Effects of allopurinol and preconditioning on apoptosis due to ischemia-reperfusion on a double jejunum-segment canine model

Abstract

Purpose: To investigate the duration of apoptosis caused by ischemia-reperfusion in the intestine in a new double jejunum-segment model, and to analyze the protective effects of allopurinol or ischemic preconditioning (IPC). Methods: In Experiment I for harvesting the double jejunum-segment model after laparotomy a 30-cm-long jejunum part was selected on mongrel dogs (n=24). End-to-end anastomoses were performed at both ends and in the middle of the jejunum part, creating two equal segments. In one segment ischemia was induced by occluding the supplying vessels, the other segment served as control. Tissue samples for detecting apoptosis were taken at 30th minutes, 1st, 2nd, 4th, 6th, 8th, 12th and 24th hours of reperfusion. In Experiment II using the same model the 4-hour reperfusion time period, allopurinol (50 mg/kg) pre-treated and IPC (3 cycles of 5x1) groups (n=5 per each) were also investigated. Results:In Experiment I the greatest apoptotic activity was detected at the 4th and 6th hour of reperfusion (14. Effects of allopurinol and preconditioning on apoptosis due to ischemia-reperfusion on a double jejunum-segment canine modelREsUMO Objetivo: Investigar a duração da apoptose causada pela isquemia-reperfusão no intestino em um novo modelo de duplo segmento de jejuno e analisar os efeitos protetores do alopurinol ou precondicionamento isquêmico (IPC). Métodos: No experimento I para obter o modelo do duplo segmento de jejuno, após a laparotomia, uma parte de 30cm de comprimento de jejuno foi selecionada em cães mestiços (n=24). Anatomoses T-T foram realizadas em ambas as extremidades no meio do segmento de jejuno, criando dois segmentos iguais. Em um segmento foi induzida isquemia por oclusão dos vasos que o irrigavam e o outro segmento foi usado como controle.Amostras de tecido para detecção da apoptose foram obtidos aos 30 minutos, 1h, 2h, 4h, 6h, 8h, 12h e 24 horas de reperfusão. No experimento II usando o mesmo modelo, no tempo de reperfusão de 4 horas, foram investigados dois outros grupos (n=5 cada) usando precondicionamento com alopurinol (50 mg/kg) e IPC (3 ciclos de 5x1). Resultados: No experimento I a maior atividade de apoptose detectada foi às 4h e 6h de reperfusão (14,2 ± 1,31 e 16,3 ± 1,05 no campo visual de 40x). No experimento II usando o período de 4horas de reperfusão o pré-tratamento com alopurinol aumentou a atividade apoptótica (10,72 ± 0,47) aproximadamente 2 vezes mais do que o IPC (6,72 ± 0,46) (p<0,05). conclusões: A atividade de apoptose tem uma curva caractetística, atingindo maiores valores entre a 4ª e a 6ª horas após 30 minutos de isquemia intestinal. O precondicionamento isquêmico parece proteger contra alterações morfológicas causadas pela isquemia-reperfusão intestinal.Descritores: Isquemia. Reperfusão. Jejuno. Apoptose. Alopurinol. Precondicionamento isquêmico. Cães.

Establishment of an acute arterial mesenteric ischaemia model in canines with an endovascular approach

“…The use of canines to recapitulate the human intestine has also been reported ( 13 ). Regarding the canine AMI model, surgical clamping of the SMA ( 22 , 23 ) and mesenteric vascular ( 24 , 25 ) were usually adopted. However, these models were created for evaluating intestinal ischaemia reperfusion injury and failed to simulate the clinical scenario of embolic AMI, which is usually caused by emboli.…”

Η Επίδραση Της Απροτινίνης Στη Σπλαχνική Ισχαιμία – Επαναιμάτωση Από Πνευμοπεριτόναιο

“…Η Ν-ακετυλοκυστεΐνη χορηγούμενη σε πειραματόζωα σε διάφορα σχήματα και συνδυασμούς φαίνεται να ελαττώνει τις οξειδωτικές βλάβες από ισχαιμία -επαναιμάτωση στο ήπαρ, στο νεφρό και στο έντερο 230,231,232 . Oι αναστολείς του μετατρεπτικού ενζύμου της αγγειοτενσίνης και οι ανταγωνιστές ασβεστίου επίσης έχουν ευεργετική επίδραση στην ισχαιμία -επαναιμάτωση του μυοκαρδίου 233,234 , ενώ η αλλοπουρινόλη χορηγούμενη στους επίμυες σε συνδυασμό με preconditioning μειώνει τις οξειδωτικές βλάβες 235,236 . Τέλος, η βιταμίνη Ε και τα παράγωγα της έχουν δοκιμαστεί σε αρκετά πειραματικά μοντέλα με θετικά αποτελέσματα 237,238 .…”