Middle cerebral artery velocity correlates with nitroglycerin-induced headache onset

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.