Inhibition by dipyridamole of neutrophil adhesion to vascular endothelium during coronary bypass surgery.

BACKGROUND: Release of reactive oxygen radicals by activated neutrophils and neutrophil adhesion to endothelial cells have been observed after cardiopulmonary bypass. The aim of the present study was to evaluate the effects of preoperative dipyridamole treatment on neutrophil superoxide anion generation and endothelial cell-neutrophil interactions. METHODS: Two groups of patients scheduled for elective coronary artery bypass grafting were randomized to receive oral dipyridamole or a placebo. Nitro blue tetrazolium scores of circulating neutrophils, neutrophil CD11b/CD18 expression, and their adhesion to human umbilical vein endothelial cells were assayed before anesthesia, 30 minutes after the beginning of cardiopulmonary bypass, at the end of bypass, and 60 minutes postoperatively. RESULTS: In both groups, cardiopulmonary bypass resulted in a significant increase in nitro blue tetrazolium scores in circulating neutrophils as well as a significant increase in both neutrophil CD11b/CD18 expression and neutrophil adhesion to endothelial cells. The extent of neutrophil superoxide anion generation was higher in the control group; a significant (p < 0.01) reduction in neutrophil adhesion to endothelial cells was observed 1 hour postoperatively in the dipyridamole group. In 5 patients treated with dipyridamole, the incubation of activated polymorphonuclear leukocytes with adenosine deaminase significantly increased their adhesion to endothelial cells (p < 0.05). CONCLUSIONS: Our study demonstrated that preoperative treatment with oral dipyridamole significantly reduces both neutrophil superoxide anion generation and extent of neutrophil adhesion to endothelial cells after coronary bypass grafting procedures with cardiopulmonary bypass. The mechanism is probably mediated by endogenous adenosine.

Nitric oxide modulation of neutrophil-endothelium interaction: difference between arterial and venous coronary bypass grafts.

OBJECTIVES: This study sought to evaluate the relation between the pattern of neutrophil-endothelial adhesion in saphenous vein (SV) and internal mammary artery (IMA) grafts and the endothelial production of nitric oxide (NO). BACKGROUND: Autologous IMA and SV grafts (SVGs) are increasingly used as conduits for coronary bypass grafting. Previous studies have demonstrated a greater production of endothelial-derived relaxing factor (NO) from IMA than from SVGs. Because of the well known role of NO in modulating the adhesion of polymorphonuclear leukocytes to the endothelium, we studied the pattern of neutrophil adhesion to the endothelium of IMA and SVs under basal conditions and after inhibition of NO synthesis. METHODS: Segments of IMA and SVs were obtained from 20 patients undergoing coronary artery bypass graft surgery. We evaluated the adhesion of both unstimulated and activated neutrophils to the endothelial surface of IMA and SVs in both basal conditions and after inhibition of NO synthesis with Nomega-nitro-L-arginine methyl ester. RESULTS: Under basal conditions, no difference in unstimulated neutrophil adhesion to endothelium was observed between the two vessel conduits. After neutrophil activation, a significantly (p < 0.05) greater adhesion of neutrophils was observed in the SV than in the IMA. After inhibition of NO release, the adhesion of activated neutrophils increased in both vessels, and no significant difference between them was observed. The increased adhesion was attenuated by both L-arginine and sodium nitroprusside. CONCLUSIONS: The lesser neutrophil adhesion to the endothelium of the IMA is a consequence of enhanced release of NO at this level; this effect could be responsible for the better early and long-term patency of this conduit over the SVG in coronary bypass grafting.

Reduction by indobufen of neutrophil activation in peripheral arterial occlusive disease.

We evaluated the effectiveness of indobufen administration in reducing neutrophil activation in a clinical model of ischemia-reperfusion. Thirty stable patients with intermittent claudication due to occlusive peripheral arterial disease of the leg were randomly assigned to two groups. Patients in group I were treated with indobufen [200 mg orally twice daily (p.o. b.i.d.) for a week]; patients in group II received a placebo. Both groups of patients were submitted to standardized treadmill exercise until onset of claudication. Plasma levels of thromboxane B2 (TxB2) and 6-keto-prostaglandin F1alpha(6-k-PGF1alpha) neutrophil filterability, and neutrophil activation (by nitro-blue tetrazolium test) were assessed in blood samples from the femoral vein draining the ischemic leg. The values were obtained at rest and 5, 30, and 60 min after onset of claudication. Urinary albumin excretion was measured at rest and 1 h after onset of claudication. Plasma levels of TxB2 and 6-k-PGF1alpha increased significantly in the placebo group 5 min after onset of claudication, whereas only a slight nonsignificant increase was observed in the indobufen-treated group at the same timepoint.