The relationship between MTHFR genotype, serum homocysteine and folate levels.
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Alleles↗
Biomedical subjects
H S Markus
Publications and source records attributed to H S Markus.
Use of a decibel threshold in detecting Doppler embolic signals.
BACKGROUND AND PURPOSE: To improve reproducibility and reliability in the identification of embolic signals detected with the use of Doppler ultrasound, many studies have used an intensity threshold. However, variable thresholds between 3 and 12 dB have been used, and often the method of measurement of intensity is not stated. Potentially different methods of measurement could result in different intensity measurements for the same embolic signal. We determined the effect of these differences using commercial transcranial Doppler systems. METHODS: We analyzed 81 embolic signals recorded from the middle cerebral arteries of patients with carotid artery disease using three different methods of measuring intensity that had been previously used in research studies. In method 1 individual time frames of the frequency spectra were analyzed, in method 2 a color-coded intensity scale was used, and in method 3 automated software was used. RESULTS: There was a highly significant correlation between measurements made by the different techniques (method 1 versus method 2: r = .68, P < .0001; method 1 versus method 3: r = .66, P < .0001; method 2 versus method 3: r = .70, P < .0001). However, the absolute values of intensity for the same embolic signals varied markedly for the different methods. For example, a 4-dB threshold according to method 1 was equivalent to an approximately 7-dB threshold measured by method 2. These differences had major effects on the proportion of embolic signals detected with the use of the same decibel threshold but with intensity measured in the different ways. For example, using a threshold of 7 dB would result in only 4.9% of signals being missed by method 2 but 42.2% and 51.4% being missed by methods 1 and 3, respectively. CONCLUSIONS: Our results demonstrate that the intensities of the same embolic signals, recorded with the same parameters, are markedly different when analyzed in the different ways used in previous studies. This has important implications when a decibel threshold is used and emphasizes that criteria developed by one investigator on one machine cannot be used by another investigator without initial reevaluation. This could account for some of the differences in frequencies of embolic signals reported in previous clinical studies.
Differential Threshold↗
Intercenter agreement in reading Doppler embolic signals. A multicenter international study.
BACKGROUND AND PURPOSE: Different frequencies of asymptomatic Doppler embolic signals have been reported in studies. There has been concern that different criteria for identification may account for some of this variation. A previous reproducibility study between two centers found good agreement, but no studies among large numbers of centers have been performed. We performed an international reproducibility study among nine centers, each of which had published recent studies of embolic signal detection in peer-reviewed journals. METHODS: Each center performed blinded analysis of a taped audio Doppler signal composed of transcranial Doppler middle cerebral artery recordings from 6 patients with symptomatic carotid artery stenosis. The exact time of any embolic signal was recorded. Six centers also measured the intensity increase of any embolic signals detected. Interobserver agreement was determined by a method based on the proportion of specific agreement. RESULTS: Seven centers reported between 39 and 55 signals, but one center reported 142 embolic signals. The probability of agreement between observers was .678, which rose to .791 when the data from the highest reporting center were excluded. Introducing a decibel threshold resulted in a significant increase in the probability of agreement; a decibel threshold of > 7 dB resulted in a probability of agreement of .902. Intensity measurements made by different centers were usually highly correlated, but this was not always the case, and 3 of the 15 correlations were not significant. The absolute values of the intensities measured varied between centers by as much as 40%. CONCLUSIONS: Although most centers report similar numbers of embolic signals, some use less specific criteria and report more events. The use of a decibel threshold improves reproducibility. However, intensity thresholds developed by one center cannot be directly transferred without validation to another center; differing methods of measurement are being used, and this results in different intensity values for the same embolic signals, even when the same equipment is used.
Carotid Stenosis↗
Impaired dynamic cerebral autoregulation in carotid artery stenosis.
