thromboxane-a2 and Intermittent-Claudication

Topics: Anticoagulants; Arteriosclerosis; beta-Thromboglobulin; Blood Platelets; Clinical Trials as Topic; Humans; Intermittent Claudication; Leg; Platelet Aggregation; Platelet Factor 4; Suloctidil; Thiophenes; Thrombosis; Thromboxane A2; Ticlopidine

In a double-blind placebo-controlled trial, buflomedil was shown to cause a significant increase both in median claudication provoking time from 63 sec (range: 24-136 sec) to 124 sec (range: 53-261 sec) (p less than 0.01), and in maximum walking distance (MWD) from 169m (range: 157-308 m) to 293 m (range: 107-429 m) (p less than 0.01). The MWD after three months' buflomedil treatment was also significantly (p = 0.05) prolonged when compared with the MWD in the appropriate placebo group. In contrast, treatment with the placebo caused no significant change in these indices. Subjective improvement was observed in 12 out of 14 patients on buflomedil, whilst it occurred in only 6 out of 14 patients on the placebo (p less than 0.05). The clinical improvement was not associated with an increase in the ankle pressure index or a reduction in platelet aggregation and thromboxane A2 release.

Topics: Aged; Blood Pressure; Double-Blind Method; Female; Humans; Intermittent Claudication; Male; Middle Aged; Platelet Aggregation; Pyrrolidines; Thromboxane A2

Topics: Anticoagulants; Arteriosclerosis; beta-Thromboglobulin; Blood Platelets; Clinical Trials as Topic; Humans; Intermittent Claudication; Leg; Platelet Aggregation; Platelet Factor 4; Suloctidil; Thiophenes; Thrombosis; Thromboxane A2; Ticlopidine

Percutaneous transluminal angioplasty is an acute, local stimulus to platelets which activation is regarded as an important factor for a later restenosis. The balance between the production of prostacyclin and thromboxane A2 is of (patho)physiological importance due to their opposite actions on vascular tone and platelet reactivity. In this study we investigated the influence of percutaneous transluminal angioplasty of the peripheral arteries on prostacyclin and thromboxane A2 productions in vivo by measuring the excretions of their urinary index metabolites, 2,3-dinor-6-ketoprostaglandin F1 alpha and 11-dehydrothromboxane B2, respectively, in 10 patients. We found a twofold increase in thromboxane A2, but no significant change in prostacyclin, production after peripheral transluminal angioplasty which shifted prostacyclin/thromboxane A2 balance to the direction of thromboxane A2 formation. This gives theoretical support to the use of thromboxane A2 synthase inhibitors and receptor antagonists as well as prostacyclin analogues in combination with peripheral percutaneous transluminal angioplasty to prevent thrombosis and restenosis.

Topics: 6-Ketoprostaglandin F1 alpha; Aged; Aged, 80 and over; Angiography; Angioplasty, Balloon; Arteries; Female; Humans; Intermittent Claudication; Male; Middle Aged; Thromboxane A2; Thromboxane B2

Topics: Alprostadil; Angioplasty, Balloon; Anti-Bacterial Agents; Anticoagulants; Arterial Occlusive Diseases; Arteriosclerosis; Aspirin; Dipyridamole; Endarterectomy; Exercise Therapy; Fibrinolysis; Humans; Hyperlipidemias; Hypertension; Infusions, Intra-Arterial; Intermittent Claudication; Prostaglandins E; Serotonin Antagonists; Sympathectomy; Thromboxane A2

Prostacyclin is a very unstable prostaglandin, which is continuously synthetized and released by blood vessels. It fulfills 2 main functions, namely strong inhibition of platelet aggregation and vasodilation. Thus it acts as an important defense mechanism of the vascular wall, which is directed against overwhelming platelet aggregation and against the development of atherosclerosis. Besides endogenous prostacyclin is an important antihypertensive factor. In several diseases, as diabetes mellitus, obliterative arteriopathy and haemolytic-uraemic syndrome, the reduced prostacyclin-synthesis is thought to be a key mechanism for the development of vascular lesions. On the other hand the haemorrhagic diathesis of uraemics is seen in connection with an increased vascular prostacyclin release. Synthetic prostacyclin is now under trial for therapy in peripheral obliterative arteriopathy and extracorporeal circulation, as haemodialysis and cardiopulmonary bypass.

Topics: Arteriosclerosis; Diabetic Angiopathies; Epoprostenol; Female; Hemolytic-Uremic Syndrome; Humans; Intermittent Claudication; Muscle, Smooth, Vascular; Platelet Aggregation; Pre-Eclampsia; Pregnancy; Prostaglandins; Purpura, Thrombotic Thrombocytopenic; Thromboxane A2; Vasodilation