Perioperative stroke.

Ischaemic or haemorrhagic perioperative stroke (that is, stroke occurring during or within 30 days following surgery) can be a devastating complication following surgery. Incidence is reported in the 0.1-0.7% range in adults undergoing non-cardiac and non-neurological surgery, in the 1-5% range in patients undergoing cardiac surgery and in the 1-10% range following neurological surgery. However, higher rates have been reported when patients are actively assessed and in high-risk populations. Prognosis is significantly worse than stroke occurring in the community, with double the 30-day mortality, greater disability and diminished quality of life among survivors. Considering the annual volume of surgeries performed worldwide, perioperative stroke represents a substantial burden. Despite notable differences in aetiology, patient populations and clinical settings, existing clinical recommendations for perioperative stroke are extrapolated mainly from stroke in the community. Perioperative in-hospital stroke is unique with respect to the stroke occurring in other settings, and it is essential to apply evidence from other settings with caution and to identify existing knowledge gaps in order to effectively guide patient care and future research.

Postoperative stroke assessment inconsistencies in cardiac surgery: Contributors to higher stroke-related mortality?

OBJECTIVES: In-hospital stroke mortality is surprisingly much worse than for strokes occurring outside of the hospital. Cardiac surgery patients are amongst the highest risk groups for in-hospital stroke and experience high stroke-related mortality. Variability in institutional practices appears to play an important role in the diagnosis, management, and outcome of postoperative stroke. We therefore tested the hypothesis that variability in postoperative stroke management of cardiac surgical patients exists across institutions. MATERIALS AND METHODS: A 13 item survey was employed to determine postoperative stroke practice patterns for cardiac surgical patients across 45 academic institutions. RESULTS: Less than half (44%) reported any formal clinical effort to preoperatively identify patients at high risk for postoperative stroke. Epiaortic ultrasonography for the detection of aortic atheroma, a proven preventative measure, was routinely practiced in only 16% of institutions. Forty-four percent (44%) reported not knowing whether a validated stroke assessment tool was utilized for the detection of postoperative stroke, and 20% reported that validated tools were not routinely used. All responders, however, confirmed the availability of stroke intervention teams. CONCLUSIONS: Adoption of a best practices approach to the management of postoperative stroke is highly variable and may improve outcomes in postoperative stroke after cardiac surgery.

Preoperative cognition predicts clinical stroke/TIA and mortality after surgical aortic valve replacement in older adults.

Stroke and death remain risks of surgical aortic valve replacement (SAVR). Preoperative cognitive screeners repeatedly show that reduced scores predict postoperative outcome, but less is known about comprehensive neuropsychological measures predicting risk. This study had two aims: 1) investigate whether preoperative cognitive measures predicted postoperative clinical stroke/transient ischemic attack (TIA) and mortality in older adults undergoing SAVR, and 2) identify the best predictors within a comprehensive cognitive protocol. A total of 165 participants aged 65 + with moderate-to-severe aortic stenosis completed a comprehensive cognitive test battery preoperatively. Postoperative stroke evaluations were conducted by trained stroke neurologists preoperatively and postoperatively, and mortality outcomes were obtained by report and records. Logistic regressions were conducted to evaluate preoperative cognitive predictors of clinical stroke/TIA within 1 week of surgery and mortality within 1 year of surgery. Multivariate models showed measures of delayed verbal memory recall (OR = 0.86; 95% CI 0.74-0.99) and visuospatial skills (OR = 0.95; 95% CI 0.90-1.01) predicted clinical stroke/TIA within 1 week of surgery, R2 = .41, p < .001, ƒ2 = .69. Measures of naming ability (OR = 0.88; 95% CI 0.80-0.96), verbal memory recall (OR = 1.23; 95% CI 0.99-1.51), visual memory recall (OR = 0.90; 95% CI 0.80-1.00), medical comorbidities (OR = 1.71; 95% CI 1.22-2.65), and sex (OR = 2.39; 95% CI 0.90-7.04) were significant predictors of death within 1 year of surgery, R2 = .68, p < .001, ƒ2 = 2.12. Preoperative cognitive measures reflecting temporal and parietal lobe functions predicted postoperative clinical stroke/TIA within 1 week of SAVR and mortality within 1 year of SAVR. As such, cognitive measures may offer objective and timely indicators of preoperative health, specifically vulnerabilities in cerebral hypoperfusion, which may inform intervention and/or intensive postoperative monitoring and follow-up after SAVR.

