thromboxane-a2 and Arteriosclerosis-Obliterans

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal; Arachidonic Acid; Arteriosclerosis; Arteriosclerosis Obliterans; Aspirin; Cell Division; Cells, Cultured; Clinical Trials as Topic; Eicosanoids; Eicosapentaenoic Acid; Epoprostenol; Fibrinolytic Agents; Growth Inhibitors; Hemostasis; Humans; Hypolipidemic Agents; Muscle, Smooth, Vascular; Platelet Aggregation; Platelet Aggregation Inhibitors; Rats; Signal Transduction; Thrombophilia; Thrombosis; Thromboxane A2

Effects of picotamide (900 mg in 3 oral administrations for 7 days) on ex vivo and in vivo platelet TxA2 production and on platelet aggregation were evaluated in 8 patients with peripheral arteriopathy and in 8 normal subjects. Picotamide significantly reduced ADP-induced platelet aggregation, but had no effect on that induced by arachidonic acid or the thromboxane analogue U46619. Though ex vivo platelet TxA2 production (TxB2 concentration after arachidonic-acid-induced aggregation) was reduced from 946 +/- 141 (mean +/- SD) to 285 +/- 91 ng/ml in controls and from 1515 +/- 673 to 732 +/- 420 ng/ml in patients with arteriopathy, there was no effect on urinary excretion of 2,3-dinor-TXB2 (in vivo indicator of platelet TxA2 production), or on in vivo PGI2 production (urinary excretion of 6-keto-PGF1 alpha and 2,3-dinor-6-keto-PGF1 alpha). In the same subjects, single-dose aspirin reduced ex vivo TxB2 production by at least 98% and 2,3-dinor-TxB2 excretion from 116.7 +/- 61.4 to 32.6 +/- 17.0 ng/g creatinine in control subjects, and from 156.3 +/- 66.1 to 59.1 +/- 19.2 ng/g creatinine in patients with peripheral arteriopathy. Our data suggest that inhibition of platelet TxA2 production in vivo may not be picotamide's main mechanism of action.

Topics: Aged; Arteriosclerosis Obliterans; Epoprostenol; Humans; Male; Middle Aged; Phthalic Acids; Platelet Aggregation Inhibitors; Thromboxane A2

After a brief survey of the already well known functions of tromboxane and prostacyclin both in physiological and pathological conditions, the data found in the literature on the therapeutical use of prostacyclin are discussed. The positive results obtained in the treatment of arteriosclerosis obliterans of the lower limbs, of Raynaud's syndrome, of ischaemic stroke and of ischaemic heart diseases, together with the very modest side effects of prostacyclin, suggest to continue with prostacyclin therapy even if its mechanism of action is not yet clear.

Topics: Arachidonic Acid; Arachidonic Acids; Arteriosclerosis Obliterans; Cardiovascular Diseases; Cerebrovascular Disorders; Coronary Disease; Cytochrome P-450 Enzyme System; Epoprostenol; Humans; Intramolecular Oxidoreductases; Raynaud Disease; Thromboxane A2

Infusion of PGI2 at a dose of 5 or 10 ng/kg/min during 72 hours into patients with peripheral vascular disease was followed by increased susceptibility of platelets to proaggregatory action of ADP and collagen but not that of arachidonate. The above effects were observed 24 hours after termination of infusion of PGI2. A tendency to an increased formation of TXA2 in PRP aggregated by arachidonate was also noticed. Infusion of PGI2 at a dose of 2 mg/kg/min during 72 hours into the patients caused the decreased platelet aggregability to ADP and arachidonate but not to collagen, and a decreased tendency to production of TXA2 in PRP aggregated by arachidonate. The existence of a "rebound effect" in platelets after a long term PGI2 therapy is suggested.

Topics: Adenosine Diphosphate; Adult; Aged; Arachidonic Acid; Arachidonic Acids; Arteriosclerosis Obliterans; Blood Platelets; Collagen; Epoprostenol; Female; Humans; Middle Aged; Platelet Aggregation; Prostaglandins; Thromboangiitis Obliterans; Thromboxane A2