Cerebral hemodynamic alterations in patients with Covid-19

Background/aim: Coronavirus 2019 disease (Covid-19) was first seen in December 2019 and afterwards it became pandemic. Several systemic involvements have been reported in Covid-19 patients. In this study, it was aimed to investigate the cerebrovascular hemodynamics in patients with Covid-19. Materials and methods: The sample of this study included 20 patients hospitalized in our clinic diagnosed with Covid-19 via PCR modality and 20 healthy volunteers of similar age and sex. Bilateral middle cerebral arteries were investigated with transcranial Doppler ultrasonography. Basal cerebral blood flow velocities and vasomotor reactivity rates were determined and statistically compared. Results: When patient and control groups were compared, the mean blood flow velocity was found to be higher in Covid-19 patients than in the healthy volunteers and it was statistically significant (P = 0.00). The mean vasomotor reactivity rates values were found to be lower in the Covid-19 group than the healthy group and was also statistically significant (P = 0.00). Conclusion: An increase in basal cerebral blood velocity and a decrease in vasomotor reactivity rates in patients with Covid-19 can be considered as an indicator of dysfunction of cerebral hemodynamics in the central nervous system and this can be evaluated as a result of endothelial dysfunction.

Is cerebral vasomotor reactivity impaired in Parkinson disease?

PURPOSE: The ability of a blood vessel to change diameter in response to a change in carbon dioxide concentration is often referred to as vasomotor reactivity. This study aimed to determine whether vasomotor reactivity is impaired in patients with idiopathic Parkinson's Disease in comparison to healthy controls. METHODS: Transcranial Doppler was used to measure cerebral blood flow velocity in the middle cerebral arteries at baseline and under hypocapnic conditions in 40 patients with idiopathic Parkinson's disease and 50 healthy controls. RESULTS/CONCLUSIONS: Vasomotor reactivity, assessed under hypocapnic conditions, is not impaired in patients with idiopathic Parkinson's Disease in comparison to healthy controls.

Detecting gas-induced vasomotor changes via blood oxygenation level-dependent contrast in healthy breast parenchyma and breast carcinoma.

PURPOSE: To evaluate blood oxygenation level-dependent (BOLD) contrast changes in healthy breast parenchyma and breast carcinoma during administration of vasoactive gas stimuli. MATERIALS AND METHODS: Magnetic resonance imaging (MRI) was performed at 3T in 19 healthy premenopausal female volunteers using a single-shot fast spin echo sequence to acquire dynamic T2 -weighted images. 2% (n = 9) and 5% (n = 10) carbogen gas mixtures were interleaved with either medical air or oxygen in 2-minute blocks, for four complete cycles. A 12-minute medical air breathing period was used to determine background physiological modulation. Pixel-wise correlation analysis was applied to evaluate response to the stimuli in breast parenchyma and these results were compared to the all-air control. The relative BOLD effect size was compared between two groups of volunteers scanned in different phases of the menstrual cycle. The optimal stimulus design was evaluated in five breast cancer patients. RESULTS: Of the four stimulus combinations tested, oxygen vs. 5% carbogen produced a response that was significantly stronger (P < 0.05) than air-only breathing in volunteers. Subjects imaged during the follicular phase of their cycle when estrogen levels typically peak exhibited a significantly smaller BOLD response (P = 0.01). Results in malignant tissue were variable, with three out of five lesions exhibiting a diminished response to the gas stimulus. CONCLUSION: Oxygen vs. 5% carbogen is the most robust stimulus for inducing BOLD contrast, consistent with the opposing vasomotor effects of these two gases. Measurements may be confounded by background physiological fluctuations and menstrual cycle changes. J. Magn. Reson. Imaging 2016;44:335-345.

Late gadolinium enhancement on cardiac magnetic resonance predicts coronary vasomotor abnormality and myocardial lactate production in patients with chronic heart failure.

