The effects of thromboxane receptor blockade on platelet aggregation and digital skin blood flow in patients with secondary Raynaud's syndrome.
Raynaud's syndrome (RS) is characterized by intense blood vessel spasm resulting in finger blanching. Treatment primarily involves vasodilation. Thromboxane A2 (TXA2) has been shown to be a potent vasoconstrictor and platelet aggregant. It may be possible to produce a vasodilatory and anti-thrombotic effect by blockade of the TXA2 receptors. ICI 192,605 is a potent TXA2 receptor antagonist and we studied its effects on platelet aggregation and digital blood flow in patients with RS. Sixteen patients with RS completed this double-blind, randomized, placebo controlled study. Each patient was seen on three separate occasions and was given ICI 192,605 (100 mg orally) on one occasion and matching placebo tablets on the other two. We measured platelet aggregation using platelet rich plasma (PRP) stimulated by U46619, a thromboxane (TX) mimetic. The concentration of U46619 required to cause just over 50% platelet aggregation before the administration of either ICI 192,605 or placebo (pre-dose) was noted. The same concentration of U46619 was used to stimulate the PRP sample at 1 h after the administration of ICI 192,605 or placebo (post-dose) and the percentage of platelet aggregation was again noted. Fingertip skin blood flow was also measured 1.25 h post-dose using a laser Doppler flowmeter. Patients were seated in a temperature controlled chamber which was initially heated to 40 degrees C to induce centrally mediated vasodilatation. The temperature was then lowered to 12 degrees C followed by rewarming to 40 degrees C. Steady blood flow values at these temperatures were measured and the rates of cooling and rewarming were also noted.(ABSTRACT TRUNCATED AT 250 WORDS)
Lau
C S
CS
Department of Medicine, Ninewells Hospital and Medical School, Dundee, UK.
Khan
F
F
McLaren
M
M
Bancroft
A
A
Walker
M
M
Belch
J J
JJ
D000328:Adult; D000368:Aged; D003080:Cold Temperature; D004146:Dioxanes / Q000494:pharmacology*; D004311:Double-Blind Method; D005260:Female; D005385:Fingers; D006801:Humans; D007834:Lasers; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects* / Q000502:physiology; D011928:Raynaud Disease / Q000097:blood* / Q000503:physiopathology*; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors*; D017482:Receptors, Thromboxane; D012039:Regional Blood Flow / Q000187:drug effects; D012867:Skin / Q000098:blood supply*
D004146:Dioxanes; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; C057498:ICI 192605