Multi-Site Optical Monitoring of Spinal Cord Ischemia during Spine Distraction.

Optimal surgical management of spine trauma will restore blood flow to the ischemic spinal cord. However, spine stabilization may also further exacerbate injury by inducing ischemia. Current electrophysiological technology is not capable of detecting acute changes in spinal cord blood flow or localizing ischemia. Further, alerts are delayed and unreliable. We developed an epidural optical device capable of directly measuring and immediately detecting changes in spinal cord blood flow using diffuse correlation spectroscopy (DCS). Herein we test the hypothesis that our device can continuously monitor blood flow during spine distraction. Additionally, we demonstrate the ability of our device to monitor multiple sites along the spinal cord and axially resolve changes in spinal cord blood flow. DCS-measured blood flow in the spinal cord was monitored at up to three spatial locations (cranial to, at, and caudal to the distraction site) during surgical distraction in a sheep model. Distraction was halted at 50% of baseline blood flow at the distraction site. We were able to monitor blood flow with DCS in multiple regions of the spinal cord simultaneously at ∼1 Hz. The distraction site had a greater decrement in flow than sites cranial to the injury (median -40 vs. -7%,). This pilot study demonstrated high temporal resolution and the capacity to axially resolve changes in spinal cord blood flow at and remote from the site of distraction. These early results suggest that this technology may assist in the surgical management of spine trauma and in corrective surgery of the spine.

Cognition and Cerebral Infarction in Older Adults After Surgical Aortic Valve Replacement.

BACKGROUND: Aortic valve replacement (AVR) for calcific aortic stenosis is associated with high rates of perioperative stroke and silent cerebral infarcts on diffusion-weighted magnetic resonance imaging (MRI), but cognitive outcomes in elderly AVR patients compared with individuals with cardiac disease who do not undergo surgery are uncertain. METHODS: One hundred ninety AVR patients (mean age 76 ± 6 years) and 198 non-surgical participants with cardiovascular disease (mean age 74 ± 6 years) completed comprehensive cognitive testing at baseline (preoperatively) and 4 to 6 weeks and 1 year postoperatively. Surgical participants also completed perioperative stroke evaluations, including postoperative brain MRI. Mixed model analyses and reliable change scores examined cognitive outcomes. Stroke outcomes were evaluated in participants with and without postoperative cognitive dysfunction. RESULTS: From reliable change scores, only 12.4% of the surgical group demonstrated postoperative cognitive dysfunction at 4 to 6 weeks and 7.5% at 1 year. Although the surgical group had statistically significantly lower scores in working memory/inhibition 4 to 6 weeks after surgery, the groups did not differ at 1 year. In surgical participants, postoperative cognitive dysfunction was associated with a greater number (p < 0.01) and larger total volume (p < 0.01) of acute cerebral infarcts on MRI. CONCLUSIONS: In high-risk, aged participants undergoing surgical AVR for aortic stenosis, postoperative cognitive dysfunction was surprisingly limited and was resolved by 1 year in most. Postoperative cognitive dysfunction at 4 to 6 weeks was associated with more and larger acute cerebral infarcts.

Laser safety in fiber-optic monitoring of spinal cord hemodynamics: a preclinical evaluation.

The prevention and treatment of spinal cord injury are focused upon the maintenance of spinal cord blood flow, yet no technology exists to monitor spinal cord ischemia. We recently demonstrated continuous monitoring of spinal cord ischemia with diffuse correlation and optical spectroscopies using an optical probe. Prior to clinical translation of this technology, it is critically important to demonstrate the safety profile of spinal cord exposure to the required light. To our knowledge, this is the first report of in situ safety testing of such a monitor. We expose the spinal cord to laser light utilizing a custom fiber-optic epidural probe in a survival surgery model (11 adult Dorset sheep). We compare the tissue illumination from our instrument with the American National Standards Institute maximum permissible exposures. We experimentally evaluate neurological and pathological outcomes of the irradiated sheep associated with prolonged exposure to the laser source and evaluate heating in ex vivo spinal cord samples. Spinal cord tissue was exposed to light levels at ∼18 × the maximum permissible exposure for the eye and ∼ ( 1 / 3 ) × for the skin. Multidisciplinary testing revealed no functional neurological sequelae, histopathologic evidence of laser-related injury to the spinal cord, or significant temperature changes in ex vivo samples. Low tissue irradiance and the lack of neurological, pathological, and temperature changes upon prolonged exposure to the laser source offer evidence that spinal cord tissues can be monitored safely with near-infrared optical probes placed within the epidural space.

