Sp Hanley

Differential inhibition by low-dose aspirin of human venous prostacyclin synthesis and platelet thromboxane synthesis.

The capacity of venous tissue for prostacyclin synthesis was determined in 68 patients undergoing surgery for removal of varicose veins. A single dose of aspirin (81 mg or 300 mg) taken 14 h preoperatively strongly inhibited its synthesis, and the effect of 300 mg was still evident 48 h after ingestion. A single dose of 40 mg aspirin taken 14 h preoperatively had no effect on prostacyclin synthesis. The capacity of blood platelets to synthesise thromboxane (measured as malondialdehyde) was determined in volunteers before and at various times after ingestion of 300 mg or 40 mg aspirin. Both doses had an inhibitory effect that lasted for at least 96 h. The length of time for which the amount of thromboxane synthesised was insufficient to support platelet aggregation and the platelet release reaction depended on both the donor and the dose of aspirin. If prostacyclin and thromboxane are important in the pathogenesis of thrombosis, then doses of aspirin much lower than those used previously should be tested. The long-lasting effect of 300 mg aspirin on both venous tissue and platelets indicates that this dose is unlikely to produce a favourable prostacyclin/thromboxane balance.

A regimen for low-dose aspirin?

The effects of different regimens of 40 mg aspirin on platelet thromboxane A2 synthesis and vascular prostacyclin synthesis were determined in patients who were undergoing elective surgery for removal of varicose veins. Aspirin 40 mg taken at intervals of 48 hours consistently reduced platelet thromboxane A2 synthesis to a level at which it failed to support platelet aggregation and the associated release reaction. This effect lasted for at least 36 hours. In contrast, aspirin 40 mg every 72 hours did not have the same consistent effect. Both dose regimens led to a reduction in vascular prostacyclin synthesis 12 hours after the last dose, but 36 or 72 hours after the last dose prostacyclin synthesis was not reduced; thus the inhibition of prostacyclin synthesis was short lived. If the balance between platelet thromboxane A2 and vascular prostacyclin synthesis is important in thrombosis 40 mg aspirin every 48 hours may have the maximum antithrombotic effect.

Prostaglandins and the Lung

The series 2 prostaglandins and thromboxane A2 are synthesized by human lung tissue. When inhaled or infused, prostaglandins exert marked effects on both the airways and the pulmonary circulation. Increases in prostaglandin and thromboxane A2 synthesis occur in asthma, the adult respiratory distress syndrome, and pulmonary hypertension and are implicated as causes of these disorders. Inhibition of prostaglandin synthesis may improve or worsen asthma.

Monoamine Oxidase Activity in Diabetes

Monoamine oxidase (MAO) activities were measured in platelets from insulin-dependent and non-insulin-dependent diabetic subjects and in platelets from nondiabetic controls. Circulating levels of glycosylated hemoglobin (HbA1) were determined simultaneously. Mean MAO activities were not significantly different in any of these groups. MAO activity did not relate to the age of the individual, but mean values for females were higher than mean values for males in healthy controls and in insulin-dependent diabetics. In this study mean HbA1 levels were higher in female than in male diabetics. There was no relationship between MAO activity and HbA1, level when results for males and females were analyzed separately.

The influence of age, sex and smoking on human venous prostacyclin synthesis

Increasing age, being a man, and smoking are important risk factors in arterial thrombotic disease (1). The incidence of venous thrombosis is also positively correlated with age, however, men and women are equally affected when the effects of the oral contraceptive and pregnancy are removed (2). Smoking has an equivocal effect on the incidence of venous thrombosis (3,4,5) and may even reduce thrombosis in some clinical situations such as the recovery phase post-myocardial infarction or post-operatively (6,7).