Modulation of thrombotic responses in moderately stenosed arteries by cigarette smoking and aspirin ingestion.

Abstract

Cigarette smoking is a known risk factor for cardiovascular disease in men and women, and it has been suggested that this risk is linked to enhanced formation of platelet thromboxane A 2 (TxA 2 ). This led us to investigate the effect of cigarette smoking and TxA 2 formation on collagen-induced thrombogenesis in flowing nonanticoagulated human blood. Thrombus formation in blood from smokers and nonsmokers was compared before and 2 hours after ingestion of a single oral dose of 990 mg aspirin, which is sufficient to block platelet TxA 2 formation. Nonanticoagulated blood was drawn directly from an antecubital vein over collagen fibrils in a parallel-plate perfusion chamber by a peristaltic roller pump placed distalry to the chamber. Wall shear rates at the collagen surface were characteristic for medium-sized (650 s" 1 ) and moderately stenosed (2600 s" 1 ) arteries. Blood-collagen interactions were morphologically quantified, and markers of platelet release, £-thromboglobulin (0-TG), and activation of coagulation, fibrinopeptide A (FPA), were measured immediately distal to the perfusion chamber. The thrombus volume in blood from cigarette-smoking individuals was S everal prospective studies have demonstrated that cigarette smoking is a major risk factor for cardiovascular disease. 16 Enhanced thromboxane A 2 (TxA 2 ) synthesis in platelets has been implicated as a possible source of risk, since biochemical studies have shown increased TxA 2 production in cigarette smokers. 7The TxA 2 molecule is a potent vasoconstrictor and platelet aggregation agonist. Both events are closely associated with cardiovascular disorders.A single oral dose of 1 g aspirin blocks the platelet production of TxA 2 8 by irreversible acetylation of platelet cyclooxygenase. 9 The effect of blocking TxA 2 is partial inhibition of the aggregation response to low concentrations of ADP and collagen. Ingestion of aspirin abolishes acute and chronic effects of enhanced platelet aggregation observed in healthy habitual smokers. -11The goal of the present study was to investigate the effect of cigarette smoking on collagen-induced thrombogenesis in flowing nonanticoagulated human blood and to evaluate the effect of a 990-mg single oral dose of aspirin in both smokers and nonsmokers at arterial blood flow conditions. A well-characterized human ex

Assessment of fibronectin conformation adsorbed to polytetrafluoroethylene surfaces from serum protein mixtures and correlation to support of cell attachment in culture

“…In fact, extremely tight binding of serum albumin to uoroplasma-deposited surfaces [8], high levels of bronectin and hemoglobin on PVDF [9], and various serum proteins [10] and signi cant brinogen [11] on PTFE have been detected in vitro. Importantly, protein adsorption to uoropolymers is also observed in vivo [12,13] and is correlated with platelet activation responses often observed on expanded PTFE (e-PTFE) vascular graft materials in vivo [12,14,15].…”

Antiplatelet Agents and Stroke Prevention

“…35 Atherosclerotic patients have increased hydrolysis of aspirin requiring higher doses to obtain a platelet ef-444 fect.38 Inhibition of platelet hyperreactivity to shear stress in coronary bypass patients is dose dependent and requires doses greater than 300 mglday, suggesting a mechanism different from that of interference of thromboxane formation.39 Increased hyperreactivity to shear stress in disease states requires increasing doses. [40][41][42] The disaggregation response,43 decreased platelet membrane fluidity,44 generation of thrombin," inhibition of smooth muscle cell growth,46 inhibition of megakaryocyte cyclooxygenase,47 and altered response to aspirin in disease state~32~48. 49 have been shown to be more responsive to higher doses.…”

Aspirin with and without Dipyridamole

“…Inhibition of platelet hyperreactivity to shear stress in coronary bypass patients is dose-dependent and requires doses greater than 300 mg/day, suggesting a mechanism different from that of interference of thromboxane formation [26]. Increased hyperreactivity to shear stress in disease states requires increasing doses [27][28][29]. The disaggregation response [30], decreased platelet membrane fluidity, [31], generation of thrombin [32], inhibition of smooth-muscle cell growth [32] inhibition of megakaryocyte cyclooxygenase [34] and altered response to aspirin in disease states [35][36][37] have been shown to be more responsive to higher doses.…”