Carotid stenosis in patients with atrial fibrillation. Prevalence, risk factors, and relationship to stroke in the Stroke Prevention in Atrial Fibrillation Study.

BACKGROUND: Several mechanisms contribute to the increased stroke rate of patients with atrial fibrillation (AF). We assessed the frequency of carotid artery stenosis in patients with AF and its relationship to stroke during aspirin or warfarin therapy. METHODS: Carotid ultrasonography was done in 676 patients with AF enrolled in the Stroke Prevention in Atrial Fibrillation Study to detect cervical carotid stenosis of 50% or more of the luminal diameter. The presence of carotid stenosis was correlated with patient features and subsequent stroke during a mean of 2.6 years of follow-up. RESULTS: In patients with AF who were older than 70 years, the frequency of carotid stenosis was 12% in men and 11% in women. Carotid stenosis was independently associated with systolic hypertension (relative risk, 2.4; P = .002), diabetes (relative risk, 1.8; P = .04), and tobacco use (relative risk, 1.8; P = .02). Carotid stenosis did not add significantly to prediction of stroke when analyzed with other clinical risk factors for stroke in patients with AF (relative risk, 1.3; 95% confidence interval, 0.5 to 3.6; P = .55). CONCLUSIONS: Carotid artery stenosis of 50% or more occurs in about 12% of elderly patients with AF, reflecting the substantial prevalence of hypertension and diabetes in these patients. Carotid stenosis was not usefully predictive of stroke in patients with AF who were given aspirin or warfarin. Routine ultrasonography to detect carotid stenosis does not appear warranted in patients with AF without previous symptoms of brain ischemia.

Acoustic shadowing on B-mode ultrasound of the carotid artery predicts ischemic stroke: the Atherosclerosis Risk in Communities (ARIC) study.

BACKGROUND AND PURPOSE: We examined the relationship of carotid artery lesions (CALs), with and without acoustic shadowing (AS), to incident ischemic stroke events in the Atherosclerosis Risk in Communities study cohort. METHODS: The study population consisted of 13 123 men and women aged 45 to 64 years, and free of stroke, examined during 1986-1989. Over an average follow-up time of 8.0 years, 226 incident ischemic stroke cases (thromboembolic brain infarctions) were identified and classified by a standardized protocol. Three levels of exposure were defined on the basis of the presence of B-mode ultrasound-detected CALs and AS in a 3-cm segment of the carotid arteries centered at the bifurcation. RESULTS: The hazard ratio for ischemic stroke adjusted for age, ethnicity, and study site for women with a CAL without AS, compared with those without a CAL, was 1.92 (95% CI, 1.23, 3.01), and the hazard ratio comparing those with a CAL with AS with those without a CAL was 4.01 (95% CI, 2.28, 7.06). The corresponding hazard ratios for men were 1.99 (95% CI, 1.36, 2.91) and 2.23 (95% CI, 1.32, 3.79). Although adjustment for diabetes, hypertension medication, systolic blood pressure, left ventricular hypertrophy score, fibrinogen, von Willebrand factor antigen, and smoking status attenuated these associations somewhat, when compared with no evidence of CALs, CALs with AS remained statistically significant predictors of ischemic stroke in women, while CALs without AS were predictive of ischemic stroke in men. CONCLUSIONS: B-mode ultrasound-detected CALs and AS serve as markers of atherosclerosis and thus are predictive of ischemic stroke.

Antiphospholipid antibodies and cerebral ischemia in young people.

The importance of a prothrombotic state as a cause of ischemic stroke in young adults is ill defined. We examined 46 unselected patients under age 50 years with cerebral ischemia for anticardiolipin antibody (aCL) and lupus anticoagulants (LA), over a 3-year-period. Age- and sex-matched patients with other neurologic diseases served as a noncerebral ischemia comparison group to test whether (1) stroke/transient ischemic attacks (TIA) in young people is associated with aCL and/or LA, and (2) their presence is specific to cerebral ischemia. In the stroke/TIA group, 21 patients had aCL or LA and 25 had neither, whereas in the control group, 2 patients had aCL and 24 had neither. Equal numbers of stroke/TIA patients with and without antiphospholipid antibodies (aPL) had other stroke risk factors. Patients with aPL and cerebral ischemia, however, had a more frequent history of multiple events than those without them. These antibodies occur with undue frequency in young patients with stroke/TIA and are not associated with a concurrent diagnosis of systemic lupus in most cases. A coexistent aPL-associated prothrombotic state may be a key determinant of whether patients with atherosclerosis, mitral valve prolapse, or other structural lesions experience recurrent ischemia.

