The role of activators in assembly of RNA polymerase II transcription complexes

Since the negative results of the international Bypass Study, extracranial-intracranial (EC-IC) bypass surgery is infrequently employed in the treatment of patients with cerebral ischemia. Newly acquired evidence concerning the pathophysiology of cerebral ischemia, however, has facilitated the identification of a small subgroup of patients with "hemodynamic" cerebral ischemia. Characteristically, these patients demonstrate severely impaired cerebrovascular reserve capacity due to occlusive disease and insufficient collateral blood supply. Over an 8-year period, 28 patients were defined by clinical and laboratory criteria as suffering from hemodynamic cerebral ischemia. All patients had recurring episodes of focal cerebral ischemia due to unilateral internal carotid artery occlusion. Computerized tomography (CT) scans either were normal or showed evidence of border zone infarction. The cerebrovascular reserve capacity was studied using 133Xe single-photon emission CT and acetazolamide challenge and was found to be significantly impaired in all patients. Based on these criteria, superficial temporal artery-middle cerebral artery anastomosis was performed to augment collateral flow to the ischemic hemispheres. Two patients died from myocardial infarction, one 4 days and the other 2 months postoperatively. One patient died from massive brain infarction and another suffered a postoperative stroke with incomplete recovery, resulting in a major morbidity and mortality rate of 14%. Minor morbidity included one patient with a subdural hematoma who subsequently recovered completely. The postoperative course was uneventful in 23 patients (82%). Over a mean follow-up period of almost 3 years, no patient had another episode of brain ischemia. Bypass patency was confirmed by postoperative angiography in 26 patients. Follow-up studies of cerebral blood flow (CBF) and cerebrovascular reserve capacity showed significant improvement of the latter while the resting CBF was essentially unchanged. In view of these findings, the authors conclude that EC-IC bypass surgery constitutes appropriate therapy for a subgroup of patients with recurrent focal cerebral ischemia, defined using the strict selection criteria employed in this study.     

Odorant evoked magnetic fields in humans

To verify the optimal hematocrit (Hct) level in the treatment of cerebral ischemia, cerebral oxygen transport (CTO2) and cerebral oxygen metabolism (CMRO2) in graded isovolemic hemodilution were evaluated during cerebral ischemia. Isovolemic hemodilution with low molecular weight dextran to stepwise lower Hct from 43% to 36%, 31%, and 26% was carried out in 13 splenectomized dogs, 6 h after global cerebral ischemia. Global ischemia of the animals was produced by multiple intra- and extracranial ligations of cerebral arteries. Cerebral blood flow (CBF) was measured with radioisotope labeled microspheres. CTO2, CMRO2, and oxygen extraction fraction (OEF) were calculated from CBF, arterial oxygen content (CaO2), and venous oxygen content (CvO2). In dogs with global cerebral ischemia, CBF increased with graded isovolemic hemodilution (r=-0.73, P<0.05). CTO2 reached its highest value at a Hct level of 31.3%. CTO2 at Hct of 36.1% and 31.3% was statistically different from the value measured at a Hct of 43.3%, and there was a decrease when Hct was lowered to 25.9%. CMRO2 was the highest when Hct was at 31.3% and differed significantly from the value measured at a Hct of 43.3%. There was a 10% increase of OEF when Hct was at 25.9%; however this change was not statistically significant compared with the OEF at Hct of 36.1% and 31.3%, respectively. These findings indicate that CTO2 and CMRO2 were the highest when Hct was reduced to 31% in hemodilution. Hct at 31% is the optimum for cerebral metabolism in ischemic status. Uncoupling of CTO2, CMRO2 with CaO2 was also observed in this study. This phenomenon suggests that hemodilution to augment cerebral circulation may be at least partially attributed to the beneficial effects of hemorheologic improvement in the microcirculation of the ischemic brain.     

