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Reply to: The impact of early ischemic preconditioning on spinal cord injury (Yao 747)
Reply to: The impact of early ischemic preconditioning on spinal cord injury (Yao 747): T. Ueno and T. Itoh
References 1. Ueno, T., Chao, Z. L., Okazaki, Y. et al. The Impact of ischemic preconditioning on spinal cord blood flow and paraplegia. Cardiovascular Surgery, 2001, 9, 575–579. 2. Toumpoulis, I. K., Anagnostopoulos, C. E., Drossos, G. E. et al. Does ischemic preconditioning reduce spinal cord injury because of descending thoracic aortic occlusion? Journal of Vascular Surgery, 2003, 37, 426–432. 3. Toumpoulis, I. K., Anagnostopoulos, C. E., Drossos, G. E. et al. Early ischemic preconditioning without hypotension prevents spinal cord injury caused by descending thoracic aortic occlusion.
Journal of Thoracic and Cardiovascular Surgery, 2003, 125, 1030–1036. 4. Sakurai, M., Hayashi, T., Abe, K. et al. Enhancement of heat shock protein expression after transient ischemia in the preconditioned spinal cord of rabbits. Journal of Vascular Surgery, 1998, 27, 720–725. 5. Zvara, D. A., Colonna, D. M., Deal, D. D. et al. Ischemic preconditioning reduces neurologic injury in a rat model of spinal cord ischemia. The Annals of Thoracic Surgery, 1999, 68, 874– 880. Paper accepted 24 April 2003
doi:10.1016/S0967-2109(03)00072-3
Cardiovascular Surgery, Vol. 11, No. 5, pp. 430–431, 2003 2003 The International Society for Cardiovascular Surgery Published by Elsevier Ltd. All rights reserved. 0967-2109/03 $30.00
www.elsevier.com/locate/cardiosur
Reply to: The impact of early ischemic preconditioning on spinal cord injury (Yao 747) T. Ueno∗ and T. Itoh† ∗
Ureshino National Hospital, Department of Cardiovascular Surgery, 2436 ureshino-machi Fujitsugun, Saga, 843-0393, Japan and †Saga Medical School, Saga 849-9501, Japan
We appreciate very instructive comments by Toumpoulis and Anagnostopoulos on our manuscript about the impact of ischaemic preconditioning (IPC) on spinal cord blood flow and paraplegia [1]. They addressed important and up-to-dated issues: the second window of protection (SWOP) induced by IPC and significance to avoid hypotension after spinal cord ischaemia. In-depth knowledge about pathophysiology of both issues can contribute to further reduction in incidence of paraplegia, one of the most devastating complications after operation on descending thoracic or thoracoabdominal aorta. A number of investigations have been performed to examine whether the SWOP induced by IPC could attenuate post-ischaemic progressive dysfunction in later phase. In the rabbit spinal cord ischemia model, motor function can deteriorate progressively from several hours up to 24 hours after clamping the abdominal aorta. Jacobs and co-workers showed that progressive breakdown of blood-spinal cord barrier developed 8-24 hours later, contributed to this
Tel.: +81-954-43-1120; fax: +81-954-12-2452; e-mail: [email protected]
430
unique phenomenon [2]. Toumpoulis and Anagnostopoulos criticized our description related to the SWOP in the discussion of our manuscript. In our understanding, the term SWOP has been used when delayed myocardial or neuronal dysfunction 24-48 hours after ischaemic stress was attenuated by IPC through its undefined physiological mechanisms such as new synthesis of cytoprotective proteins that were supposed to work in delayed phase. We are not sure whether the term SWOP should be limited to be used only under the conditions in which the animals preconditioned 24-48 hours ahead, showed better neurological outcomes in immediate phase (the first window phase) or in delayed phase (the second window phase) after lethal spinal cord ischemia as they pointed out. If so, is the term SWOP not allowed to be used when IPC would offer neurological improvement in delayed phase after lethal ischaemia through, for example, the attenuation of breakdown of blood-spinal cord barrier? Our description in this part of the discussion was based on our understanding about SWOP described above. However, we are not confident whether our concept of SWOP will be universally proved to be right. We totally agree with their strategy to maintain blood pressure and spinal cord perfusion pressure CARDIOVASCULAR SURGERY
OCTOBER 2003 VOL 11 NO 5
Reply to: The impact of early ischemic preconditioning on spinal cord injury (Yao 747): T. Ueno and T. Itoh