The bleeding time effects of a single dose of aspirin in subjects receiving omega-3 fatty acid dietary supplementation.

Dietary supplementation with omega-3 fatty acids reduces platelet aggregation in subjects who usually eat a diet low in these fatty acids. Aspirin also has an antiplatelet effect. The clinical effects of the concomitant administration of these agents were examined in this double-blind controlled crossover trial. Twelve healthy adults were randomized to supplement their diet for 21 days with 8 g of omega-3 fatty acids or identical-looking olive oil capsules. At the end of each treatment period, bleeding times were obtained before and after the administration of one 325-mg aspirin tablet. Overall, percent change in bleeding time after omega-3 fatty acid supplementation was significantly prolonged compared with olive oil supplementation before aspirin administration but not after. Bleeding times were influenced significantly by the order of randomization in the two treatment groups. Changes in post-aspirin bleeding time varied in subjects after they received olive oil. Post-aspirin bleeding times after omega-3 fatty acid supplementation were prolonged compared with baseline values but not significantly prolonged when compared with those after olive oil administration. The authors concluded that the concomitant administration of a single dose of aspirin does not prolong bleeding time in subjects who eat a diet enriched by omega-3 fatty acids versus a diet enriched by olive oil.

A new dynamic method for detection of internal jugular valve incompetence using air contrast ultrasonography.

The internal jugular (IJ) valve is the only valve between the heart and the brain, preventing venous reflux into the IJ vein. Internal jugular valve competence has been tested by IJ venography. Doppler ultrasonography of the IJ vein and M-mode ultrasonography of the IJ valve, and color flow imaging (CFI) of the IJ vein. However, interpretation of venous Doppler and CFI is difficult, and venography is invasive. The purpose of this study was to evaluate the feasibility of a new dynamic method to test IJ valve competency, and to review the literature regarding the potential clinical importance of this pathophysiology. Ten patients had intravenous injection of agitated air and saline during Valsalva maneuver with B-mode monitoring and CFI of the right IJ vein. Contrast bubbles were clearly identified refluxing into the right IJ vein in 50% of patients. Air contrast studies more often showed IJ valve incompetence than CFI. Bubbles appeared in the IJ vein within 19.2 sec and persisted up to 282 sec. Bubble aggregation was also observed. There was no correlation between positive bubbles and the presence of spontaneous echo contrast on baseline B-mode imaging. Air contrast ultrasound venography (ACUV) is a new noninvasive method to assess competency of the IJ valves. This technique is feasible, appears to be more sensitive than CFI, and adds a new dimension to the study of the venous system in cerebrovascular disease. Potential clinical application includes evaluation of patients with increased central venous pressure, those with morning headaches, and those on positive end-expiratory pressure ventilators.

Clinical cerebrovascular applications of arterial ultrasound volume flow rate estimates.