Frequency and severity of asymptomatic coronary disease in patients with different causes of stroke

BACKGROUND AND PURPOSE: We sought (1) to compare the frequency and severity of asymptomatic coronary artery disease (CAD) in patients with different causes of brain ischemia and (2) to determine profiles of patients with brain ischemia who are at highest risk of asymptomatic CAD. METHODS: Sixty-nine patients with transient ischemic attack or stroke and without overt CAD underwent a cardiac stress test and a diagnostic evaluation to determine the cause of brain ischemia. The frequency of abnormal cardiac stress tests was compared in patients with large-artery cerebrovascular disease versus other causes of brain ischemia (90% of whom had penetrating artery disease or cryptogenic stroke). Additionally, the frequencies of vascular risk factors, resting electrocardiographic abnormalities, and cause of stroke (large-artery disease versus other causes) were compared in patients with abnormal stress tests versus patients with normal stress tests. RESULTS: The frequency of abnormal stress tests was 50% (15 of 30) in patients with large-artery cerebrovascular disease versus 23% (9 of 39) in patients with other causes of brain ischemia (P = .04). Moreover, 60% of abnormal stress tests (9 of 15) in patients with large-artery cerebrovascular disease suggested severe underlying CAD that was confirmed in 7 of 7 patients who underwent coronary angiography. On the other hand, less than 25% of abnormal stress tests (2 of 9) in patients with other causes of brain ischemia suggested severe underlying CAD. Features that were more common in patients with abnormal stress tests were smoking (P = .006), large-artery cerebrovascular disease (P = .02), veteran status (P = .02), and left ventricular hypertrophy (P = .07). CONCLUSIONS: Patients with penetrating artery disease or cryptogenic stroke have a significantly lower frequency of asymptomatic CAD than patients with large-artery cerebrovascular disease. Large-artery cerebrovascular disease, smoking, veteran status, and possibly left ventricular hypertrophy may be useful features for identifying patients with transient ischemic attack or stroke who are at highest risk of harboring asymptomatic CAD.     

Safe hemoglobin or hematocrit levels in surgical patients

The terminology and fundamental aspects of the delivery, consumption, and deficits of oxygen are recalled. In chronic and acute, nonseptic states, red blood cell (RBC) transfusion is capable of increasing oxygen consumption (VO2). In acute septic states, the response of VO2 to RBC transfusion is variable and unpredictable, but attempts to increase oxygen delivery (DO2) should be made if the clinical picture raises the suspicion of a potentially lethal oxygen deficit. Therapeutic interventions raising the cardiac index to "supranormal" values in critically ill patients improve their chances of survival; and maintenance of hemoglobin or hematocrit values around 11 g/dl or 33%, respectively, is one part of such interventions. Opinions differ on the general tolerance of anemia, as witnessed by postulated "critical levels" of the hemoglobin concentration between approximately 11 and 4 to 5 g/dl or hematocrit values between 33% and 12% to 15%, respectively. The common denominator underlying these vastly different opinions is the variable behavior of several "non-Hb variables," which influence the venous oxygen tensions apart from the hemoglobin or hematocrit. Abnormalities of these non-Hb variables-typically encountered in the critically ill-increase the dependence of patients on hemoglobin or hematocrit levels that suffice to protect them against an oxygen deficit. For this reason, the "critical" hemoglobin or hematocrit is an individual value, and a generally valid "transfusion trigger" does not exist. Finally, the entity now known as silent myocardial ischemia (SMI) is a decisive factor for the tolerance of anemia. Solid clinical evidence is now available to support the concept that patients over age 40 should not, as an elective procedure, be subjected to levels < 10 g/dl or < 30%, respectively, without prior exclusion of SMI by appropriate investigations.     

Cerebral blood flow and the response to acetazolamide during the acute, subacute, and chronic stages of aneurysmal subarachnoid hemorrhage

