C. M. Guth1, W. Luo1, O. Jolayemi1, J. Cheung-Flynn1, C. M. Brophy1,2 1Vanderbilt University Medical Center,Nashville, TN, USA 2VA TN Valley Healthcare System,Nashville, TN, USA
Introduction: Surgical traction injury occurs to human saphenous veins (HSV) at the time of harvest. This injury is associated with vasomotor dysfunction and is reversible by treatment after injury with FCF, a purinergic (P2X7R) inhibitor. Thus, we hypothesized that stretch-induced ATP release acts as a mediator of injury by activating P2X7R, propagating further ATP release, and impairing vascular smooth muscle function.
Methods: A model of stretch injury was developed using rat aorta (RA). Tissue was stretched to twice the resting ex vivo length, which represented the haptic endpoint (subfailure overstretch). ATP release was measured using an ATP Bioluminescent Assay Kit. Contractile responses to phenylephrine were determined in a muscle bath. To verify ATP was the mediator of stretch-induced injury, non-stretched RA was treated with exogenous ATP. Both subfailure overstretched- and exogenous ATP-injured RA were treated with A438079 and oATP, antagonists to P2X7R, to examine the role of P2X7R activation in vascular injury.
Results: Subfailure overstretch injury of RA led to ATP release and decreased contractile function as compared to non-stretched controls (p < 0.05). Contractile function was partially restored in subfailure overstretch RA when treated with A438079 after injury (p < 0.05). RA subjected to exogenous ATP treatment had decreased contractile function (p < 0.05) that was mitigated by co-treatment with oATP (p < 0.05).
Conclusion: Data using a subfailure overstretch RA model suggests that vascular dysfunction after surgical traction stretch injury is associated with ATP release, induced by exogenous ATP, and partially restored by treatment with P2X7R antagonists. These data suggest that ATP represents a molecular mediator of surgical traction injury to blood vessels and that P2X7R represents a novel target for drug therapy for reducing pathologic vascular response to injury.
