Nitric oxide donors in pregnancy: fetomaternal hemodynamic effects induced in mild pre-eclampsia and threatened preterm labor.
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OBJECTIVE: The present study was performed to determine whether there are significant differences in the effects of the nitric oxide donor, glyceryl trinitrate, administration in pregnancies complicated by mild pre-eclampsia compared to the effects in pregnancies which are uncomplicated by this pathology. Glyceryl trinitrate is able to release nitric oxide (NO); deficiency of NO has been hypothesized in the pathogenesis of pre-eclamptic disorders. METHODS: In this prospective study, ten patients with threatened preterm labor and ten patients with mild preeclampsia were studied at around 30 weeks of pregnancy. The maternal blood pressure, maternal heart rate, fetal heart rate and flow velocity waveforms of the placental uterine artery, umbilical artery and fetal middle cerebral artery, evaluated by means of color Doppler and pulsed Doppler, were recorded before and 10, 20 and 30 min after the sublingual administration of 0.3 mg of glyceryl trinitrate or placebo. The pulsatility index (PI) was calculated. The percentage change from the control period (delta %) was calculated for each parameter at 10, 20 and 30 min. Ten normal pregnant women at the same gestational age were used as controls and were administered a placebo. RESULTS: The maternal blood pressure recorded as systolic and diastolic values, demonstrated a significant decrease in the pre-eclampsia group after glyceryl trinitrate administration; the delta % at any time considered was significantly higher in the pre-eclampsia group than in the threatened preterm labor group. The PI of the placental uterine artery showed a significant decrease in both groups after 20 and 30 min from drug administration; the delta % at 20 and 30 min was significantly higher in the pre-eclampsia group than in the threatened preterm labor group. The PI of the umbilical artery showed a significant decrease after 30 min from the glyceryl trinitrate administration. The fetal heart rate showed no significant variations during the study in either group. The PI of the fetal middle cerebral artery showed no significant variations during the study in either group. No parameter was changed in the control group. CONCLUSION: Glyceryl trinitrate administration was followed by a greater reduction of the resistance to blood flow in the fetoplacental circulation of the pregnancies affected by mild pre-eclampsia compared to pregnancies uncomplicated by this pathology. This effect can be attributed to the NO released by the drug which offsets the decreased production of NO, postulated to contribute to the pathogenesis of pre-eclampsia. (+info)
Predictors of clinical improvement, angiographic recanalization, and intracranial hemorrhage after intra-arterial thrombolysis for acute ischemic stroke.
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BACKGROUND AND PURPOSE: We sought to evaluate predictors of clinical outcome, angiographic success, and adverse effects after intra-arterial administration of urokinase for acute ischemic stroke. METHODS: We designed a Brain Attack program at University Hospitals of Cleveland for diagnosis and treatment of patients presenting within 6 hours of onset of neurological deficit. Patients with ischemia referable to the carotid circulation were treated with intra-arterial urokinase. Angiographic recanalization was assessed at the end of medication infusion. Intracerebral hemorrhage was investigated immediately after and 24 hours after treatment. Stroke severity was determined, followed by long-term outcome. RESULTS: Fifty-four patients were treated. There was improvement of >/=4 points on the National Institutes of Health Stroke Scale from presentation to 24 hours after onset in 43% of the treated patients, and this was related to the severity of the initial deficit. Forty-eight percent of patients had a Barthel Index score of 95 to 100 at 90 days, and total mortality was 24%. Cranial CT scans revealed intracerebral hemorrhage in 17% of patients in the first 24 hours, and these patients had more severe deficits at presentation. Eighty-seven percent of patients received intravenous heparin after thrombolysis, and 9% of them developed a hemorrhage into infarction. Angiographic recanalization was the rule in complete occlusions of the horizontal portion of the middle cerebral artery, but distal carotid occlusions responded less well to thrombolysis. CONCLUSIONS: The intra-arterial route for thrombolysis allows for greater diagnostic precision and achievement of a higher concentration of the thrombolytic agent in the vicinity of the clot. Disadvantages of this therapy lie in the cost and delay. Severity of stroke and site of angiographic occlusion may be important predictors of successful treatment. (+info)
Effects of spontaneous recanalization on functional and electrophysiological recovery in acute ischemic stroke.
