Fettah EREN, Şerefnur ÖZTÜRK, Ali Tamer ÜNAL, Hülagu BARIŞKANER, Ceylan UĞURLUOĞLU

DENEYSEL İSKEMİ REPERFÜZYON MODELİNDE GEÇ TROMBOLİTİK TEDAVİ ÖNCESİ MAGNEZYUM SÜLFATIN ETKİNLİĞİ

AMAÇ: İskemik inmenin primer tedavisi oklüde vasküler yapıların rekanalizasyonudur. Bunun için kullanılan medikal tedavi doku plazminojen aktivatörü (tPA)’dür. Endikasyon süresi intravenöz ilk 4,5 saat ile sınırlı olduğundan, hastaların büyük kısmı bu tedaviye ulaşamamaktadır. Bu yüzden geç trombolitik tedavi öncesi magnezyum sülfat (MgSO4)’ın etkinliğinin değerlendirildiği deneysel bir çalışma planlanmıştır. GEREÇ VE YÖNTEM: 52 sıçan rastgele altı gruba ayrıldı. 1. grup, kontrol grubuydu ve herhangi bir işlem yapılmadı. 2. grup, sham grubuydu ve paratrakeal kas diseksiyonu ile karotis artere ulaşıldı. 3. gruba, karotis klemp oklüzyou sonrası 345. dakikada tPA (10mg/kg) başlandı. 4. gruba, oklüzyon sonrası 345. dakikada tPA, 120. dakikada MgSO4 (90 mg/kg) başlandı. 5. gruba, 300. dakikada MgSO4, 345. dakikada tPA başlandı. 6. gruba, 120. ve 300. dakikalarda MgSO4, 345. dakikada tPA başlandı. Tüm gruplarda 360. dakikada reperfüzyon sağlandı. 24 saat sonra tüm sıçanların nörolojik muayeneleri yapıldı. Kan ve beyin dokusu örnekleri alındı. Kandan nöron spesifik enolaz (NSE) ve iskemi modifiye albümin (IMA) çalışıldı. Beyin dokusu Hematoksilen Eozin ve krezil viyole ile boyandı. Dejenere piramidal nöronlar değerlendirildi. BULGULAR: Grup 3’de mortalite oranı %40, grup 4’de %22,2, grup 5’de %30 ve grup 6’da %11,11 idi. Grup 4’te %17,8, grup 5’te %10 ve grup 6’da %28,9 oranında mortalitede azalma vardı. Grup 6’nın fonksiyonel dizabilitesi ve dejenere nöronal yüzdesi en azdı (p=0,04; p=0,005). NSE seviyesi düşüklüğü fonksiyonel iyilik durumu ve tedavi etkinliği ile ilişkiliydi (r=0,54; p=0,005). IMA seviyesi arttıkça fonksiyonel dizabilite artmaktaydı (p=0,003; r=0,47). Ancak MgSO4 verilen gruplar arasında IMA seviyelerinde farklılık yoktu (p=0,06). SONUÇ: Geç trombolitik tedavi öncesi, MgSO4’ın erken başlanması ve doz tekrarı ile daha iyi fonksiyonel ve histopatolojik sonuçlar elde edilmektedir. NSE ise tedavi etkinliği ve özürlülük durumu ile ilişkili bir biyobelirteçtir.

Anahtar Kelimeler:

Reperfüzyon, geç trombolitik, magnezyum sülfat, biyobelirteç

THE EFFICACY OF MAGNESIUM SULFATE BEFORE DELAYED THROMBOLYTIC TREATMENT IN EXPERIMENTAL MODEL OF ISCHEMIA REPERFUSION

OBJECTIVE: The primary treatment of ischemic stroke is recanalization of occluded vascular structure. The treatment for that is tissue plasminogen activator (tPA). Since the indication period is limited to the first 4.5 hours, the majority of patients can not reach this intravenous treatment. Therefore an experimental study was planned to evaluate the efficacy of magnesium sulfate (MgSO4) before delayed thrombolytic therapy.MATERIAL AND METHODS: 52 rats were randomly divided to six groups. Group 1 was the control group and no operation was performed. Group 2 was sham group and paratracheal muscles were dissected and carotid artery was reached. In group 3, carotid artery was occluded and tPA was started after 345 minutes. In group 4, tPA was started after 345 minutes and MgSO4 was started after 120 minutes. In group 5, MgSO4 was started after 300 minutes and tPA was started after 345 minutes. In group 6, MgSO4 was started after 120 and 300 minutes; After 345 minutes, tPA was started. All groups were reperfused after 360 minutes. After 24 hours, neurological examinations of all rats were performed. Blood and brain tissue specimens were taken. Neuron specific enolase (NSE) and ischemia modified albumin (IMA) were analyzed from blood. Brain tissue was stained with Hematoxylin Eosin and cresyl violet. Degenerated pyramidal neurons were evaluated.RESULTS: The mortality rate was 40% in group 3, 22.2% in group 4, 30% in group 5 and 11.11% in group 6. Mortality reduction was detected 17.8% for group 4, 10% for group 5 and 28.9% for group 6. Functional disability and percentage of degenerated neurons was the least in group 6 (p=0.04). Decreased NSE level was associated with functional improvement and treatment efficacy (p=0.005; r=0.54). Functional disability correlated with increasing of IMA level (p=0.003; r=0.47). But there was no difference in IMA levels among MgSO4-treated groups (p=0.06).CONCLUSIONS: Early onset and repetetive dose MgSO4 have the best functional and histopathologic results in delayed thrombolytic treatment. NSE is a biomarker that is associated with treatment efficacy and disability.

Keywords:

Reperfusion injury, Intravenous thrombolysis, Magnesium sulfate,

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