Myocardial fibrosis and microvascular dysfunction are key determinants of outcome in heart failure (HF); we examined their relationship in patients with HF. Our study included 61 consecutive patients with HF but without coronary stenosis. All underwent gadolinium-enhanced cardiac magnetic resonance to evaluate late gadolinium enhancement (LGE) and an acetylcholine (ACh) provocation test to evaluate microvascular dysfunction. During the ACh provocation test, we sampled blood simultaneously from the coronary sinus and aortic root to compare lactate concentrations. We quantified coronary blood flow volume using an intracoronary Doppler-tipped guidewire. We detected LGE in 34 patients (LGE-positive); 27 were LGE-negative. Coronary blood flow volume increased significantly after the ACh provocation test only in LGE-negative patients (before vs. after ACh, 47.5 ± 36.8 vs. 69.2 ± 48.0 ml/min, respectively; p = 0.004). The myocardial lactate extraction ratio (LER) significantly decreased after the ACh test in both groups (LGE-negative, p = 0.001; LGE-positive, p < 0.001), significantly more so in the LGE-positive group (p = 0.017). Multivariate logistic regression analysis showed that a post-ACh LER < 0 (indicating myocardial lactate production) was a significant predictor of LGE-positivity (odds ratio 4.54; 95 % confidence interval 1.38-14.93; p = 0.013). In the LGE-positive group, an LGE volume greater than the median significantly predicted a post-ACh LER of <0 (p = 0.042; odds ratio 6.02; 95 % confidence interval 1.07-33.86). ACh-provoked coronary vasomotor abnormality is closely correlated with myocardial fibrosis in patients with HF but without organic coronary stenosis. Coronary vasomotor abnormalities in fibrotic myocardium may worsen HF.

Cerebral vasomotor reactivity and risk of mortality: the Rotterdam Study.

BACKGROUND AND PURPOSE: Accumulating vascular pathology in cerebral arteries leads to impaired cerebral vasomotor reactivity. In turn, impaired cerebral vasomotor reactivity is a risk factor for stroke in clinical populations. It remains unclear whether impaired cerebral vasomotor reactivity also reflects more systemic vascular damage. We investigated whether cerebral vasomotor reactivity is associated with the risk of mortality, focusing particularly on cardiovascular mortality independent from stroke. METHODS: Between 1997 and 1999, 1695 participants from the Rotterdam Study underwent cerebral vasomotor reactivity measurements using transcranial Doppler. Follow-up was complete until January 1, 2011. We assessed the associations between cerebral vasomotor reactivity and mortality using Cox proportional hazards models, adjusting for age, sex, and blood pressure changes and subsequently for cardiovascular risk factors. We additionally censored for incident stroke. RESULTS: During 17 004 person-years, 557 participants died, of whom 181 due to a cardiovascular cause. In the fully adjusted model, the hazard ratio per SD decrease in vasomotor reactivity was 1.10 (95% confidence interval [CI], 1.01-1.19) for all-cause mortality, 1.09 (95% CI, 0.94-1.26) for cardiovascular mortality, and 1.10 (95% CI, 0.99-1.21) for noncardiovascular mortality. These associations remained unchanged after censoring for incident stroke. CONCLUSIONS: We found that lower cerebral vasomotor reactivity is associated with an increased risk of death. Incident stroke does not affect this association, suggesting that a lower cerebral vasomotor reactivity reflects a generally impaired vascular system.

Assessment of coronary vasoreactivity by multidetector computed tomography: feasibility study with rubidium-82 cardiac positron emission tomography.

