondialdehyde (MDA) levels of all groups and, MDA and myeloperoxidase (MPO) levels of liver, lung, small bowel and kidney were measured. In addition, neutrophil counts were obtained from all organs. After I-R, MDA levels of plasma and all organs increased and then returned to normal by CsA administration. This observations revealed the role of free oxygene radicals in I-R injury. But CsA-induced MPO decrease was obtained in only small bowel. In addition, reduction in neutrophil infiltration by CsA was seen in small bowel and kidney. We concluded that, CsA has a beneficial effect on I-R-induced organ injury. But, at least in liver and lung, these results couldn't attributed to reduced neutrophil infiltration. However, increase of CsA dose may cause widespread reduction in neutrophil counts. Further investigations are necessary to clarify the exact role of CsA on I-R injury.

SIÇANLARDA, HEMORAJÝK ÞOK VE REPERFÜZYON SONRASI GÖRÜLEN ORGAN HASARINDA SÝKLOSPORÝN A'NIN ROLÜ

Ýskemiye maruz kalan organlarda, reperfüzyon sonrasý görülen hasarýn (I-R hasarý) ortaya çýkmasýnda nötrofiller önemli rol oynamaktadýr. Nötrofil aracýlýðýyla geliþen I-R hasarý önlemek amacýyla, deneysel koþullarda, çeþitli maddelerin yaný sýra siklosporin A (CsA) ve FK506 gibi immünosupresif ajanlar da kullanýlmýþtýr. Ancak immünosupresiflerin nötrofiller üzerindeki etki mekanizmalarý henüz tam olarak anlaþýlamamýþtýr. Hipovolemik þok oluþturulan sýçanlarda, nötrofil aracýlýðýyla oluþan I-R hasarýna CsA'nýn etkilerini araþtýrmayý amaçladýk. Çalýþmamýzda, her biri 10 diþi Wistar albino sýçan içeren 4 grup oluþturuldu. G1: Kontrol, G2: Þok, G3: Þok+Reperfüzyon, G4: CsA. Þok oluþturmak için, deneklerden femoral ven yoluyla yaklaþýk 2,5 ml kan alýndý. Reperfüzyon gruplarýnda, alýnan kan 20 dk sonra ayný yoldan reperfüze edildi. G4'te, reperfüzyondan 5 dk önce IV20 mg/kg CsA verildi. Postop 24.cü saatte sakrifiye edilen deneklerde plazmada malonildialdehit (MDA); karaciðer, akciðer, ince barsak ve böbreklerde ise MDA ve miyeloperoksidaz (MPO) ölçümü ve nötrofil sayýmý yapýldý. I-R sonrasý plazma ve tüm dokularda artan MDA deðerleri, CsA verildikten sonra normale inmiþtir. Bu bulgular, I-R hasarýnda serbest oksijen radikallerinin (SOR) rolünü göstermektedir. Ancak, MPO deðerleri CsA verilmesi ile sadece ince barsakta normale inmiþtir. CsA'nýn nötrofil infiltrasyonunu azaltýcý etkileri de yine ince barsak ve böbrekte görülmüþtür. Sonuç olarak, CsA tedavisinin I-R hasarýný azaltýcý yönde etkiye sahip olduðu saptanmýþtýr. Ancak bu etkinin, en azýndan karaciðer ve akciðerde, nötrofil infiltrasyonunu azaltmak yoluyla olmadýðýný düþünmekteyiz. CsA'nýn dozu arttýrýldýðý taktirde, bu etki belki tüm dokularda yaygýnlaþabilir. CsA'nýn I-R hasarýndaki etki mekanizmasýnýn tam olarak anlaþýlabilmesi için yeni araþtýrmalara ihtiyaç vardýr.