Pathogenesis and Risk Factors for Cerebral Infarct After Surgical Aortic Valve Replacement.

BACKGROUND AND PURPOSE: Stroke is a potentially devastating complication of cardiac surgery. Identifying predictors of radiographic infarct may lead to improved stroke prevention for surgical patients. METHODS: We reviewed 129 postoperative brain magnetic resonance imagings from a prospective study of patients undergoing surgical aortic valve replacement. Acute infarcts were classified as watershed or embolic using prespecified criteria. RESULTS: Acute infarct on magnetic resonance imaging was seen in 79 of 129 patients (61%), and interrater reliability for stroke pathogenesis was high (κ=0.93). Embolic infarcts only were identified in 60 patients (46%), watershed only in 2 (2%), and both in 17 (13%). In multivariable logistic regression, embolic infarct was associated with aortic arch atheroma (odds ratio [OR], 3.4; 95% confidence interval [CI], 1.0-12.0; P=0.055), old subcortical infarcts (OR, 5.5; 95% CI, 1.1-26.6; P=0.04), no history of percutaneous transluminal coronary angioplasty or coronary artery bypass graft (OR, 4.0; 95% CI, 1.2-13.7; P=0.03), and higher aortic valve gradient (OR, 1.3 per 5 mm Hg; 95% CI, 1.09-1.6; P=0.004). Watershed infarct was associated with internal carotid artery stenosis ≥70% (OR, 11.7; 95% CI, 1.8-76.8; P=0.01) and increased left ventricular ejection fraction (OR, 1.6 per 5% increase; 95% CI, 1.08-2.4; P=0.02). CONCLUSIONS: The principal mechanism of acute cerebral infarction after aortic valve replacement is embolism. There are distinct factors associated with watershed and embolic infarct, some of which may be modifiable.

Stroke after aortic valve surgery: results from a prospective cohort.

BACKGROUND: The incidence and impact of clinical stroke and silent radiographic cerebral infarction complicating open surgical aortic valve replacement (AVR) are poorly characterized. METHODS AND RESULTS: We performed a prospective cohort study of subjects ≥65 years of age who were undergoing AVR for calcific aortic stenosis. Subjects were evaluated by neurologists preoperatively and postoperatively and underwent postoperative magnetic resonance imaging. Over a 4-year period, 196 subjects were enrolled at 2 sites (mean age, 75.8±6.2 years; 36% women; 6% nonwhite). Clinical strokes were detected in 17%, transient ischemic attack in 2%, and in-hospital mortality was 5%. The frequency of stroke in the Society for Thoracic Surgery database in this cohort was 7%. Most strokes were mild; the median National Institutes of Health Stroke Scale was 3 (interquartile range, 1-9). Clinical stroke was associated with increased length of stay (median, 12 versus 10 days; P=0.02). Moderate or severe stroke (National Institutes of Health Stroke Scale ≥10) occurred in 8 (4%) and was strongly associated with in-hospital mortality (38% versus 4%; P=0.005). Of the 109 stroke-free subjects with postoperative magnetic resonance imaging, silent infarct was identified in 59 (54%). Silent infarct was not associated with in-hospital mortality or increased length of stay. CONCLUSIONS: Clinical stroke after AVR was more common than reported previously, more than double for this same cohort in the Society for Thoracic Surgery database, and silent cerebral infarctions were detected in more than half of the patients undergoing AVR. Clinical stroke complicating AVR is associated with increased length of stay and mortality.

Optical monitoring and detection of spinal cord ischemia.

Spinal cord ischemia can lead to paralysis or paraparesis, but if detected early it may be amenable to treatment. Current methods use evoked potentials for detection of spinal cord ischemia, a decades old technology whose warning signs are indirect and significantly delayed from the onset of ischemia. Here we introduce and demonstrate a prototype fiber optic device that directly measures spinal cord blood flow and oxygenation. This technical advance in neurological monitoring promises a new standard of care for detection of spinal cord ischemia and the opportunity for early intervention. We demonstrate the probe in an adult Dorset sheep model. Both open and percutaneous approaches were evaluated during pharmacologic, physiological, and mechanical interventions designed to induce variations in spinal cord blood flow and oxygenation. The induced variations were rapidly and reproducibly detected, demonstrating direct measurement of spinal cord ischemia in real-time. In the future, this form of hemodynamic spinal cord diagnosis could significantly improve monitoring and management in a broad range of patients, including those undergoing thoracic and abdominal aortic revascularization, spine stabilization procedures for scoliosis and trauma, spinal cord tumor resection, and those requiring management of spinal cord injury in intensive care settings.