BACKGROUND: Positron emission tomography (PET) during the cold pressor test (CPT) has been used to assess endothelium-dependent coronary vasoreactivity, a surrogate marker of cardiovascular events. However, its use remains limited by cardiac PET availability. As multidetector computed tomography (MDCT) is more widely available, we aimed to develop a measurement of endothelium-dependent coronary vasoreactivity with MDCT and similar radiation burden as with PET. METHODS AND RESULTS: A study group of 18 participants without known cardiovascular risk factor (9F/9M; age 60±6 years) underwent cardiac PET with (82)Rb and unenhanced ECG-gated MDCT within 4h, each time at rest and during CPT. The relation between absolute myocardial blood flow (MBF) response to CPT by PET (ml·min(-1)·g(1)) and relative changes in MDCT-measured coronary artery surface were assessed using linear regression analysis and Spearman's correlation. MDCT and PET/CT were analyzed in all participants. Hemodynamic conditions during CPT at MDCT and PET were similar (P>0.3). Relative changes in coronary artery surface because of CPT (2.0-21.2%) correlated to changes in MBF (-0.10-0.52ml·min(-1)·g(1)) (ρ=0.68, P=0.02). Effective dose was 1.3±0.2mSv for MDCT and 3.1mSv for PET/CT. CONCLUSIONS: Assessment of endothelium-dependent coronary vasoreactivity using MDCT CPT appears feasible. Because of its wider availability, shorter examination time and similar radiation burden, MDCT could be attractive in clinical research for coronary status assessment.

Vasomotor reactivity as a predictor for syncope in patients with orthostatism.

OBJECTIVES: Syncope in patients with orthostatic hypotension (OH) may be the result of impaired cerebral autoregulation. Cerebral autoregulation status can be determined by assessing cerebral vasomotor reactivity (VMR). We assessed and compared VMR in patients with OH with and without syncope. MATERIAL AND METHODS: Twenty-nine patients with OH underwent transcranial Doppler (TCD) and the Diamox test (1 g acetazolamide IV) for assessing VMR during elaboration of their OH syndrome. The percent difference between cerebral blood flow velocities (BFV) in the middle cerebral (MCA) and vertebral (VA) arteries before and after acetazolamide was defined as VMR%. We considered increases of BFV of ≥ 40% as being indicative of good VMR and classified our study patients as having good or impaired VMRs accordingly. RESULTS: Mean VMR% values of the MCA and VA in patients with OH with syncope (n = 12) were significantly lower as compared with patients with OH without syncope (n = 17): 25.2 ± 20.5% and 42.5 ± 18.6%; 20.9 ± 15.5% and 40.8 ± 28.5%, respectively (P < 0.05). CONCLUSIONS: Among patients with OH, we found an association between the presence of syncope and impaired VMR. Assessment of VMR among patients with OH may predict those who are at higher risk to faint and fall and to support more aggressive intervention.

Effects of intermittent theta burst stimulation on cerebral blood flow and cerebral vasomotor reactivity.

OBJECTIVES: To determine whether intermittent theta burst stimulation influences cerebral hemodynamics, we investigated changes induced by intermittent theta burst stimulation on the middle cerebral artery cerebral blood flow velocity and vasomotor reactivity to carbon dioxide (CO(2)) in healthy participants. The middle cerebral artery flow velocity and vasomotor reactivity were monitored by continuous transcranial Doppler sonography. Changes in cortical excitability were tested by transcranial magnetic stimulation. METHODS: In 11 healthy participants, before and immediately after delivering intermittent theta burst stimulation, we tested cortical excitability measured by the resting motor threshold and motor evoked potential amplitude over the stimulated hemisphere and vasomotor reactivity to CO(2) bilaterally. The blood flow velocity was monitored in both middle cerebral arteries throughout the experimental session. In a separate session, we tested the effects of sham stimulation under the same experimental conditions. RESULTS: Whereas the resting motor threshold remained unchanged before and after stimulation, motor evoked potential amplitudes increased significantly (P = .04). During and after stimulation, middle cerebral artery blood flow velocities also remained bilaterally unchanged, whereas vasomotor reactivity to CO(2) increased bilaterally (P = .04). The sham stimulation left all variables unchanged. CONCLUSIONS: The expected intermittent theta burst stimulation-induced changes in cortical excitability were not accompanied by changes in cerebral blood flow velocities; however, the bilateral increased vasomotor reactivity suggests that intermittent theta burst stimulation influences the cerebral microcirculation, possibly involving subcortical structures. These findings provide useful information on hemodynamic phenomena accompanying intermittent theta burst stimulation, which should be considered in research aimed at developing this noninvasive, low-intensity stimulation technique for safe therapeutic applications.

