To compare the inhibitory effects of aspirin on prostaglandin synthesized by vessel walls and platelets, we obtained vein segments from five subjects before they were given 150 or 300 mg of aspirin and at various intervals afterward. We then measured prostacyclin (PGI2) synthesis with a radioimmunoassay for its stable metabolite, 6-keto-prostaglandin F1 alpha. Platelet production of thromboxane A2 was measured with a radioimmunoassay for its stable metabolite, thromboxane B2. Two hours after aspirin had been given, 81 to 100 per cent inhibition of PGI2 synthesis was demonstrated; 86 per cent inhibition was still evident in one subject tested eight hours after administration. Simultaneously, platelet production of thromboxane B2 was completely inhibited for more than 24 hours. We conclude that there is little difference between the initial inhibitory response of platelet cyclooxygenase and that of vessel-wall cyclooxygenase to these doses of aspirin. Our results also indicate that in male subjects the prolonged template bleeding time after aspirin is not the consequence of selective inhibition of platelet production of thromboxane.

1 The pharmacokinetic profile and biochemical efficacy of idrapril calcium, a novel angiotensin converting enzyme (ACE) inhibitor, were evaluated in healthy volunteers after multiple dosing for 5 days at the doses of 100, 200 and 400 mg twice daily. The study was conducted as a double-blind, cross-over comparison of idrapril calcium against placebo. 2 Plasma concentrations of idrapril were determined by an indirect enzymatic method. Urinary concentrations were measured by reverse phase high performance liquid chromatography (h.p.l.c.). Plasma samples were also analysed for ACE activity. 3 The pharmacokinetics of idrapril calcium did not change significantly between day 1 and day 5. The values of Cmax and AUC were dose-related over the range of doses tested; tmax was 3-4 h and apparent elimination half-life was 1.4-1.6 h. 4 Plasma ACE activity was maximally inhibited (94-96%) at all dose levels and remained more than 80% depressed from 2 to at least 6 h after idrapril calcium. Although the maximum effect was not dose-related, the duration of inhibition showed some dose-dependency, ACE activity returning to 56, 45 and 29% of the basal value 12 h after the 100, 200 and 400 mg doses, respectively. 5 There were no clinically significant adverse events experienced by the volunteers.No dose-related effects on blood pressure or heart rate were observed. There were no changes in clinical pathology tests, urine analyses or electrocardiograms after dosing with idrapril calcium. 6 Idrapril calcium, the prototype of a new class of ACE inhibitors, appears to be well-tolerated. Its pharmacokinetics were not significantly changed after repeated administration in man. Plasma ACE activity was markedly depressed for more than 12 h even after the lowest dose tested (100 mg) and inhibition was correlated to the levels of circulating drug, the ex vivo IC5o being practically identical (12 ng ml-') on day 1 and day 5.

We kuve observed blood doiring in blood administration sets nhere Hurtmann 's solution ( TravenoI) has preceded blood trunsfusion. This is due 10 calcium ions (Ca' ') contained in the Hartmann's solution and is more likely to occur at 37'C. We suggest that [hi.$ porential hazard be more widely realised and that the practice cease. Key wordsComplicarions; blood clotting. Inns; calcium. Transfusion; stored blood.Hartmann's solution is frequently used as volume replacement fluid during emergency and routine surgical procedures. Last year in our district, which serves a population of 245000, approximately 5000 litres of Hartmann's solution were used.One of us (J.M.) has noticed that clotting occurs in the blood administration sets if blood is infused following Hartmann's solution. No instructions against this practice can be found. No adverse patient reactions have been observed in patients here, but our findings suggest that the practice be reviewed. Methods and resultsFollowing the observation of clotting in routine clinical practice, we repeated standard practice procedures under controlled conditions in the laboratory. Expired whole blood was passed under gravity into a blood administration set (Travenol) to which was attached a blood warmer set connected to a Fenwal blood warmer. The blood was infused at a rate of 6 ml/minute. The infusion sets were primed with standard Hartmann's solution (Travenol) and a similar isotonic solution made without calcium by our district pharmacy.The experiment was carried out with the blood warmer switched on and with it off. Clot formation was seen in the distal drip chamber of the blood warmer set within 45 minutes of starting the blood infusion (Fig. I.). The clots extended into the two distal loops of the warmer set. Clots were only seen when Hartmann's solution (with calcium) was used as prime with the blood warmer switched on.In a simple mixing experiment carried out in plasticCorrespondence should be addressed to Dr P.J. Wyld please.

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