An organized, comprehensive, and security-enabled strategic response to the Haiti earthquake: a description of pre-deployment readiness preparation and preliminary experience from an academic anesthesiology department with no preexisting international disaster response program.

BACKGROUND: On Tuesday, January 12, 2010 at 16:53 local time, a magnitude 7.0 M(w) earthquake struck Haiti. The global humanitarian attempt to respond was swift, but poor infrastructure and emergency preparedness limited many efforts. Rapid, successful deployment of emergency medical care teams was accomplished by organizations with experience in mass disaster casualty response. Well-intentioned, but unprepared, medical teams also responded. In this report, we describe the preparation and planning process used at an academic university department of anesthesiology with no preexisting international disaster response program, after a call from an American-based nongovernmental organization operating in Haiti requested medical support. The focus of this article is the pre-deployment readiness process, and is not a post-deployment report describing the medical care provided in Haiti. METHODS: A real-time qualitative assessment and systematic review of the Hospital of the University of Pennsylvania's communications and actions relevant to the Haiti earthquake were performed. Team meetings, conference calls, and electronic mail communication pertaining to planning, decision support, equipment procurement, and actions and steps up to the day of deployment were reviewed and abstracted. Timing of key events was compiled and a response timeline for this process was developed. Interviews with returning anesthesiology members were conducted. RESULTS: Four days after the Haiti earthquake, Partners in Health, a nonprofit, nongovernmental organization based in Boston, Massachusetts, with >20 years of experience providing medical care in Haiti contacted the University of Pennsylvania Health System to request medical team support. The departments of anesthesiology, surgery, orthopedics, and nursing responded to this request with a volunteer selection process, vaccination program, and systematic development of equipment lists. World Health Organization and Centers for Disease Control guidelines, the American Society of Anesthesiology Committee on Trauma and Emergency Preparedness, published articles, and in-country contacts were used to guide the preparatory process. CONCLUSION: An organized strategic response to medical needs after an international natural disaster emergency can be accomplished safely and effectively within 6 to 12 days by an academic anesthesiology department, with medical system support, in a center with no previously established response system. The value and timeliness of this response will be determined with further study. Institutions with limited experience in putting an emergency medical team into the field may be able to quickly do so when such efforts are executed in a systematic manner in coordination with a health care organization that already has support infrastructure at the site of the disaster.

Acute anemia elicits cognitive dysfunction and evidence of cerebral cellular hypoxia in older rats with systemic hypertension.

BACKGROUND: Postoperative cognitive dysfunction occurs frequently after cardiac, major vascular, and major orthopedic surgery. Aging and hypertensive cerebrovascular disease are leading risk factors for this disorder. Acute anemia, common to major surgery, has been identified as a possible contributor to postoperative cognitive dysfunction. The effect of hypoxia upon cognition and the cellular and molecular processes involved in learning and memory has been well described. Cerebrovascular changes related to chronic hypertension may expose cells to increased hypoxia with anemia. METHODS: Young to aged spontaneously hypertensive rats underwent testing for visuospatial memory and learning in the Morris water maze, measurement of cerebral tissue oxygenation via tissue oxygen probe, and measurement of hypoxia-sensitive genes and proteins, under conditions of sham and experimental isovolemic anemia. RESULTS: Acute isovolemic anemia elicited evidence of aging-dependent visuospatial working memory and learning impairment. Isovolemic anemia did not result in cerebral tissue hypoxia, when measured via tissue oxygen probe. Evidence of cellular hypoxia was, however, identified in response to the anemic challenge, as hypoxia-sensitive genes and proteins were up-regulated. Importantly, cellular hypoxic gene responses were increased with anemia in an age-dependent manner in this model of aging with chronic hypertension. CONCLUSIONS: In a translational model of chronic hypertension, clinically relevant levels of acute anemia were associated with an age-dependent visuospatial working memory and learning impairment that was matched by an age-dependent cellular sensitivity to anemic hypoxia. These data offer support for a possible link between anemic hypoxia and postoperative cognitive dysfunction in humans.

