Measurement of Aspirin Concentrations in Portal and Systemic Blood in Pigs: Effect on Platelet Aggregation, Thromboxane and Prostacyclin Production

Abstract

SummaryLow doses of enteric-coated aspirin were administered orally to pigs. Plasma aspirin concentrations measured in blood obtained simultaneously from permanent catheters in a systemic artery and portal vein for 6 hours after dosage showed a large variation in the plasma aspirin concentration : time profile between pigs. After 50 mg single dose the ratio of the arterial : portal area under the plasma concentration versus time curve (AUC) was 0.63 ± 0.08 (mean ± SE, n = 6). In three pigs which received all three dosage regimens, the arterial : portal AUC ratios were 0.48 ± 0.05 after 50 mg single dose, 0.52 ± 0.02 after 100 mg single dose and 0.47 ± 0.02 after 100 mg daily for 1 week. Platelet aggregation in response to sodium arachidonate (1.65 mM) was completely abolished after chronic aspirin administration of 100 mg daily. Thromboxane production (pg/ 106 platelets) induced by this stimulus decreased from 536 ± 117 before aspirin to 57 ± 14 after aspirin (mean ± SE, n = 4; p = 0.03). Aortic prostacyclin synthesis, measured as 6-keto PGF1α (ng/disc after 10 min incubation), was 1.66 ± 0.28 (mean ± SE, n = 4) in untreated pigs and 0.95 ± 0.25 (n = 5) in treated pigs (p = 0.07). Results from this study support the idea that a difference between aspirin concentrations in the portal and systemic circulations can be achieved. Whether this can be translated into a clinically useful differential effect on the vessel wall compared to the platelet remains to be determined.

Investigation of Gastric and Duodenal Mucosal Defects Caused by Low-dose Aspirin in Patients With Ischemic Heart Disease

“…Aspirin suppresses TXA2-platelet synthesis, which is irreversible. 11 The cause of gastrointestinal disorder is classified into local stimulus action and general action. The former is caused by direct contact of acetylsalicylic acid with gastrointestinal mucosa.…”

Endoscopic survey of low‐dose‐aspirin‐induced gastroduodenal mucosal injuries in patients with ischemic heart disease

“…Because the elderly population in Japan is increasing, the number of patients who will need low-dose aspirin treatment is expected to also increase in the near future. Aspirin inhibits the synthesis of cyclooxygenase-1 (COX-1), 7 which induces its analgesic and antiinflammatory effects. Aspirin produces its antithrombotic effect through irreversible acetylation of a serine in COX-1 of platelets, 8 which abolishes production of thromboxane A2 for the life of the platelet.…”

Comparative Arterial Antithrombotic Activity of Clopidogrel and Acetyl Salicylic Acid in the Pig

“…This could mean that, in this model, in the pig, ADP plays a more important role than thromboxane A 2 and endoperoxydes in arterial thrombogenesis (20). Indeed, clopidogrel is a potent inhibitor of ADP-induced platelet aggregation and has no significant effect on arachidonic acid-induced aggregation, while aspirin has opposing behaviour, as already shown in the pig by Bochner et al (21). For this reason, the two drugs could not be administered at equi-effective doses, based on their antiplatelet effect.…”