We read with great interest the article titled “Evaluation of Rapid Ischemic Preconditioning in a Rabbit Model of Spinal Cord Ischemia.”1We congratulate Kakimoto et al.  on their study of rapid ischemic preconditioning (IPC) to provide ischemic spinal cord protection. This is an interesting study that consists of three experimental groups and evaluates the effect of rapid IPC on spinal cord ischemic injury after a short (24-h) and a relatively long (7-day) recovery period.

Ischemic preconditioning has been found to protect various organs from ischemic injury, and there is experimental evidence that IPC protects the spinal cord after aortic cross clamping. IPC is a biphasic phenomenon, with an early phase and a late phase of protection, and these two phases have been documented in the spinal cord as well.2,3In this study, Kakimoto et al.  evaluated the effect of rapid IPC in a rabbit model of infrarenal aortic occlusion by using 5 min of brief ischemia, 30 min of reperfusion, and 17 min of aortic cross clamping. They found that rapid IPC reduced spinal cord injury when compared with the controls at 24 h (P < 0.05), but there was no difference in the number of normal neurons between the rapid IPC group and control group at 7 days after reperfusion, suggesting that the efficacy of rapid IPC on the spinal cord may be transient.

In a study by Caparrelli et al. ,4in a rabbit model very close that of Kakimoto et al.  (5 min of brief ischemia, 30 min of reperfusion, and 20 min of infrarenal aortic occlusion), when six animals with rapid IPC compared to seven controls, although the IPC group seemed to have a better outcome compared with the control, this difference did not reach statistical significance at either 24 or 48 h, whereas the two groups had similar histologic scores.

In a recent published study, our group demonstrated that rapid IPC without hypotension prevents spinal cord injury in a porcine model of descending thoracic aortic occlusion.2We used 20 min of brief ischemia and 80 min of reperfusion, and the duration of the occlusion of the descending thoracic aorta was 35 min. We assessed the neurologic outcome of our animals at the fifth postoperative day after reperfusion, taking into consideration the efficacy of rapid IPC on the spinal cord beyond 2 days after reperfusion. In our study, it was important to maintain arterial systolic blood pressure higher than 100 mmHg during the 80-min reperfusion interval. Two animals had an arterial systolic blood pressure of 80–90 mmHg during the reperfusion period. Although they had a Tarlov score of 4 at 24 h postoperatively, these two animals became paraplegic at 48 h, and the histologic examination showed loss of neurons and a moderate grade of inflammation.

In the study by Caparrelli et al. , there was a level of hypotension during the reperfusion interval in the IPC group, although mean arterial blood pressure recovered to nearly baseline before cross clamping was applied. This hypotension may be an explanation for the neurologic outcome and the failure of rapid IPC to protect the spinal cord. In addition, Griepp et al.  5mentioned indirect clinical evidence of this kind of protection, and in their study, it was of great importance to maintain mean arterial blood pressure at high normal levels during the sacrifice of intercostals.

In the study of Kakimoto et al. , it is mentioned in the published manuscript that proximal arterial blood pressure was monitored continuously during the experimental procedure. Their table 2 illustrates changes in proximal arterial pressure only at baseline, at a half-time point of 17 min of ischemia, and at 10 min after reperfusion. Was there any difference in mean arterial pressure during the 30 min of reperfusion in comparison to baseline mean arterial pressure in the rapid IPC group? That is, did the authors observe any hypotension during this reperfusion interval, and how did they deal with it?

Also, the role of inflammation in ischemic spinal cord injury after temporary aortic occlusion has been demonstrated by several investigators.2,3,6The authors discussed the beneficial effects of rapid IPC, which may involve an antiinflammatory process. Did the authors have any additional histopathologic data in both the rapid IPC and control groups regarding the grade of inflammation to corroborate the neurologic outcome with the development of inflammation?

* University Hospital of Ioannina, Ioannina, Greece. toumpoul@otenet.gr

Kakimoto M, Kawaguchi M, Sakamoto T, Inoue S, Furuya H, Nakamura M, Konishi N: Evaluation of rapid ischemic preconditioning in a rabbit model of spinal cord ischemia. Anesthesiology 2003; 99:1112–7
Toumpoulis IK, Anagnostopoulos CE, Drossos GE, Malamou-Mitsi VD, Pappa LS, Katritsis DG: Early ischemic preconditioning without hypotension prevents spinal cord injury caused by descending thoracic aortic occlusion. J Thorac Cardiovasc Surg 2003; 125:1030–6
Toumpoulis IK, Anagnostopoulos CE, Drossos GE, Malamou-Mitsi VD, Pappa LS, Katritsis DG: Does ischemic preconditioning reduce spinal cord injury because of descending thoracic aortic occlusion? J Vasc Surg 2003; 37:426–32
Caparrelli DJ, Cattaneo SM, Bethea BT, Shake JG, Eberhart C, Blue ME, Marban E, Johnston MV, Baumgartner WA, Gott VL: Pharmacological preconditioning ameliorates neurological injury in a model of spinal cord ischemia. Ann Thorac Surg 2002; 74:838–44
Griepp RB, Ergin MA, Galla JD, Lansman S, Khan N, Quintana C, McCollough J, Bodian C: Looking for the artery of Adamkiewicz: A quest to minimize paraplegia after operations for aneurysms of the descending thoracic and thoracoabdominal aorta. J Thorac Cardiovasc Surg 1996; 112:1202–13
Cassada DC, Tribble CG, Long SM, Laubach VE, Kaza AK, Linden J, Nguyen BN, Rieger JM, Fiser SM, Kron IL, Kern JA: Adenosine A2A analogue ATL-146e reduces systemic tumor necrosing factor-alpha and spinal cord capillary platelet-endothelial cell adhesion molecule-1 expression after spinal cord ischemia. J Vasc Surg 2002; 35:994–8