Arterial wall rather than platelets is responsible for diminished thrombogenicity during isradipine therapy.
We investigated whether the vessel wall or platelets are primarily responsible for the decreased thrombogenicity induced by the calcium channel blocker isradipine after endothelium removal. In a cross-perfusion model, rabbit aorta and iliac artery endothelium of receiver animals were removed by balloon catheter before being perfused with the blood of the blood donor rabbits. Donor and/or receiver animals were treated with 0.3 mg/kg isradipine intravenously (i.v.) daily for 1 week or with 10 mg acetylsalicylic acid (ASA) in addition. The other animals received vehicle only or ASA. The animals were divided into four groups (I-IV, total n = 24) consisting of four subgroups of 6 animals each. In all, 96 rabbits were examined. Immediately after the last administration of the respective drug, native blood from a donor rabbit was circulated (30 ml/min) through a deendothelialized segment of a receiver rabbit. The contract (C) and spread (S) platelets as well as the denuded surface covered with platelet aggregates (> 5 microns high) were quantified by morphometry. Deposition of [111In]oxine-labeled platelets was quantitatively determined per surface unit. In addition, prostaglandin I2 (PGI2) formation by the denuded aortic and iliac artery segment was determined. In group I, receiver rabbit pretreatment with isradipine exhibited decreased adhesion and aggregation of platelets, even when the donor rabbit was treated with solvent or ASA. In group II, concomitant treatment of donor animals with ASA and isradipine had no significant effect, whereas ASA isradipine treatment of receiver animals enhanced thrombogenicity.(ABSTRACT TRUNCATED AT 250 WORDS)
Sinzinger
H
H
Wilhelm Auerswald-Atherosclerosis Research Group (ASF) Vienna, Austria.
Keiler
A
A
O'Grady
J
J
D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D004730:Endothelium, Vascular / Q000502:physiology; D011464:Epoprostenol / Q000096:biosynthesis / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D007205:Indium Radioisotopes; D017275:Isradipine / Q000494:pharmacology*; D008297:Male; D010477:Perfusion; D011817:Rabbits; D013927:Thrombosis / Q000097:blood / Q000503:physiopathology*; D013929:Thromboxane B2 / Q000096:biosynthesis / Q000097:blood
D007205:Indium Radioisotopes; D013929:Thromboxane B2; D011464:Epoprostenol; D001241:Aspirin; D017275:Isradipine