Cerebral blood flow (CBF) and response to acetazolamide were measured during the acute, subacute, and chronic stages after aneurysmal subarachnoid hemorrhage and correlated with symptomatic vasospasm and clinical outcome in 45 patients who underwent early clipping of ruptured cerebral aneurysms, of whom 18 had symptomatic vasospasm and 27 did not. Xenon-enhanced computed tomography was used to measure CBF in both groups during the acute, subacute, and chronic stages, defined as days 0-4, 5-20, and > or = 21, respectively. Vasoresponse was assessed by the CBF increase in response to 1 g of acetazolamide administered after the baseline CBF study, except in the subacute stage of patients with symptomatic vasospasm. Outcome was scored based on activities of daily living 2-3 months after subarachnoid hemorrhage. CBF values and the response to acetazolamide were preserved during the acute stage but CBF values fell considerably below control values during the subacute stage in patients with vasospasm. The regions with flow values below 15 ml/100 g/min subsequently converted to infarction and the regions with those above 19 ml/100 g/min remained intact without infarction. During the chronic stage, low CBF persisted, but the response to acetazolamide was higher than that of the control group. Outcome scores were good and fair. CBF values were normal during all stages in patients without vasospasm. The response to acetazolamide fell transiently during the subacute stage. All outcome scores were excellent. In conclusion, the CBF informations soon after the onset of symptomatic vasospasm are useful to predict a reversibility of ischemic brain tissue and a final outcome. We suggest that vasospasm may cause a pathological or ischemic insult to brain tissue during the subacute stage, and the brain may remain metabolically depressed thereafter, leading to a poor outcome. Even clinically asymptomatic patients may suffer mildly vasospastic or ischemic conditions during the subacute stage.     

A new method for quantitative regional cerebral blood volume measurements using computed tomography

BACKGROUND AND PURPOSE: Knowledge of cerebral blood volume (CBV) is invaluable in identifying the primary cause of brain swelling in patients with stroke or severe head injury, and it might also help in clinical decision making in patients thought to have hemodynamic transient ischemic attacks (TIAs). This investigation is concerned with the development and clinical application of a new method for quantitative regional CBV measurements. METHODS: The technique is based on consecutive measurements of cerebral blood flow (CBF) by xenon/CT and tissue mean transit time (MTT) by dynamic CT after a rapid iodinated contrast bolus injection. CBV maps are produced by multiplication of the CBF and MTT maps in accordance with the Central Volume Principle: CBV = CBF x MTT. The method is rapid and easily implemented on CT scanners with the xenon/CBF capability. It yields CBV values expressed in milliliters of blood per 100 grams of tissue. RESULTS: The method was validated under controlled physiological conditions causing changes that were determined both with our technique and from pressure-volume index (PVI) measurements. The two independent estimates of CBV changes were in agreement within 15%. CBV measurements using this method were carried out in normal volunteers to establish baseline values and to compare with values using the ratio-of-areas method for calculating both CBF and CBV from the dynamic study alone. Average CBV was 5.3 mL/100 g. The method was also applied in 71 patients with severe head injuries and in 1 patient with hemodynamic TIAs. CONCLUSIONS: The primary conclusions from this study were (1) the proposed method for measuring CBV accurately determines changes in CBV; (2) the MTT x CBF determinations are in agreement with the ratio-of-areas method for CBV measurements in normal volunteers and are consistent with other methods reported in the literature; (3) MTTs are significantly prolonged early after severe head injury, which when combined with the finding of decreased CBF and increased arteriovenous difference of oxygen indicates increased cerebrovascular resistance due to narrowing of the microcirculation consistent with the presence of early ischemia; and (4) CBV in the patient with TIAs was increased in the hemisphere with the occluded internal carotid artery, indicating compensatory vasodilation and probable hemodynamic cause.     

Benzodiazepine receptors in chronic cerebrovascular disease: comparison with blood flow and metabolism