high and avoid hypotension after release of aortic clamping. There is no doubt about the beneficial effect of increasing blood pressure and spinal cord perfusion pressure on recovery of the spinal cord jeopardized by ischaemic injury. Cheung and coworkers showed that five of eight patients with delayed paraplegia made a full neurological recovery by increasing blood pressure and decreasing cerebrospinal fluid pressure [3]. In our experiment, we did not perform any anti-hypotensive agents and volume overload for hypotension following release of aortic clamping for IPC and lethal ischaemia simply because one of our objectives was to examine the impact of transient (IPC) and prolonged aortic clamping on systemic blood pressure. If the infusion of catecholamines or fluid overload would be performed to treat hypotension, leading to a significantly better neurological function in IPC group, it will be difficult to tell which contributed to better neurological outcomes and to what extent. IPC alone, or high blood pressure with high cardiac output. The latter could offer a beneficial effect on the condition of spinal cord perfusion until the end of the experiment even though these strategies would be applied transiently. In our previous experiments related to spinal cord protection [4] we have not found any significant relationship between pathological findings and functional outcomes. A possible reason for the absence of that relationship was that pathological findings to
CARDIOVASCULAR SURGERY
OCTOBER 2003 VOL 11 NO 5
demonstrate ischaemic injury in the spinal cord differed from one slice to another in the same animal associated with inconsistent pathological grades of ischaemic injury even in the same slice making proper pathological evaluation quite difficult. Although the presence of significant relationship between pathological and functional results is undoubtedly preferable in these experiments we did not perform pathological examination with the reason described above. We look forward to another exciting research works to come by Toumpoulis and Anagnostopoulos and other experienced investigators towards common final goal of cardiovascular surgeons on the earth, elimination of dreadful complication, paraplegia.
References 1. Ueno, T., Chao, Z. L., Okazaki, Y. et al. The impact of ischaemic preconditioning on spinal cord blood flow and paraplegia. Cardiovascular Surgery, 2001, 9, 575–579. 2. Jacobs, T. P., Kempski, O., McKinley, D. et al. Blood flow and vascular permeability during motor dysfunction in a rabbit model of spinal cord ischemia. Stroke, 1992, 23, 367–373. 3. Cheung, A. T., Weiss, S. J., McGarvey, M. L. et al. Interventions for reversing delayed-onset post-operative paraplegia after thoracic aortic reconstruction. Ann Thorac Surg, 2002, 74, 413–421. 4. Ueno, T., Itoh, T., Hirahara, K. et al. Protection against spinal cord ischaemia: one-shot infusion of hypothermic solution. Cardiovascular Surgery, 1994, 2, 374–378. Paper accepted 24 April 2003
431
References 1. Ueno, T., Chao, Z. L., Okazaki, Y. et al. The Impact of ischemic preconditioning on spinal cord blood flow and paraplegia. Cardiovascular Surgery, 2001, 9, 575–579. 2. Toumpoulis, I. K., Anagnostopoulos, C. E., Drossos, G. E. et al. Does ischemic preconditioning reduce spinal cord injury because of descending thoracic aortic occlusion? Journal of Vascular Surgery, 2003, 37, 426–432. 3. Toumpoulis, I. K., Anagnostopoulos, C. E., Drossos, G. E. et al. Early ischemic preconditioning without hypotension prevents spinal cord injury caused by descending thoracic aortic occlusion.
Journal of Thoracic and Cardiovascular Surgery, 2003, 125, 1030–1036. 4. Sakurai, M., Hayashi, T., Abe, K. et al. Enhancement of heat shock protein expression after transient ischemia in the preconditioned spinal cord of rabbits. Journal of Vascular Surgery, 1998, 27, 720–725. 5. Zvara, D. A., Colonna, D. M., Deal, D. D. et al. Ischemic preconditioning reduces neurologic injury in a rat model of spinal cord ischemia. The Annals of Thoracic Surgery, 1999, 68, 874– 880. Paper accepted 24 April 2003
doi:10.1016/S0967-2109(03)00072-3
Cardiovascular Surgery, Vol. 11, No. 5, pp. 430–431, 2003 2003 The International Society for Cardiovascular Surgery Published by Elsevier Ltd. All rights reserved. 0967-2109/03 $30.00
www.elsevier.com/locate/cardiosur
Reply to: The impact of early ischemic preconditioning on spinal cord injury (Yao 747) T. Ueno∗ and T. Itoh† ∗
Ureshino National Hospital, Department of Cardiovascular Surgery, 2436 ureshino-machi Fujitsugun, Saga, 843-0393, Japan and †Saga Medical School, Saga 849-9501, Japan
We appreciate very instructive comments by Toumpoulis and Anagnostopoulos on our manuscript about the impact of ischaemic preconditioning (IPC) on spinal cord blood flow and paraplegia [1]. They addressed important and up-to-dated issues: the second window of protection (SWOP) induced by IPC and significance to avoid hypotension after spinal cord ischaemia. In-depth knowledge about pathophysiology of both issues can contribute to further reduction in incidence of paraplegia, one of the most devastating complications after operation on descending thoracic or thoracoabdominal aorta. A number of investigations have been performed to examine whether the SWOP induced by IPC could attenuate post-ischaemic progressive dysfunction in later phase. In the rabbit spinal cord ischemia model, motor function can deteriorate progressively from several hours up to 24 hours after clamping the abdominal aorta. Jacobs and co-workers showed that progressive breakdown of blood-spinal cord barrier developed 8-24 hours later, contributed to this
