Drescher Wolf, Li Haisheng, Lundgaard Anette, Bünger Cody, Hansen Ebbe-Stender
Department of Orthopaedic Surgery, University Hospital Schleswig-Holstein, Campus Kiel, Michaelisstr. 1, D-24105 Kiel, Germany.
J Bone Joint Surg Am. 2006 Nov;88 Suppl 3:173-9. doi: 10.2106/JBJS.F.00773.
With regard to the pathogenesis of corticosteroid-associated femoral head osteonecrosis, only intravascular and extravascular factors have been discussed. Wall constriction of the lateral epiphyseal arteries, which are the main supplying arteries within the femoral head, has not previously been investigated. This study examined the effect of long-term corticosteroid treatment on vasoconstriction of the lateral epiphyseal arteries of the femoral head in a porcine model.
The immature female Danish Landrace pig was chosen as the model for our study because femoral head osteonecrosis can be induced in this animal and because the lateral epiphyseal arteries of the femoral heads are of the appropriate size for myographic investigation. Twenty-four female Danish Landrace pigs (two siblings from each of twelve litters for a total of twelve sibling pairs) were divided by randomly separating the sibling pairs into two groups, with a total of twelve pigs in each group. One group of twelve animals received a daily dose of 100 mg of methylprednisolone orally for three months. The other group of twelve pigs served as controls and received no corticosteroids. After the animals were killed with an intravenous injection of pentobarbital, the lateral epiphyseal arteries of the femoral head were isolated from the cancellous bone. These arteries were mounted as ring preparations on a small-vessel myograph for measurement of isometric force development. The effects on the resected vessels of the vasoactive agents endothelin-1, noradrenaline, bradykinin, substance P, and nitrous oxide were investigated.
Vasoconstriction induced by increasing doses of endothelin-1 was increased after three months of methylprednisolone treatment compared with the vasoconstriction in vessels from control animals. Sensitivity to noradrenaline was not altered by this treatment. After submaximal precontraction by noradrenaline, vasorelaxation was elicited by substance P, nitrous oxide, and increasing doses of bradykinin without differences between the corticosteroid-treated and the control groups.
Endothelin-1-induced vasoconstriction of the epiphyseal arteries of the femoral head was increased in this corticosteroid-treated pig model. Such vasoconstriction may lead to a reduction in femoral head blood flow and to local ischemia and thus may be a newly described factor in the multifactorial pathomechanism of osteonecrosis of the femoral head.
关于皮质类固醇相关的股骨头坏死的发病机制，此前仅讨论了血管内和血管外因素。股骨头内主要供血动脉——外侧骨骺动脉的血管收缩情况此前尚未被研究。本研究在猪模型中检测了长期皮质类固醇治疗对股骨头外侧骨骺动脉血管收缩的影响。
选择未成年雌性丹麦长白猪作为研究模型，因为这种动物可诱发股骨头坏死，且其股骨头的外侧骨骺动脉大小适合进行肌动描记法研究。24只雌性丹麦长白猪（来自12窝，每窝2只同胞仔猪，共12对同胞仔猪）通过随机将同胞对分开分为两组，每组共12只猪。一组12只动物口服每日剂量100mg的甲泼尼龙，持续3个月。另一组12只猪作为对照，不接受皮质类固醇治疗。在用静脉注射戊巴比妥处死动物后，从松质骨中分离出股骨头的外侧骨骺动脉。将这些动脉制成环状标本安装在小型血管肌动描记仪上，用于测量等长力的产生。研究了血管活性药物内皮素-1、去甲肾上腺素、缓激肽、P物质和一氧化氮对切除血管的影响。
与对照动物血管相比，甲泼尼龙治疗3个月后，内皮素-1剂量增加所诱导的血管收缩增强。这种治疗未改变对去甲肾上腺素的敏感性。在用去甲肾上腺素进行次最大预收缩后，P物质、一氧化氮和剂量增加的缓激肽可引起血管舒张，皮质类固醇治疗组和对照组之间无差异。
在这个接受皮质类固醇治疗的猪模型中，内皮素-1诱导的股骨头骨骺动脉血管收缩增强。这种血管收缩可能导致股骨头血流减少和局部缺血，因此可能是股骨头坏死多因素发病机制中一个新描述的因素。