The brain benzodiazepine (BZD) receptor distribution in patients with chronic cerebrovascular disease was assessed with 123I-iomazenil (IMZ) SPECT, and the findings were compared with the data for the cerebral blood flow (CBF) and cerebral metabolism. METHODS: We examined nine patients with chronic cerebrovascular diseases, six patients with cerebral infarction and three with moyamoya disease. Iodine-123-IMZ SPECT images were obtained for 15 min, 3 hr after the administration of 167 or 222 MBq 123I-IMZ. In seven patients, the CBF and oxygen metabolism were measured by the 50 steady-state method. In two patients, the CBF and glucose metabolism were measured by 99mTc-HMPAO SPECT and 18F-fluoro-2-deoxy-D-glucose-PET, respectively. The brain was initially classified into 18 regions, and abnormalities in the BZD receptor distribution, CBF and cerebral metabolism were visually evaluated. The count ratio of lesion-to-contralateral normal region (L-to-C ratio) was then used for comparison. RESULTS: In the core of the infarct, the 123I-IMZ uptake decreased (L-to-C ratios of the blood flow 0.42 +/- 0.26; metabolism 0.45 +/- 0.24; and 123I-IMZ uptake 0.46 +/- 0.14). In the peri-infarct region, the 123I-IMZ uptake slightly decreased (L-to-C ratios of 0.81, 0.82 and 0.89, respectively). In the region of misery perfusion, the 123I-IMZ uptake was preserved (L-to-C ratios of 0.73, 1.07 and 1.02, respectively). In the remote deafferentiated areas in the ipsilateral cerebrum, the 123I-IMZ uptake was preserved (L-to-C ratios of 0.76 +/- 0.10, 0.75 +/- 0.04 and 0.98 +/- 0.05, respectively). In the remote areas in the contralateral cerebellum, the 123I-IMZ uptake was preserved (L-to-C ratios of 0.84 +/- 0.08, 0.85 +/- 0.04 and 0.94 +/- 0.05, respectively). CONCLUSION: The BZD receptor distribution, as measured by 123I-IMZ SPECT, is not considered to reflect neuronal function, but it may reflect neuronal cell viability. Iodine-123-IMZ SPECT may, therefore, hold promise as a potential probe for neuronal damage.     

Effect of Ouabain on cerebral blood flow (author's transl)

The effect of 0.25 mg ouabain on cerebral blood flow (CBF) was investigated in patients with and without cerebrovascular disease using the xenon clearance method. The 36 patients included in this study did not show any signs of heart failure. Ouabain increased the CBF and this effect was demonstrable 15, as well as 90 min. after administration. This effect was proven statistically using the t-test for a comparison of the values with spontaneous changes in a control group without medication. The perfusion of pathologically-supplied brain regions was altered in the same way as the hemispheric flow; changes in the distribution of blood in the way of a steal effect were not observed. The haemodynamic parameters do not indicate a primary cardiac effect. Hence, an influence of ouabain on cerebral vessels might be responsible. The present results support reported clinical experience with ouabain for the treatment of patients with cerebrosvascular disease.     

A rapid method for DNA extraction from fine-needle aspiration biopsies of thyroid tumors, and subsequent RET mutation analysis

In 22 consecutive patients with tetralogy of Fallot (TF), a total correction was attempted without the use of a homologous blood transfusion from September 1995 to March 1997. The 22 patients were divided into two groups according to their surgical procedures; namely, either a simple correction (group I: n = 14) or a complex correction including the relief of peripheral pulmonary stenosis and/or the division of a previous systemic-pulmonary shunt (group II: n = 8). In 77% of all patients, surgery was performed without a homologous blood transfusion. No differences were found in the non-transfusion rate and the hematocrit (Ht) values between the two groups and, as a result, we thus confirm that this additional procedure is not a risk factor for surgery without a homologous blood transfusion. According to the correlation of the red blood cell volume before and after surgery, the preoperative Ht value corresponding to the postoperative Ht of 30% could be accurately predicted. The calculated Ht values were 41.0% in the patient weighing 15 kg, 42.5% in those weighing 10 kg, and 46.9% in those weighing 5 kg. These data suggest that a surgical correction without a homologous blood transfusion can therefore be safely performed in almost all patients with TF.     