BACKGROUND AND PURPOSE: If it could be determined whether cerebral blood flow can be maintained (autoregulated) during transient falls in arterial blood pressure, we might be able to identify patients with carotid stenosis who are at risk of stroke. However, conventional methods of determining autoregulation in such patients are invasive and/or expensive. METHODS: We used a new noninvasive method to estimate dynamic cerebral autoregulation in 27 patients with carotid stenosis and 21 age-matched normal controls. After a stepwise fall in arterial blood pressure, we determined the rate of rise of middle cerebral artery blood flow velocity compared with that of arterial blood pressure. We compared the method with a conventional method of determining cerebral hemodynamics, CO2 reactivity. RESULTS: Autoregulatory index (ARI) was significantly reduced in middle cerebral arteries ipsilateral to a stenosed/ occluded carotid artery: mean +/- SD 3.3 +/- 2.2 compared with normal controls (6.3 +/- 1.1; P < .0001) and nonstenosed carotid arteries in patients (5.9 +/- 2.1; P < .002). A subgroup of patients with severe impairment was identified. ARI returned to normal after carotid endarterectomy was performed. In a number of cases, ARI was impaired in the presence of CO2 reactivity. CONCLUSIONS: This simple technique allows identification of impaired autoregulation in patients with carotid artery disease. It may allow identification of patients at risk from transient falls of blood pressure as may occur at the onset of antihypertensive therapy and during surgery. It may allow a subgroup of patients with asymptomatic carotid stenosis who are at risk of hemodynamic stroke to be identified.
Aged↗
A common polymorphism in the methylenetetrahydrofolate reductase gene, homocysteine, and ischemic cerebrovascular disease.
BACKGROUND AND PURPOSE: A common polymorphism (T/t) in the gene encoding the methylenetetrahydrofolate reductase (MTHFR) enzyme has been associated with elevated serum homocysteine, itself a risk factor for stroke. Some studies have reported an association with ischemic heart disease, but no published studies have examined its relationship with stroke. METHODS: We determined the TT genotype frequency and T allele frequency in 345 patients with ischemic cerebrovascular disease (CVD) and 161 control subjects. In a subgroup we also determined serum homocysteine and folate concentrations. RESULTS: In the patient group there was a significant relationship between TT genotype and homocysteine concentration after we controlled for other risk factors. Controlling for serum folate weakened this relationship, and folate itself was independently related to serum homocysteine. There was no difference between patients and control subjects in either TT genotype frequency (10.7% versus 13.7%; P = .34) or T allele frequency (0.68 versus 0.67; P = .67). There was no association when analysis was limited to individuals deficient in folate (serum folate < 25th centile) or to younger individuals (< 65 years). There was no association between TT genotype and any stroke subtype or with degree of carotid stenosis. CONCLUSIONS: In patients with CVD we confirmed a relationship between the MTHFR genotype and serum homocysteine concentration and an interaction with serum folate concentration. We found no association between CVD and genotype. However, the interaction with serum folate suggests that the genotype could still be a risk factor in populations with a low folic acid intake.
Aged↗
Relationship between lipoprotein (a) and both stroke and carotid atheroma.
