Citations

Background and Purpose —During focal cerebral ischemia, the ischemic penumbra or border-zone regions of moderate cortical blood flow reductions have a heterogeneous development of intracellular cortical acidosis. This experiment tested the hypotheses that (1) this acidosis is secondary to glucose utilization and (2) this intracellular acidosis leads to recruitment of potentially salvageable tissue into infarction. Methods —Brain pH i , regional cortical blood flow, and NADH redox state were measured by in vivo fluorescent imaging, and infarct volume was assessed by triphenyltetrazolium chloride histology. Thirty fasted rabbits divided into 6 groups of 5 each were subjected to 4 hours of permanent focal ischemia in the presence of hypoglycemia (≈2.8 mmol/L), moderate hyperglycemia (≈11 mmol/L), and severe hyperglycemia (>28 mmol/L) under either normoxia or moderate hypoxia (Pa o 2 ≈50 mm Hg). Results —Preischemic hyperglycemia led to a more pronounced intracellular acidosis and retardation of NADH regeneration than in the hypoglycemia groups under both normoxia and moderate hypoxia in the ischemic penumbra. For example, 4 hours after ischemia, brain pH i in the severe hyperglycemia/normoxia group measured 6.46, compared with 6.84 in the hypoglycemia/normoxia group ( P <0.01), and NADH fluorescence measured 173% compared with 114%. Infarct volume in the severe hyperglycemia/normoxia group measured 35.1±6.9% of total hemispheric volume, compared with 13.5±4.2% in the hypoglycemia/normoxia group ( P <0.01). Conclusions —Hyperglycemia significantly worsened both cortical intracellular brain acidosis and mitochondrial function in the ischemic penumbra. This supports the hypothesis that the evolution of acidosis in the ischemic penumbra is related to glucose utilization. Furthermore, the observation that hypoglycemia significantly decreased infarct size supports the postulate that cortical acidosis leads to recruitment of ischemic penumbra into infarction.

Background and Purpose —The cause of pretruncal (perimesencephalic) nonaneurysmal subarachnoid hemorrhage is not known. MRI of the brain or spine is often performed to exclude any other vascular abnormalities. Its diagnostic value is not known. Methods —We used MR imaging of the brain with routine sequences, gadolinium enhancement, and additional thin T1-weighted axial sections following a triple dose of contrast. Results —We performed MR imaging of the brain in 18 patients with a pretruncal nonaneurysmal subarachnoid hemorrhage. The focal nature of the subarachnoid hemorrhage exclusively in front of the brain stem was confirmed in 14 patients studied within 7 days of the ictus. No vascular abnormalities were found in 17 cases, including 14 patients with gadolinium enhancement. An incidental capillary telangiectasia was found in 1 patient. Fluid-attenuated inverse recovery MR additionally documented blood in the sulci due to cerebrospinal fluid recirculation of blood. Five patients underwent MR imaging of the spine, and no arteriovenous malformations were found. Conclusions —MR imaging did not reveal a source of pretruncal subarachnoid hemorrhage. The cost of MR imaging probably outweighs the benefit in the evaluation of this variant of subarachnoid hemorrhage.

Background and Purpose —There is scant information available on the incidence of transient ischemic attack (TIA) in a defined population. This study defines incidence rates of first TIA and subtypes of TIA during 1985–1989 and compares the incidence to that obtained from a 1960–1972 cohort study. Methods —Medical records of all residents of Rochester with potential diagnosis of TIA during 1985–1989 were screened to determine whether the case met the criteria for TIA. All available data were used to determine the vascular distribution of the TIA. Average annual age- and sex-adjusted incidence rates were calculated for 1985–1989, and results were compared with incidence rates determined in a Rochester-based 1960–1972 cohort study. Results —Two hundred two cases of first TIA or amaurosis fugax occurred among Rochester residents during 1985–1989. The age- and sex-adjusted incidence rate for any TIA was 68/100 000 population. Incidence of amaurosis fugax was 13/100 000; anterior circulation (cerebral) TIA, 38/100 000; and vertebrobasilar distribution TIA, 14/100 000. Rates were similar to those determined from a 1960–1972 cohort study. Conclusions —The incidence rate of TIA is 41% that of stroke incidence. TIA incidence in Rochester, Minn, is higher than has been previously reported for other sites throughout the world. Although comparison with prior time periods is difficult because of ascertainment issues, it appears that there has been no significant change in TIA incidence since the decade of the 1960s or earlier. This suggests that the most common mechanism for TIA (atherosclerosis) has not changed in prevalence, nor have risk factors leading to this mechanism.