A variety of disorders affect cerebral hemodynamics. Volume flow rate (VFR) estimates now allow accurate quantification of the effect of cerebrovascular lesions on the conduit vessels, with excellent in vivo and in vitro correlation. Four selected cases with VFR data and angiographic correlation are presented to illustrate potential clinical uses of this method. The VFR estimates were obtained with a color M-mode-based velocity imaging technique, which uses time-domain processing (P-700 Color Velocity Imaging System, Philips Ultrasound International, Irvine, CA). In a patient awaiting coronary artery surgery, with unilateral internal carotid artery occlusion and contralateral angiographic stenosis (50-80%, reader variation), the baseline and acetazolamide-challenged common carotid artery VFRs showed excellent conduit function ipsilateral to this stenosis. Thus, the angiographic stenosis did not have significant hemodynamic effects and endarterectomy was avoided. In a patient with an arteriovenous malformation fed by the left vertebral and left external carotid arteries, high in the left cervical region, VFR estimates of two to three times normal predicted the feeding vessels, influenced management, and proved helpful in follow-up. In a patient with subclavian steal syndrome, VFR estimates quantified the steal after brachial hyperemia. Finally, in a patient with delayed vasoconstriction after subarachnoid hemorrhage, very low VFR estimates preceded clinical deterioration. Quantification of hemodynamic changes with VFR estimates was useful for the diagnosis, management, and follow-up of these patients with four types of cerebrovascular disease, and should be applicable in many others.

Angle correction in transcranial Doppler sonography.

Since the introduction of transcranial Doppler sonography in the early 1980s, flow velocity estimates have assumed a 0- to 30-degree angle of insonation. Based on limited radiological and anatomical studies, such as assumption appeared justified, and seemed to confer only minimal potential for error due to the cosine function in the Doppler formula. The introduction of transcranial color duplex sonography allows the direct evaluation of this assumption and the effect on flow velocities. Fifteen healthy volunteers were studied bilaterally using a unilateral transtemporal approach from the right. Velocity measurements were taken from the middle, anterior, and posterior cerebral arteries. Flow velocities were obtained with and without angle correction (0 degree). After completion of the color duplex study, velocities were obtained with a conventional, "blind" Doppler transducer at corresponding depths. For all insonated vessels the average angle of insonation was around 30 degrees. However, there was a wide variability of individual angles of insonation (0-70 degrees) in specific vessels. In 74.5% of all vessels, the angle-corrected flow velocity did not exceed the uncorrected velocity by more than 25%. In 14.5% the angle-corrected velocity was 25 to 50% higher and in 10.8% it was more than 50% higher as compared to the uncorrected velocity. Thus, the angle of insonation was unpredictable and often higher than originally expected. Angle-corrected velocities were higher than uncorrected values, and were more than 25% higher in about one-fourth of the vessels studied. Understanding of the clinical importance of such differences requires further study.

Color velocity imaging: introduction to a new ultrasound technology.

Noninvasive ultrasound is the preferred methodology for the initial evaluation of carotid atherosclerosis. Since the early use of continuous-wave Doppler to assess carotid artery flow velocity blindly, neurosonology has progressed through crude B-mode imaging, spectral analysis of the Doppler signal, and gray-scale duplex Doppler/B-mode imaging, to color-flow Doppler duplex imaging. The latter allows color coding of Doppler data based on the velocity of blood flow. The combination of color-flow Doppler with gray-scale B-mode imaging allows simultaneous visual display of anatomical and hemodynamic information. Physical limitations of color-flow duplex Doppler imaging may affect the clinical utility of these techniques. Problems with pulse repetition frequency, aliasing, resolution capability of the color data, and interpolation of data make some applications difficult. Color velocity imaging uses the data contained in the gray-scale B-mode image scan lines to determine velocity of blood flow, and it offers potential advantages over conventional color-flow duplex Doppler for the assessment of carotid atherosclerosis and hemodynamics. Initial comparison of spectral Doppler and color velocity imaging data suggests that the latter is an accurate method to assess blood flow velocity. Understanding of the validity, utility, and prognostic advantages offered by color velocity imaging awaits careful prospective clinical trials.

Peak velocity overestimation and linear-array spectral Doppler.

