Schaser K D, Vollmar B, Menger M D, Schewior L, Kroppenstedt S N, Raschke M, Lübbe A S, Haas N P, Mittlmeier T
Department of Trauma and Reconstructive Surgery, Charité, Humboldt-University of Berlin, Germany.
J Orthop Res. 1999 Sep;17(5):678-85. doi: 10.1002/jor.1100170509.
Major loss of tissue is an almost invariable consequence of severe closed soft-tissue injury. Clinically, the extent of soft-tissue trauma determines the outcome of complex injuries and significantly influences bone healing. With use of a new animal model, this study quantitatively analyzed microcirculation, i.e., nutritive perfusion and leukocyte-endothelial cell interaction, in skeletal muscle after standardized closed soft-tissue injury. By means of a computer-assisted controlled-impact technique, a severe standardized closed soft-tissue injury was induced in the left hindlimb of 28 rats. The rats were assigned to four experimental groups (n = 7 per group) that differed by time of analysis (1.5, 24, 72, and 120 hours after injury); rats that were not injured served as controls (n = 7). Intramuscular pressure was measured, and microcirculation in the rat extensor digitorum longus muscle was analyzed by in vivo fluorescence microscopy, which allowed assessment of microvascular diameters, functional capillary density, number of rolling and adherent leukocytes in venules, and microvascular permeability. Edema weight gain was quantified by the ratio of wet to dry weight of the extensor digitorum longus muscle. Microvascular perfusion of the skeletal muscle was characterized by a significant reduction in functional capillary density, which was paralleled by an increase in capillary diameter throughout the 120 hours of observation when compared with the controls. Trauma-induced inflammatory response was reflected by a markedly increased rolling and adherence of leukocytes, primarily restricted to the endothelium of postcapillary venules; this was accompanied by increased microvascular permeability, indicative of a substantial loss of endothelial integrity. The microcirculation surrounding the core of the damaged tissue area resembled that of ischemia-reperfusion injury in skeletal muscle, i.e., heterogeneous capillary perfusion, pronounced microvascular leakage, and adherence of leukocytes. Enhanced vascular leakage and leukocyte adherence (24-72 hours after injury) coincided with the maximum intramuscular pressure (which was not indicative of compartment syndrome) and edema formation. These results demonstrate that initial changes, leading to ultimate tissue death, after closed soft-tissue injury are caused on the microcirculatory level. This standardized model provides further insight into microvascular pathophysiology and cellular interactions following closed soft-tissue injury. Thus, it is an adequate tool for testing novel therapeutic interventions.
严重闭合性软组织损伤几乎总会导致大量组织丧失。临床上，软组织创伤的程度决定了复杂损伤的预后，并对骨愈合有显著影响。本研究使用一种新的动物模型，对标准化闭合性软组织损伤后骨骼肌的微循环，即营养性灌注和白细胞 - 内皮细胞相互作用进行了定量分析。通过计算机辅助控制撞击技术，在28只大鼠的左后肢诱导了严重的标准化闭合性软组织损伤。将大鼠分为四个实验组（每组n = 7），根据分析时间（损伤后1.5、24、72和120小时）不同；未受伤的大鼠作为对照（n = 7）。测量肌内压，并通过体内荧光显微镜分析大鼠趾长伸肌的微循环，这可以评估微血管直径、功能性毛细血管密度、小静脉中滚动和黏附白细胞的数量以及微血管通透性。通过趾长伸肌湿重与干重之比来量化水肿增重。骨骼肌的微血管灌注表现为功能性毛细血管密度显著降低，与对照组相比，在整个120小时的观察期内毛细血管直径增加。创伤诱导的炎症反应表现为白细胞滚动和黏附明显增加，主要局限于毛细血管后小静脉的内皮；这伴随着微血管通透性增加，表明内皮完整性大量丧失。受损组织区域核心周围的微循环类似于骨骼肌缺血再灌注损伤，即毛细血管灌注不均一、微血管渗漏明显和白细胞黏附。血管渗漏增强和白细胞黏附（损伤后24 - 72小时）与最大肌内压（这并不提示骨筋膜室综合征）和水肿形成同时出现。这些结果表明，闭合性软组织损伤后导致最终组织死亡的初始变化发生在微循环水平。这个标准化模型为深入了解闭合性软组织损伤后的微血管病理生理学和细胞相互作用提供了进一步的认识。因此，它是测试新型治疗干预措施的合适工具。
