Summary
Background
Fibrin deposition, the primary step in the formation of post-surgical adhesions, is
the result of a disbalance between the fibrinforming and the fibrin-dissolving capacity
of the peritoneum. Literature data suggest a transient reduction in local plasminogen
activator activity after peritoneal trauma, which results in a reduction of fibrinolysis
and permits deposited fibrin to become organized into fibrous, permanent adhesions.
In the present study, the fibrinolytic parameters tissue-type plasminogen activator
(tPA; antigen and activity) and plasminogen activator inhibitor type-1 (PAI-1; antigen
and activity) were measured in peritoneal fluid, in peritoneal biopsies and in plasma
to establish the time course of changes in fibrinolytic activity.
Design
A standardized peritoneal adhesion model in the rat.
Outcome Measures
Analysis, over a 72-h period following surgical trauma, of the main fibrinolytic parameters
in peritoneal lavage, in biopsies of damaged and undamaged peritoneum, and in plasma,
and determination of fibrin and fibrin(ogen)-degradation products in peritoneal lavage
fluid.
Results
At all time intervals, tPA antigen was found to be about six-fold increased in peritoneal
lavage after surgical trauma. This significant rise in tPA antigen was accompanied
by a large increase in its main inhibitor PAI-1, resulting in tPA activity levels
similar to, or slightly higher than, those found in control animals. tPA activity
was lowest at 4 h and increased thereafter. Also in biopsies from damaged peritoneum,
tPA antigen was significantly increased. Tissue tPA activity was also lowest at 4
h, after which it increased, significantly so at 24 and 72 h. Similar, though smaller,
changes were seen in the biopsies from undamaged areas of the peritoneal wall in operated
rats. PAI-1 (antigen and activity) was not detected in peritoneal biopsies. Fibrin-related
material (especially fibrin monomer/fibrinogen, an indicator of forming fibrin) in
peritoneal fluid was slightly increased at 4 h, and abundantly present at 16 and 24
h, returning to control levels at 72 h. Fibrin degradation products were always present.
From 2 h onward, adhesions were found.
Conclusions
In contrast to the view that adhesions are formed as a result of a reduced fibrinolytic
activity, our results demonstrate that tPA activity remained unchanged or slightly
increased after surgical trauma, and point to increased fibrin formation rather than
diminished fibrinolytic activity as the main cause of fibrin deposition after peritoneal
trauma. Therapies directed at prevention of adhesion formation should therefore aim
at avoiding massive fibrin production and at promoting fibrinolytic activity during
the early period after trauma.
Key words
Rat - peritoneum - adhesions - fibrin - fibrinolysis - tissue-type plasminogen activator
- plasminogen activator inhibitor type-1
