A comparative study of reactive hyperemia in human forearm skin and muscle MS 1225 / 2007 , Revision 1

Reactive hyperemia (RH) in forearm muscle or skin microcirculation has been considered as a surrogate endpoint in clinical studies of cardiovascular disease. We evaluated two potential confounders that might limit such use of RH, namely laterality of measurement and intake of nonsteroidal anti-inflammatory drugs (NSAIDS). 23 young non-smoking healthy adults were enrolled. In Experiment 1 (n=16), the RH elicited by 3 minutes of ischemia was recorded in the muscle (strain gauge plethysmography, hand excluded) and skin (laser Doppler imaging) of both forearms. In Experiment 2 (n=7), RH was determined in the dominant forearm only, one hour following oral acetylsalicylic acid (1 g) or placebo. In Experiment 1, peak RH was identical in both forearms, and so were the corresponding durations of responses. RH lasted significantly less in muscle than in skin (p = 0.003), a hitherto unrecognized fact. In skin, acetylsalicylate reduced duration (43 seconds vs 57.4 for placebo, p=0.03), without affecting the peak response. In muscle, duration tended to decrease with acetylsalicylate (21.4 vs 26.0 sec with placebo, p=0.06) and the peak increase in blood flow was blunted (27.2 vs 32.4 ml/min/100 ml tissue with placebo, p = 0.003). We conclude that, when using RH as a surrogate endpoint in studies of cardiovascular disease, confounding by laterality of measurement need not be feared, but NSAIDS may have an influence, although perhaps not on the peak response in the skin.