Repeatability of local forearm vasoconstriction to @entity2232 measured by XXXX plethysmography.

@entity432 @entity1 @entity1009 @entity2232
AIMS: We investigated the repeatability of the forearm blood flow response to intra-arterial infusion of @entity2232 ( @entity2232 ), assessed by @entity432 -plethysmography. METHODS: In eight healthy @entity1 (aged 18-50 years), on four separate occasions, @entity2232 (2.5 or 10 pmol @entity1009 ) was infused for 120 min via a 27 SWG cannula sited in the brachial artery of the nondominant arm. Each dose level was administered twice on consecutive visits. The dose order was randomized. Results are expressed as percentage change from baseline at 120 min (mean +/- s.e. mean). RESULTS: @entity2232 caused significant vasoconstriction (P < 0.0001 anova) at both doses (38 +/- 3%, 2.5 pmol @entity1009 and 62 +/- 3%, 10 pmol @entity1009 ). There was no difference in the response to either dose on repeated challenge. Responses appeared to be less variable when expressed as percentage change in the ratio of blood flow (infused:noninfused) in both arms than as percentage change in blood flow in the infused arm alone, as indicated by repeatability coefficients (15% vs 21%, 2.5 pmol @entity1009 and 11% vs 13%, 10 pmol @entity1009 ; ratio vs infused arm alone). CONCLUSIONS: We have shown dose-dependent vasoconstriction in the forearm vascular bed to intra-arterial infusion of @entity2232 and that this response is less variable when expressed as percentage change in the ratio of forearm blood flow than percentage change in the infused arm. These data should also provide useful information to determine the power of early clinical pharmacology studies investigating the activity of endothelin receptor antagonists.
