Fibrinolytic drugs prevent pericardial adhesions in the rabbit.
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.
Wiseman
D M
DM
Adhesions Research, Johnson & Johnson Medical, Inc. (presently Adhesions Research, Ethicon, Inc.), Somerville, New Jersey 08876.
Kamp
L
L
Linsky
C B
CB
Jochen
R F
RF
Pang
R H
RH
Scholz
P M
PM
D000818:Animals; D002482:Cellulose; D004337:Drug Carriers; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D006331:Heart Diseases / Q000517:prevention & control*; D008297:Male; D010446:Peptide Fragments / Q000008:administration & dosage / Q000627:therapeutic use; D010496:Pericardium; D011183:Postoperative Complications; D011817:Rabbits; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D013205:Staphylococcal Protein A / Q000008:administration & dosage / Q000627:therapeutic use; D013300:Streptokinase / Q000008:administration & dosage / Q000627:therapeutic use; D000267:Tissue Adhesions / Q000517:prevention & control*; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000627:therapeutic use
D004337:Drug Carriers; D005343:Fibrinolytic Agents; D010446:Peptide Fragments; D011994:Recombinant Proteins; D013205:Staphylococcal Protein A; D002482:Cellulose; D013300:Streptokinase; D010959:Tissue Plasminogen Activator; C059835:tissue plasminogen activator-(staphylococcal A, B fragment) dimer