Effects of the allosteric modification of hemoglobin on brain oxygen and infarct size in a feline model of stroke

BACKGROUND AND PURPOSE: Cerebral ischemia and stroke are leading causes of morbidity and mortality. An approach to protecting the brain during ischemia is to try to increase the delivery of oxygen via the residual blood flow through and around ischemic tissue. To test this hypothesis, we used a novel oxygen delivery agent, RSR-13 (2-[4-[[(3,5-dimethylanilino)-carbonyl]-methyl]phenoxy]-2-methylpr opionic acid). Intravenous administration of RSR-13 increases oxygen delivery through allosteric modification of the hemoglobin molecule, resulting in a shift in the hemoglobin/oxygen dissociation curve in favour of oxygen delivery. METHODS: We studied RSR-13 in a feline model of permanent middle cerebral artery occlusion to assess its effects on cerebral oxygenation and infarct size. A randomized, blinded study of RSR-13 (n = 6) versus 0.45% saline (n = 12) was conducted, after an RSR-13 dose-escalation study (n = 4). Drug was administered as a preocclusion bolus followed by a continuous infusion for the duration of the experiment (5 hours). Brain oxygen was measured continuously with the use of a Clark oxygen electrode. Infarct size was measured at 5 hours after occlusion with computer-assisted volumetric analysis. RESULTS: The drug treatment group had consistently higher mean brain oxygen tension than controls (33 +/- 5 and 27 +/- 6 mm Hg, respectively) and significantly smaller infarcts (21 +/- 9% versus 33 +/- 9%, respectively, P < .008). We observed an inverse relationship between the dose response of RSR-13 (the shift in the hemoglobin/oxygen dissociation curve) and infarct size. CONCLUSIONS: These results are evidence that allosteric hemoglobin modification is protective to the brain after acute focal ischemia, providing a new opportunity for neuroprotection and raising the possibility of enhancing the protective effect of thrombolysis and ion channel blockade.     

Levels of serum granulocyte colony-stimulating factor in patients with cerebrovascular diseases

The role of leukocytes in the pathogenesis of cerebrovascular disease, in particular, cerebral ischemic disease has recently become a focus of research. Several studies have reported that a positive correlation between increased functional activities of neutrophils and the risk of cerebral ischemic disease. Granulocyte colony-stimulating factor (G-CSF) is known to be not only a granulocyte proliferating factor but also a potent activator of mature neutrophils. In this study, we measured the serum G-CSF levels in 143 patients with cerebrovascular diseases and in 100 patients with other diseases, using our established enzyme-linked immunosorbent assay (ELISA) for G-CSF The minimal detection level was 20 pg/ml G-CSF. In patients with cerebral infarction, G-CSF could be detected in 18.3% and in patients with cerebral hemorrhage, it could be detected in 9.8% of analyzed samples. On the other hand, 6% of the patients with other diseases had measurable levels of G-CSF. The differences among these three groups were statistically significant according to the chi 2 test (p < 0.01). Our findings that there was a significantly high frequency of elevated levels of G-CSF among patients with cerebrovascular diseases, may indicate that the action of G-CSF as a potent activator of neutrophils plays some role in the occurrence of cerebrovascular disease, in particular, cerebral infarction.     

Cerebral revascularization using muscle free flap for ischemic cerebrovascular disease in adult patients

The efficacy of encephalo-myo-synangiosis (EMS) using muscle free flap was evaluated for the treatment of ischemic cerebrovascular disease in adult patients. Three patients with adult moyamoya disease and three patients with atherosclerotic ischemic cerebrovascular disease were treated. EMS used four latissimus dorsi muscles and two serratus anterior muscles. Postoperative selective angiography showed collateral circulation from the transferred muscle to the brain in four of the six patients. The other two patients showed patent nutrient artery of the transferred muscle flap. Cerebral blood flow study disclosed postoperative improvement of perfusion reserve capacity in all sides. One patient suffered a perioperative stroke by hemoconcentration due to poor control of diabetes mellitus. The mean follow-up period was 23 months. EMS using muscle free flap is a possible procedure in selected patients with impaired cerebral perfusion reserve capacity due to multiple stenosis or occlusion of cerebral arteries including moyamoya disease or who required cerebral blood flow augmentation in the anterior and/or posterior cerebral artery territories due to internal carotid artery occlusion.     