Ultrasound instruments are used to evaluate blood flow velocities in the human body. Most clinical instruments perform velocity calculations based on the Doppler principle and measure the frequency shift of a reflected ultrasound beam. Doppler-only instruments use single-frequency, single-crystal transducers. Linear- and annular-array multiple-crystal transducers are used for duplex scanning (simultaneous B-mode image and Doppler). Clinical interpretation relies primarily on determination of peak velocities or frequency shifts as identified by the Doppler spectrum. Understanding of the validity of these measurements is important for instruments in clinical use. The present study examined the accuracy with which several ultrasound instruments could estimate velocities based on the identification of the peak of the Doppler spectrum, across a range of different angles of insonation, on a Doppler string phantom. The string was running in a water tank at constant speeds of 50, 100, and 150 cm/sec and also in a sine wave pattern at 100- or 150-cm/sec amplitude. Angles of insonation were 30, 45, 60, and 70 degrees. The single-frequency, single-crystal transducers (PC Dop 842, 2-MHz pulsed-wave, 4-MHz continuous-wave) provided acceptably accurate velocity estimates at all tested velocities independent of the angle of insonation. All duplex Doppler instruments with linear-array transducers (Philips P700, 5.0-MHz; Hewlett-Packard Sonos 1000, 7.5-MHz; ATL Ultramark 9 HDI, 7.5-MHz) exhibited a consistent overestimation of the true flow velocity due to increasing intrinsic spectral broadening with increasing angle of insonation.(ABSTRACT TRUNCATED AT 250 WORDS)

Serial transcranial Doppler monitoring after transient ischemic attack.

The natural course of ultrasonically detectable microembolism in patients with a symptomatic extracranial atherosclerotic lesion is not completely understood. Furthermore, the potential impact of therapeutic management on microemboli detection is anecdotal. A 58-year-old man who experienced a left-hemisphere transient ischemic attack presented with an extracranial ipsilateral high-grade carotid stenosis. He was studied 12 times in 12 months during different medical management, during which time he was symptom free, even though transcranial Doppler evidence of microemboli continued for 5 months.

Middle cerebral artery flow velocity correlates with common carotid artery volume flow rate after CO2 inhalation.

Cerebral vasoreactivity can be studied with transcranial Doppler (TCD) by monitoring CO2-induced middle cerebral artery (MCA) velocity changes. Expected MCA mean velocity (Vm) changes due to changes in end-expiratory CO2 (EE-CO2) are established, but reactivity of common carotid artery (CCA) volume flow rate (VFR) has not been extensively reported. The authors assess the relationship between MCA Vm, CCA VFR, and EE-CO2. Ten normal individuals without cerebrovascular disease and with CCA diameters of more than 3.0 mm were studied. CCA VFR was obtained by Color Velocity Imaging Quantification and Ipsilateral MCA Vm by standard TCD methods. Each side was studied before, during, and after inhalation of 5% CO2. EE-CO2, blood pressure, and pulse rate were monitored. Four women and 6 men with mean age of 36 years were included. Significant correlations between MCA Vm and EE-CO2, CCA VFR and EE-CO2, and MCA Vm and CCA VFR were found. MCA Vm and CCA VFR increased 5.2% and 4.3% per mm Hg increase in EE-CO2, respectively. MCA Vm increased 0.3 cm/s for each ml/min increase in CCA VFR. In normal individuals, there is a direct correlation between MCA Vm, CCA VFR, and EE-CO2. Measurement of CCA VFR changes during CO2 inhalation may be an alternative method to estimate cerebral vasoreactivity when the MCA velocity cannot be obtained because of inadequate acoustic temporal windows.

In vitro validation of color velocity imaging and spectral Doppler for velocity determination.

Color velocity imaging (CVI) is a new non-Doppler ultrasound technique for vascular color flow imaging. Using information contained in the two-dimensional B-mode, gray-scale image to determine velocity, CVI offers potential advantages over Doppler color flow imaging methods. In order to be used clinically, velocity determination with CVI must be validated by other current methods. A Doppler string phantom was studied with a Philips CVI ultrasound system. Velocity measurements were obtained by both CVI and duplex Doppler spectral analysis for constant string speeds from 10 to 200 cm/sec, at intervals of 10 cm/sec. Twenty separate estimates were obtained with each method, at each string speed. Linear regression assessed the relationship between estimated and actual string velocities, with CVI and spectral Doppler analysis yielding highly valid results (CVI = -0.713 + 1.000997 x phantom; r 2 = 0.9979). At all string speeds tested, the averaged estimated and the actual velocities for both methods were within the 95% confidence estimates. The range for the CVI 95% confidence limits from the regression line varied from +/-1.07 cm/sec at the lowest speed of 10 cm/sec (11.6%) to +/-7.72 cm/sec at 200 cm/sec (3.87%). Based on in vitro testing, CVI is as accurate as Doppler spectral analysis for the estimation of flow velocity.

