Aliev G, Cirillo R, Salvatico E, Paro M, Prosdocimi M
Department of Vascular Biology, Fidia Research Laboratories, Abano Terme, Italy.
Microvasc Res. 1993 Jul;46(1):65-76. doi: 10.1006/mvre.1993.1035.
Peripheral ischemia was induced in the rabbit by occlusion of the left iliac artery for 6 hr, followed by 24 hr of reperfusion. Biochemical and morphological investigations were performed to evaluate the extent of vascular and tissue injury. Blood samples for plasma enzyme determinations (creatine kinase (CK) and lactate dehydrogenase (LDH) activities) were obtained at times t = 0, t = 6, t = 30 hr. Plasma CK and LDH activities in ischemic animals were approximately twice as high as those in sham-operated animals at the end of reperfusion, although no difference was observed at the end of the period of ischemia. Morphological and morphometric analysis of extensor digitorum longus muscle from ischemic animals showed a reduction in the number of patent capillary vessels per muscle fiber (1.54 +/- 0.1 and 1.04 +/- 0.09, P < 0.05, in sham and ischemic groups, respectively; mean +/- SEM). In addition, the number of microvilli on endothelial surfaces were considerably increased in the ischemic group (0.14 +/- 0.02 and 0.41 +/- 0.01 microns -2, P < 0.001, in sham and ischemic groups, respectively). A great number of adhered leucocytes were found on the vessel surface with some leucocytes having migrated through the vessel wall. Microcirculatory damage was accompanied by the formation of microthrombi which sometimes occluded the entire vessel lumen. The infusion of 1 mg/kg/hr of cloricromene for 6 hr prevented ischemic injury in microvessels and also prevented swelling of muscle mitochondria. In the treated group the number of patent capillaries per muscle fiber was very similar to that found in sham-operated animals (1.49 +/- 0.08; P < 0.01 vs. ischemic control). In conclusion, several different cell types are involved in the pathophysiological changes which occur in microvessels during ischemia/reperfusion injury. Pharmacological interventions, which inhibit the interactions of blood cells with endothelium, may be of value in the treatment of peripheral ischemia/reperfusion injury.
通过闭塞家兔左髂动脉6小时，随后再灌注24小时来诱导外周缺血。进行生化和形态学研究以评估血管和组织损伤的程度。在时间t = 0、t = 6、t = 30小时采集血样用于测定血浆酶（肌酸激酶（CK）和乳酸脱氢酶（LDH）活性）。尽管在缺血期末未观察到差异，但在再灌注结束时，缺血动物的血浆CK和LDH活性约为假手术动物的两倍。对缺血动物的趾长伸肌进行形态学和形态计量学分析显示，每根肌纤维的开放毛细血管数量减少（假手术组和缺血组分别为1.54±0.1和1.04±0.09，P < 0.05；均值±标准误）。此外，缺血组内皮表面的微绒毛数量显著增加（假手术组和缺血组分别为0.14±0.02和0.41±0.01μm -2，P < 0.001）。在血管表面发现大量黏附的白细胞，一些白细胞已穿过血管壁迁移。微循环损伤伴随着微血栓的形成，微血栓有时会阻塞整个血管腔。以1mg/kg/小时的剂量输注氯克罗孟6小时可预防微血管的缺血性损伤，并防止肌肉线粒体肿胀。在治疗组中，每根肌纤维的开放毛细血管数量与假手术动物非常相似（1.49±0.08；与缺血对照组相比，P < 0.01）。总之，几种不同的细胞类型参与了缺血/再灌注损伤期间微血管中发生的病理生理变化。抑制血细胞与内皮细胞相互作用的药理学干预可能对外周缺血/再灌注损伤的治疗有价值。
