Effect of Tisseel® on expression of tissue plasminogen activator and plasminogen activator inhibitor-1

Objective To examine the effect of fibrin sealant on mRNA expression of factors regulating plasminogen activator activity in human peritoneal cells. Plasminogen activator activity is thought to play a pivotal role in degradation of the proteinaceous mass that develops after surgical procedures. Reduction of plasminogen activator activity, as occurs with tissue trauma, results in increased postoperative adhesion development. Design Tissue culture for 6, 12, 24, and 48 hours. Setting University research laboratory. Patients Source of mesothelial cells with fibroblasts. Intervention(s) Measurement of mRNA expression of tissue plasminogen activator (t-PA) and plasminogen activator inhibitor 1 (PAI-1). Main outcome measure(s) Multiplex reverse transcriptase/polymerase chain reaction (RT/PCR) was used to determine relative change in t-PA and PAI-1 mRNA levels under six conditions: [1] fibrin sealant (Tisseel®); [2] fibrin sealant (Tisseel®) two components diluted 1:2; [3] fibrin sealant (Tisseel®) sealer protein component reconstituted without aprotinin (a protease inhibitor); [4] fibrin sealant (Tisseel®) sealer protein component reconstituted without aprotinin, both components diluted 1:2; [5] fibrin sealant (Tisseel®) components diluted to physiologic concentrations; and [6] control (culture media). Results The mRNA levels of t-PA and PAI-1 by human peritoneal cells were unchanged during 48 hours. In mesothelial cells, the addition of the compositions increased t-PA mRNA levels. A selective increase was observed in the normal peritoneal fibroblasts at the later time points; similar increases were identified in adhesion fibroblast cultures. In mesothelial cells, the more concentrated compositions generally increased PAI-1 mRNA above control levels, whereas in normal peritoneal fibroblasts PAI-1 levels generally remained unchanged. In contrast, in adhesion fibroblasts, PAI-1 levels decreased over time with treatment. Conclusion(s): Fibrin sealant, in the presence and absence of aprotinin, increases both t-PA and PAI-1 expression by human peritoneal cells; changes not seen with physiologic concentrations of fibrin sealant. These observations suggest that in addition to its ability to help achieve hemostasis, fibrin sealant affects the healing process by altering components of the plasminogen activator system, which may be of benefit in the reduction of postoperative adhesions.