Amlodipin'in sıçan inferior epigastrik arter cilt ada flebinde iskemi-reperfüzyon hasarına etkisi
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Tarih
2020
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Yayıncı
Dicle Üniversitesi, Tıp Fakültesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Giriş ve Amaç: Plastik Cerrahi'nin uğraş alanlarından biri olan flep cerrahisinde iskemi reperfüzyon (İ/R) hasarı flep yaşayabilirliğini etkileyen en önemli faktörlerden birisidir. Fleplerde iskemi reperfüzyon hasarının olumsuz etkisini araştıran ve farklı farmakolojik ajanların kullanıldığı çok sayıda çalışma vardır. Kalsiyum kanal blokerlerinden olan Amlodipin' in beyin, kalp ve karaciğer gibi dokularda iskemi reperfüzyon hasarına karşı koruyucu etkileri gösterilmiştir. Ancak fleplerde iskemi reperfüzyon hasarına karşı etkileri ile ilgili yeterli çalışma bulunmamaktadır. Farklı dokularda iskemi reperfüzyon hasarı üzerine olumlu etkileri gösterilen Amlodipin'in flepler üzerindede de bu etkisinin olabileceği hipoteziyle bu çalışma planlanmıştır. Gereç ve Yöntem: Çalışmamızda herbir grup 8 adet rattan oluşmak üzere 24 adet Sprague Dawley cinsi dişi rat kullanıldı. Gruplar, Grup I; sham, Grup II; kontrol (İ/R) ve Grup III; tedavi (İ/R + Amlodipin) olacak şekilde ayrıldı. Çalışmada 3x6 cm lik rat inferior epigastrik arter cilt ada flebi kullanıldı. Sham grubundaki (Grup I) 8 rata 6x3 cm inferior epigastrik arter cilt ada flebi kaldırıldıktan sonra iskemi ve ilaç uygulanmadan 3/0 ipekle flep yerine sütüre edildi. Grup II (kontrol) ve grup III (tedavi)'e 8 saat iskemi ve 12 saat reperfüzyon uygulandı. Kontrol grubundaki (Grup II) 8 rata cerrahi girişim öncesi 7 gün ve cerrahi girişim sonrası 7 gün boyunca oral gavaj yoluyla 1cc izotonik solüsyonu verildi. Tedavi grubuna (Grup III) girişim öncesi 7 gün ve girişim sonrası 7 gün 5mg/kg/gün Amlodipin (ilacın tablet formu ezildi ve serum fizyolojik ile çözelti haline getirildi) oral gavaj yoluyla verildi. Bütün ratlardan girişim sonrası yirmibirinci saatte histopatolojik ve biyokimyasal analizler için flep uzun aksının orta 1/3 lük kısmından her biri 1x0,5 cm olmak üzere iki adet biyopsi alındı. Bütün ratlarda girişim sonrası yedinci gün 1 mm2 lik alanlar şeklinde çizilen transparan asetat üzerine canlı ve doku kaybına uğrayan alanlar çizildi. Çizilen alanlar sayılarak canlı alan, total flep alanına bölünerek fleplerde sağ kalım oranı % olarak hesaplandı. Ardından ratlar, genel anestezi altında(50 mg/kg ketamin hidroklorür+10 mg/kg ksilazin hidroklorür-intraperitoneal) servikal dislokasyon yöntemiyle sakrifiye edildi. Bulgular: Flep canlılık oranları, tedavi (İ/R+Amlodipin) grubunda kontrol (İ/R) grubuna göre anlamlı şekilde yüksek bulundu (p<0,05). Tedavi (İ/R+Amlodipin) grubunda nötrofil sayısı (p=0,021), MDA (p=0,016) ve MPO (p=0,040) değerleri kontrol(İ/R) grubuna göre anlamlı şekilde düşük bulundu (p<0,05). Damar çapları açısından tedavi ve kontrol grubu arasında anlamlı fark bulunmadı (p=0,141). Sham grubunda, kontrol grubuna (İ/R) göre flep canlılık oranları ve damar çapı anlamlı şekilde yüksek iken, nötrofil sayısı, MDA ve MPO ise anlamlı şekilde düşük bulundu (p<0,05). Sham grubunda, tedavi grubuna (İ/R+Amlodipin) göre flep canlılık oranları anlamlı şekilde yüksek (p<0,05), nötrofil sayısı ve MDA düzeyleri anlamlı şekilde düşük (p<0,05) bulundu. Damar çapları (p=0,674) ve MPO (p=0,208) düzeyleri açısından ise anlamlı fark bulunmadı. Damar çapları açısından üç grup karşılaştırıldığında, gruplar arasında bir farklılık saptanmadı (p=0,081). Sonuç: Çalışmamızdan elde ettiğimiz bulgular sonucunda, başka amaçlarla klinik uygulamalarda yeri olan Amlodipin'in cilt fleplerinde iskemi-reperfüzyon hasarını önlemede etkili olabileceği sonucuna varıldı.
