Elsevier

Cardiovascular Pathology

Volume 22, Issue 6, November–December 2013, Pages 493-500
Cardiovascular Pathology

Clinical Case Report
Rapidly progressing fatal reperfusion syndrome caused by acute critical ischemia of the lower limb

https://doi.org/10.1016/j.carpath.2013.02.006Get rights and content

Abstract

The most severe complication of ischemia–reperfusion injury following lower limb arterial surgery is reperfusion syndrome. Therefore, our aim was to describe the extent of muscle damage and the reperfusion syndrome-related remote organ lesions in detail, through a well-documented case of long-lasting infrarenal aorta thrombosis. After urgent revascularization, several clinical signs of multiple organ dysfunction were detectable, including the circulatory, urinary, respiratory, gastrointestinal, and hemostatic systems. Upon histological examination, intraoperative muscle biopsy showed severe muscle damage. Muscle fiber viability was assessed with a special nitroblue tetrazolium staining-based viability test developed by our team; the obtained results indicated significant degree of muscle damage before this was confirmed by conventional histological methods. Thorough postmortem examination confirmed the presence of remote organ damage. The pathological findings included acute tubular necrosis, myocardial and jejunal infarctions, ischemic pancreatitis, and diffuse alveolar damage with hyaline membrane formation in the lungs and focal centrilobular liver necrosis. By using special staining techniques, the presence of myoglobin and lipofuscin deposits was confirmed in the kidney samples. In this paper, we present a patient who developed all major complications following long-lasting arterial occlusion. We also introduce a novel method to assess the degree of ischemic injury, which may be suitable in the near future for the rapid detection of irreversible muscle injury. Therefore, the mortality of the disease might be reduced.

Introduction

Severe ischemic damage may occur in the lower limbs due to prolonged vascular occlusions. After long-lasting ischemia, reconstructive vascular surgery may paradoxically aggravate the tissue damage caused by the ischemia alone. This phenomenon is called ischemicreperfusion (I-R) injury. Metabolic changes occurring during ischemia lead to the accumulation of toxic metabolic products. During reperfusion, as a result of I-R muscle damage, rhabdomyolysis leads to release of high concentrations of toxic substances (myoglobin, ionized calcium, creatine kinase, potassium, organic acids, and other enzymes and electrolytes) and inflammatory mediators into the circulation. Rhabdomyolysis may lead to severe systemic complications, such as acute renal failure (ARF) (mainly due to myoglobin), cardiac arrhythmias, compartment syndrome, and disseminated intravascular coagulopathy [1].

In addition to the adverse metabolic changes, tissue swelling may develop as a result of ion channel malfunction, which generates increase in tissue pressure. In the case of extremities, the closed fascial compartments are very vulnerable to this increased tissue pressure, resulting in capillary occlusion and subsequent secondary ischemia [2]. The resulting clinical picture is called compartment syndrome. Compartment syndrome is the most severe local consequence of lower limb I-R injury, which can only be treated with sufficient fasciotomy.

The release of toxic products and inflammatory mediators may also cause a systemic, generalized inflammatory reaction (systemic inflammatory response syndrome), which can further lead to multiple organ failure (MOF). This whole process is called reperfusion syndrome. If the progression of the reperfusion syndrome is not interrupted in due time, irreversible damage can develop, which may result in patient death.

Unfortunately, there are very limited therapeutic options in preventing the progression of reperfusion syndrome. Supportive intense therapy, hemodyalysis, plasma exchange, or ultrafiltration with the elimination of toxic products from the circulation might reduce the degree of multiple organ injury.

Therefore, our aim was to draw attention to reperfusion syndrome and the underlying mechanism by investigating a well-documented case.

Section snippets

Medical history

S.B. is a 55-year-old male patient, who was a heavy smoker with a previous history of proximal selective vagotomy, hypertension, hyperlipidemia, ischemic heart disease, chronic atrial fibrillation, chronic bronchitis, depression, cholecystectomy, and abdominal wall reconstruction. In a 7-year period before his current admission, the patient underwent several vascular reconstructions (right iliac percutaneous transluminal angioplasty, right-to-left iliofemoral crossover bypass, right iliofemoral

Autopsy findings

During autopsy, total occlusion of the excluded abdominal aorta section was found; however, the lumen of the newly implanted aortobifemoral bypass graft was free (Fig. 2A). The right femoropopliteal bypass was not occluded either. By gross examination, muscles of the lower extremities were swollen, tight, and found to be protruding through the fasciotomy apertures (Fig. 3A).

The kidneys were swollen with a pale, slightly granulated surface. On the cut surface, the cortex and medulla were sharply

Materials and methods

Biopsy samples were taken from skeletal muscles during surgeries (before establishing reperfusion). Taking and processing of the biopsy samples are possible owing to the Hungarian License of the Scientific and Research Ethics Committee No. 92/2011. The pectineus muscle (control sample) and the anterior tibial muscle (injured sample) were the sites of intraoperative biopsies. A part of the muscle samples were frozen in liquid nitrogen, and cross-sections were cut and stained for nicotinamide

Results

H&E stained sections of intraoperative biopsy material from control muscle showed mostly intact tissue structure (Fig. 5A), whereas in the samples of the edematous ischemic tissue taken during the first surgery, congestion was observed (Fig. 5C). In the injured samples from the second surgery, disintegration of muscle fibers and severe necrosis were found (Fig. 5E). The NBT test showed significant reduction of viability in the injured muscle biopsy samples (Fig. 5B, D, F). In comparison to the

Discussion

Reperfusion syndrome is the umbrella term for complications of I-R injury. The currently accepted definition of reperfusion syndrome was provided by F. William Blaisdell: “complex syndrome with local and systemic consequences developing after a major I-R injury affecting a large amount of tissues” [3].

After aortoiliac artery reconstruction surgeries, mortality is mainly determined by the development of MOF. MOF can manifest in ARF, ALI, hematologic dysfunction, circulatory failure (mainly due

Acknowledgments

Authors are thankful for the thorough linguistic revisions of H.A. Vohra, M.D. (Southampton General Hospital, Southampton, UK), and G. Baskai (Semmelweis University, Budapest, Hungary).

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  • Diabetes worsens ischemia-reperfusion brain injury in rats through GSK-3β

    2015, American Journal of the Medical Sciences
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    The results demonstrated that limb I/R was associated with injury and apoptosis in the hippocampal CA1 region and in cortical areas, and that this was aggravated by diabetes. There is now substantial evidence that I/R injury comprises a series of inflammatory responses, induced by hypoxia of the ischemic limb and subsequent reperfusion, which can result in both local and remote damage.22 Although various remote organs, including the heart, brain, liver, lungs, kidneys and gastrointestinal tract, are potentially susceptible to injury,7 it is well known that pyramidal cells in the hippocampal CA1 region are particularly vulnerable to ischemia23 and hence may also be more prone to secondary injury from limb I/R. For this reason, the CA1 region in the hippocampus likely represents an important area of the brain that can be easily injured after I/R.

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1

These authors contributed equally to this study.

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