Tel.: +81-954-43-1120; fax: +81-954-12-2452; e-mail: [email protected]
430
unique phenomenon [2]. Toumpoulis and Anagnostopoulos criticized our description related to the SWOP in the discussion of our manuscript. In our understanding, the term SWOP has been used when delayed myocardial or neuronal dysfunction 24-48 hours after ischaemic stress was attenuated by IPC through its undefined physiological mechanisms such as new synthesis of cytoprotective proteins that were supposed to work in delayed phase. We are not sure whether the term SWOP should be limited to be used only under the conditions in which the animals preconditioned 24-48 hours ahead, showed better neurological outcomes in immediate phase (the first window phase) or in delayed phase (the second window phase) after lethal spinal cord ischemia as they pointed out. If so, is the term SWOP not allowed to be used when IPC would offer neurological improvement in delayed phase after lethal ischaemia through, for example, the attenuation of breakdown of blood-spinal cord barrier? Our description in this part of the discussion was based on our understanding about SWOP described above. However, we are not confident whether our concept of SWOP will be universally proved to be right. We totally agree with their strategy to maintain blood pressure and spinal cord perfusion pressure CARDIOVASCULAR SURGERY
OCTOBER 2003 VOL 11 NO 5
Reply to: The impact of early ischemic preconditioning on spinal cord injury (Yao 747): T. Ueno and T. Itoh
high and avoid hypotension after release of aortic clamping. There is no doubt about the beneficial effect of increasing blood pressure and spinal cord perfusion pressure on recovery of the spinal cord jeopardized by ischaemic injury. Cheung and coworkers showed that five of eight patients with delayed paraplegia made a full neurological recovery by increasing blood pressure and decreasing cerebrospinal fluid pressure [3]. In our experiment, we did not perform any anti-hypotensive agents and volume overload for hypotension following release of aortic clamping for IPC and lethal ischaemia simply because one of our objectives was to examine the impact of transient (IPC) and prolonged aortic clamping on systemic blood pressure. If the infusion of catecholamines or fluid overload would be performed to treat hypotension, leading to a significantly better neurological function in IPC group, it will be difficult to tell which contributed to better neurological outcomes and to what extent. IPC alone, or high blood pressure with high cardiac output. The latter could offer a beneficial effect on the condition of spinal cord perfusion until the end of the experiment even though these strategies would be applied transiently. In our previous experiments related to spinal cord protection [4] we have not found any significant relationship between pathological findings and functional outcomes. A possible reason for the absence of that relationship was that pathological findings to
CARDIOVASCULAR SURGERY
OCTOBER 2003 VOL 11 NO 5
demonstrate ischaemic injury in the spinal cord differed from one slice to another in the same animal associated with inconsistent pathological grades of ischaemic injury even in the same slice making proper pathological evaluation quite difficult. Although the presence of significant relationship between pathological and functional results is undoubtedly preferable in these experiments we did not perform pathological examination with the reason described above. We look forward to another exciting research works to come by Toumpoulis and Anagnostopoulos and other experienced investigators towards common final goal of cardiovascular surgeons on the earth, elimination of dreadful complication, paraplegia.
References 1. Ueno, T., Chao, Z. L., Okazaki, Y. et al. The impact of ischaemic preconditioning on spinal cord blood flow and paraplegia. Cardiovascular Surgery, 2001, 9, 575–579. 2. Jacobs, T. P., Kempski, O., McKinley, D. et al. Blood flow and vascular permeability during motor dysfunction in a rabbit model of spinal cord ischemia. Stroke, 1992, 23, 367–373. 3. Cheung, A. T., Weiss, S. J., McGarvey, M. L. et al. Interventions for reversing delayed-onset post-operative paraplegia after thoracic aortic reconstruction. Ann Thorac Surg, 2002, 74, 413–421. 4. Ueno, T., Itoh, T., Hirahara, K. et al. Protection against spinal cord ischaemia: one-shot infusion of hypothermic solution. Cardiovascular Surgery, 1994, 2, 374–378. Paper accepted 24 April 2003
431