Brinker M R, Lippton H L, Cook S D, Hyman A L
Department of Orthopaedic Surgery, Tulane University School of Medicine, New Orleans, Louisiana 70112.
J Bone Joint Surg Am. 1990 Aug;72(7):964-75.
A study was undertaken to investigate the reactivity of the circulation of bone and to pharmacologically characterize the receptor populations that may be present in this poorly described vascular bed. The nutrient artery of the tibia in skeletally mature mongrel dogs was cannulated, under direct vision, through a posterolateral operative approach. An extracorporeal circuit was established so that the nutrient artery of the tibia could be perfused in vivo under conditions of constant blood flow. Diverse vasoactive substances were injected into the perfusion circuit in small volumes as a bolus close to the nutrient artery of the tibia. A range of doses of nitroglycerin, acetylcholine, isoproterenol, methoxamine, U46619 (a thromboxane A2 mimic), dibutyryl cyclic AMP, 8-bromo-cyclic GMP, and endothelin-1 were injected in a randomized sequence for each experiment. The antagonists that were used were atropine (a non-selective muscarinic receptor antagonist), ICI 118551 (a selective beta 2-adrenoceptor antagonist), ONO 3708 (a prostaglandin H2/thromboxane A2 receptor antagonist), and prazosin (an alpha 1-adrenoceptor antagonist). The results of changes in bone-perfusion pressure under conditions of constant blood flow indicated that the vascular bed of bone actively responds to various vasoconstrictor mechanisms, whereas vasodilator mechanisms appear to be considerably less active. Intra-arterial injections of nitroglycerin, acetylcholine, and 8-bromo-cyclic GMP resulted in dose-related decreases in bone-perfusion pressure that were weak relative to concomitant changes in systemic arterial pressure. Intra-arterial administration of methoxamine, U46619, and endothelin-1 resulted in a potent dose-related increase in bone-perfusion pressure. The results of intra-arterial injections of isoproterenol and dibutyryl cyclic AMP were surprising; both substances caused a substantial rise in bone-perfusion pressure. The responses to acetylcholine, methoxamine, and U46619 were blocked in a competitive manner after administration of atropine, prazosin, and ONO 3708, respectively.
开展了一项研究，以调查骨骼的循环反应性，并从药理学角度对这个描述较少的血管床中可能存在的受体群体进行表征。在直视下，通过后外侧手术入路，将骨骼成熟的杂种犬胫骨的营养动脉插管。建立体外循环，以便在恒定血流条件下对胫骨的营养动脉进行体内灌注。将各种血管活性物质以小体积推注的方式注入靠近胫骨营养动脉的灌注回路中。在每个实验中，以随机顺序注射一系列剂量的硝酸甘油、乙酰胆碱、异丙肾上腺素、甲氧明、U46619（一种血栓素A2类似物）、二丁酰环磷腺苷、8-溴环鸟苷和内皮素-1。所使用的拮抗剂分别是阿托品（一种非选择性毒蕈碱受体拮抗剂）、ICI 118551（一种选择性β2肾上腺素能受体拮抗剂）、ONO 3708（一种前列腺素H2/血栓素A2受体拮抗剂）和哌唑嗪（一种α1肾上腺素能受体拮抗剂）。在恒定血流条件下骨灌注压变化的结果表明，骨骼的血管床对各种血管收缩机制有积极反应，而血管舒张机制似乎活性要低得多。动脉内注射硝酸甘油、乙酰胆碱和8-溴环鸟苷导致骨灌注压呈剂量相关下降，相对于同时出现的体动脉压变化而言较为微弱。动脉内给予甲氧明、U46619和内皮素-1导致骨灌注压呈剂量相关的显著升高。动脉内注射异丙肾上腺素和二丁酰环磷腺苷的结果令人惊讶；这两种物质都导致骨灌注压大幅升高。分别给予阿托品、哌唑嗪和ONO 3708后，对乙酰胆碱、甲氧明和U46619的反应以竞争性方式被阻断。