Color Doppler ultrasound for evaluation of vasomotor activity in patients with carpal tunnel syndrome.

BACKGROUND: Patients with carpal tunnel syndrome (CTS) have a variety of vasomotor symptoms. Here, we aimed to study the vasomotor activity of the radialis indicis (RI) artery (median nerve territory) and the radial palmar digital (RPD) artery of the little finger (ulnar nerve territory) before and after sympathetic stimulation in CTS patients using color Doppler ultrasound. METHODS: We performed a cross-sectional study of 46 consecutive CTS patients plus 36 healthy controls. All patients underwent electromyography studies and were classified into mild and moderate/severe groups according to electrodiagnostic findings. Color Doppler examination of the RI artery and the RPD artery of the little finger were performed with the participants in a relaxed sitting position and after a deep breath followed by a cough (sympathetic stimulation). The pulsatility index (PI) was recorded at the point of maximal change in waveform, before and after this stimulus. RESULTS: The PI of RI artery was significantly lower (p < 0.01) in CTS patients than healthy controls, both before and after stimulation. The changes in PI of RI artery after stimulation were significantly lower in CTS patients than healthy controls (1.18 ± 0.37 vs. 5.41 ± 0.87; p < 0.001). The same pattern was seen for PI of RI artery when comparing patients with mild vs. moderate/severe CTS. No difference was found in PI of RPD artery of the 5th finger between patients vs. controls and between patients with mild vs. moderate/severe CTS, both before and after stimulation. CONCLUSIONS: We showed that color Doppler ultrasound can readily determine impaired vasomotor activity in CTS patients.

Pulsed wave Doppler ultrasound is useful to assess vasomotor response in patients with multiple system atrophy and well correlated with tilt table study.

The study aim was to assess sympathetic vasomotor response (SVR) by using pulsed wave Doppler (PWD) ultrasound in patients with multiple system atrophy (MSA) and correlate with the tilt table study. We recruited 18 male patients and 10 healthy men as controls. The SVR of the radial artery was evaluated by PWD, using inspiratory cough as a provocative maneuver. The response to head-up tilt was studied by a tilt table with simultaneous heart rate and blood pressure recording. The hemodynamic variables were compared between groups, and were examined by correlation analysis. Regarding SVR, MSA patients exhibited a prolonged latency and less heart rate acceleration following inspiratory cough. Compared with the tilt table test, the elevation of heart rate upon SVR was positively correlated to the increase of heart rate after head-up tilt. The correlation analysis indicated that the magnitude of blood pressure drop from supine to upright was positively associated with the SVR latency but negatively correlated with the heart rate changes upon SVR. The present study demonstrated that blunted heart rate response might explain MSA's vulnerability to postural challenge. PWD may be used to predict cardiovascular response to orthostatic stress upon head-up tilt in MSA patients.

Principles and pitfalls in coronary vasomotor function testing.

BACKGROUND: Coronary vasomotor dysfunction can be diagnosed in a large proportion of patients with angina in the presence of non-obstructive coronary artery disease (ANOCA) using comprehensive protocols for coronary vasomotor function testing (CFT). Although consensus on diagnostic criteria for endotypes of coronary vasomotor dysfunction has been published, consensus on a standardised study testing protocol is lacking. AIMS: In this review we provide an overview of the variations in CFT used and discuss the practical principles and pitfalls of CFT. METHODS: For the purposes of this review, we assessed study protocols that evaluate coronary vasomotor response as reported in the literature. We compared these protocols regarding a number of procedural aspects and chose six examples to highlight the differences and uniqueness. RESULTS: Currently, numerous protocols co-exist and vary in vascular domains tested, the manner in which to test these domains (e.g., preprocedural discontinuation of medication, provocative agent, solution, infusion time, and target artery) and techniques used for measurements (e.g., Doppler vs thermodilution technique). CONCLUSIONS: This lack of consensus on a uniform functional testing protocol hampers both a broader clinical acceptance of the concepts of coronary vasomotor dysfunction, and the widespread adoption of such testing protocols in current clinical practice. Furthermore, the endotype of coronary vasomotor dysfunction might differ among the few specialised centres that perform CFT as a result of the use of different protocols.

