Role of platelet activation in catheter-induced vascular wall injury.
OBJECTIVE
To investigate the role of smooth muscle cell (SMC) response and platelet activation in peripheral venous catheterization using a model of catheter injury associated with thrombocytopenic treatment.


METHODS
Silicon elastic catheters were inserted into New Zealand White rabbit external jugular veins from 24 hours to 60 days. Immunocytochemical procedures with antibodies to differentiation markers specific for SMCs, myofibroblasts, and endothelial cells were used to ascertain the phenotypic features of injured venous SMCs and the tissue sleeve formed around the catheter. Thrombocytopenia was induced in rabbits by busulfan treatment and the effect on catheter injury development examined after 15 days. The putative direct effect of this drug on the venous SMC proliferation, migration, and differentiation was assayed in vitro for 48 hours.


RESULTS
Catheter injury is characterized by the progressive formation of (1) a neointima, containing differentiating SMCs, which are derived from the media and adventitial layer, and (2) by the organizing thrombus formed around the catheter, which contains myofibroblasts. In busulfan-treated thrombocytopenic animals, there was no evidence for either neointimal development or thrombus formation. A direct role of this drug in the unresponsiveness of vascular wall can be excluded by the unchanged proliferation and migration pattern of cultured venous SMCs treated with busulfan compared to control cultures.


CONCLUSIONS
In our model, accumulation of differentiated SMCs in the neointima and myofibroblast appearance in the thrombus are linked, although distinct, events regulated by platelet activation, which is able to furnish the appropriate microenvironment for vascular SMC recruitment from the media/adventitial layer.
Zolpi
Elisa
E
Department of Pediatrics, University of Padua, Viale G. Colombo 3, I-35121 Padua, Italy.
Filipetto
Cinzia
C
Bertipaglia
Barbara
B
Taiani
Jenny
J
Gasparotto
Lisa
L
Chiavegato
Angela
A
Gamba
Piergiorgio
P
Sartore
Saverio
S
D000818:Animals; D015153:Blotting, Western; D002066:Busulfan / Q000494:pharmacology; D002406:Catheterization, Peripheral / Q000009:adverse effects*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000293:injuries / Q000473:pathology*; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D015539:Platelet Activation; D011817:Rabbits; D013921:Thrombocytopenia / Q000378:metabolism
D007166:Immunosuppressive Agents; D002066:Busulfan