The effect of indobufen on the thrombogenic potential of a Dacron prosthesis in an artificial circulation.

We have evaluated the effect of indobufen on the potential thrombogenicity of a Dacron vascular prosthesis in an artificial circulation. In a randomised double blind crossover study, ten healthy volunteers received indobufen 200 mg or placebo twice daily for one week. The artificial circulation, incorporating a 15 cm length of 8 mm Dacron graft was perfused for 60 mins with volunteer blood containing autologous 111In labelled platelets. Graft thrombogenicity was assessed by changes in platelet function, isotope labelled platelet studies and scanning electron microscopy. Platelet count fell significantly during graft perfusion (P less than 0.05) and aggregation was significantly inhibited by treatment with indobufen pre perfusion compared with the placebo group (P less than 0.02). While deposition of labelled platelets was not statistically significant, consumption of these platelets was greater in the placebo group (P less than 0.01). Field counts of adherent platelets made from scanning electron micrographs of the indobufen treated group were significantly lower (P less than 0.01) compared with the placebo group. We conclude that indobufen can reduce the thrombogenic potential of Dacron vascular grafts and suggest that it may be an effective antiplatelet agent for use following Dacron bypass surgery.

The measurement of limb blood flow using technetium-labelled red blood cells.

A method for measuring blood flow below the knee during reactive hyperaemia induced by 3 min of arterial occlusion has been developed. Subjects are positioned with lower limbs within the field of view of a gamma camera and pneumatic cuffs are placed below the knees to isolate the blood and induce a hyperaemic response. The remaining blood pool is labelled with 99Tcm-labelled red cells. Blood flows have been derived from the initial gradients of time-activity curves and from equilibrium blood sampling. The technique has been validated using a tissue-equivalent leg phantom and peristaltic pump. The method has been applied to a small group of patients with peripheral vascular disease and to normal controls. The mean value (+/- SD) of limb perfusion for normal controls was found to be 16.4 +/- 3.0 ml/100 ml/min and for patients with intermittent claudication was 5.1 +/- 2.6 ml/100 ml/min. Flow measurements are found to correlate with clinical findings and with symptoms. Reproducibility (established by repeated measurements) is high. The method is well tolerated even by patients suffering from rest pain.

Acetylsalicylic acid and dipyridamole improve the early patency of aorta-coronary bypass grafts. A double-blind, placebo-controlled, randomized trial.

A total of 125 patients undergoing aorta-coronary bypass grafting for disabling angina were randomized to receive either 330 mg of acetylsalicylic acid (aspirin) plus 75 mg of dipyridamole three times daily or a placebo for 6 months postoperatively. In addition, all patients were given warfarin for 3 months. Repeat angiography was performed at 6 months in 103 patients. In the treatment group 95 grafts were implanted in 48 patients, of which 87 were patent (91.6% patency rate). This figure compares with 88 grafts patent out of 118 implanted in 55 patients in the placebo group (74.6% patency rate) (p less than 0.01). We conclude that antiplatelet therapy improves the early patency of saphenous vein aorta-coronary bypass grafts.

Microthrombus formation on hemodialysis membranes: a placebo controlled randomized trail of two doses of Indobufen.

The role of Indobufen in preventing the formation of microthrombi on hemodialysis membranes has been investigated in 18 patients in a placebo controlled randomized double-blind cross-over study. All patients had been on regular maintenance hemodialysis for at least 3 months. Indobufen was given as 100 mg b.d. and 200 mg b.d. each for a 7 day period with a 7 day wash-out period between the treatments. Both Indobufen regimens prevented the fall in platelet count, reduced the increase in plasma BTg levels during dialysis, increased the post dialysis plasma heparin levels (p less than 0.05) and inhibited pre-dialysis platelet aggregation with collagen (p less than 0.05), when compared with placebo treatment. Scanning electron microscopy demonstrated minimal fibrin and reduced platelet deposition following Indobufen treatment. There was no difference in the effect of 100 mg b.d. and 200 mg b.d. Indobufen doses. The drug was well tolerated, despite the relatively high levels measured, only one patient withdrew because of side effects. This study indicates that Indobufen when added to a routine hemodialysis treatment schedule, can significantly reduce platelet activation and the thrombus formation on the hemodialysis membranes.

Prevention of platelet deposition and thrombus formation on hemodialysis membranes: a double-blind randomized trial of aspirin and dipyridamole.

A double-blind crossover study comparing low-dose aspirin (ASA) and dipyridamole (DPM) (100 mg ASA + 75 mg DPM, t.d.s.), high-dose ASA and DPM (300 mg ASA + 75 mg DPM, t.d.s.), and placebo on platelet deposition and thrombus formation on hemodialysis membranes was undertaken in 17 long-term dialysis patients. The high-dose combination significantly reduced the fall in platelet count during dialysis and also significantly increased postdialysis heparin concentrations. Scanning electron microscopy of the Cuprophan membranes showed a reduction in platelet deposition and fibrin formation during both treatment schedules, but this was most marked with the high-dose combination. The results of this study indicate that there is a graded response to combined ASA-DPM treatment and that this can significantly reduce platelet consumption and contact activation of fibrin during hemodialysis with Cuprophan membranes.