Pulsed wave Doppler ultrasonography for the assessment of peripheral vasomotor response in an elderly population.

PURPOSE: To assess sympathetic vasomotor activity and its changes with age, using pulsed wave Doppler ultrasound. METHODS: We recruited 20 young adults (24-37 years old) and 20 older individuals (60-81 years old). Pulsed wave Doppler ultrasound was applied over the right radial artery to measure blood flow at rest and after a voluntary inspiratory cough eliciting sympathetic activation. The maximal (Vmax), minimal (Vmin), time-averaged (TAMaxV) blood flow velocity, and the pulsatility index (PI) were calculated and compared between groups. RESULTS: At rest, PI was similar in both groups but Vmax and TAMaxV were higher in the older group (p < 0.05). Vmax, Vmin, and TAMaxV decreased, and PI increased after inspiratory cough in both groups (p ≤ 0.001), but this increase was lower in the older group (p < 0.001). TAMaxV after coughing was higher in the older group (p < 0.05). Heart rate did not differ significantly within or between groups. CONCLUSIONS: The older group exhibited reduced vasomotor reactivity of the radial artery after sympathetic stimulus. Peripheral vasomotor response should be interpreted with caution in elderly populations.

Asymmetric dimethylarginine predicts impaired epicardial coronary vasomotion in patients with angina in the absence of obstructive coronary artery disease.

BACKGROUND: Impaired epicardial coronary vasomotion is a potential mechanism of angina and a predictor of adverse cardiovascular outcomes in patients without angiographic evidence of obstructive coronary artery disease (CAD). We sought to evaluate the association of asymmetric dimethylarginine (ADMA)-a marker of nitric oxide-mediated vascular dysfunction-with epicardial coronary vasomotor dysfunction in this select population. METHODS: Invasive testing for epicardial vasomotor dysfunction was performed using intracoronary acetylcholine in the left anterior descending coronary artery. Impaired vasomotor response was defined as a luminal constriction of >20% on quantitative coronary angiography. Plasma ADMA levels were measured using high performance liquid chromatography. A robust multivariate linear mixed-effect model approach and Akaike information criterion were used to determine predictors of vasomotor dysfunction. RESULTS: In 191 patients with angina in the absence of obstructive CAD, abnormal epicardial vasomotion was observed in 137 (71.7%) patients. Median ADMA rose as the extent of impairment progressed: none (0.48 [0.44-0.59] µM), any (0.51 [0.46-0.60] µM, p = 0.12), focal (0.54 [0.49,0.61] µM, p = 0.17), and diffuse (0.55 [0.49,0.63] µM, p = 0.02). In unadjusted analysis, ADMA was highly predictive of vasomotor dysfunction (χ2=15.1, p = 0.002). Notably, ADMA remained a significant predictor even after adjusting for other factors in the best fit model (χ2=10.0, p = 0.02). CONCLUSIONS: ADMA is an independent predictor of epicardial coronary vasomotor dysfunction in patients with angina in the absence of obstructive CAD. These data support a very early mechanistic role of ADMA in the continuum of atherosclerotic heart disease.

Persistent Dysfunction of Coronary Endothelial Vasomotor Responses is Related to Atheroma Plaque Progression in the Infarct-Related Coronary Artery of AMI Survivors.

