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J Thorac Cardiovasc Surg 2009;138:1409-1416
© 2009 The American Association for Thoracic Surgery

Evolving Technology/Basic Science

Cannabinoid 1 receptor mediation of spinal cord ischemic tolerance induced by limb remote ischemia preconditioning in rats

Binxiao Su, MD*, Hailong Dong, MD, PhD*, Rui Ma, MD, Xijing Zhang, MD, PhD, Qian Ding, MD, Lize Xiong, MD, PhD*

Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China

Received for publication February 10, 2009; revisions received June 18, 2009; accepted for publication July 5, 2009.

* Address for reprints: Lize Xiong, MD, PhD, Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, Shaanxi, China. (Email: hldong6{at}hotmail.com; lxiong{at}fmmu.edu.cn).

Objective: The aim of this study was to examine the influence of endogenous cannabinoids on neuroprotection of the spinal cord afforded by limb remote ischemic preconditioning.

Methods: In experiment 1 (RIPC group), 3 cycles of limb remote ischemic preconditioning within different episodes (2, 3, or 5 minutes) were induced before spinal cord ischemia in rats (N = 5, n = 8). In experiment 2, animals were pretreated intravenously by the vehicles, cannabinoid 1 (AM251, 1 mg/kg) or cannaboid 2 (AM630, 1 mg/kg) receptor antagonist 15 minutes before remote ischemic preconditioning, or else they were subjected to a sham operation. Thirty minutes after the pretreatment, spinal cord ischemia was induced (N = 8, n = 8). In experiment 3, the arachidonylethanolamide and 2-arachidonoylglycerol contents in the spinal cord after remote ischemic preconditioning and spinal cord ischemia were detected in rats (N = 2, n = 12). Spinal cord ischemia was induced by 12 minutes of thoracic aorta occlusion in rats. Neurologic function was assessed 24 and 48 hours after reperfusion. Histopathologic examination was performed and the number of normal neurons in anterior spinal cord were counted.

Results: In experiment 1, 3 cycles of limb remote ischemic preconditioning (3 minutes of ischemia/3 minutes of reperfusion) induced ischemic tolerance on the spinal cords of the rats. The RIPC group showed a significant reduction in motor deficit index (P < .01) as well as an increase in the number of normal neurons (P < .01). In experiment 2, the cannabinoid 1 receptor antagonist AM251 pretreatment abolished the protective effects of remote preconditioning. In experiment 3, arachidonylethanolamide content in spinal cord was elevated by remote ischemic preconditioning in rats.

Conclusion: These results indicated that endogenous cannabinoids, through acting on cannabinoid 1 receptors, were involved in the neuroprotective phenomenon on spinal cords of limb remote ischemic preconditioning.

Abbreviations and Acronyms AEA = arachidonylethanolamide; 2-AG = 2-arachidonoylglycerol; CB = cannabinoid; IPC = ischemic preconditioning; I/R = ischemia/reperfusion; MDI = motor deficit index; PaCO 2 = arterial carbon dioxide tension; PaO 2 = arterial oxygen tension; RIPC = remote ischemic preconditioning






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