ABSTRACT İntroduction: İschemia reperfusion (I / R) damage is one of the most important factors affecting flap viability in flap surgery, which is one of the main professions of Plastic Surgery. There are many studies investigating the negative effects of ischemia reperfusion damage in flaps and using different pharmacological agents. Protective effects of amlodipine, which is a calcium channel blockers, against ischemia reperfusion damage in tissues such as brain, heart and liver have been demonstrated. However, there are not enough studies about its effects against ischemia reperfusion damage in flaps. This study is planned with the hypothesis that Amlodipine, that has positive effects on ischemia reperfusion damage in different tissues, may also have such an effect on flaps. Material and Method: In our study, 24 female Sprague Dawley rats were used, each group consisting of 8 rats. Groups were divided as: Group I; sham, Group II; control (I / R) and Group III; treatment (I / R + Amlodipine). In the study, a 3x6 cm rat inferior epigastric artery skin island flap was used. After elevating the 6x3 cm inferior epigastric artery skin island flap in 8 rats of the sham group (Group I), flaps were resutured with 3/0 silk without application of ischemia and treatment. 8 hours of ischemia and 12 hours of reperfusion were applied in group II (control) and group III (treatment) . The 8 rats in the control group (Group II) were given 1cc isotonic solution by oral gavage for 7 days before surgery and 7 days after surgery. 5mg / kg / day Amlodipine (tablet form of the drug was crushed and mixed with isotonic solution) was administered to the treatment group (Group III) 7 days before and 7 days after the intervention. Twenty-one hour after intervention, for histopathological and biochemical analysis, two biopsies, 1x0.5 cm each, were taken from the middle 1/3 of the long axis of the flap from all rats. In all rats, live and necrotic areas were drawn on the seventh day after intervention on transparent acetate, which was drawn as 1 mm2 areas. The drawn areas were counted and survival rate of flaps was calculated as % by dividing the live area into the total flap area. Then the rats were sacrificed under general anesthesia (50 mg / kg ketamine hydrochloride + 10 mg / kg xylazine hydrochloride-intraperitoneal) by cervical dislocation. Results: Flap viability rates were significantly higher in the treatment (I / R + Amlodipine) group compared to the control (I / R) group (p <0.05). Neutrophil count (p = 0.021), MDA (p = 0.016) and MPO (p = 0.040) values in the treatment (I / R + Amlodipine) group were significantly lower than the control (I / R) group (p <0.05). No significant difference was found between the treatment and control groups in terms of vessel diameters (p = 0.141). Flap viability rates and vessel diameter were significantly higher in the sham group compared to the control group (I / R), while neutrophil count, MDA and MPO were significantly lower (p <0.05). In the sham group, flap viability rates were significantly higher (p <0.05), neutrophil count and MDA levels were significantly lower (p <0.05) compared to the treatment group (I / R + Amlodipine). No significant difference was found in terms of vessel diameters (p = 0.674) and MPO (p = 0.208) levels. When the three groups were compared in terms of vessel diameters, there was no difference between the groups (p = 0.081). Conclusion: As a result of the findings obtained from our study, it was concluded that Amlodipine, which is used for other purposes in clinical applications, may be effective in preventing ischemia-reperfusion damage in skin flaps.