In vitro studies provide mechanisms by which elevated lipoprotein (a) [Lp(a)] concentrations may promote both thrombosis and atherogenesis. Case-control studies have reported raised Lp(a) concentrations in patients with stroke, but prospective studies have failed to confirm the association. A potential confounding factor is that Lp(a) may rise acutely after stroke. We determined Lp(a) concentrations in 164 patients studied at least 21 days after stroke or transient ischaemic attack, and in 91 controls. In the patient group we correlated Lp(a) concentrations with both the degree of carotid stenosis estimated on duplex ultrasonography, and with stroke subtype (large vessel disease, lacunar infarction, and cardioembolic and unknown pathogenesis). There was no difference between Lp(a) concentration in cases and controls [median (quartiles) 0.10 (0.04, 0.39) versus 0.12 (0.04, 0.30) g/L, P = 0.34]. There was no difference in the proportion of cases compared with controls with a markedly elevated Lp(a) of > 0.4 g/L (21.3 versus 16.5%, P = 0.34). There was non-significant trend towards higher median Lp(a) concentrations in women [median (quartiles) 0.16 (0.04, 0.32) g/L versus 0.12 (0.04, 0.28) g/L, P = 0.3]. In view of this trend we analysed the differences between cases and controls for each sex separately. Lp(a) concentrations in men were median (quartiles) 0.08 (0.04, 0.26) g/L in the 101 cases and 0.12 (0.04, 0.28) g/L in the 43 controls (P = 0.6). Lp(a) concentrations in women were median (quartiles) 0.25 (0.04, 0.44) g/L in the 63 cases, and 0.16 (0.04, 0.32) g/L in the 48 controls (P = 0.16). Within the patient group there was no difference between Lp(a) concentrations in the different stroke subgroups. There was no relationship between Lp(a) concentrations and mean percentage carotid stenosis (rs = 0.14, P = 0.07). Our results suggest that in an unselected population of men studied more than 3 weeks post event there is no relationship between lipoprotein(a) concentrations and either stroke/transient ischaemic attack, or carotid atheroma. The relationship in women requires further study.
Aged↗
Improvement in cerebral hemodynamics after carotid angioplasty.
BACKGROUND AND PURPOSE: Carotid percutaneous transluminal angioplasty ( PTA) may offer an alternative treatment to carotid endarterectomy. However, in contrast to carotid endarterectomy, which has been shown to normalize impaired cerebral hemodynamics, the effects of carotid PTA are unknown. Therefore, we prospectively studied the effect of carotid PTA on both perioperative and postoperative cerebral hemodynamics. METHODS: Eleven patients undergoing carotid PTA for symptomatic carotid artery stenosis were prospectively studied. Transcranial Doppler recordings from the ipsilateral middle cerebral artery (MCA) were performed during the procedure. In addition, MCA blood flow velocity and CO2 reactivity were determined before PTA and at 2 days, 1 month, and 6 months after procedure. The results were compared with those in 11 similar patients undergoing carotid endarterectomy in whom measurements were performed before and 1 month after the operation. RESULTS: During carotid PTA, in 2 of 11 patients during passage of the balloon catheter through the stenosis, MCA blood flow velocity fell transiently. In 6 of 11 patients there was a reduction in flow velocity (>50%) during balloon deflation, but this lasted only a few seconds. After the procedure there was a significant improvement in ipsilateral hypercapnic reactivity: preoperative value, 59.8+/-42.2% (mean+/-SD); 2 days, 77.9+/-31.4%; 1 month, 88.7+/-45.0%; 6 months, 89.8+/-33.9%; and (ANOVA P=.003) preoperative value versus 1 month, P<.02; versus 6 months, P<.02. In all cases in which reactivity was significantly impaired preoperatively, it returned to the normal range. Pulsatility index also increased significantly: preoperative value, 0.827+/-0.251 (mean+/-SD); 2 days, 0.992+/-0.262 (P=.002). Contralateral MCA hypercapnic reactivity also improved after carotid PTA. There was a similar improvement in ipsilateral hypercapnic reactivity after carotid endarterectomy. CONCLUSIONS: Carotid PTA results in a normalization of impaired hemodynamics, as assessed by CO2 reactivity. The degree of improvement is similar to that seen after carotid endarterectomy.
Angioplasty, Balloon, Coronary↗
Multigated Doppler ultrasound in the detection of emboli in a flow model and embolic signals in patients.
