Reproducibility of forearm vasodilator response to intra‐arterial infusion of calcitonin gene‐related peptide assessed by venous occlusion plethysmography

Abstract

AimsTo assess the reproducibility of the forearm blood flow (FBF) response to intra-arterial infusion of calcitonin-gene related peptide (CGRP), measured by venous occlusion plethysmography. In addition, to compare different ways of expressing the F BF response and perform sample size calculations. MethodsOn two separate visits, CGRP (10 ng min -1 dl -1 forearm) was infused for 45 min into the brachial artery of six healthy subjects. Reproducibility was assessed by calculating mean difference, repeatability coefficient, within-subject coefficient of variation (WCV) and intraclass correlation coefficient. ResultsCGRP increased FBF from 2.8 ± 0.4 and 3.2 ± 0.7 (at baseline) to 15.4 ± 1.4 and 15.2 ± 1.5 ml min -1 dl -1 forearm (at 45 min) on visits 1 and 2, respectively ( P < 0.0001 for both visits). Mean difference in FBF at 45 min between both visits was 0.3 ml min -1 dl -1 forearm (repeatability coefficient: 4.1 ml min -1 dl -1 forearm). This FBF response appeared to be more reproducible when expressed as absolute FBF in the infused arm (WCV 11%) compared with absolute FBF-ratio between both arms (WCV 37%), percentage change from baseline in FBF in the infused arm (WCV 29%) and percentage change from baseline in FBF-ratio (WCV 40%). When expressed as absolute FBF, a sample size of five (95% confidence interval: 2-12) subjects gives 90% power at a type I error probability of 0.05 to detect a 25% shift in FBF response. ConclusionsIntra-arterial infusion of CGRP results in a forearm vasodilator response which is reproducible between days. This response is most reproducible when expressed as absolute FBF. The presented methodology provides a suitable pharmacodynamic model to assess the in vivo activity of CGRP-receptor antagonists in a small number of subjects.

Reproducibility of the capsaicin‐induced dermal blood flow response as assessed by laser Doppler perfusion imaging

“…In the present study, reproducibility of the summary response AUC 0−30 was not consistently better compared with reproducibility of the single time point measure t 30 . This is in agreement with previous findings of our group [45]. Here the use of the AUC as a summary measure accurately accentuates the inferiority of period‐to‐period compared with arm‐to‐arm reproducibility.…”

Calcitonin Gene-Related Peptide8-37 Antagonizes Capsaicin-Induced Vasodilation in the Skin: Evaluation of a Human in Vivo Pharmacodynamic Model

“…Second, the capsaicin-induced increase in DBF in the noninfused arm did not differ from the DBF responses in the noninfused arm during the other study periods, including the screening period. Finally, the slight increase in diastolic blood pressure after L-NMMA infusion is most likely procedure-related, because it was also seen in the other treatment periods and reported by others using intraarterial brachial infusion even when infusing vasodilators (Vanmolkot and de Hoon, 2005). Therefore, we are confident to conclude that there is no substantial contribution of de novo synthesized NO to capsaicin-induced neurogenic inflammation.…”

Analysis of Short‐term Reproducibility of Arterial Vasoreactivity by Pulse‐wave Analysis After Pharmacological Challenge

“…18,[27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42] Reproducibility studies using forearm occlusion plethysmography to assess postischaemic blood flow or flow responses to vasodilator agents have reported CV values between 6.1 and 40% and ICC values between -0.22 and 0.82. 43,44 The results of these studies indicate a wide range of reproducibility that may reflect differences in study populations, operators and techniques, as well as variability in arterial vasoreactivity over time.…”