beraprost and Coronary-Artery-Disease

1. Previous clinical studies with prostaglandin I(2) (PGI(2)) analogue beraprost sodium suggested the potential effects on protection of cardiovascular events in patients with peripheral artery disease. Although the mechanism is not well known, experimental studies have shown protective effects of endothelial cells. This study was designed to examine the effects of beraprost sodium on vascular endothelial function in the forearm of patients with coronary artery disease. 2. Beraprost sodium (120 microg/day) was orally administered to 14 coronary artery disease patients for 4 weeks and then stopped for 4 weeks. Eleven control patients did not receive beraprost sodium treatment. Reactive hyperemia was induced in the forearm, endothelium-dependent vasodilatation was assessed by plethysmography, and urinary 8-iso-prostaglandin F(2alpha) (8-iso-PGF(2alpha)) was measured at baseline, 4 weeks and 8 weeks. 3. Both groups had similar reactive hyperemic responses at baseline. In the control group, reactive hyperemic response and urinary 8-iso-PGF(2alpha) remained unchanged for 8 weeks. In the beraprost group, maximum forearm blood flow increased significantly (P = 0.01) after 4 weeks of treatment and returned to baseline at 8 weeks. Duration of hyperemia increased significantly (P = 0.003) after 4 weeks, and remained greater than baseline at 8 weeks (P = 0.02). Urinary 8-iso-PGF(2alpha) decreased significantly (P = 0.03) after 4 weeks, and tended to be lower at 8 weeks (P = 0.07). Changes in reactive hyperemia correlated weakly but significantly with changes in 8-iso-PGF(2alpha) (P < 0.001). 4. Beraprost sodium decreased oxidative stress and improved forearm endothelium-dependent vasodilatation in coronary artery disease patients. The favorable effects on vascular endothelium could potentially lead to a decrease in vascular events.

Topics: Aged; Coronary Artery Disease; Dinoprost; Double-Blind Method; Endothelium, Vascular; Epoprostenol; Female; Forearm; Hemodynamics; Humans; Hyperemia; Male; Prospective Studies; Regional Blood Flow; Vasodilation; Vasodilator Agents

The present study was conducted to examine the effects of acute administration of prostacyclin derivatives on plasma levels of adhesion molecules, endothelial function, and pulse wave velocity in patients with coronary heart disease.. In 20 patients with coronary heart disease, plasma levels of vascular cell adhesion molecule-1, P-selectin, and beta-thromboglobulin, endothelial function, and pulse wave velocity were assessed before and after the cold pressor test. These assessments were performed again 2 hr after the oral administration of prostacyclin derivatives (beraprost sodium 40 micrograms) or placebo. Endothelial function was assessed by changes in forearm blood flow before and after reactive hyperemia. Pulse wave velocity was determined by the volume rendering method.. Prostacyclin derivatives significantly improved endothelial function and decreased plasma beta-thromboglobulin level, but did not affect blood pressure and pulse wave velocity. Prostacyclin derivatives did not prevent the elevations of blood pressure and pulse wave velocity induced by the cold pressor test, but did prevent the elevations of P-selectin and beta-thromboglobulin induced by the cold pressor test.. Prostacyclin derivatives improved endothelial function and prevented platelet activation induced by the cold pressor test. Prostacyclin apparently has an anti-atherogenic effect.

Topics: Aged; Anti-Inflammatory Agents; Arteriosclerosis; beta-Thromboglobulin; Coronary Artery Disease; Endothelium, Vascular; Epoprostenol; Female; Humans; Male; Middle Aged; Pulse; Vascular Cell Adhesion Molecule-1

Thyroid hormones have been reported to have significant effects on the peripheral vascular system, including relaxation of vascular smooth muscle cells and prevention of atherosclerosis. To exert its biological activity, thyroxine (T4) needs to be converted to 3,5,3'-triiodothyronine (T3) by type 1 and type 2 iodothyronine deiodinases. We have previously identified type 2 iodothyronine deiodinase (D2) expression in cultured human coronary artery smooth muscle cells (hCASMCs). In the present study, we have characterized the regulation of D2 expression in hCASMCs by stable prostacyclin analogue beraprost sodium (BPS) and platelet derived growth factor (PDGF), and the roles of thyroid hormones in the functions of hCASMCs. BPS increased D2 expression, whereas PDGF suppressed BPS stimulated D2 expression without affecting cAMP production in hCASMCs. PDGF increased DNA synthesis, while BPS, T3 or T4 suppressed PDGF stimulated DNA synthesis in hCASMCs. Inhibition of D2 activity by 3,3',5'-triiodothyronine (rT3) partially restored T4 suppression of PDGF stimulated DNA synthesis in hCASMCs. PDGF increased migration activity, whereas BPS, T3 or T4 suppressed PDGF stimulated migration activity of hCASMCs. These results suggest that D2 expression is increased by BPS and suppressed by PDGF in hCASMCs, and that intracellular thyroid hormone activation may be involved in the suppression of DNA synthesis and migration activity of hCASMCs.

Topics: Blotting, Northern; Cell Movement; Cells, Cultured; Coronary Artery Disease; Coronary Vessels; Cyclic AMP; Epoprostenol; Gene Expression Regulation; Humans; In Vitro Techniques; Iodide Peroxidase; Iodothyronine Deiodinase Type II; Muscle, Smooth, Vascular; Platelet-Derived Growth Factor; RNA, Messenger; Thyroid Hormones; Vasodilator Agents

Two episodes of hypotension caused by oral beraprost sodium administration following cardiac surgery are described. The first case was a 67-year-old female who underwent concomitant surgery for mitral valve replacement, tricuspid annuloplasty, and a radiofrequency maze procedure for atrial fibrillation. The second case was a 45-year-old female who underwent 4-vessel coronary artery bypass grafting associated with endarterectomy in the right coronary artery. Beraprost sodium was administered for the treatment of residual pulmonary hypertension in the first case, and was initiated as an antiplatelet agent following coronary endarterectomy in the second case. Hypotension occurred at approximately one hour after beraprost sodium administration in both cases. Careful observation to prevent this adverse effect is critical after the administration of beraprost sodium, especially in patients who have undergone cardiac surgery.

Topics: Aged; Atrial Fibrillation; Cardiac Surgical Procedures; Catheter Ablation; Coronary Artery Bypass; Coronary Artery Disease; Diabetes Complications; Endarterectomy; Epoprostenol; Female; Heart Valve Prosthesis Implantation; Humans; Hypotension; Middle Aged; Mitral Valve; Mitral Valve Stenosis; Postoperative Complications; Tricuspid Valve Insufficiency; Vasodilator Agents