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BACKGROUND AND PURPOSE: Transcranial Doppler ultrasound (TCD) studies have shown that spontaneous recanalization results in a better clinical improvement after the onset of stroke. However, its effect on electrophysiological recovery is still unknown. The aim of this study was to determine the effects of spontaneous recanalization on the change in central motor conduction time (CMCT) in acute ischemic stroke. METHODS: Seventeen healthy subjects and 38 consecutive patients with a first acute ischemic stroke involving the middle cerebral artery territory were included. TCD was used to detect spontaneous recanalization. Transcranial magnetic stimulation was used to determine the change in CMCT on days 1 and 14. Improvement of the CMCT at day 14 was indicated if it decreased in comparison with previous data recorded at day 1 or when a nonrecordable motor response at day 1 reappeared at day 14. No CMCT improvement was indicated when there was no recordable motor response at day 1 and day 14 or the CMCT at day 14 worsened, becoming absent or more delayed. The Pearson chi(2) test was used to assess the statistical significance of the results in this study. RESULTS: Spontaneous recanalization was observed in 62% of the patients: 24% before 24 hours and 38% after this period. No recanalization was observed in 14 patients. The CMCT improved in 87% of the patients who had recanalized before 24 hours and 62% in the recanalized after 24 hours group (P=0.005). In contrast, CMCT improved in only 17% of the patients in the non-recanalized group CONCLUSIONS: These data show that spontaneous recanalization results in a better recovery of the central motor pathway leading to a better CMCT improvement in acute ischemic stroke. (+info)
Lateralization of cerebral blood flow velocity changes during cognitive tasks. A simultaneous bilateral transcranial Doppler study.
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BACKGROUND AND PURPOSE: Transcranial Doppler ultrasonography (TCD) permits the assessment of cognitively induced cerebral blood flow velocity (BFV) changes. We sought to investigate the lateralization of BFV acceleration induced by a variety of cognitive tasks and to determine the influence of age, gender, IQ, and quality of the performance on the relative BFV changes. METHODS: Simultaneous bilateral TCD monitoring of BFV in the middle cerebral arteries (MCAs) was performed in 90 normal right-handed volunteers during 13 verbal and visuospatial tasks and their preceding rest periods. RESULTS: All tasks induced a significant bilateral BFV increase in the MCAs compared with the preceding rest periods. Five verbal tasks showed a significant left-hemispheric BFV acceleration. Linguistic tasks that required active or creative processing of the verbal stimuli, such as sentence construction or word fluency, elicited the most asymmetric response. Five visuospatial tasks revealed a significant right-hemispheric BFV shift. Paradigms that combined visuospatial attention and visuomotor manipulation showed the most lateralized acceleration. Older volunteers (aged >50 years) showed higher relative BFV changes, but lateralization was not influenced by age. Gender, IQ, and performance quality did not reveal significant effects on BFV change. CONCLUSIONS: Bilateral TCD is a noninvasive technique that has the potential to connect the particular change in flow pattern of the MCA distribution with selective cognitive activity and thus offers specific functional information of scientific and clinical value. (+info)
Effects of some guanidino compounds on human cerebral arteries.
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BACKGROUND AND PURPOSE: Accumulation of endogenous guanidino-substituted analogues of L-arginine in chronic renal failure might contribute to some of the vascular and neurological disorders of this pathology. We tested the hypothesis that in human cerebral arteries, some guanidino compounds may increase vascular tone, through nitric oxide (NO) synthase inhibition, and impair endothelium-dependent relaxation. METHODS: Rings of human middle cerebral artery were obtained during autopsy of 26 patients who had died 3 to 12 hours before. The rings were suspended in organ baths for isometric recording of tension. We then studied the responses to N(G)-monomethyl-L-arginine (L-NMMA), N(G),N(G)-dimethyl-L-arginine (asymmetrical dimethylarginine; ADMA), aminoguanidine (AG), and methylguanidine (MG). RESULTS: L-NMMA (10(-6) to 3x10(-4) mol/L) and ADMA (10(-6) to 3x10(-4) mol/L) caused concentration- and endothelium-dependent contractions (median effective concentrations [EC(50)]=1.1x10(-5) and 1.6x10(-5) mol/L, respectively; E(max)=35. 5+/-7.9% and 43.9+/-5.9% of the response to 100 mmol/L KCl). AG (10(-5) to 3x10(-3) mol/L) and MG (10(-5) to 3x10(-3) mol/L) produced endothelium-independent contractions (E(max)=44.3+/-8.8% and 45.7+/-5.8% of the response to 100 mmol/L KCl, respectively). L-Arginine (10(-3) mol/L) prevented the contractions by L-NMMA and ADMA but did not change contractions induced by AG and MG. L-NMMA and ADMA inhibited endothelium-dependent relaxation induced by acetylcholine in a concentration-dependent manner; AG and MG were without effect. CONCLUSIONS: The results suggest that the contractions induced by L-NMMA and ADMA are due to inhibition of endothelial NO synthase activity, whereas AG and MG do not affect the synthesis of NO. An increase in the plasma concentration of L-NMMA and ADMA associated with uremia is likely to represent a diminished release or effect of NO, and consequently, an increased cerebrovascular tone in uremic patients is highly conceivable. (+info)
Larger anastomoses in angiotensinogen-knockout mice attenuate early metabolic disturbances after middle cerebral artery occlusion.
