己酮可可碱可预防因缺血再灌注损伤导致的内皮损伤。

Pentoxifylline prevents endothelial damage due to ischemia and reperfusion injury.

作者信息

Coe D A, Freischlag J A, Johnson D, Mudaliar J H, Kosciesza S A, Traul D K, Chiang P C, Cambria R A, Seabrook G R, Towne J B

机构信息

Department of Vascular Surgery, Medical College of Wisconsin, Milwaukee, USA.

出版信息

J Surg Res. 1997 Jan;67(1):21-5. doi: 10.1006/jsre.1996.4940.

DOI:10.1006/jsre.1996.4940

PMID:9070176

Abstract

BACKGROUND

Endothelial injury after ischemia and reperfusion is characterized by an increase in permeability, cellular edema, and loss of acetylcholine-mediated vasorelaxation. Three hours of ischemia followed by 2 hr of reperfusion in the New Zealand white rabbit hindlimb has been shown to result in loss of acetylcholine-induced superficial femoral artery vasorelaxation. The purpose of this study was to evaluate the effect of intraarterial pentoxyfylline (PTX) on this endothelial injury.

METHODS

New Zealand white rabbits underwent 3 hr of complete hindlimb ischemia followed by 2 hr of reperfusion. Twenty milliliters of either 100 microM PTX or normal saline was infused over 20 min via the circumflex iliac artery at initiation of reperfusion. Superficial femoral artery rings were then evaluated in vitro for endothelial cell-mediated relaxation. Rings were exposed to standardized incremental doses of acetylcholine after norepinephrine-induced contraction and percentage relaxation was measured. Sections of arteries were also sent for hematoxylin and eosin staining.

RESULTS

Similar contraction responses following NE stimulation were observed between control and PTX-treated rings. Control rings relaxed a mean of 14.97 +/- 3.64, 23.17 +/- 5.61, and 31.84 +/- 8.43% in response to acetylcholine doses of 6 x 10(-8), 1 x 10(-7), and 1.5 x 10(-7) M, respectively. In contrast, PTX-treated segments relaxed a mean of 47.52 +/- 8.88, 62.32 +/- 6.83, and 76.73 +/- 4.91% to the same doses of acetylcholine. Differences in relaxation between control and PTX-treated vessels were significantly different at each dose (P < 0.05, Student's t test). Histologic examination of the PTX-treated and control arteries revealed an intact endothelium without morphologic differences between the two groups.

CONCLUSION

In this model of rabbit hindlimb ischemia, endothelial cell-mediated vasorelaxation was preserved with the administration of intraarterial PTX during reperfusion compared to controls. The different relaxation responses could not be attributed to altered arterial contractility in response to norepinephrine, or explained by histologic changes in the arterial wall. These studies demonstrate a potential modality for therapeutic intervention to reduce reperfusion injury after acute limb ischemia.

摘要

背景

缺血再灌注后的内皮损伤表现为通透性增加、细胞水肿以及乙酰胆碱介导的血管舒张功能丧失。新西兰白兔后肢缺血3小时，再灌注2小时，已证实会导致乙酰胆碱诱导的股浅动脉血管舒张功能丧失。本研究的目的是评估动脉内注射己酮可可碱（PTX）对这种内皮损伤的影响。

方法

新西兰白兔经历3小时的完全后肢缺血，随后再灌注2小时。在再灌注开始时，通过旋髂动脉在20分钟内注入20毫升100微摩尔/升的PTX或生理盐水。然后在体外评估股浅动脉环的内皮细胞介导的舒张功能。在去甲肾上腺素诱导收缩后，将环暴露于标准化递增剂量的乙酰胆碱，并测量舒张百分比。动脉切片也送去进行苏木精和伊红染色。

结果

在对照环和PTX处理的环之间，观察到去甲肾上腺素刺激后类似的收缩反应。对照环对乙酰胆碱剂量分别为6×10⁻⁸、1×10⁻⁷和1.5×10⁻⁷摩尔/升时，平均舒张分别为14.97±3.64%、23.17±5.61%和31.84±8.43%。相比之下，PTX处理的节段对相同剂量的乙酰胆碱平均舒张为47.52±8.88%、62.32±6.83%和76.73±4.91%。在每个剂量下，对照血管和PTX处理血管之间的舒张差异均具有显著统计学意义（P<0.05，学生t检验）。对PTX处理和对照动脉的组织学检查显示内皮完整，两组之间无形态学差异。