Background and Purpose —This study was conducted to determine the risk factors for ischemic stroke in a defined Russian population. Methods —Our data are based on a population-based case-control study of 237 patients with first-ever ischemic stroke and 237 age- and sex-matched controls. Logistic regression methods for matched pairs were used to estimate the relative risk for the variables studied. Results —In a multivariate analysis, hypertension, left ventricular hypertrophy on electrocardiography, ischemic heart disease, mitral valve disease, current cigarette smoking, and high body mass index were significant and independent risk factors for ischemic stroke in this Russian community. Conclusions —The significant risk factors for ischemic stroke in Novosibirsk are similar to those from other populations and cohorts. This study, the first of stroke risk factors in Russia, has implications for clinical practice and the planning of stroke prevention in the population.

Background and Purpose —We sought to evaluate cerebral autoregulation in patients with orthostatic hypotension (OH). Methods —We studied 21 patients (aged 52 to 78 years) with neurogenic OH during 80° head-up tilt. Blood flow velocities (BFV) from the middle cerebral artery were continuously monitored with transcranial Doppler sonography, as were heart rate, blood pressure (BP), cardiac output, stroke volume, CO 2 , total peripheral resistance, and cerebrovascular resistance. Results —All OH patients had lower BP ( P <.0001), BFV_diastolic ( P <.05), CVR ( P <.007), and TPR ( P <.02) during head-up tilt than control subjects. In control subjects, no correlations between BFV and BP were found during head-up tilt, suggesting normal autoregulation. OH patients could be separated into those with normal or expanded autoregulation (OH_NA; n=16) and those with autoregulatory failure (OH_AF; n=5). The OH_NA group showed either no correlation between BFV and BP (n=8) or had a positive BFV/BP correlation ( R 2 >.75) but with a flat slope. An expansion of the “autoregulated” range was seen in some patients. The OH_AF group was characterized by a profound fall in BFV in response to a small reduction in BP (mean ΔBP <40 mm Hg; R 2 >.75). Conclusions —The most common patterns of cerebral response to OH are autoregulatory failure with a flat flow-pressure relationship or intact autoregulation with an expanded autoregulated range. The least common pattern is autoregulatory failure with a steep flow-pressure relationship. Patients with patterns 1 and 2 have an enhanced capacity to cope with OH, while those with pattern 3 have reduced capacity.

Background and PurposeThe mechanisms underlying smooth muscle relaxations of cerebral arteries in response to nitric oxide (NO) and cyclic GMP (cGMP) are still not completely understood. The present study was designed to determine the role of potassium channels in the relaxations to NO donors 3-morpholinosydnonimine (SIN-1) and sodium nitroprusside (SNP), as well as 8-bromo-3′,5′-cGMP (a synthetic analogue of cGMP) and zaprinast (a selective cGMP phosphodiesterase inhibitor).MethodsRings of canine middle cerebral arteries without endothelium were suspended in Krebs-Ringer bicarbonate solution for isometric tension recording. The levels of cGMP were measured by radioimmunoassay. Relaxations to NO donors 8-bromo-cGMP and zaprinast were studied in the presence and in the absence of K+channel blockers charybdotoxin (large-conductance Ca2+-activated K+channels), glyburide (ATP-sensitive K+channels), 4-aminopyridine (delayed rectifier K+channels), and BaCl2(multiple types of K+channels).ResultsConcentration-dependent relaxations caused by NO donors (SIN-1 and SNP) were significantly reduced in arteries treated with BaCl2(3×10−4mol/L) or charybdotoxin (3×10−8mol/L). Relaxations to 8-bromo-cGMP were not affected by the same concentrations of BaCl2and charybdotoxin; however, they were reduced by higher concentrations of BaCl2(3×10−3mol/L) and charybdotoxin (10−7mol/L). Zaprinast-induced relaxations were significantly reduced by BaCl2(3×10−4mol/L) or charybdotoxin (3×10−8mol/L). Glyburide (10−5mol/L) and 4-aminopyridine (10−3mol/L) did not alter the relaxations to SIN-1 or SNP. The production of cGMP stimulated by SIN-1 in the vascular smooth muscle was not affected by BaCl2(3×10−3mol/L) or charybdotoxin (10−7mol/L).ConclusionsThese results indicate that in canine middle cerebral arteries, a significant portion of relaxations to NO liberated from nitrovasodilators is mediated by large-conductance Ca2+-activated K+channels. Other K+channels, sensitive to BaCl2, may also be involved in the mechanism of relaxations induced by NO.