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Abnormalities in the homeostasis of the renin-angiotensin system have been implicated in the pathogenesis of vascular disorders, including stroke. The authors investigated whether angiotensinogen (AGN) knockout mice exhibit differences in brain susceptibility to focal ischemia, and whether such differences can be related to special features of the collateral circulation. Wild-type and AGN-knockout mice were submitted to permanent suture occlusion of the middle cerebral artery (MCA). The collateral vascular system was visualized by systemic latex infusion, and the ischemic lesions were identified by cresyl-violet staining. The core and penumbra of the evolving infarct were differentiated by bioluminescence and autoradiographic imaging of ATP and protein biosynthesis, respectively. In wild-type mice, mean arterial blood pressure was 95.0 +/- 8.6 mm Hg, and the diameter of fully relaxed anastomotic vessels between the peripheral branches of the anterior and middle cerebral arteries 26.6 +/- 4.0 microm. In AGN knockouts, mean arterial blood pressure was significantly lower, 71.5 +/- 8.5 mm Hg (P < .01), and the anastomotic vessels were significantly larger, 29.4 +/- 4.6 microm (P < .01). One hour after MCA occlusion, AGN-knockout mice exhibited a smaller ischemic core (defined as the region of ATP depletion) but a larger penumbra (the area of disturbed protein synthesis with preserved ATP). At 24 hours after MCA occlusion, this difference disappeared, and histologically visible lesions were of similar size in both strains. The observations show that in AGN-knockout mice the more efficient collateral blood supply delays ischemic injury despite the lower blood pressure. Pharmacologic suppression of angiotensin formation may prolong the therapeutic window for treatment of infarcts. (+info)
Spectral analysis of arterial blood pressure and cerebral blood flow velocity during supine rest and orthostasis.
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This study evaluates the effect of orthostasis on the low frequency (LF, 0.04 to 0.15 Hz) fluctuations in the blood flow velocity of the middle cerebral artery (MCAFV) in relation to its arterial blood pressure (ABP) equivalent to further define and quantify this relationship in cerebrovascular regulation. Spectral analysis was performed on 22 healthy subjects during supine rest and head-up tilt. The power in the LF range can be used to quantify the LF fluctuations, and four types of LF power data could be obtained for each individual: LF power of supine MCAFV, LF power of supine ABP, LF power of tilt MCAFV, and LF power of tilt ABP. By comparing LF power of MCAFV with LF power of ABP, two power ratios could be generated to describe the flow-pressure relationship during supine rest and head-up tilt, respectively, supine power ratio (LF power of supine MCAFV/ LF power of supine ABP) and tilt power ratio (LF power of tilt MCAFV/ LF power of tilt ABP). In addition, an index for dynamic autoregulation in response to orthostasis can be calculated from these two power ratios (tilt power ratio/supine power ratio). The authors found that this index was dependent on the extent of orthostatic MCAFV changes, and the dependency could be mathematically expressed (r = 0.61, P = .0001), suggesting its involvement in cerebrovascular regulation. Moreover, these data further support the previous observation that the LF fluctuations of MCAFV might result from modulation of its ABP equivalent, and the modulation effect could be quantified as the power ratio (LF power of MCAFV/ LF power of ABP). These observations could be an important step toward further insight into cerebrovascular regulation, which warrants more research in the future. (+info)
Disseminated coccidioidomycosis complicated by vasculitis: a cause of fatal subarachnoid hemorrhage in two cases.
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We describe two cases of disseminated coccidioidomycosis that were complicated by fatal subarachnoid hemorrhage. In the first case, a left middle cerebral artery aneurysm and long-segment vasculitis occurred. In the second case, MR imaging revealed an enlarging coccidioidal granuloma at the tip of the basilar artery, and the artery subsequently ruptured. Fatal intracranial hemorrhage is a rare complication of disseminated coccidioidomycosis. (+info)