Sex, aging, and preexisting cerebral ischemic disease in patients with aortic stenosis.

BACKGROUND: Patients undergoing cardiac surgery have a high frequency of preexisting cerebral ischemic lesions, the presence of which appears to predict cognitive sequelae. Patients undergoing aortic valve replacement for aortic stenosis (AS) incur an exceptionally high risk for perioperative cerebral ischemia. The extreme risk in this subgroup may arise from the preexisting burden of cerebral ischemic disease. We tested the hypotheses that increasing age, female sex, coronary artery disease, and the severity of AS are predictive of the severity of preexisting cerebral ischemic lesions. METHODS: A total of 95 subjects were included in this study. Subjects were imaged on 1.5 Tesla magnetic resonance imaging scanners to obtain multimodal image sets which were used for the automatic segmentation of cerebral lesion volume. The dependence of lesion volume upon age, sex, coronary artery disease, and the severity of AS were tested. RESULTS: The results demonstrate a strong correlation between aging, female sex, and white matter and ischemia-like lesion volume in patients with aortic stenosis. CONCLUSIONS: Women and those of advanced age presenting for aortic valve replacement for AS may incur a particularly high risk for postoperative neurologic sequelae due to an exceptional preexisting burden of cerebral ischemic disease.

Detection of lactate with a hadamard slice selected, selective multiple quantum coherence, chemical shift imaging sequence (HDMD-SelMQC-CSI) on a clinical MRI scanner: Application to tumors and muscle ischemia.

Lactate is an important metabolite in normal and malignant tissues detectable by NMR spectroscopy; however, it has been difficult to clinically detect the lactate methyl resonance because it is obscured by lipid resonances. The selective homonuclear multiple quantum coherence transfer technique offers a method for distinguishing lipid and lactate resonances. We implemented a three-dimensional selective homonuclear multiple quantum coherence transfer version with Hadamard slice selection and two-dimensional phase encoding (Hadamard encoded-selective homonuclear multiple quantum coherence transfer-chemical shift imaging) on a conventional clinical MR scanner. Hadamard slice selection is explained and demonstrated in vivo. This is followed by 1-cm(3) resolution lactate imaging with detection to 5-mM concentration in 20 min on a 3-T clinical scanner. An analysis of QSel gradient duration and amplitude effects on lactate and lipid signal is presented. To demonstrate clinical feasibility, a 5-min lactate scan of a patient with a non-Hodgkin's lymphoma in the superficial thigh is reported. The elevated lactate signal coincides with the T(2)-weighted image of this tumor. As a test of selective homonuclear multiple quantum coherence transfer sensitivity, a thigh tourniquet was applied to a normal volunteer and an increase in lactate was detected immediately after tourniquet flow constriction. In conclusion, the Hadamard encoded-selective homonuclear multiple quantum coherence transfer-chemical shift imaging sequence is demonstrated on a phantom and in two lipid-rich, clinically relevant, in vivo conditions.

Integrity of the cerebral blood-flow response to hyperoxia after cardiopulmonary bypass.

OBJECTIVE: In this study, the hypothesis that cardiopulmonary bypass (CPB) alters the cerebral blood flow (CBF) vasoconstrictive response to hyperoxia was tested. DESIGN: A prospective, observational study was conducted. SETTING: The study was conducted at a single university hospital. PARTICIPANTS: Subjects were patients who presented for cardiac surgery with CPB. INTERVENTIONS: CBF was measured before and after CPB in 12 subjects while breathing 21% O(2) and 100% O(2). CBF was measured by using continuous arterial spin labeling (CASL) perfusion magnetic resonance imaging. Arterial pO(2) (mmHg), pCO(2) (mmHg), hemoglobin (Hgb), and oxygen content (CaO(2)) were also measured. MEASUREMENTS AND MAIN RESULTS: Mean age of the 12 subjects was 63 +/- 16 years. Hgb decreased from 12.0 (+/-2.4) g/dL to 9.2 (+/-2.9) g/dL postoperatively (p = 0.008). CBF increased by 39%, from 37.2 (+/-10.8) mL/100 g/min to 49.2 (+/-14.3)mL/100 g/min postoperatively (p = 0.01). In response to the hyperoxic challenge CBF decreased by 8.0 (+/-7.1) mL/100 g/min (21%) preoperatively and by 9.4 (+/-6.4) mL/100 g/min (19%) postoperatively (p = 0.58). By using multiple regression, the contribution of CPB to the hyperoxic CBF response (DeltaCBF) was evaluated, while controlling for other potentially important covariates known to influence CBF, including age, baseline CBF on 21% O(2), and changes in arterial pO(2), pCO(2), and CaO(2). CPB state was not found to be a significant covariate in controlling the CBF response to hyperoxia. CONCLUSIONS: CPB does not impair the CBF response to hyperoxia.

