Evolution of Spinal Cord Injury in a Porcine Model of Prolonged Aortic Occlusion John C. Papakostas, MD,* Miltiadis I. Matsagas, MD,* ,1 Ioannis K. Toumpoulis, MD,† Vasiliki D. Malamou-Mitsi, MD,‡ Lina S. Pappa, MD,‡ Constantina Gkrepi, MD,‡ Constantine E. Anagnostopoulos, MD,† , § and Angelos M. Kappas, MD* *Department of Surgery–Vascular Surgery Unit, †Department of Cardiothoracic Surgery, and ‡Department of Pathology, School of Medicine, University of Ioannina, Ioannina, Greece; and §St. Luke’s/Roosevelt Hospital Center at Columbia University, New York, New York Submitted for publication August 12, 2005 Background. Spinal cord injury and subsequent paraplegia remains an unpredictable and devastating complication of thoracoabdominal aortic surgery. The aim of this study was to investigate spinal cord injury due to prolonged thoracoabdominal aortic occlusion. Materials and methods. We used a highly reproduc- ible porcine model of 45-min thoracoabdominal aortic occlusion, which was accomplished by two balloon oc- clusion catheters. Neurological evaluation after the end of experiment was performed by an independent observer according to the Tarlov scale. The lower tho- racic and lumbar spinal cords were harvested at 10, 48, and 120 h (n  6 animals per time point) and examined histologically with hematoxylin and eosin (H&E) stain and TUNEL method. Tarlov scores, number of neu- rons, and the grade of inflammation were analyzed. Results. H&E staining revealed reduction in the number of motor neurons which occurred in two phases (between 0 and 10 h and between 48 and 120 h of reperfusion), as well as development of inflamma- tion in spinal cord sections during the reperfusion period, reaching a peak at 48 h. TUNEL reaction was negative for apoptotic neurons at any time point. Conclusions. In this porcine model, we demon- strated that, after 45 min of thoracoabdominal aortic occlusion, motor neuron death seems to occur in two phases (immediate and delayed). Inflammation was a subsequent event of transient prolonged spinal cord ischemia and possibly a major contributor of delayed neuronal death. Using TUNEL straining we found no evidence of neuronal apoptosis at any time point of reperfusion. © 2006 Elsevier Inc. All rights reserved. Key Words: spinal cord; ischemia; apoptosis; inflam- mation; aneurysm; prolonged aortic clamp; para- plegia. INTRODUCTION Spinal cord injury caused by occlusion of the thora- coabdominal aorta remains an unpredictable and dev- astating complication of aortic surgery for the resection of thoracoabdominal aneurysms. Neurological deficits resulting from this injury may be immediate or delayed with an incidence that ranges from 1.3% up to 32% depending on the type of resected aneurysm [1–5]. Interruption of spinal cord blood flow, as it happens during aortic occlusion (AOC), may cause irreversible motor neuron damage, which, according to its severity, can be manifested as paraplegia or paraparesis, or can have no clinical consequences. Observations from the clinical practice of thoracoabdominal aortic surgery have created evidence that the severity of spinal cord injury is directly correlated to the duration of the AOC and consequently to the duration of spinal cord isch- emia. Svensson et al. originally emphasized the impor- tance of AOC time, as an independent risk factor for the development of postoperative paraplegia [5]. Lately, Cambria et al., using the clamp and sew tech- nique with adjunctive epidural cooling of spinal cord, reported the same experience, as they found that the patients with prolonged AOC time had a 5-fold higher risk for postoperative paraplegia [6]. The application of distal perfusion techniques and cerebrospinal fluid 1 To whom correspondence and reprint requests should be ad- dressed at Department of Surgery–Vascular Surgery Unit, Univer- sity Hospital of Ioannina, S. Niarchos Avenue, 45500, Ioannina, Greece. E-mail: mimats@cc.uoi.gr. Journal of Surgical Research 133, 159 –166 (2006) doi:10.1016/j.jss.2005.10.007 159 0022-4804/06 $32.00 © 2006 Elsevier Inc. All rights reserved.