Control for carbon dioxide-related changes in flow velocity by transcranial Doppler monitoring.

Transcranial Doppler ultrasonography can monitor changes in intracranial blood flow velocity over time in a variety of experimental and clinical settings with excellent temporal resolution. Alterations in arterial carbon dioxide pressure exert a profound influence on blood flow velocity. Such changes exhibit important individual fluctuation depending on respiratory status. This limits the ability of transcranial Doppler to accurately study subtle changes in blood flow velocity, independent of the respiratory state of the subject. Suggested here is a method to control for the respiration artifact on blood flow velocity. The middle cerebral artery of 7 healthy male volunteers was studied with transcranial Doppler under resting conditions, monitoring end-tidal carbon dioxide concentration and blood flow velocity. Hyperventilation was performed both voluntarily and with pharmacological induction by human corticotropin-releasing hormone. These studies were carried out both with and without the use of counterregulation of the end-tidal carbon dioxide concentration via a respiration unit, with an adjustable carbon dioxide-oxygen gas supply preventing significant changes in end-tidal carbon dioxide. The blood flow velocity in the middle cerebral artery during maximal voluntary hyperventilation decreased from baseline values of 100% to 44.4 +/- 4.3% (a 55.6% decrease), and with human corticotropin-releasing hormone-induced involuntary hyperventilation, to 65.1 +/- 5.3% (a 34.9% decrease). With the control method, blood flow velocities during voluntary and pharmacological hyperventilation were 100 +/- 1.6% and 100 +/- 2.8%, respectively. This method allows for control of respiration-induced artifacts during transcranial Doppler monitoring, and can be used to assess the effect of direct or indirect blood flow velocity stimuli independent of respiratory status.

Ultrasonography for diagnosis and management of carotid artery atherosclerosis. A position paper of the American Society of Neuroimaging.

The importance of identifying patients with carotid artery stenosis has attained greater significance in light of recent treatment trials of the efficacy of medical and surgical treatment of both symptomatic and asymptomatic carotid stenosis. Doppler and B-mode ultrasonography can accurately diagnose and quantify stenosis at the cervical carotid artery bifurcation. The development of duplex color-flow instruments has enhanced the sensitivity and specificity of this examination. Ultrasonography should be employed as an initial examination to identify patients with carotid artery stenosis and determine whether further evaluation or treatment is necessary.

Mirror-image artifact can affect transcranial Doppler interpretation.

Transcranial Doppler ultrasonography (TCD) allows evaluation of blood-flow velocity in intracranial arteries detection and monitoring of vasospasm in patients with subarachnoid hemorrhage. Spectral Doppler artifacts can affect TCD data. A 1-month series of TCD findings showed marked fluctuation in blood-flow velocity values in both the middle and anterior cerebral arteries of a patient with subarachnoid hemorrhage. A mirror-image artifact of the Doppler fast Fourier transform velocity spectrum resulted in erroneous interpretation of higher flow velocity in certain vessels. This artifact may cause misinterpretation of TCD flow-velocity data and lead to improper diagnosis of the condition and treatment of patients.

Lack of relation between severity of stroke and severity of extracranial internal carotid artery lesions in Taiwanese first-ever ischemic stroke patients.

