Wiseman D M, Kamp L, Linsky C B, Jochen R F, Pang R H, Scholz P M
Adhesions Research, Johnson & Johnson Medical, Inc. (presently Adhesions Research, Ethicon, Inc.), Somerville, New Jersey 08876.
J Surg Res. 1992 Oct;53(4):362-8. doi: 10.1016/0022-4804(92)90062-5.
Epicardial adhesions are believed to form secondarily to impaired pericardial fibrinolytic activity. This activity was reconstituted in a rabbit pericardial adhesion model with single doses of the fibrinolytic agents tissue plasminogen activator (t-PA), t-PA analog (Fb-Fb-CF), and streptokinase (SK), resulting in reductions in the extent and tenacity of adhesion formation. Adhesions of the median strip of the anterior cardiac surface were reduced in area from 89% (n = 22) in controls, to 28% (n = 5) by treatment with Fb-Fb-CF (0.94 mg), and to 49% (n = 7) by treatment with SK (93,750 IU). A modified fabric of oxidized regenerated cellulose (mTC7) used to deliver the agent to the cardiac surface did not interfere with the activity of these agents (Fb-Fb-CF 19%, n = 14; SK 33%, n = 7). t-PA (0.94 mg) was also found to reduce adhesion formation in combination with mTC7 (4%, n = 4), although the appearance of significant postoperative bruising and bleeding resulted in a decision to terminate the treatment of further animals with t-PA with and without mTC7. Postoperative bruising, bleeding, and swelling, to a lesser extent, were associated with SK and Fb-Fb-CF. Despite the efficacy of the these fibrinolytic drugs further work is required to assess their safety before they are used clinically.
心外膜粘连被认为是心包纤维蛋白溶解活性受损继发形成的。在兔心包粘连模型中,通过单剂量使用纤维蛋白溶解剂组织型纤溶酶原激活剂(t-PA)、t-PA类似物(Fb-Fb-CF)和链激酶(SK)恢复了这种活性,从而减少了粘连形成的程度和强度。心脏前表面中间条带的粘连面积从对照组的89%(n = 22),经Fb-Fb-CF(0.94 mg)治疗后降至28%(n = 5),经SK(93,750 IU)治疗后降至49%(n = 7)。用于将药物递送至心脏表面的改良氧化再生纤维素织物(mTC7)不会干扰这些药物的活性(Fb-Fb-CF为19%,n = 14;SK为33%,n = 7)。还发现t-PA(0.94 mg)与mTC7联合使用时可减少粘连形成(4%,n = 4),尽管术后出现明显的瘀伤和出血导致决定停止对更多使用和未使用mTC7的动物进行t-PA治疗。术后瘀伤、出血以及程度较轻的肿胀与SK和Fb-Fb-CF有关。尽管这些纤维蛋白溶解药物有效,但在临床使用前还需要进一步研究以评估其安全性。