Menger Michael D, Laschke Matthias W, Amon Michaela, Schramm Rene, Thorlacius Henrik, Rücker Martin, Vollmar Brigitte
Institute for Clinical and Experimental Surgery, University of Saarland, 66421 Homburg/Saar, Germany.
Langenbecks Arch Surg. 2003 Oct;388(5):281-90. doi: 10.1007/s00423-003-0426-y. Epub 2003 Oct 7.
During the past decade, experimental studies have provided convincing evidence that microcirculatory dysfunction plays a pivotal role in the manifestation of tissue injury in ischemia-reperfusion and osteomyocutaneous flap transfer. The study of the mechanisms of injury, however, requires sophisticated experimental in vivo models. With the use of microsurgical techniques, osteomyocutaneous flap transfer can successfully be performed in rat hind limbs, allowing in vivo fluorescent microscopic analysis of post-ischemic microcirculatory dysfunction in all tissues involved, including periosteum, striated muscle, subcutis and skin. The drawback of this "acute" model is that the period of analysis is restricted to a few hours only.
To overcome this limitation, the "chronic" dorsal skinfold chamber preparation, containing striated muscle and subcutis, can be used. This model allows one to study microcirculatory dysfunction after both tourniquet-induced and pressure-induced ischemia-reperfusion-induced tissue injury over a period of up to 3 weeks.
With the use of these models, recent investigations have demonstrated that ischemia-reperfusion and osteomyocutaneous flap transfer are associated with capillary perfusion failure (no-reflow), mediated by intravascular hemoconcentration, endothelial swelling and endothelin (ET)-1-mediated microvascular constriction. In addition, post-ischemic reperfusion provokes an inflammatory response (reflow paradox) in post-capillary venules, which is characterized by beta2-integrin-mediated and intercellular adhesion molecule (ICAM)-1-mediated leukocyte adhesion and vascular hyperpermeability, which results in interstitial edema formation. Treatment studies have produced evidence that isovolemic hemodilution and heat shock protein induction are successful in ameliorating capillary no-reflow, while blockade of adhesion molecules, inactivation of oxygen radicals and, also, induction of heat shock proteins, are capable of reducing the post-ischemic inflammatory response.
These experimental results not only demonstrate the importance of the use of advanced in vivo methods to delineate pathophysiological mechanisms in complex disease models, but may also provide a basis for potential prospective randomized trials to test the benefit for the patient in the daily clinical routine.
在过去十年中，实验研究提供了令人信服的证据，表明微循环功能障碍在缺血再灌注和骨肌皮瓣转移的组织损伤表现中起关键作用。然而，对损伤机制的研究需要复杂的体内实验模型。利用显微外科技术，可在大鼠后肢成功进行骨肌皮瓣转移，从而对包括骨膜、横纹肌、皮下组织和皮肤在内的所有相关组织缺血后的微循环功能障碍进行体内荧光显微镜分析。这种“急性”模型的缺点是分析期仅限制在几个小时。
为克服这一局限性，可使用包含横纹肌和皮下组织的“慢性”背部皮褶腔制备模型。该模型可让人研究止血带诱导和压力诱导的缺血再灌注诱导的组织损伤后长达3周的微循环功能障碍。
利用这些模型，最近的研究表明，缺血再灌注和骨肌皮瓣转移与毛细血管灌注衰竭（无复流）有关，这是由血管内血液浓缩、内皮肿胀和内皮素（ET）-1介导的微血管收缩介导的。此外，缺血后再灌注会在毛细血管后微静脉引发炎症反应（再流悖论），其特征是β2整合素介导和细胞间黏附分子（ICAM）-1介导的白细胞黏附和血管通透性增加，从而导致间质水肿形成。治疗研究已证明，等容血液稀释和热休克蛋白诱导可成功改善毛细血管无复流，而阻断黏附分子、使氧自由基失活以及诱导热休克蛋白均能够减轻缺血后炎症反应。
这些实验结果不仅证明了在复杂疾病模型中使用先进的体内方法来描述病理生理机制的重要性，而且还可能为潜在的前瞻性随机试验提供基础，以在日常临床实践中测试对患者的益处。
