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Fibrinolytic drugs prevent pericardial adhesions in the rabbit
D M Wiseman1, L Kamp, C B Linsky
1Adhesions Research, Johnson & Johnson Medical, Inc. (presently Adhesions Research, Ethicon, Inc.), Somerville, New Jersey 08876.
Abstract:
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.
Insights
Fibrinolytic agents like t-PA, Fb-Fb-CF, and streptokinase effectively reduced epicardial adhesions in a rabbit model. Further research is needed to evaluate the safety of these treatments for clinical use.
Area of Science:
- Cardiovascular Research
- Regenerative Medicine
- Biomaterials Science
Background:
- Epicardial adhesions often result from reduced pericardial fibrinolytic activity.
- These adhesions can lead to complications following cardiac surgery.
Purpose of the Study:
- To investigate the efficacy of fibrinolytic agents in reducing epicardial adhesions.
- To evaluate the role of a modified oxidized regenerated cellulose (mTC7) delivery system.
Main Methods:
- A rabbit pericardial adhesion model was utilized.
- Single doses of tissue plasminogen activator (t-PA), Fb-Fb-CF, and streptokinase (SK) were administered.
- Adhesion extent and tenacity were quantified, with and without the mTC7 delivery system.
Main Results:
- Fb-Fb-CF and SK significantly reduced adhesion area (to 28% and 49%, respectively).
- The mTC7 delivery system did not impede fibrinolytic agent efficacy.
- t-PA demonstrated efficacy but caused significant postoperative bruising and bleeding.
Conclusions:
- Fibrinolytic agents show promise in mitigating epicardial adhesion formation.
- Postoperative bleeding and bruising are potential side effects requiring further investigation.
- Safety assessments are crucial before clinical application of these agents.