Middle Cerebral Artery Velocity Correlates with Nitroglycerin‐induced Headache Onset

Abstract

Headache often accompanies treatment with nitroglycerin, but the cerebral hemodynamic effects and the exact mechanism of the headache are incompletely understood. Transcranial Doppler monitoring allows evaluation and monitoring of changes in blood flow velocity in the large intracranial arteries. The objective of this study was to assess middle cerebral artery (MCA) blood flow velocities with transcranial Doppler monitoring in subjects receiving continuous low-dose nitroglycerin intravenously or by patch, and correlate these with clinical headache. Twenty-eight normal adult men received nitroglycerin (0.12 micrograms/kg/min intravenously [n = 14] or 0.6 mg/min by transdermal patch [n = 14]), for up to 120 minutes, with monitoring of clinical headache status (standard 4-point scale), blood pressure, heart rate, end-expiratory PCO2 (CO2), and right MCA velocity. All subjects developed headache (mean time to onset, 34 min), reaching moderate or severe levels in 20. There were no differences in age, weight, mean blood pressure, mean heart rate, or resting end-tidal CO2 between those whose headache reached a moderate to severe level and those whose headache remained mild. MCA velocity decreased from baseline values at all levels of clinical headache (onset, -17%; moderate, -18%; severe, -16%; nitroglycerin stopped, -19%) (p, 0.0001 by t test for each stage of headache). MCA velocity remained decreased at the time of headache resolution (-14%; p < 0.001). Blood pressure, heart rate, and CO2 did not change significantly. There were no differences related to route of nitroglycerin dosing. These data show that continuous low doses of nitroglycerin by patch or intravenously produce headache in normal male subjects. MCA velocities were significantly decreased at headache onset and at all levels of headache severity. Changes in MCA velocity persisted beyond the clinical headache. These results suggest a direct MCA vasodilatory effect of nitroglycerin. This method may also be used to evaluate the intracranial hemodynamic effects of other vasoactive drugs, even in clinical settings.

Transcranial Doppler in Migraine Attacks Before and After Treatment With Oral Zolmitriptan or Sumatriptan

“…There were no statistical differences in baseline velocity among the 3 groups of patients and controls. In contrast to results reported by other investigators, we found no significant changes in PI in the groups of subjects during the entire evaluation 15,16 …”

“…In our subjects, BFV in the MCA decreased significantly in migraineurs during headache attacks caused by nitroglycerin, but did not in controls; in the treated groups with migraine, BFV increased significantly after zolmitriptan and sumatriptan administration. Our results are in agreement with the findings of other investigators 6,12,16,17 …”

Intracranial hemodynamics during intravenous infusion of glyceryl trinitrate

“…In contrast, the headache had disappeared at this time point making it unlikely that dilation per se of MCA is the cause of NO-induced headache. This is supported by findings in another study on GTN, where MCA velocities remained decreased (14%, P  < 0.001) at the time of headache resolution [31]. In addition, dilation of the MCA outlasted the headache response after intravenous dipyridamole [32] and sildenafil-induced migraine in migraine patients, but did not affect MCA velocity [33].…”

Magnetic Resonance Angiography Shows Dilatation of the Middle Cerebral Artery after Infusion of Glyceryl Trinitrate in Healthy Volunteers

“…Similarly, in the present study, the automated approach also gave the smallest numeric values of the MCA. Former studies have reported a correlation between the onset of pharmacologically induced headache and dilation of the MCA (33,34). We did an explorative post-hoc correlation analysis of the headache score and cross-sectional MCA area for the whole observation period.…”