A model for the regulation of cerebral oxygen delivery

On the basis of the assumption that oxygen delivery across the endothelium is proportional to capillary plasma PO2, a model is presented that links cerebral metabolic rate of oxygen utilization (CMRO2) to cerebral blood flow (CBF) through an effective diffusivity for oxygen (D) of the capillary bed. On the basis of in vivo evidence that the oxygen diffusivity properties of the capillary bed may be altered by changes in capillary PO2, hematocrit, and/or blood volume, the model allows changes in D with changes in CBF. Choice in the model of the appropriate ratio of Omega identical with (DeltaD/D)/(DeltaCBF/CBF) determines the dependence of tissue oxygen delivery on perfusion. Buxton and Frank (J. Cereb. Blood Flow. Metab. 17: 64-72, 1997) recently presented a limiting case of the present model in which Omega = 0. In contrast to the trends predicted by the model of Buxton and Frank, in the current model when Omega > 0, the proportionality between changes in CBF and CMRO2 becomes more linear, and similar degrees of proportionality can exist at different basal values of oxygen extraction fraction. The model is able to fit the observed proportionalities between CBF and CMRO2 for a large range of physiological data. Although the model does not validate any particular observed proportionality between CBF and CMRO2, generally values of (DeltaCMRO2/CMRO2)/(DeltaCBF/CBF) close to unity have been observed across ranges of graded anesthesia in rats and humans and for particular functional activations in humans. The model's capacity to fit the wide range of data indicates that the oxygen diffusivity properties of the capillary bed, which can be modified in relation to perfusion, play an important role in regulating cerebral oxygen delivery in vivo.     

The effects of normal as compared with low hematocrit values in patients with cardiac disease who are receiving hemodialysis and epoetin

BACKGROUND: In patients with end-stage renal disease, anemia develops as a result of erythropoietin deficiency, and recombinant human erythropoietin (epoetin) is prescribed to correct the anemia partially. We examined the risks and benefits of normalizing the hematocrit in patients with cardiac disease who were undergoing hemodialysis. METHODS: We studied 1233 patients with clinical evidence of congestive heart failure or ischemic heart disease who were undergoing hemodialysis: 618 patients were assigned to receive increasing doses of epoetin to achieve and maintain a hematocrit of 42 percent, and 615 were assigned to receive doses of epoetin sufficient to maintain a hematocrit of 30 percent throughout the study. The median duration of treatment was 14 months. The primary end point was the length of time to death or a first nonfatal myocardial infarction. RESULTS: After 29 months, there were 183 deaths and 19 first nonfatal myocardial infarctions among the patients in the normal-hematocrit group and 150 deaths and 14 nonfatal myocardial infarctions among those in the low-hematocrit group (risk ratio for the normal-hematocrit group as compared with the low-hematocrit group, 1.3; 95 percent confidence interval, 0.9 to 1.9). Although the difference in event-free survival between the two groups did not reach the prespecified statistical stopping boundary, the study was halted. The causes of death in the two groups were similar. The mortality rates decreased with increasing hematocrit values in both groups. The patients in the normal-hematocrit group had a decline in the adequacy of dialysis and received intravenous iron dextran more often than those in the low-hematocrit group. CONCLUSIONS: In patients with clinically evident congestive heart failure or ischemic heart disease who are receiving hemodialysis, administration of epoetin to raise their hematocrit to 42 percent is not recommended.     

Fastigial stimulation increases ischemic blood flow and reduces brain damage after focal ischemia

Electrical stimulation of the cerebellar fastigial nucleus (FN) increases CBF and reduces brain damage after focal ischemia. We studied whether FN stimulation "protects" the brain from ischemic damage by increasing blood flow to the ischemic territory. Sprague-Dawley rats were anesthetized (halothane 1-3%) and artificially ventilated through a tracheal cannula inserted transorally. CBF was monitored by a laser-Doppler probe placed over the convexity at a site corresponding to the area spared from infarction by FN stimulation. Arterial pressure (AP), blood gases, and body temperature were controlled, and the electroencephalogram (EEG) was monitored. The stem of the middle cerebral artery (MCA) was occluded. After occlusion, the FN was stimulated for 60 min (100 microA; 50 Hz; 1 s on-1 s off) while AP was maintained at 97 +/- 11 mm Hg (mean +/- SD) by controlled hemorrhage. Rats were then allowed to recover, and infarct volume was determined 24 h later in thionin-stained sections. In unstimulated rats (n = 7), proximal MCA occlusion reduced CBF and the amplitude of the EEG. One day later, these rats had infarcts involving neocortex and striatum. FN stimulation after MCA occlusion (n = 12) enhanced CBF and EEG recovery [61 +/- 34 and 73 +/- 43%, respectively at 60 min; p < 0.05 vs. unstimulated group; analysis of variance (ANOVA)] and reduced the volume of the cortical infarct by 48% (p < 0.05). In contrast, hypercapnia (PCO2 = 64 +/- 4; n = 7) did not affect CBF and EEG recovery or infarct volume (p > 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Cerebral oxygenation during warming after cardiopulmonary bypass