BACKGROUND AND PURPOSE: The ability to detect asymptomatic circulating cerebral emboli may contribute to the management of patients with stroke, but its clinical usefulness will depend on effective systems for automatically detecting embolic signals (ES) and differentiating them from artifact. A new method involves the use of a multidepth probe that allows recording from both distal and proximal sample volumes along the same vessel. Theoretically, an embolus should appear sequentially, with a time delay, between the two channels, whereas an artifact should appear simultaneously in the two channels. METHODS: We evaluated this method in an in vitro flow model and in patients. In an in vitro model, with a flow pattern mimicking intracerebral flow, 181 air bubbles and 193 thrombus emboli were compared with the signals resulting from 368 episodes of artifact; a sample volume of 5 mm and a channel separation of 10 mm were used. ES from two groups of patients-those with carotid artery stenosis (141 ES) and those with mechanical prosthetic cardiac valves (125 ES)-were studied and compared with 222 episodes of artifact produced in the same patients. RESULTS: In the model the mean (SD) time delay was 17.32 (9.94) ms for air emboli and 17.78 (10.66) ms for thrombus emboli compared with -0.01 (0.39) ms for artifact (air and thrombus emboli versus artifact, P < .0001). A sensitivity of 100% and specificity of 100% were obtained when a cutoff of > 2 ms was used for an embolus. The method allowed equally good detection of those air emboli that resulted in receiver overload and aliasing. In patients the mean (SD) time delay was 29.6 (28.2) ms for valve ES and 14.9 (15.42) for carotid ES compared with 0.00 (0.46) for artifact (carotid and valve ES versus artifact, P < .0001). Considering only those signals that were visible in both Doppler time domains resulted in a sensitivity for valve ES of 98.9% and for carotid ES of 94.0%, with a specificity of 99.0%. However, in one patient in the valve group some ES were visible only in the proximal channel, possibly because of passage of emboli down branch vessels between the two sample volumes. In addition, for the less intense carotid ES some signals were unclear or absent in one or both of the time domain signals at either depth, although visible in the post-fast Fourier transform spectra. Including those ES visible in only one channel reduced the sensitivity to 75.2% for valve ES and 92.6% for carotid ES. CONCLUSIONS: The multigated technique offers a new method of detecting ES and differentiating them from artifact and is the first reliable method for differentiating intense ES resulting in receiver overload from artifact. Occasionally its sensitivity is reduced when ES do not appear in the distal channel, probably because they pass down a side branch; this may be reduced by reducing gate separation. Some less intense carotid ES can be difficult to detect if the amplitude increase is small compared with the amplitude of the background Doppler signal.
Aged↗
Experimental aspects of high-intensity transient signals in the detection of emboli.
Experimental studies in the 1960s and 1970s demonstrated the high sensitivity of Doppler ultrasound in detecting gaseous bubbles. More recent studies have shown that microscopic air bubbles, as well as glass microspheres as small as 5 mu to 20 mu, cause characteristic high-intensity signals. Recently it has been demonstrated that less echogenic embolic materials such as thrombus, platelet aggregates, and atheroma can also be detected with a high sensitivity. Such "solid," or formed-element, emboli as small as 200 mu to 400 mu can be detected; the lower size limit of detection was due to an inability to make smaller embolic particles rather than to the sensitivity of the detection process itself. Analysis of the Doppler signals provides some information about embolus size and composition, but accurate characterization in clinical practice is not possible using current technology. Studies in experimental models have allowed the detailed description of embolic signals; they appear as a short-duration, frequency-focused increase in intensity, predominantly unidirectional in the direction of flow, and usually contained within the spectral envelope. In contrast, artifacts appear as a bidirectional, high-intensity increase with maximum intensity at low frequencies. These differences have been exploited to develop automatic embolus detection programs, and an off-line version has been successfully validated in an experimental model.
Animals↗
Patterns of regional cerebral blood flow in corticobasal degeneration studied using HMPAO SPECT; comparison with Parkinson's disease and normal controls.
