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The exercise-induced increase in albumin excretion was measured in six patients with insulin-dependent diabetes mellitus, in whom there was no evidence of established diabetic renal disease. Urinary albumin excretion was measured on urine samples taken at rest and immediately after a 20 minute period of exercise on a bicycle ergometer at 600 kpm/min. Following a three week course of aspirin (330 mg)--dipyridamole (75 mg) taken three times daily there was significant reduction in exercise-induced albuminuria (expressed as the ratio of albumin excretion rate during exercise to that at rest before exercise) when compared to administration of placebo (P less than 0.05). These results suggest that aspirin-dipyridamole might modify the development of persistent proteinuria in patients with insulin-dependent diabetes mellitus.

1. Platelet survival in 27 insulin-dependent diabetic patients with severe retinopathy was studied in a double-blind cross-over trial using placebo, aspirin (990 mg/day) and a combination of dipyridamole (225 mg/day) with aspirin at two dosage levels (330 mg and 990 mg/day). 2. Twenty patients (group I) had 51Cr-labelled-platelet survival after treatment with placebo and the high-dose-aspirin/dipyridamole combination. The remaining seven patients (group II) had platelet-regeneration times measured after each of the four treatment periods. 3. Treatment of group I patients with the high-dose-aspirin/dipyridamole combination resulted in significant (P less than 0.001) prolongation of platelet survival from 7.3 +/- 0.2 (mean +/- SEM days to 8.4 +/- 0.1 days. 4. In group II patients, when compared with the mean placebo result of 7.2 +/- 0.2 days, the mean aspirin-labelled-platelet-regeneration time was significantly (P less than 0.01) longer only after high-dose-aspirin/dipyridamole (9.8 +/- 0.5 days) but not after low-dose-aspirin/dipyridamole (8.3 +/- 0.5 days) or aspirin alone (7.3 +/- 0.3 days). 5. These results suggest that it may be premature to consider reducing the dose of aspirin in aspirin/dipyridamole combinations below 1 g/day when used as antithrombotic therapy.

We assessed in a pilot study the effect on some aspects of renal function of 6 weeks' administration of a combination of aspirin-dipyridamole (990 mg/225 mg daily) administered on a double-blind crossover schedule in 16 insulin-dependent diabetic patients with nephropathy. Total 24-h urinary protein excretion (16 patients) was significantly reduced during aspirin-dipyridamole administration from a geometric mean (range) of 1.9 (0.4-7.7) g/24 h to 1.4 (0.5-9.9) g/24 h (2P less than 0.05). Indium-labelled platelet survival (eight patients), glomerular filtration rate and renal blood flow (eight patients) showed no significant change following aspirin-dipyridamole therapy, even though plasma creatinine concentration increased from 118 (65-371) to 130 (76-438) mumol/l (2P less than 0.05). Diabetic control and blood pressure remained unchanged throughout the study. Although the results showed that this treatment significantly reduced proteinuria in patients with diabetic nephropathy, the mechanism of action was not entirely clear.

We studied post-occlusive reactive hyperaemia using ecg-triggered mercury strain-gauge plethysmography in eight normal subjects treated with incremental doses of aspirin (27.5-1200 mg). The reactive hyperaemic response was measured in the finger (predominantly skin blood flow) and the calf (predominantly muscle). Concentrations of TXB2 and 6-oxo-PGF1 alpha were measured in venous effluent blood from the hand by RIA, following arterial occlusion. Levels of TXB2 were significantly higher at 0-10 and 60-70 seconds (p less than 0.01), and 90-100 seconds (p less than 0.05) following release of occlusion compared to pre-occlusion values. However there was no significant change in concentrations of 6-oxo-PGF1 alpha and therefore by this method release of prostacyclin during reactive hyperaemia in the hand. Aspirin had no influence on finger or calf reactive hyperaemia 90 minutes after dosing, despite marked inhibition of platelet MDA production (75% after 110 mg, maximal inhibition after 1200 mg). These data provide no support for the hypothesis that prostacyclin is involved in the determination of the post-occlusive reactive hyperaemic response in the finger and calf in man.