AIM: Although coronary endothelial vasomotor dysfunction predicts future coronary events, there are few human studies showing the relationship between endothelial vasomotor dysfunction and atheroma plaque progression in the same coronary artery. This study examined whether endothelial vasomotor dysfunction is related to atheroma plaque progression in the infarct-related coronary artery of ST-segment elevation myocardial infarction (STEMI) survivors using serial assessment of coronary plaque size with intravascular ultrasound (IVUS) and coronary vasomotor responses to acetylcholine (ACh). METHODS: This study included 50 patients with a first acute STEMI due to occlusion of the left anterior descending coronary artery (LAD) and successful reperfusion therapy with percutaneous coronary intervention (PCI). IVUS and vasomotor response to ACh in the LAD were measured within two weeks of acute myocardial infarction (AMI) (1st test) and repeated six months (2nd test) after AMI under optimal anti-atherosclerotic therapies. RESULTS: Percent atheroma volume (PAV) and total atheroma volume (TAV) in the LAD progressed over six months of follow-up in 18 and 14 patients, respectively. PAV and TAV progression was significantly associated with persistent impairment of epicardial coronary artery dilation and coronary blood flow increase in response to ACh at both the 1st and 2nd tests. PAV and TAV progression had no significant association with traditional risk factors, PCI-related variables, medications, and the coronary vasomotor responses to sodium nitroprusside, an endothelium-independent vasodilator. CONCLUSIONS: Persistent impairment of endothelial vasomotor function in the conduit arterial segment and the resistance arteriole was related to atheromatous plaque progression in the infarct-related coronary arteries of STEMI survivors.

Impaired hyperaemic and rhythmic vasomotor response in type 1 diabetes mellitus patients: a predictor of early peripheral vascular disease.

OBJECTIVES: The smooth muscle of distal vascular networks exhibits periodical contraction and relaxation known as rhythmical vasomotion. The nature of microvascular vasomotion has been shown to correlate with severity of peripheral vascular disease. We present basal and post-ischaemic hyperaemic laser doppler flowmetry vasomotion in control and type 1 adult diabetic patients. DESIGN: Prospective case control study. METHODS: Laser Doppler flowmetry was used to measure vasomotion and hyperaemic responses in age and body mass index matched male subjects (25 type 1 Diabetes Mellitus and 13 controls), all with ankle/brachial pressure index (ABPI) >1.0 but <1.2. RESULTS: The frequency of resting vasomotion was raised in diabetics compared to controls 8 (5-9)min(-1) vs. 5 (4-6)min(-1) (median (range); p<0.0001). The post ischaemic hyperaemia response was significantly higher in the diabetic group compared to the controls 11 (7-12)min(-1) vs. 6 (5-7)min(-1) (median (range); p<0.05). Post ischaemic hyperaemic flux (expressed as percent increase from resting) was significantly lower in the diabetic group compared to controls (234+/-62 vs. 453+/-155%, p<0.01). The time to achieve peak post ischaemic response was also significantly increased in the diabetic group compared to control: 21.4+/-0.4 vs. 12.8+/-5.4sec (mean+/-SD, p<0.05). CONCLUSIONS: Vasomotion frequency and its change during hyperaemic insult is significantly different in Type 1 Diabetes Mellitus subjects compared to controls. The results are similar to patients with macrovascular atherosclerosis. Long term studies of these groups of patients will be required to determine the significance of these findings and whether these changes could be used as a non invasive screening test to predict peripheral early vascular disease in type 1 diabetic patients.

Cerebral vasomotor reactivity is reduced in patients with erectile dysfunction.

BACKGROUND: Erectile dysfunction (ED) is not only evidence of diffuse atherosclerosis but also an index of early endothelial damage. We investigated cerebrovascular reactivity, expression of early arterial damage, in patients with isolated ED (ED+) and controls (ED-). MATERIALS AND METHODS: Fifteen ED+ and 15 ED- subjects, matched for age (ED+: 58+/-6, ED-: 59 +/- 4 years) and vascular risk factors, were submitted to carotid duplex ultrasound and transcranial Doppler. Cerebrovascular reactivity was assessed on both middle cerebral arteries simultaneously calculating (a) the total vasomotor range (VMR) measured after breath holding and hyperventilation and (b) the rate of change (VMR/CO(2)) after breath holding. RESULTS: Carotid Duplex scanning showed a light carotid stenosis only in 3 (2 in the ED+ and 1 in the ED- group). No differences were observed in intima-media thickness between ED+ and ED-. Slightly slower mean middle cerebral artery flow velocities were observed in ED+ with respect to ED-. ED+ patients showed a reduced VMR (p < 0.001) and a slower VMR/CO(2) rate of change (p < 0.001) compared to ED-. CONCLUSIONS: The reduced reactivity in patients with isolated ED may represent a marker of early cerebral vasomotor dysfunction due to subclinical endothelial damage.

