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.

Fig. 1

Comparison of the medians of the degrees of lung injury among the different groups analyzed (Kruskal-Wallis P=0.0029; "a" P<0.01 in relation to I/R group; "b" P<0.001 in relation to I/R group).

Fig. 2

Photomicrographs of histological changes of the pulmonary parenchyma of the I/R group considering the classification of Greca et al.^[10]. Major changes are observed predominantly, grade 4: haemorrhage (h); blood vessel congestion (bvc); cell necrosis (black arrow); neutrophils (white arrow); alveolar wall (red arrow); focal edema (fe); fibrosis (f ). HE, 10x and 40x.

Fig. 6

Photomicrographs of the pulmonary parenchyma of the SHAM group according to Greca et al.^[10]. Focal edema (fe); alveolus (A). HE, 10x and 40x.

Fig. 3

Photomicrographs of the pulmonary parenchyma of the IPC group according to Greca et al.^[10]. It is observed: bronchus; blood vessel (BV); focal edema (fe); neutrophil (arrow); alveolus (A). HE, 10x and 40x.

Fig. 4

Photomicrographs of the pulmonary parenchyma of the IPC+A group according to Greca et al.^[10]. Bronchiolus (bc); blood vessel (bv); inflammation (arrow). HE, 10x and 40x.

Fig. 5

Photomicrographs of the pulmonary parenchyma of group A according to the classification of Greca et al.^[10]. Focal edema (fe); alveolus (A). HE, 10x and 40x.