Importance of Platelets in Neutrophil Adhesion and Vasoconstriction After Deep Carotid Arterial Injury by Angioplasty in Pigs

Abstract

In previous studies we have shown that platelets can support neutrophil adhesion to the injured vessel wall in vitro and that neutrophils contribute to vascular tone regulation after arterial injury in vivo. In this study, we investigated the implication of platelets in neutrophil adhesion and the vasomotor response to arterial injury in vivo. 111In-labeled neutrophil adhesion and angiographic vasoconstriction were quantified after deep carotid arterial injury by balloon angioplasty in normal (n = 8), thrombocytopenic (n = 7), and aspirin-treated (2 mg/kg IV, n = 7) pigs. Thrombocytopenia was produced by a polyclonal antiplatelet serum that depleted circulating platelet count by 84% without influencing neutrophil count. In the control animals, neutrophil adhesion (x 10(4)/cm2) at the site of deep arterial injury averaged 26.8 +/- 4.0 and decreased significantly to 11.5 +/- 2.3 and 11.2 +/- 2.4 in the thrombocytopenic and aspirin groups, respectively. The degree of vasconstriction was also reduced significantly, from 55.5 +/- 3.8% in the control group to 31.4 +/- 6.2% after platelet depletion and to 23.6 +/- 4.5% in the aspirin-treated group. Neutrophil adhesion to intact noninjured adjacent arterial segments was low in all groups and was not affected by the antiplatelet serum or by aspirin. In in vitro superfusion flow chambers, neutrophil adhesion to damaged arterial segments increased in the presence of platelets in a concentration-dependent manner and was not influenced by the antiplatelet serum. This study demonstrates that platelets can modulate neutrophil adhesion to the deeply injured arterial wall and that both elements may influence the degree of postangioplasty vasoconstriction in vivo.

Selectin Blockade Reduces Neutrophil Interaction With Platelets at the Site of Deep Arterial Injury by Angioplasty in Pigs

“…10 In this model, we have found that platelet depletion was associated with decreased neutrophil adhesion to damaged arterial surfaces, 11 confirming our previous findings showing increased neutrophil adhesion in the presence of platelets 12 in a concentration-dependent manner. 11 These studies provide strong evidence for platelets involvement in neutrophil adhesion to damaged arterial surfaces. The interaction between platelets and neutrophils have been shown to be dependent on P-selectin (CD62P, GMP-140, or PADGEM) expression on activated platelets.…”

“…10,11,33 The animals were sedated by intramuscular injection of 20 mg/kg ketamine and 3 mg/kg azaperone, intubated, and mechanically ventilated with O 2 /air. Anesthesia was maintained with 0.5% to 1% halothane.…”

“…10,11 This method involves sedimentation with 4% dextran, centrifugation on Ficoll-Paque gradient and hypotonic lysis of red blood cells. The isolated neutrophil suspension was incubated with 250 Ci of 111 In-tropolone (Merck Frosst Canada Inc) for 30 minutes.…”

“…10,11,33 A 9F-introducer sheath was inserted into the right femoral artery for introduction of the balloon dilation catheter, and an 8F-introducer sheath was inserted into the femoral vein for blood sampling and drug infusion. Five minutes before the angioplasty procedure, animals received either CY-1503 (15 mg/kg, IV bolus, nϭ7) (Cytel Corporation) or saline (IV, nϭ8).…”

Abciximab Attenuates Coronary Microvascular Endothelial Dysfunction After Coronary Stenting

“…6 Although well tolerated, balloon inflation causes deep arterial injury, resulting in endothelial denudation, platelet and leukocyte activation, oxidative stress, and vasoconstrictor release. 7 In a small subset of patients, this leads to adverse effects on the microvasculature, resulting in clinical events. 8 Balloon angioplasty has been shown to cause immediate and prolonged endothelial dysfunction of conduit vessels.…”