Regional cerebral blood flow and cerebrovascular reactivity during chronic stage of stroke-like episodes in MELAS -- implication of neurovascular cellular mechanism.

BACKGROUND: Ischemic vascular hypothesis as a causative role in the pathogenesis of stroke-like episodes in MELAS remains to be debated. METHODS: This study consisted of two parts. Part 1 is a clinicoradiological study during acute stage of 18 consecutive stroke-like episodes in six patients with MELAS. Part 2 is a SPECT study to assess the regional cerebrovascular reactivity (rCVR) to acetazolamide during chronic stage in five patients with MELAS. RESULTS: Headache and epileptic seizure were the most common presenting symptoms. Unique features of acute stroke-like lesions included progressive spread of cortical lesions with vasogenic edema, focal periodic epileptiform discharges, focal hyperperfusion, and cortical laminar necrosis during subacute stage. During chronic stage, SPECT showed hypoperfusion in non-affected occipital cortex in three patients as well as in previously affected regions in four. The rCVR was preserved in three patients, focally impaired in one, and extensively impaired in one, but relatively preserved in the occipital cortex in all patients. CONCLUSIONS: Stroke-like episodes could be non-ischemic neurovascular events initiated by neuronal hyperexcitability. Once neuronal hyperexcitability develops in a focal brain region, epileptic activities depolarize adjacent neurons, leading to a propagation of epileptic activities into the surrounding cortex, and resulting in energy imbalance. The mechanisms for neuronal hyperexcitability remain to be elucidated.

Larger perfusion defects with exercise compared with dipyridamole SPECT (exercise-dipyridamole mismatch) may reflect differences in epicardial and microvascular coronary dysfunction: when the stressor matters.

BACKGROUND: Previous studies have reported larger myocardial perfusion defects with exercise as compared with dipyridamole. The aim of this study was to assess the hypothesis that this mismatch may reflect differences in epicardial and microvascular coronary vasomotor function. METHODS AND RESULTS: The response to intracoronary acetylcholine, nitroglycerin, and adenosine was studied in 36 patients with suspected angina and normal or near-normal coronary angiography findings who underwent both exercise and dipyridamole perfusion imaging. Of the patients, 27 (75%) had reversible defects with exercise (group I) and 9 had normal scans or nonreversible defects (group II). Repeated imaging with dipyridamole showed significant improvement or disappearance of perfusion defects in group I patients. The mean summed difference score (SDS) decreased from 5.52 +/- 3.19 with exercise to 1.11 +/- 1.60 with dipyridamole (P = .0001) in group I and did not change in group II. An abnormal epicardial response to acetylcholine, reflecting endothelial dysfunction, occurred in 93% of group I patients compared with only 33% of group II patients (chi(2) = 9.46, P = .002) and was significantly related to exercise SDS (r = 0.49, P = .002) but not to dipyridamole SDS. By contrast, most patients showed normal epicardial and microvascular responses to the mainly non-endothelium-dependent vasodilators nitroglycerin and adenosine with no differences in coronary flow reserve between groups (2.91 +/- 0.72 vs 2.98 +/- 0.52, P = .79). CONCLUSIONS: Exercise-dipyridamole perfusion mismatch may reflect differences in epicardial endothelial and microvascular dysfunction.

Diagnostic value of PET-measured heterogeneity in myocardial blood flows during cold pressor testing for the identification of coronary vasomotor dysfunction.

