Elsevier

Injury

Volume 37, Issue 5, May 2006, Pages 380-387
Injury

Does propofol or caffeic acid phenethyl ester prevent lung injury after hindlimb ischaemia-reperfusion in ventilated rats?

https://doi.org/10.1016/j.injury.2006.01.004Get rights and content

Summary

Background

To investigate the effects of propofol and caffeic acid phenethyl ester (CAPE) on prevention of lung injury as a remote organ after performing hindlimb ischaemia-reperfusion (IR) in a rat model.

Methods

The animals were divided randomly into one of four groups: sham, no IR (n = 8), control, IR, (n = 8), CAPE group, IR with CAPE, (n = 8), propofol group, IR with P, (n = 8). After the rats were anaesthetised, the animals in the CAPE group received CAPE of 10 μmol, in the propofol group received propofol 50 mg/kg, in the control group received a similar volume of saline solution by means of intraperitoneal injection 1 h before reperfusion. After 4 h of ischaemia the tourniquet was removed and the animals were released for reperfusion for 4 h thereafter. At the end of the reperfusion period, a median sternotomy was performed. A blood sample was obtained for plasma malondialdehyde (MDA). The lung tissues were also removed for MDA assays, myeloperoxidase (MPO) activity, and histopathological examination.

Results

Plasma and lung MDA levels, and lung MPO activity were significantly higher in the control group compared to the other groups (p < 0.0005). In the CAPE group, these were significantly lower compared to the control group (p < 0.0005). Also, propofol caused a marked reduction in the MDA levels and MPO activity compared with control group (p < 0.0005), with no significant difference compared to that of the sham group. Histopathologically, the scores resulted in a grade zero (8/8) in the sham group, 3 (3/8) or 4 (5/8) in the control group, 1 (2/8) or 2 (6/8) in the CAPE group, and 1 (3/8) or 2 (5/8) in the propofol group.

Conclusion

Propofol and CAPE seem to be effective in protecting against lung injury caused by increased oxidative stress and neutrophil accumulation after hindlimb IR in a rat model.

Introduction

Lower limb ischaemia followed by reperfusion is an important and common clinical event. Reperfusion initiates both local and systemic damage, in part through rapid oxygen free radical generation and inflammatory mediators.16 Restoration of the blood flow can save the limb, but may result in multiple organ dysfunction syndrome. One of these target organs after hindlimb ischaemia-reperfusion (IR) injury is the lung, and clinically, the pulmonary damage in this condition may cause from acute lung injury with mild dysfunction to severe respiratory failure or adult respiratory distress syndrome. The main pathological defect in lung injury after reperfusion is the endothelial cell damage caused by activated neutrophils and the formation of free radicals.11 Pulmonary vasoconstriction, hypertension, and increased pulmonary vascular permeability are common results of impaired endothelial cell function.3 Therefore, inhibiting neutrophil activation or blocking reactive oxygen species could be the key to preventing clinical outcomes of the lung tissue damage caused by hindlimb IR injury.9

Many chemicals have been tested to attenuate IR injury. One of these, caffeic acid phenethyl ester (CAPE), a flavonoid like compound, is one of the major components of honeybee propolis. CAPE, with no harmful effects on normal cells, has several biological and pharmacological properties: antioxidant, anti-inflammatory, anti-carcinogenic, antiviral, and immunomodulatory activities. In many studies, it is clearly showed that CAPE, at a concentration of 10 μmol, completely blocks production of reactive oxygen species in human neutrophils.9

Propofol (2,6-diisopropylphenol) is a widely used intravenous anaesthetic, and is chemically similar to phenol-based free radical scavengers. Importantly, it is also a potent antioxidant, and has anti-inflammatory properties. Propofol may be expected to have beneficial effects in the management of patients with acute lung injury and adult respiratory distress syndrome.8 Propofol can increase the antioxidant capacity of the tissues by the inhibition of lipid peroxidation in cell membranes following reperfusion injury.17 Additionally, it attenuates IR induced lipid peroxidation when given in therapeutic doses for the induction and maintenance of general anaesthesia.10

We performed this study to examine the effectiveness of propofol and CAPE pretreatment in preventing lung injury caused by lower limb IR during mechanical ventilation with positive end-expiratory pressure in a rat model. For this purpose, we assessed biochemical parameters and histopathological analysis of the lungs.

Section snippets

Animals and groups

Thirty-two adult male Sprague Dawley rats, weighing 270–320 g, were used. All animal procedures were in strict accordance with the National Institutes of Health Guidelines on the Care and Use of Laboratory Animals. The approval of the Karadeniz Technical University, Faculty of Medicine, Animal Care and Ethics Committee was obtained before the study began.

Animals were allocated randomly into one of 4 groups: I; sham group, no IR, (n = 8), II; control group; IR, (n = 8), III; CAPE group; IR with CAPE,

Results

There were no significant differences between the groups in terms of body weight, time between induction of anaesthesia and start of procedure.

Discussion

The role of neutrophils and oxidative damage in the lung following lower IR injury is well-established. Almost 25 years ago, it was reported that limb IR injury may not only lead to increased vascular permeability in the skeletal muscle but also in the lung.7 In this study, we also showed that the lung, as a remote organ, is affected by IR of the lower extremities. Supporting this, MDA levels in plasma and lung tissue were found to be higher in the control group. In addition, higher MPO

Conclusion

On the basis of our experimental results, we have shown that CAPE or propofol cause a significant inhibition of MDA production and neutrophil infiltration in the lungs, and that, histopathologically, these may have a protective effect in hindlimb IR-induced lung injury. At this point, and more importantly, we determined that propofol is as effective in preventing the injury as CAPE. Therefore, these results indicate that there may be a benefit from using propofol as an anaesthetic agent in

Acknowledgments

We would like to thank Asst. Prof. Dr. Murat Topbaş MD for providing statistical analysis and Yıldıray Yığcı for providing expert technical assistance.

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