Background and PurposeConcentration of hydrogen ions is an important regulator of cerebral arterial tone under physiological and pathological conditions. Previous studies demonstrated that in cerebral arteries, relaxations to hypercapnia are due to decrease in extracellular pH. The present study was designed to determine the role of potassium channels in mediation of cerebral arterial relaxations induced by extracellular acidosis.MethodsRings of canine basilar arteries without endothelium were suspended for isometric force recording. Acidosis (pH 7.3 to 7.0) was produced by incremental addition of hydrochloric acid (1.0N). The concentration of hydrogen ions was continuously monitored with a pH meter.ResultsDuring contractions to UTP, acidosis (pH 7.3 to 7.0) induced pH-dependent relaxations. These relaxations were abolished in arteries contracted by potassium chloride (20 mmol/L). A nonselective potassium channel inhibitor, BaCl2(10−3and 10−4mol/L), and an ATP-sensitive potassium channel inhibitor, glyburide (5×10−6mol/L), significantly reduced relaxations to acidosis. Furthermore, BaCl2(10−3mol/L) and glyburide (5×10−6mol/L) abolished relaxations to an ATP-sensitive potassium channel opener, cromakalim (10−8to 3×10−5mol/L). However, these potassium channel inhibitors did not affect relaxations to a voltage-dependent calcium channel inhibitor, diltiazem (10−8to 10−4mol/L), and glyburide (5×10−6mol/L) did not alter relaxations to a nitric oxide donor, SIN-1 (10−9to 10−4mol/L). A calcium-activated potassium channel inhibitor, charybdotoxin (10−7mol/L), and a delayed rectifier potassium channel inhibitor, 4-aminopyridine (10−3mol/L), did not affect relaxations to acidosis.ConclusionsThese results suggest that extracellular acidosis causes relaxations of cerebral arteries in part by activation of potassium channels. ATP-sensitive potassium channels appear to contribute to acidosis-induced decrease in cerebral arterial tone.

Background and Purpose Many patients with acute basilar artery occlusion may require endotracheal intubation and mechanical ventilation. The circumstances and predictive value for outcome in these patients are not well documented. Methods We reviewed the medical records of 25 patients admitted into the intensive care unit with a clinical diagnosis of acute basilar artery occlusion and need for mechanical ventilation. The medical records were reviewed for clinical features, breathing patterns, mode of mechanical ventilation, ability to wean from the ventilator, and neurological outcome. Results Apneic episodes resulted in endotracheal intubation in 8 patients. In the remaining 17 patients, intubation was needed for airway protection. Seven of 8 patients presenting with apneic episodes lost all brain stem reflexes. All 17 patients intubated for airway protection could be successfully weaned to a T-tube circuit. Outcome was generally poor and 22 patients died, of whom 7 died of early systemic complications. Only 3 of 25 patients, all with locked-in syndrome, survived. Conclusions Mortality is high in patients who require mechanical ventilation after acute basilar artery occlusion. No neurological improvement beyond a locked-in syndrome occurred in survivors. Recurrent apnea appears to predict further progression to brain stem death.