Introduction 1 2 3 5 6 7 8 9 10 9 2 11 12 7 Patients and methods Patients 13 Exclusion criteria were as follows: use of any kind of daily medication including prophylactic headache therapy but excluding oral contraceptives; pregnancy or breastfeeding; excessive use of analgesics or alcohol; serious somatic or psychiatric disorders; ischaemic heart disease; a supine systemic blood pressure more than 160/90 or less than 110/75 mmHg at entry of study. Patients were informed that they were free to withdraw at any time and all gave written informed consent. The study was approved by the local ethics committees of Copenhagen and Copenhagen County (KA 96054) and complied with the Declaration of Helsinki. Design and procedure 14 15 V 2 V 2 7 Methods 133 133 16 17 V mean V mean 2 Statistics 2 V mean 2 t P Results During CGRP infusion, two volunteers experienced a substantial decrease in blood pressure (70/50 and 65/25, respectively) causing the infusion to be terminated ahead of time. Signs and symptoms were pallor, cold sweat, stomach ache, nausea and palpitation. The situation was restored after placing the volunteers in head-down tilt for 7 and 20 min, respectively. No rCBF and TCD measurements were taken during this time period, and therefore, results from these two volunteers were excluded from the calculations below. 2 2 P P 2 P t 2 Transcranial Doppler measurements V mean 2 18 \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document} $$ V_{{{\text{mean(korr}})}} = V_{{{\text{mean}}({\text{meas}})}} \exp {\left( {0.04{\left( {{\text{pCO}}_{{2({\text{Basal}})}} - {\text{pCO}}_{{2(n)}} } \right)}} \right)}. $$\end{document} V mean P P V mean P t P t 1 1 V mean r P Fig. 1 V mean squares triangles X y V mean squares P P triangles P P Table 1 V mean Time (min) V mean 2 2 CGRP Placebo CGRP Placebo CGRP% Placebo% 0 81.6 (10.7) 79.9 (12.3) 81.6 (10.7) 79.9 (12.3) 0 0 15–20 66.9 (13.5)* 79.5 (12.4) 70.7 (14.2)* 80.3 (12.7) −13.5 (11.4)* 0.6 (5.6) 75–80 76.6 (9.9) 77.4 (12.7) 80.6 (11.3) 79.2 (13.6) −0.7 (11.6) −0.9 (6.4) Values within parentheses represent the standard deviation (SD) 2 18 2 P * Significant changes compared with baseline Regional cerebral blood flow 2 (korr) (meas) 2(Basal) n V mean P P P t P t 1 2 Table 2 Regional cerebral blood flow rCBF in the MCA territory recorded 50 and 90 mm above the orbitomeatal plane (OM) Cerebral blood flow (ml blood/100 g/min) Time (min) MCA (OM 50 + OM 90) in the territory used for TCD examination 2 2 Absolute data Absolute data Data in % of baseline CGRP Placebo CGRP Placebo CGRP Placebo 0 70.8 (13.7) 67.7 (9.3) 70.8 (13.7) 67.7 (9.3) 0 0 15–20 66.8 (9.4) 65.3 (11.6) 71.1 (10.5) 66.7 (11.4) 1.2 (1.7) −1.6 (3.1) 75–80 69.3 (7.9) 65.0 (9.8) 72.8 (8.7) 66.7 (10.4) 4.2 (3.0) −1.6 (2.8) Values within parentheses represent the standard deviation (SD) 2 18 2 P 2 2 2 P t P t (MCA) r P Blood pressure P P P t P 3 P Table 3 The mean arterial blood pressure (MABP), systolic and diastolic blood pressure (mmHg) and heart rate (bpm) after CGRP and placebo treatment Blood pressure (mmHg) Heart rate (bpm) Time (min) MABP Systolic BP Diastolic BP CGRP Placebo CGRP Placebo CGRP Placebo CGRP Placebo 0 87.8 (9.6) 91.6 (9.5) 117.0 (11.1) 119.0 (12.6) 73.2 (9.5) 77.9 (9.4) 63.0 (6.0) 64.4 (7.2) 15 78.0 (7.5)* 90.0 (9.2) 110.7 (9.6) 117.2 (12.5) 61.7 (7.8) 76.4 (8.7) 92.9 (10.2)* 63.8 (6.8) 20 76.9 (10.1)* 93.5 (8.3) 112.2 (13.3) 123.9 (11.6) 59.3 (9.1) 78.3 (7.6) 98.9 (11.2)* 65.5 (7.1) 75 86.5 (9.2) 91.4 (8.7) 117.6 (12.0) 121.9 (13.4) 71.0 (8.9) 76.2 (7.2) 76.1 (7.0)* 62.9 (6.0) 80 85.3 (9.2) 91.3 (9.9) 116.4 (13.2) 123.3 (11.3) 69.7 (8.4) 75.3 (9.7) 75.3 (7.7)* 64.4 (5.3) Values within parentheses represent ±standard deviation (±SD)  P Heart rate P P P t P t 3 Other signs P P 7 Discussion 14 15 12 12 50 19 50 The blinding of the present study can be criticized. Signs (increased heart rate) and symptoms (facial flushing and feeling of warmth) during CGRP infusion made it difficult to keep the study completely blinded. However, the present design is the best one available, because no technique is available to disguise such symptoms. 20 πr 2 r 2 V a V b r b 2 r a 2 20 21 12 22 r P 12 23 1 12 12 24 24 12 1 25 25 14 15 7