OBJECTIVES: To evaluate jugular venous oxygen saturation (SjVO2), measured with a fiberoptic oximetry catheter, and brain tissue oxygen saturation, measured by near-infrared spectroscopy (NIRSO2), as monitors of cerebral oxygenation during cardiopulmonary bypass surgery. DESIGN: Prospective, clinical study. SETTING: Operating room of a Veterans Administration Hospital. PATIENTS: Nineteen patients undergoing moderate hypothermic cardiopulmonary bypass surgery. INTERVENTIONS: SjvO2 and NIRSO2 were monitored in the patients during the surgical procedure. MEASUREMENTS AND MAIN RESULTS: Moderate hypothermic cardiopulmonary bypass surgery had two distinct cerebral hemodynamic phases. While the patients were hypothermic, SjvO2 averaged 80 +/- 7% and none of the patients had an increase in cerebral lactate production. During the rewarming period, however, reductions in SjvO2 to < 50% occurred in 16 (84%) patients and increased cerebral anaerobic metabolism developed in 11 (58%) patients. SjvO2 during rewarming was dependent on mean arterial pressure, with 60 mm Hg appearing to be a critical value. Two other factors appeared to also contribute to the jugular desaturation, a low hematocrit and a rapid warming time. The SjvO2 catheter had excellent performance during the surgery. The average difference between paired measurements of SjvO2 by the catheter and in blood samples was -0.4 +/- 4.25%, and the correlation between the two measurements was highly significant (r2 = .93; p < .001). The NIRSO2 trended with the SjvO2 in most patients (r2 = .63; p < .001). CONCLUSIONS: The study confirms other studies showing that jugular venous desaturation can occur during rewarming after cardiopulmonary bypass surgery. Presently, SjvO2 appears to be a better monitor of cerebral oxygenation than NIRSO2. However, NIRSO2 has promise as a noninvasive monitor of cerebral oxygenation if future developments allow more quantitative measurements of oxygen saturation.     

Assessment of cerebral blood flow reserve using functional magnetic resonance imaging

Imaging of activated brain areas based on changes of blood deoxyhemoglobin levels is now possible with MRI. Acetazolamide (ACZ) increases cerebral blood flow (CBF) without changing cerebral oxygen consumption; this results in signal changes observed in gradient echo MR images from the areas with an increase in CBF. We assessed signal changes after ACZ application in seven healthy subjects with a conventional 1.5-T MRI scanner. The susceptibility-sensitized three-dimensional fast low-angle shot (FLASH) sequence was used to visualize signal changes induced by ACZ. We analyzed anatomic localization of different ranges of detected signal changes. ACZ caused significant signal changes in the gray matter and at the edge of the cerebral cortex, the latter corresponding to draining surface veins. No significant differences were seen among different brain areas within the same slice. Using the maximal intensity projection technique, we were able to partially separate signal changes originating in draining veins from signal originating in the gray matter microvasculature. Signal changes from the microvessels reflect cerebrovascular reserve. Blood-oxygen-level-dependent (BOLD) based MRI can evaluate CBF reserve with high spatial and temporal resolution. To assess cerebrovascular reserve, it is necessary to separate signal changes originating in large vessels from signal from brain microvasculature.     

