Vascular
Postconditioning of the Lower Limb—Protection Against the Reperfusion Syndrome

https://doi.org/10.1016/j.jss.2009.10.014Get rights and content

Background

Postconditioning—alternating brief cycles of reperfusion/reocclusion applied at the beginning of revascularization—is a potent therapeutic technique, attenuating ischemia-reperfusion injury. Vascular surgery on the lower limb with ischemia-reperfusion injury may give rise to serious systemic complications [organ dysfunction syndrome (MODS), systemic inflammatory response syndrome (SIRS)], a phenomenon called reperfusion-syndrome.

Material and Methods

We studied the effects of postconditioning on reperfusion-syndrome in a rodent experimental model. Wistar rats underwent 180 min of bilateral lower limb ischemia using an infrarenal crossclamping of the abdominal aorta. Postconditioning consisted of six cycles of 10-s aortic occlusion/10-s declamping at the beginning of reperfusion. Microcirculation of the lower limb was detected with laser Doppler flowmeter. After 4 h of reperfusion, plasma, urine, and histologic samples were collected.

Results

One hundred eighty-minute ischemia resulted in significant hemodynamic changes after reperfusion. Postconditioning affected the character of the microcirculatory flow, the limb circulation stabilized with hyperemia during reperfusion. Postconditioning caused a significant reduction in systemic inflammatory response (TNF-α, oxygen-derived free radicals). The laboratory and histologic samples implied a significant decrease in distant organ (lung and renal) dysfunctions after postconditioning.

Conclusion

Postconditioning proves to be capable of conferring protection against different organ injuries caused by longer circulatory occlusions during elective major vascular operations.

Introduction

During major vascular surgeries of the lower limb arteries and the abdominal aorta, the lower extremities are unavoidably subjected to ischemia. Restoration of the blood supply results in a further insult to the tissues, aggravating the injury caused by ischemia, termed as ischemia-reperfusion-injury (IR-injury). The IR-injury of extensive muscle tissue mass and the sensitive vascular tissues and endothelium often leads to systemic complications with distant organ damage of major clinical importance, a phenomenon called reperfusion syndrome [1].

The IR-injury of the vascular endothelium results in endothelial cell dysfunction and local inflammation. This process may give rise to a generalized inflammation (systemic inflammatory response syndrome (SIRS) with activation of different immune cells, release of a vast number of inflammatory mediators, reactive free radicals, and vasoactive substances [2]. This process may cause severe dysfunction and morphologic alteration of distant organs, and progrediate into multiple organ dysfunction syndrome (MODS), consisting of diffuse alveolar damage of the lungs, local inflammatory processes in the liver, increased permeability of the intestinal mucosa, and rhabdomyolysis-induced myohemoglobinuric acute renal failure 3, 4.

Postconditioning is a powerful cardioprotective surgical technique capable of reducing IR-injury in the heart [5]. It consists of several cycles of brief interruptions in the blood supply at the very onset of an organ's reperfusion additionally to its prolonged ischemia.

The aim of the present study was to investigate the application of postconditioning in major vascular surgery for the first time not in terms of the IR-injury of the lower limbs, but in terms of the postoperative complications of these operations, termed as reperfusion syndrome.

Section snippets

Animals

Male Wistar rats, weighing 250–280 g, were used in the experiment (Charles River Hungary Ltd., Budapest, Hungary). The experimental design was regulated and approved by Act XXVIII of 1998 and Government Decree 243/1998 (XII. 31). In specific, pathogen-free conditions at 22–24 °C, the rats were maintained on standard rat chow and water ad libitum.

Operative Procedure

Animals were anaesthetized with an intraperitoneal injection of ketamine (75 mg/kg) and xylazine (7.5 mg/kg). Deep anesthesia was maintained by the

Histology

No pathologic lesions were found in most samples taken from the rectus femoris muscle. Mild rhabdomyolysis was apparent only in few cases in the control group, but this was far from reaching any significance (Fig. 1).

Sections from each lung of the control rats exhibited partial atelectasis, defined by collapsed and pinched alveoli, thicker and felted alveolar walls, while in the sections of the postconditioned group, only slight alterations were detected (Fig. 2).

Kidney histology showed

Discussion

A clinically most relevant feature of major vascular operations (e.g., aortic aneurysm repairs, reconstructions of the lower extremity arteries) is the necessity for clamping of major arteries. Thus, tissues distal to the clamp incur ischemic-reperfusion injuries, most notably a huge mass of skeletal muscle [7].

We report for the first time that postconditioning may effectively be used in major vascular operations (i.e., aorta-clamping) to reduce the systemic and distant organ complications

Acknowledgments

The authors express their special thanks to Andras Kiss, M.D., Ph.D. and Zsuzsa Schaff, M.D., Ph.D., D.Sc. for their excellent technical assistance and support in the histopathologic analysis. The authors owe thanks to Viktor Hegedus and Anna Blazovics, M.D., Ph.D., D.Sc. for the antioxidant measurements. Grateful acknowledgments are due to Peter Kupcsulik, M.D., Ph.D. for general support. Ildiko Toma, M.D., Ph.D. is thanked for her writing assistance and proofreading.

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