Takehiko Fukui1, Kazuyoshi Ishida1, Yoichi Mizukami2, Kiyotaka Shiramoto1, Hidenori Harada1, Atsuo Yamashita1, Satoshi Yamashita1, Mishiya Matsumoto3. 1. Department of Anesthesiology, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi, 755-8505, Japan. 2. Center for Gene Research, Yamaguchi University, 1-1-1 Minami-Kogushi, Ube, Yamaguchi, 755-8505, Japan. 3. Department of Anesthesiology, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi, 755-8505, Japan. mishiya@yamaguchi-u.ac.jp.
Abstract
INTRODUCTION: This study aimed to determine the relative potency of direct ischemic preconditioning (DIPC) and remote ischemic preconditioning (RIPC) for protection against ischemic spinal cord injury in rabbits and to explore the mechanisms involved. METHODS: In experiment 1, we compared the neurological and histopathological outcomes of DIPC, kidney RIPC, and limb RIPC. The DIPC and kidney RIPC groups received two cycles of 5-min occlusion/15-min reperfusion of the abdominal aorta and left renal artery, respectively. The limb RIPC group received two cycles of 10-min occlusion/10-min reperfusion of the femoral arteries bilaterally. Thirty minutes after the conditioning ischemia, spinal cord ischemia was produced by occluding the abdominal aorta for 15 min. In experiments 2 and 3, we investigated whether pretreatment using a free-radical scavenger, dimethylthiourea (DMTU), an adenosine A1 receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), or a mitochondrial ATP-sensitive potassium channel antagonist, 5-hydroxydecanoate (5HD), could attenuate the protective effects of DIPC. In experiment 4, comprehensive analysis of phosphorylated proteins in the spinal cord was performed using a Proteome Profiler Array followed by immunoblotting to elucidate the signal pathway activated by DIPC. RESULTS: In experiment 1, DIPC improved the neurological and histopathological outcomes, whereas kidney and limb RIPC had no protective effects. In experiments 2 and 3, strong protective effects of DIPC were reconfirmed but were not attenuated by DMTU, DPCPX, or 5HD. In experiment 4, DIPC induced phosphorylation of Akt2. CONCLUSIONS: DIPC, but not kidney or limb RIPC, protected against ischemic spinal cord injury in rabbits. Akt2 might contribute to this protective effect.
INTRODUCTION: This study aimed to determine the relative potency of direct ischemic preconditioning (DIPC) and remote ischemic preconditioning (RIPC) for protection against ischemic spinal cord injury in rabbits and to explore the mechanisms involved. METHODS: In experiment 1, we compared the neurological and histopathological outcomes of DIPC, kidney RIPC, and limb RIPC. The DIPC and kidney RIPC groups received two cycles of 5-min occlusion/15-min reperfusion of the abdominal aorta and left renal artery, respectively. The limb RIPC group received two cycles of 10-min occlusion/10-min reperfusion of the femoral arteries bilaterally. Thirty minutes after the conditioning ischemia, spinal cord ischemia was produced by occluding the abdominal aorta for 15 min. In experiments 2 and 3, we investigated whether pretreatment using a free-radical scavenger, dimethylthiourea (DMTU), an adenosine A1 receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), or a mitochondrial ATP-sensitive potassium channel antagonist, 5-hydroxydecanoate (5HD), could attenuate the protective effects of DIPC. In experiment 4, comprehensive analysis of phosphorylated proteins in the spinal cord was performed using a Proteome Profiler Array followed by immunoblotting to elucidate the signal pathway activated by DIPC. RESULTS: In experiment 1, DIPC improved the neurological and histopathological outcomes, whereas kidney and limb RIPC had no protective effects. In experiments 2 and 3, strong protective effects of DIPC were reconfirmed but were not attenuated by DMTU, DPCPX, or 5HD. In experiment 4, DIPC induced phosphorylation of Akt2. CONCLUSIONS:DIPC, but not kidney or limb RIPC, protected against ischemic spinal cord injury in rabbits. Akt2 might contribute to this protective effect.
Authors: Henri Haapanen; Johanna Herajärvi; Oiva Arvola; Tuomas Anttila; Tuomo Starck; Mika Kallio; Vesa Anttila; Hannu Tuominen; Kai Kiviluoma; Tatu Juvonen Journal: J Thorac Cardiovasc Surg Date: 2015-07-17 Impact factor: 5.209
Authors: Derek J Hausenloy; Luciano Candilio; Richard Evans; Cono Ariti; David P Jenkins; Shyam Kolvekar; Rosemary Knight; Gudrun Kunst; Christopher Laing; Jennifer Nicholas; John Pepper; Steven Robertson; Maria Xenou; Tim Clayton; Derek M Yellon Journal: N Engl J Med Date: 2015-10-05 Impact factor: 91.245