iloprost and Aortic-Diseases

This study determines the antiplatelet effects of oral ticlopidine (100 mg/kg x day) in experimental hypercholesterolemia. Rabbits were fed either a standard diet or a cholesterol-enriched diet (0.5% for 3 months, 1% for 1 month). In normocholesterolemic controls ADP-, but not collagen-induced platelet aggregation was inhibited by ticlopidine treatment. This was accompanied by a significantly enhanced inhibition of ADP-induced platelet aggregation and stimulation of cyclic AMP accumulation by iloprost. Hypercholesterolemia considerably attenuated the inhibition of ADP-induced aggregation by ticlopidine but did not change its effect on the iloprost-induced inhibition of platelet function and cyclic AMP formation. ADP-induced platelet-derived thromboxane formation was considerably greater in hypercholesterolemic rabbits and not reduced by ticlopidine. Ticlopidine did also not significantly influence the extent and severity of atherosclerotic plaque formation although a tendency for improvement was observed in a subgroup of animals. The data suggest that hypercholesterolemia attenuates the inhibitory effect of ticlopidine on ADP-induced platelet aggregation. This might be related to the stimulation of thromboxane formation by ADP in hypercholesterolemia. The maintained protection from ADP-induced inhibition of cAMP accumulation suggests a minor role of this mechanism in the progression of hypercholesterolemia-induced vessel disease in this model.

Topics: Adenosine Diphosphate; Animals; Aortic Diseases; Arteriosclerosis; Biotransformation; Cholesterol, Dietary; Collagen; Cyclic AMP; Hypercholesterolemia; Iloprost; Indomethacin; Liver; Male; Platelet Aggregation; Rabbits; Signal Transduction; Thromboxane B2; Ticlopidine

This study examined the effects of laser-generated tissue debris from thrombus, atheroma, and normal aorta on platelet aggregation. Debris supernatant and suspension from lased thrombus induced dose-related aggregation, maximal at 48 +/- 12% and 65 +/- 2%, respectively. Debris suspension from normal aorta induced maximal aggregation of 35 +/- 12%, but the debris from atheromatous aorta surprisingly had no effect on platelet aggregation. The debris particle count was in the range of 10(10) to 10(12) per liter. Aspirin, 0.2 and 2.0 mmol/L, only weakly inhibited the debris-induced aggregation, and heparin up to 10 U/ml was ineffective. However, iloprost reduced aggregation to 40 +/- 11% of control at 0.3 ng/ml, and totally abolished it at 3 ng/ml. Soluble and particulate laser-generated debris from vascular tissue and thrombus may cause platelet aggregation in vitro. This may have implications for laser coronary angioplasty.

Topics: Aged; Angioplasty, Laser; Animals; Aorta; Aortic Diseases; Arteriosclerosis; Aspirin; Blood Coagulation; Heparin; Humans; Iloprost; In Vitro Techniques; Middle Aged; Platelet Aggregation; Swine; Thrombosis