BACKGROUND: We aimed to evaluate the diagnostic value of a positron emission tomography (PET)-measured heterogeneity in longitudinal myocardial blood flow (MBF) during cold pressor testing (CPT) and global MBF response to CPT from rest (DeltaMBF) for identification of coronary vasomotor dysfunction. METHODS AND RESULTS: In 35 patients CPT-induced alterations in epicardial luminal area were determined with quantitative angiography as the reference. MBF was assessed over the whole left ventricle as global MBF and regionally in the mid and mid-distal myocardium as MBF difference or MBF heterogeneity with nitrogen-13 ammonia and PET. The sensitivity and specificity of a longitudinal MBF difference during CPT in the identification of epicardial vasomotor dysfunction were significantly higher than the global DeltaMBF to CPT (88% vs 79% and 82% vs 64%, respectively; P < .05). Combining both parameters resulted in an optimal sensitivity of 100% at the expense of an intermediate specificity of 73%. The diagnostic accuracy was higher for the combined analysis than that for the MBF difference alone and global DeltaMBF alone (91% vs 86% and 74%, respectively; P < .05). CONCLUSIONS: The combined evaluation of a CPT-induced heterogeneity in longitudinal MBF and the change in global MBF from rest may emerge as a new promising analytic approach to further optimize the identification and characterization of coronary vasomotor dysfunction.

Effects of neuropeptide Y on coronary artery vasomotion in patients with microvascular angina.

BACKGROUND: Patients with microvascular angina (exertional angina, positive exercise tests and normal coronary arteriograms) usually have a reduced coronary blood flow reserve. Neuropeptide Y (NPY) is a potent endogenous vasoconstrictor involved in modulation of coronary vasomotor tone and may play a role in microvascular angina. METHODS: We compared the effects of NPY (0.2-1.0pmol/kg, intracoronary) on the vasomotor response of proximal and distal segments of the coronary arteries in 7 patients with microvascular angina, 9 with chronic stable angina, and 9 control individuals. The coronary response to the administration of ergonovine was also assessed in 9 other patients with microvascular angina. Computerized coronary artery diameter measurements were carried out before (baseline) and after the administration of the vasoactive agents. RESULTS: Mean baseline coronary lumen diameters were similar in control, microvascular angina, and coronary artery disease patients. NPY constricted proximal coronary segments by 8±2%, 5±2% and 6±3% and distal segments by 14±2%, 11±2% and 10±2% in control, microvascular angina, and coronary artery disease patients, respectively (p=NS between groups). In patients with microvascular angina, ergonovine constricted proximal coronary segments by 7±1.5% and distal segments by 12.5±3% (p=NS vs. NPY). During NPY administration four microvascular angina patients developed chest pain, ST segment depression, and a marked lengthening of the contrast medium run off, in the absence of epicardial coronary artery spasm. Control individuals and coronary artery disease patients did not experience chest pain, ST segment shifts, or lengthening of the run off during NPY administration. Ergonovine administration caused chest pain and lengthening of the contrast run-off, in the absence of epicardial coronary artery spasm, in one microvascular angina patient. CONCLUSIONS: Exogenous NPY causes mild epicardial coronary artery constriction which is similar in patients with non-cardiac chest pain, microvascular angina and coronary artery disease. Myocardial ischemia and marked lengthening of the contrast run off in response to NPY occurred in microvascular angina patients but not in control or coronary artery disease patients. An abnormal constrictor response to NPY at the microcirculation level could be the mechanism underlying the ischemic manifestations observed in patients with microvascular angina. CONDENSED ABSTRACT (TABLE OF CONTENTS): The vasomotor response of proximal and distal coronary artery segments was studied in twenty five patients: 7 microvascular angina, 9 chronic stable angina, and 9 control subjects. Computerized measurements of coronary diameters were carried out before and after the intracoronary administration of neuropeptide Y (NPY) and ergonovine. Constriction of epicardial arteries in response to NPY was mild and not significantly different in control, microvascular angina and coronary artery disease patients. Ergonovine-induced epicardial coronary artery constriction was similar to that of NPY. However, NPY caused transient myocardial ischemia in patients with microvascular angina (probably through constriction of the small intramyocardial vessels), but not in control subjects or coronary artery disease patients.