Dominance--one hundred and fifteen years after Mendel''s paper

Eight conscious chronically instrumented sheep were exposed to 1% inspired carbon monoxide (CO) for 35 min. In all sheep, carboxyhaemoglobin (COHb) levels at the end of the exposure were approximately 65%. Mean arterial blood pressure was unchanged with the exception of 2 sheep in which administration was stopped at 25 min following the sudden onset of hypotension. Oxygen delivery to the brain was sustained throughout the administration of CO due to a significant increase in cerebral blood flow (CBF). There was no evidence of either a metabolic acidosis or of lactate production by the brain suggesting the brain did not become hypoxic during the time-course of this study. Despite the apparent lack of hypoxia, oxygen consumption by the brain fell progressively and the sheep showed behavioural changes which varied from agitation to sedation and narcosis. The mechanism of these changes was therefore probably unrelated to hypoxia, but may have been due to raised intracranial pressure or a direct effect of CO on brain function. It is proposed that the time-course of progressive CO poisoning includes a phase in which CBF is elevated, blood pressure is unchanged and the brain is normoxic despite high COHb levels, but that this situation can rapidly evolve into a phase of haemodynamic collapse and severe hypoxia.     

Changes in cerebral blood flow and oxygen metabolism related to magnetic resonance imaging white matter hyperintensities in Alzheimer's disease

We studied changes in cerebral perfusion and oxygen metabolism to elucidate the pathophysiological nature and clinical significance of white matter hyperintensities in Alzheimer's disease (AD). METHODS: Sixteen AD patients (age 71.6 +/- 3.1 yr) whose T2-weighted MR images showed white matter hyperintensities, and 16 age-matched AD patients (age 71.0 +/- 4.3 yr) without white matter hyperintensities were compared. Regional cerebral blood flow (CBF), oxygen metabolism (CMRO2) and oxygen extraction fraction (OEF) were measured by using (15)O steady-state method and PET. RESULTS: There was no significant difference in cognitive impairment between the two groups. Compared to the patients without white matter hyperintensities, those with them had significantly low CBF values and significantly high OEF values in all cortical and white matter regions. However, there were no significant differences in CMRO2 values between the two groups. Severity of white matter hyperintensities correlated with the mean cortical and mean white matter OEF. CONCLUSION: In AD patients, white matter hyperintensities on T2-weighted MR images represent ischemic changes in which oxygen metabolism and function are fairly compensated. These changes are not disease-specific but are age-associated coincidences, as in normal aging with or without vascular risk factors.     

Effects of endoscopic variceal ligation on oxygen transport and the arterial lactate levels in patients with cirrhosis

OBJECTIVE: Despite the increased cardiac output and oxygen delivery, an impaired oxygen uptake has been noted in patients with cirrhosis. We recently observed that endoscopic variceal ligation decreased the cardiac output due to a reduction in the cardiac preload. It is thus possible that a variceal ligation decreases the oxygen delivery and thereby negatively influences tissue oxygenation in patients receiving such treatment. We thus investigated the effects of variceal ligation on oxygen delivery, oxygen uptake, and the arterial lactate levels. METHODS: There were 22 patients with compensated cirrhosis and risky esophageal varices (Child's class A:B=13:9). Twelve patients underwent an endoscopic variceal ligation and 10 patients received gastroscopy as a control. The cardiac function, blood gas status, oxygen delivery, and arterial lactate concentration were also assessed before and after variceal ligation. The oxygen uptake was calculated by the Fick equation. RESULTS: Following variceal ligation, there was an immediate decrease in the cardiac output and oxygen delivery. The reduction in oxygen delivery was associated with a slight but significant increase in the arterial lactate concentration. The decreased oxygen delivery was also associated with a concomitant decrease in the oxygen uptake. In the control subjects, gastroscopy did not alter the systemic hemodynamics, arterial oxygen status, or arterial lactate levels. CONCLUSION: We found a significant decrease in the oxygen delivery in patients undergoing an endoscopic variceal ligation. Such deteriorated tissue oxygenation may be serious especially in patients with a low oxygen transport ability such as in patients with variceal hemorrhage with anemia. However, the clinical significance of these changes remains unclear and further studies are therefore warranted.