Clinically silent cerebral ischemic events after cardiac surgery: their incidence, regional vascular occurrence, and procedural dependence.

BACKGROUND: The reported frequency of stroke after coronary artery bypass grafting varies between 1.5% and 6%, approaches 10% after aortic valve replacement, and may occur in between 40 to 70% in high-risk groups. Clinically silent infarction may be far more frequent and could contribute to long-term cognitive dysfunction in patients after cardiac procedures. Using diffusion-weighted magnetic resonance imaging we document the occurrence, vascular distribution, and procedural dependence of silent infarction after cardiac surgery with cardiopulmonary bypass. We also document the association of preexisting white matter lesions with new postoperative ischemic lesions. METHODS: Thirty-four patients underwent T2-weighted fluid attenuated inversion recovery and diffusion-weighted magnetic resonance imaging before and after cardiac surgery with cardiopulmonary bypass for coronary artery bypass grafting, aortic valve replacement, and mitral valve repair or replacement surgery. Images were evaluated by experienced neuroradiologists for number, size, and vascular distribution of lesions. RESULTS: Mean age of participants was 67 +/- 15 years. Imaging occurred before and 6 +/- 2 days after surgery. New cerebral infarctions were evident in 6 of 34 patients (18%), were often multiple, and in 67% of patients were clinically silent. The occurrence of new infarctions by surgical procedure was as follows: aortic valve replacement (2 of 6), coronary artery bypass grafting and aortic valve replacement (3 of 8), aortic valve replacement with root replacement (1 of 1), coronary artery bypass grafting and mitral valve repair or replacement (0 of 4), mitral valve repair or replacement (0 of 2), and isolated coronary artery bypass grafting (0 of 13). New infarction occurred in 6 of 15 (40%) of all procedures involving aortic valve replacement. The severity of preexisting white matter lesions trended toward predicting the occurrence of new lesions (p = 0.055). CONCLUSIONS: Diffusion-weighted imaging reveals new cerebral infarctions in nearly 40% of patients after aortic valve replacement.

Aging: impact upon local cerebral oxygenation and blood flow with acute isovolemic hemodilution.

Data from the neurosurgical critical care arena demonstrate a correlation between cerebral oxygenation, survival, and cognitive function. Transfusion may increase and hemodilution decrease cerebral oxygenation. Both acute and chronic anemia have been associated with cognitive dysfunction. Aggressive blood conservation protocols have been instituted across all age groups without conclusive evidence for their impact upon outcome. Aged subjects are at the greatest risk of cognitive sequelae after major surgery associated with significant blood loss. We hypothesize that cerebral physiologic changes associated with "normal" aging may compromise cerebral oxygenation in the presence of severe anemia.Fischer 344 rats, the NIH National Institute of Aging normal aging rat model, underwent a stepwise isovolemic hemodilution protocol. Age groups (Age Grp) studied were as follows: Age Grp-A (3 months), n=14; Age Grp-B (9 to 12 months), n=14; and Age Grp-C (24 months), n=14. Brain oxygen tension (PBrO2), laser Doppler flow, and mean arterial pressure were measured. Final hemoglobin averaged 6.1+/-0.9 g/dL. PBrO2 levels decreased from a baseline of 18.1+/-4.1 to 17.5+/-6.8 mm Hg (P=0.49), and laser Doppler flow increased by 18+/-20% (P<0.0001) after hemodilution. Employing repeated measures multiple regression, Age Grp (P=0.30) was not a significant controlling covariate of PBrO2 in response to isovolemic hemodilution. PBrO2 levels were actually higher in Age Grp-C animals at all time points of the hemodilution protocol, although this was not statistically significant. Aged animals were also fully capable of mounting a robust local cerebral hyperemic response to the anemic challenge that was not separable from the response of younger animals.