Effect of ischemic postconditioning and atorvastatin in the prevention of remote lung reperfusion injury

Abstract Objective: The aim of the present study was to evaluate the ability of ischemic postconditioning, atorvastatin and both associated to prevent or minimize reperfusion injury in the lung of rats subjected to ischemia and reperfusion by abdominal aortic clamping. Methods: We used 41 Wistar norvegic rats, which were distributed into 5 groups: ischemia and reperfusion (I/R), ischemic postcondictioning (IPC), postconditioning + atorvastatin (IPC+A), atorvastatin (A) and SHAM. It was performed a medium laparotomy, dissection and isolation of the infra-renal abdominal aorta; except for the SHAM group, all the others were submitted to the aortic clamping for 70 minutes (ischemia) and posterior clamp removal (reperfusion, 70 minutes). In the IPC and IPC+A groups, postconditioning was performed between the ischemia and reperfusion phases by four cycles of reperfusion and ischemia lasting 30 seconds each. In the IPC+A and A groups, preceding the surgical procedure, administration of 3.4 mg/day of atorvastatin was performed for seven days by gavage. After the surgical procedure, the right caudal lobe was removed from the lung for histological study, using tissue injury score ranging from grade 1 (normal tissue) to grade 4 (intense lesion). Results: The mean lung injury was 3.6 in the I/R group, 1.6 in the IPC group, 1.2 in the IPC+A group, 1.2 in the A group, and 1 in the SHAM group (P<0.01). Conclusion: Ischemic postconditioning and atorvastatin were able to minimize lung reperfusion injury, alone or in combination.

Evaluation of the effects of atorvastatin and ischemic postconditioning preventing on the ischemia and reperfusion injury: experimental study in rats

Abstract Introduction: Reperfusion injury leads to systemic morphological and functional pathological alterations. Some techniques are already estabilished to attenuate the damage induced by reperfusion. Ischemic preconditioning is one of the standard procedures. In the last 20 years, several experimental trials demonstrated that the ischemic postconditioning presents similar effectiveness. Recently experimental trials demonstrated that statins could be used as pharmacological preconditioning. Methods: 41 Wistar rats (Rattus norvegicus albinus) were distributed in 5 groups: Ischemia and Reperfusion (A), Ischemic Postconditioning (B), Statin (C), Ischemic Postconditioning + Statins (D) and SHAM (E). After euthanasia, lungs, liver, kidneys and ileum were resected and submitted to histopathological analysis. Results: The average of lung parenchymal injury was A=3.6, B=1.6, C=1.2, D=1.2, E=1 (P=0.0029). The average of liver parenchymal injury was A=3, B=1.5, C=1.2, D=1.2, E = 0 (P<0.0001). The average of renal parenchymal injury was A=4, B=2.44, C=1.22, D=1.11, E=1 (P<0.0001). The average of intestinal parenchymal injury was A=2, B=0.66, C=0, D=0, E=0 (P=0.0006). The results were submitted to statistics applying Kruskal-Wallis test, estabilishing level of significance P<0.05. Conclusion: Groups submitted to ischemic postconditioning, to pre-treatment with statins and both methods associated demonstrated less remote reperfusion injuries, compared to the group submitted to ischemia and reperfusion without protection.

Atorvastatin can prevent hepatic remote reperfusion injury / Atorvastatina é capaz de prevenir a lesão de reperfusão remota no fígado

ABSTRACT Background: Some studies have shown that statins have a promising effect on protection against reperfusion injury. Aim: To evaluate the ability of ischemic postconditioning, statins and both associated to prevent or minimize reperfusion injury in the liver of rats subjected to ischemia and reperfusion by abdominal aorta clamping. Method: Were used 41 Wistar rats, which were distributed into five groups: ischemia and reperfusion (I/R), ischemic postcondictioning (IPC), postconditioning + statin (IPC+S), statin (S) and Sham. It was performed a medium laparotomy, dissection and isolation of the infra-renal abdominal aorta; excepting Sham group, all the others were submitted to the aorta clamping for 70 min (ischemia) and posterior clamping removing (reperfusion, 70 min). In the IPC and IPC+S groups, postconditioning was performed between the ischemia and reperfusion phases by four cycles of reperfusion and ischemia lasting 30 s each. In IPC+S and S groups, preceding the surgical procedure, administration of 3.4 mg/day of atorvastatin was performed for seven days by gavage. The left hepatic lobe was removed for histological study and euthanasia was performed. Results: The mean hepatic injury was 3 in the I/R group, 1.5 in the IPC group, 1.2 in the IPC+S group, 1.2 in the S group, and 0 in the SHAM group. The I/R group had a higher degree of tissue injury compared to the others in the statistical analysis and there was no difference between the others (p<0.01). Conclusion: Ischemic postconditioning and atorvastatin were able to minimize hepatic reperfusion injury, either alone or in combination.

RESUMO Racional: Alguns estudos têm demonstrado que as estatinas apresentam efeito promissor contra a lesão de reperfusão. Objetivo: Avaliar a capacidade do pós-condicionamento, estatina e ambos associados em prevenir ou minimizar a lesão de reperfusão à distância no fígado em ratos submetidos à isquemia e reperfusão por clampeamento aórtico. Método: Foram utilizados 41 ratos Wistar distribuídos em cinco grupos: isquemia e reperfusão (I/R), pós-condicionamento isquêmico (PCI), pós-condicionamento + estatina (PCI+E), estatina (E) e SHAM. Os animais foram anestesiados, submetidos à laparotomia, dissecção e isolamento da aorta abdominal infrarrenal; exceto o grupo SHAM, todos os outros foram submetidos ao clampeamento aórtico por 70 min (isquemia) e posterior retirada do clampe (reperfusão). Nos grupos PCI e PCI+E o pós-condicionamento foi realizado entre as fases de isquemia e reperfusão por quatro ciclos de reperfusão e isquemia durando 30 s cada. Nos grupos PCI+E e E, previamente ao procedimento cirúrgico foi realizada a administração de 3,4 mg/dia de atorvastatina durante sete dias por gavagem. Resultados: A média de lesão hepática foi 3 no grupo I/R, 1,5 no grupo PCI, 1,2 no grupo PCI+E, 1,2 no grupo E e 0 no grupo SHAM. O grupo I/R teve maior grau de lesão tecidual (p<0,01). Conclusão: O pós-condicionamento isquêmico e atorvastatina foram capazes de minimizar a lesão hepática de reperfusão remota, isoladamente e em associação.