Corticobasal degeneration (CBD) is a rare syndrome characterised by an asymmetrical rigidity with localised cortical signs, particularly apraxia. Using positron emission tomography, abnormal patterns of cortical metabolism have recently been shown. We have studied patterns of regional cerebral blood flow (rCBF) using single photon emission tomography, with the tracer 99Technetium hexamethylpropylenamine (HMPAO), in subjects with CBD. In subjects with CBD, compared with 12 age-matched normal controls, in the clinically more affected hemisphere a characteristic pattern was found with significant reductions in HMPAO uptake in the posterior frontal cortex (by 11.5%), and in the superior, inferior, anterior, and posterior parietal cortex (by 12.2, 12.9, 12.9, and 9.7, respectively). Reduced uptake was also found in the caudate (9.3%), putamen (9.7%), and thalamus (8.6%). In contrast, HMPAO uptake in the temporal and occipital cortex was normal. In comparison with 12 Parkinson's disease (PD) controls, significant reduced uptake was seen in the thalamus (9.0%), posterior frontal (8.9%), and inferior (9.9%), and anterior parietal (9.5%) cortex. A similar pattern of impaired uptake was seen in the clinically less/unaffected cerebral hemisphere in patients with CBD compared with normal controls, with a significant reduction in HMPAO uptake in the thalamus (6.8%), superior parietal (9.6%) and anterior parietal (7.6%), and posterior parietal (7.3%) cortex. This implies that the disease process is bilateral even in those cases with clinically unilateral disease. This widely available technique may be useful in the early diagnosis of CBD and in differentiation from other extrapyramidal disorders.
Age Factors↗
Asymptomatic cerebral embolic signals in symptomatic and asymptomatic carotid artery disease.
Transcranial Doppler ultrasound of middle cerebral arteries (MCAs) was used to detect asymptomatic embolic signals in a prospective study in patients with symptomatic and asymptomatic carotid stenosis. Recording from each artery for 20 min, embolic signals were more common ipsilateral to symptomatic arteries (eight of 38) than ipsilateral to asymptomatic arteries (one of 28, P = 0.04), or than in the MCAs of age-matched normal controls (none of 52, P < 0.005). Recording a subgroup of patients revealed that previously embolic-signal negative symptomatic stenoses frequently became embolic-signal positive when recording was repeated on another day. Including all recording periods (mean time: symptomatic 36.2 min, asymptomatic 46.2 min) embolic signals were detected ipsilateral to 13 of 38 symptomatic stenoses but only one of 28 asymptomatic stenoses (P = 0.003). In symptomatic subjects with embolic signals, median number of signals per hour was three (mean 26). One month following carotid endarterectomy embolic signals were not detected except in one patient who continued to experience frequent amaurosis fugax; in this patient following aspirin both symptoms and embolic signals were abolished. These studies suggest asymptomatic embolic signals correlate with clinical risk. Outcome studies are required to determine whether embolic signal detection may allow prediction of stroke risk and monitoring of the effectiveness of therapy. The technique may also prove useful in studying the pathophysiology of cerebral embolism.
Adult↗
Angiotensin-converting enzyme gene deletion polymorphism. A new risk factor for lacunar stroke but not carotid atheroma.
BACKGROUND AND PURPOSE: A deletion (D)/insertion (I) polymorphism in the angiotensin-converting enzyme gene has been associated with myocardial infarction. Its relations to both stroke and atheroma remain uncertain. We examined its role as a risk factor in patients with cerebrovascular disease and its relation to carotid atheroma. METHODS: One hundred one patients with symptomatic carotid artery territory cerebral ischemia were compared with 137 age-matched control subjects. In the patient group, carotid atheroma was assessed by measurement of degree of carotid stenosis and intima-media thickness with high-resolution duplex ultrasound. The D/I polymorphism was examined using the polymerase chain reaction. RESULTS: D:I allele frequency was 0.59:0.41 in case subjects and 0.48:0.52 in control subjects (P = .01). The DD genotype was more common in patients with cerebrovascular disease compared with control subjects (36/101 versus 30/137, P = .02). The DD genotype conferred a relative risk of any type of cerebrovascular disease of 1.98 (95% confidence interval [CI], 1.11 to 3.51; P = .02). However, this was largely due to a strong association in the 18 patients with lacunar stroke, in whom the D:I ratio was 0.75:0.25 (P = .0097 versus control subjects). The odds ratio for lacunar stroke associated with the DD genotype was 5.6 (95% CI, 2.0 to 15.7) and was still significant at 4.40 (95% CI, 1.45 to 12.6; P < .009) after controlling for other risk factors. There was no significant association between angiotensin-converting enzyme genotype and cerebrovascular disease due to large-vessel stenosis. There was no association between genotype and age, sex, smoking history, diabetes, or cholesterol level. CONCLUSIONS: The deletion polymorphism in the angiotensin-converting enzyme gene is a new independent risk factor for lacunar stroke but is not a risk factor for stroke associated with carotid stenosis.
