SUMMARY1. The contribution of endogenously formed prostaglandins of the E series (PGE) to the development of reactive and functional hyperaemia was studied in the human forearm.2. Forearm blood flow was recorded using venous occlusion plethysmography. The concentration of prostaglandin E-like substances (PLS) in the venous effluent from the muscle was analysed using bio-assay. For inhibition of PG biosynthesis, indomethacin (1.25 mg/kg body weight) was administered.3. Following 5 mmn of arterial occlusion, a marked hyperaemia developed during the next 150 sec. Jndomethacin, while not affecting the resting arterial blood flow, significantly decreased the peak level as well as the duration of the hyperaemia. The total reactive hyperaemia was 25 ml

Coronary flow regulation in man is incompletely understood. We addressed the hypothesis that endogenous adenosine and prostacyclin (PGI2) affect basal coronary tone and/or the coronary flow response to increased myocardial work. In healthy volunteers coronary sinus flow and cardiac oxygen extraction were measured at rest and during leg exercise (40-50 W), before and after i.v. administration of theophylline (to block adenosine receptors) and oral administration of ibuprofen (to inhibit prostaglandin synthesis). Before drug, the basal coronary flow was 118 +/- 23 ml min-1 and the cardiac extraction of oxygen 122 +/- 3 ml l-1. Leg exercise elevated coronary flow by 89 +/- 16 ml min-1. Theophylline, at a dose blocking the coronary flow response to dipyridamole (an adenosine-dependent mechanism), induced a moderate increase in myocardial oxygen extraction (by 11%, P less than 0.05), but failed to affect either the basal coronary flow (105 +/- 16 ml min-1) or the increase during exercise (88 +/- 25 ml min-1). Ibuprofen inhibited the urinary excretion of PGI2 metabolite by about 90%, but did not affect basal coronary tone or the coronary response to exercise. These data indicate that endogenous adenosine is of limited importance for normal coronary regulation in man, and that PGI2 has no effect.

The present investigation was undertaken to study cardiac release of adenosine and prostacyclin (prostaglandin [PG] 12) in patients with ischemic heart disease (IHD), and to assess coronary vascular resistance before and after inhibition of synthesis in such patients. In 48 patients with IHD, arterial and coronary sinus blood samples were taken at rest, during atrial pacing to angina, and after pacing. Levels of purines were determined by high-performance liquid chromatography and the PGI2 metabolite 6-keto-PGF,, was measured with radioimmunoassay. Coronary sinus blood flow was determined with retrograde continuous thermodilution before and after oral administration of indomethacin, aspirin, naproxen, or ibuprofen. Atrial pacing induced myocardial ischemia, as evidenced by typical chest pain and arrested lactate extraction. Adenosine was extracted at rest, but during ischemia there was a significant release of its metabolite hypoxanthine, indicating increased myocardial breakdown of high-energy adenine nucleotides. Arterial and coronary sinus concentrations of 6-keto-PGF1, were low and no significant differences between them were found. After administration of the PG-synthesis inhibitor indomethacin, coronary vascular resistance was elevated, as was the cardiac oxygen extraction. The three other PG-synthesis inhibitors (aspirin, naproxen, and ibuprofen) did not, however, induce any change in coronary vascular resistance or in the cardiac extraction of oxygen. On the basis of these data we suggest that in patients with IHD (1) cardiac ischemia results in increased myocardial production and release of purines, (2) cardiac ischemia does not elicit any detectable increase in coronary production of prostacyclin, and (3) the increased coronary resistance induced by indomethacin does not reflect the involvement of locally formed PG in the maintenance of coronary flow, but is rather a direct effect of the drug.

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