Intra-abdominal adhesions were surgically induced in 28 rats using the ischemic button model. mRNA levels of tissue plasminogen activator (tPA), plasminogen activator inhibitor 1 (PAI-1), hypoxia-inducible factors (HIFs) 1¦Á and 2¦Á, and vascular endothelial growth factor A (VEGF-A) were measured in adhesive button tissue taken at time 0 and 1, 3, 6, 12, and 24 h after surgery in rats receiving an intraoperative peritoneal bolus (25 mg/kg) of a neurokinin-1 receptor antagonist (NK-1RA) or saline. Peritoneal fluid fibrinolytic activity was measured in peritoneal lavages taken at the same time points.
SP levels increased (P ¡Ü 0.05) within 1 h postoperatively followed by an increase (P ¡Ü 0.05) in tPA mRNA expression from 3 to 6 h after surgery along with a striking increase (P ¡Ü 0.05) in PAI-1 mRNA expression from 3 to 12 h. NK-1RA administration further increased (P ¡Ü 0.05) tPA mRNA expression and significantly blunted the increase in PAI-1 mRNA levels. The NK-1RA increased (P ¡Ü 0.05) fitbrinolytic activity in peritoneal fluid at 3, 12, and 24 h after surgery. HIF-1¦Á and VEGF-A mRNA expressions increased from 3 to 12 h (P ¡Ü 0.05) and from 1 to 3 h (P ¡Ü 0.05) after surgery, respectively, whereas HIF-2¦Á mRNA expression steadily decreased. NK-1RA delayed the rise in HIF-1¦Á mRNA and ablated the changes in HIF-2¦Á and VEGF-A mRNAs.
SP is a pleiotropic early regulator of mRNA levels of key adhesiogenic mediators after surgery, suggesting that it may be a viable therapeutic target.