Aged↗
Microembolic signal detection using ultrasound.
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Arteriosclerosis↗
Detection of asymptomatic cerebral embolic signals with Doppler ultrasound.
Can asymptomatic cerebral emboli be detected? With transcranial Doppler ultrasonography of the middle cerebral artery, short-duration high-intensity asymptomatic embolic signals were detected in 6 of 25 patients with carotid stenosis and in 9 of 24 with prosthetic cardiac valves, but not in 20 normal controls. In carotid stenosis the signals were usually unilateral and ipsilateral to the stenosis. Embolic signals were significantly more common in patients with mechanical valves than with pig xenografts (8/13 vs 1/11). With mechanical valves embolic signals were usually bilateral. Detection of asymptomatic emboli may allow identification of and preventive treatment in at-risk patients.
Aged↗
HMPAO SPECT in Parkinson's disease before and after levodopa: correlation with dopaminergic responsiveness.
Regional cerebral perfusion was evaluated by SPECT with technetium 99m hexamethylpropyleneamine oxime (99mTc HMPAO) as a tracer in 21 patients presenting with Parkinson's disease and in 11 normal controls. In the parkinsonian patients, scans were performed both off treatment, and after levodopa, and clinical dopaminergic responsiveness was evaluated. Uptake of HMPAO by the basal ganglia was significantly decreased in the parkinsonian subjects, compared with normal controls. This reduction was seen in both responders (n = 14) and non-responders (n = 7) to dopaminergic treatment. Uptake of HMPAO by the basal ganglia rose after treatment with levodopa, but the change was similar in both responders and non-responders. By contrast a striking difference in cortical HMPAO uptake was found between responders and non-responders, with significantly lower uptake in the medial temporal and posterior parietal cortex in the non-responders. This reduction was symmetrical. Basal ganglia perfusion assessed by this technique is unlikely to be of use in the diagnosis of Parkinson's disease that is responsive to dopaminergic treatment. The presence of extensive cortical involvement on a baseline scan correlates with a lack of dopaminergic responsiveness, however, and this may be useful diagnostically.
Aged↗
Carotid angioplasty. Detection of embolic signals during and after the procedure.
BACKGROUND AND PURPOSE: Carotid angioplasty may offer an effective treatment for carotid stenosis, but there has been concern about the incidence and clinical consequences of distal embolization. Transcranial Doppler monitoring in carotid endarterectomy has demonstrated embolic signals during this procedure. We used this technique in patients undergoing carotid angioplasty. METHODS: Transcranial Doppler ultrasound was used to monitor for embolic signals in the ipsilateral middle cerebral artery before and during 10 technically successful carotid angioplasties and at various standardized times in the following month. RESULTS: In the month before angioplasty asymptomatic embolic signals were detected in 3 of 10 patients. During angioplasty multiple embolic signals were detected immediately after balloon inflation in 9 of 10 subjects. A minor ipsilateral cerebral ischemic event occurred in 1 of these 9, but the other 8 were asymptomatic. Embolic signals were common immediately after the procedure and intra-arterial femoral catheter removal (8 of 10 subjects) but thereafter became less frequent and were present in 1 of 5 at 4 hours, 2 of 10 at 48 hours, 1 of 6 at 7 days, and 1 of 10 at 1 month. CONCLUSIONS: Embolization at the time of carotid angioplasty is very common but usually asymptomatic; monitoring by means of Doppler ultrasound will allow the effectiveness of measures to reduce this embolization to be studied. Late embolization occurs in a minority of patients and may account for the small but significant risk of delayed stroke. Doppler monitoring may allow identification of patients at risk and assessment of the effectiveness of prophylactic therapy.