ABSTRACT İntroduction: İschemia reperfusion (I / R) damage is one of the most important factors affecting flap viability in flap surgery, which is one of the main professions of Plastic Surgery. There are many studies investigating the negative effects of ischemia reperfusion damage in flaps and using different pharmacological agents. Protective effects of amlodipine, which is a calcium channel blockers, against ischemia reperfusion damage in tissues such as brain, heart and liver have been demonstrated. However, there are not enough studies about its effects against ischemia reperfusion damage in flaps. This study is planned with the hypothesis that Amlodipine, that has positive effects on ischemia reperfusion damage in different tissues, may also have such an effect on flaps. Material and Method: In our study, 24 female Sprague Dawley rats were used, each group consisting of 8 rats. Groups were divided as: Group I; sham, Group II; control (I / R) and Group III; treatment (I / R + Amlodipine). In the study, a 3x6 cm rat inferior epigastric artery skin island flap was used. After elevating the 6x3 cm inferior epigastric artery skin island flap in 8 rats of the sham group (Group I), flaps were resutured with 3/0 silk without application of ischemia and treatment. 8 hours of ischemia and 12 hours of reperfusion were applied in group II (control) and group III (treatment) . The 8 rats in the control group (Group II) were given 1cc isotonic solution by oral gavage for 7 days before surgery and 7 days after surgery. 5mg / kg / day Amlodipine (tablet form of the drug was crushed and mixed with isotonic solution) was administered to the treatment group (Group III) 7 days before and 7 days after the intervention. Twenty-one hour after intervention, for histopathological and biochemical analysis, two biopsies, 1x0.5 cm each, were taken from the middle 1/3 of the long axis of the flap from all rats. In all rats, live and necrotic areas were drawn on the seventh day after intervention on transparent acetate, which was drawn as 1 mm2 areas. The drawn areas were counted and survival rate of flaps was calculated as % by dividing the live area into the total flap area. Then the rats were sacrificed under general anesthesia (50 mg / kg ketamine hydrochloride + 10 mg / kg xylazine hydrochloride-intraperitoneal) by cervical dislocation. Results: Flap viability rates were significantly higher in the treatment (I / R + Amlodipine) group compared to the control (I / R) group (p <0.05). Neutrophil count (p = 0.021), MDA (p = 0.016) and MPO (p = 0.040) values in the treatment (I / R + Amlodipine) group were significantly lower than the control (I / R) group (p <0.05). No significant difference was found between the treatment and control groups in terms of vessel diameters (p = 0.141). Flap viability rates and vessel diameter were significantly higher in the sham group compared to the control group (I / R), while neutrophil count, MDA and MPO were significantly lower (p <0.05). In the sham group, flap viability rates were significantly higher (p <0.05), neutrophil count and MDA levels were significantly lower (p <0.05) compared to the treatment group (I / R + Amlodipine). No significant difference was found in terms of vessel diameters (p = 0.674) and MPO (p = 0.208) levels. When the three groups were compared in terms of vessel diameters, there was no difference between the groups (p = 0.081). Conclusion: As a result of the findings obtained from our study, it was concluded that Amlodipine, which is used for other purposes in clinical applications, may be effective in preventing ischemia-reperfusion damage in skin flaps.
Açıklama
Anahtar Kelimeler
İnferior epigastrik arter cilt ada flebi, Amlodipin, İskemi reperfüzyon, Inferior epigastric artery skin island flap, Amlodipine, Ischemia reperfusion
Kaynak
WoS Q Değeri
Scopus Q Değeri
Cilt
Sayı
Künye
Taşkan, S. (2020). Amlodipin'in sıçan inferior epigastrik arter cilt ada flebinde iskemi-reperfüzyon hasarına etkisi. Uzmanlık tezi, Dicle Üniversitesi, Diyarbakır.