BACKGROUND AND PURPOSE: The authors attempt to determine whether hemodynamically significant extracranial internal carotid artery (ICA) lesions correlate with the severity of first-ever hemispheric ischemic stroke. METHODS: Carotid duplex was used to evaluate carotid arteries. The National Institutes of Health Stroke Scale was used to describe the severity of the stroke and was stratified as follows: 1-6 = mild, 7-15 = moderate, > 15 = severe. Duplex findings were categorized according to velocity criteria into < 50% stenosis if ICA peak systolic velocity (PSV) (cm/s) < 140 and > 50% stenosis if ICA PSV > 140 or ratio of ICA and common carotid artery in PSV > 2. No detectable flow at ICA was considered occlusion. Stroke subtype was classified according to TOAST criteria. RESULTS: Two hundred nineteen consecutive patients were enrolled, including 127 with mild, 65 with moderate, and 27 with severe stroke. The prevalence of ICA stenosis > 50% in each group was 3.6%, 1.4%, 0.9%, respectively. Two patients in the severe group had total ICA occlusion. The overall prevalence of significant ICA lesions was 6.8%. CONCLUSIONS: There is no positive correlation of stroke severity with the severity of duplex findings, which may be due to low prevalence of significant ICA lesions or other stroke mechanisms. Most of the patients had mild stroke, and the majority had ICA stenosis < 50%. Small-vessel occlusion tended to have mild severity of stroke. Intracranial artery lesions or other factors causing stroke in Taiwanese should be investigated. Given the low incidence of significant extracranial carotid disease in symptomatic Taiwanese stroke patients, routine screening of symptomatic Taiwanese for extracranial carotid artery disease does not provide enough information to determine stroke mechanism, and transcranial Doppler should be added to the screening tests.

The transcranial Doppler standardization project. Phase 1 results. The TCD Study Group, American Society of Neuroimaging.

A project to pursue standardization of the performance and interpretation of transcranial Doppler studies was designed. Phase I consisted of a national survey of the current practice of transcranial Doppler in the United States. From 200 ultrasound laboratories surveyed about the use of transcranial Doppler, 60 completed questionnaires were returned. The results show that further standardization of transcranial Doppler performance and interpretation is necessary, and provide the foundation for phases II and III of the project.

Transcranial Doppler validation pilot study.

The use of transcranial Doppler sonography (TCD) for the evaluation of patients with ischemic cerebrovascular disease remains controversial. This study was organized to gather preliminary data regarding the sensitivity and specificity of TCD when compared to cerebral angiography in detecting stenosing lesions and collateral flow patterns of the anterior cerebral circulation. Forty-two patients from six medical centers were prospectively enrolled. Each received cerebral angiography and TCD testing within 24 hours of each other. Based on TCD criteria established a priori, the results were first analyzed by a blinded investigator and then by computer. Computerized analyses were then repeated with modified criteria. Collateral flow through the anterior communicating and ophthalmic arteries was detected with sensitivities of 62% and 100%, and specificities of 98% and 92%, respectively. Internal carotid artery proximal and distal severe ( greater than 70%) stenoses were detected with sensitivities of 79% and 100% and specificities of 88% and 97%. Middle and anterior cerebral artery stenoses and middle cerebral artery occlusion were detected with specificities exceeding 98%; however, the data were insufficient to determine sensitivity. Computerized analyses did not permit improvement of sensitivity and specificity of the baseline criteria. The selected TCD criteria are highly specific in detecting intracranial stenoses and collateral flow patterns of the anterior circulation. The criteria have limited but acceptable sensitivity and specificity in detecting internal carotid artery origin severe stenoses, and are highly sensitive in detecting ophthalmic artery retrograde flow. A study with a larger sample is necessary to provide definitive guidelines for diagnosis.

Validity and reliability of an ultrasound device for detecting carotid emboli.

Cardioembolic mechanisms cause 15 to 20% of all strokes and may account for the high incidence of neurological dysfunction associated with cardiopulmonary bypass. Accurate identification of high-risk subjects and/or surgical techniques would allow more effective testing and implementation of preventive or therapeutic measures to help reduce morbidity and mortality. This article reports on validity and reliability testing of a new emboli detection device that allows continuous monitoring of the common carotid artery. The instrument appears to be capable of detecting accurately particles of 193 mu or less in diameter and is highly reliable both within and between observers. In preliminary clinical use, the instrument also detected embolic signals in all patients monitored during cardiopulmonary bypass, while none were detected in healthy control subjects. These results establish the validity and reliability of a new emboli detection device and suggest its potential application to emboli detection monitoring during cardiopulmonary bypass.

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.