Aged↗
The effect of velocity on the appearance of embolic signals studied in transcranial Doppler models.
BACKGROUND AND PURPOSE: Transcranial Doppler ultrasound can be used to detect circulating cerebral emboli. Recent studies have demonstrated that embolus size is significantly related to both the relative intensity increase and duration of an embolic signal. This may allow information about embolus size to be obtained by analysis of Doppler embolic signals. However, theoretically duration will be inversely related to velocity, and therefore velocity may need to be accounted for if information on embolus size is to be derived from the duration of Doppler embolic signals. METHODS: The relation between velocity and both relative intensity increase and duration of embolic signal was investigated in an in vitro flow model, a sheep carotid artery model, and in patients with prosthetic heart valves. The same standard transcranial Doppler ultrasound machine was used for all studies. Embolic signals resulting from 99 glass microspheres (size, 210 to 250 microns) were studied in the in vitro model, as were those from 64 glass microspheres (size, 105 to 150 microns) in the sheep model. Embolic signals recorded from the six middle cerebral arteries of three patients with prosthetic cardiac valves were also studied. RESULTS: There was a significant (P < .001) inverse relation between velocity and duration of high-intensity signal (in vitro model, r = -.82; sheep model, r = -.43); the exact relations were described using best-fit equations. Correlation coefficients for this relation in patients varied between -.30 and -.55. There was also an unexpected significant positive relation between velocity and intensity in the sheep model (r = .44, P < .001) but not in the in vitro model (P > .05). This relation was also seen in some, but not all, patients. CONCLUSIONS: When the duration of embolic signals is used to provide information about the relative size of an embolus, the velocity of the embolic signal should be taken into account. A relation between velocity and relative intensity increase was found in the sheep model and in some patient recordings. It is suggested this relation may result from greater power being supplied to emboli traveling at higher velocities in the center of the vessel; this may occur under certain recording conditions.
Animals↗
Differential effect of three cyclooxygenase inhibitors on human cerebral blood flow velocity and carbon dioxide reactivity.
BACKGROUND AND PURPOSE: Prostaglandins are believed to play an important role in maintenance of cerebral blood flow and possibly in the vasodilatory response to carbon dioxide. Therefore, the nonsteroidal anti-inflammatory drugs and aspirin, which inhibit cyclooxygenase, might be expected to reduce cerebral blood flow and the response to hypercapnia. This could induce cerebral ischemia in patients with a hemodynamically critical circulation. It would also interfere with the measurement of cerebrovascular reserve using carbon dioxide. METHODS: The effect of a single dose of indomethacin and of two other cyclooxygenase inhibitors (aspirin and sulindac) on the cerebral circulation was measured using transcranial Doppler ultrasonography of the middle cerebral artery. Seven normal adults were studied in each drug group. Resting blood flow velocity and the responses to hypercapnia and to hyperventilation were measured. RESULTS: Indomethacin resulted in a fall in basal middle cerebral artery flow velocity from a mean of 48.9 cm/s to 34.0 cm/s (P < .002). It also reduced the vasoconstrictor response to hypocapnia (induced by hyperventilation) from 37.5% to 20.7% (P < .003). There was a nonsignificant reduction in the vasodilatory response to 8% carbon dioxide (mean: predrug, 87.7%; postdrug, 61.0%), with marked intersubject variability. In contrast, basal middle cerebral artery velocity and vasoconstrictor and vasodilatory responses to changes in carbon dioxide were unchanged after aspirin or sulindac administration. CONCLUSIONS: The lack of effect of aspirin on basal cerebral blood flow velocity and on vasodilatory reserve is reassuring; aspirin will not reduce cerebral blood flow or the response to a reduced perfusion pressure in patients with critically impaired cerebral hemodynamics. However, indomethacin should be avoided in such patients.
Adult↗