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.

Metabolite patterns associated with individual response to supervised exercise therapy in patients with intermittent claudication.

Objective: Supervised exercise therapy (SET) is the first line treatment for intermittent claudication owing to peripheral arterial disease. Despite multiple randomized controlled trials proving the efficacy of SET, there are large differences in individual patient's responses. We used plasma metabolomics to identify potential metabolic influences on the individual response to SET. Methods: Primary metabolites, complex lipids, and lipid mediators were measured on plasma samples taken at before and after Gardner graded treadmill walking tests that were administered before and after 12 weeks of SET. We used an ensemble modeling approach to identify metabolites or changes in metabolites at specific time points that associated with interindividual variability in the functional response to SET. Specific time points analyzed included baseline metabolite levels before SET, dynamic metabolomics changes before SET, the difference in pre- and post-SET baseline metabolomics, and the difference (pre- and post-SET) of the dynamic (pre- and post-treadmill). Results: High levels of baseline anandamide levels pre- and post-SET were associated with a worse response to SET. Increased arachidonic acid (AA) and decreased levels of the AA precursor dihomo-γ-linolenic acid across SET were associated with a worse response to SET. Participants who were able to tolerate large increases in AA during acute exercise had longer, or better, walking times both before and after SET. Conclusions: We identified two pathways of relevance to individual response to SET that warrant further study: anandamide synthesis may activate endocannabinoid receptors, resulting in worse treadmill test performance. SET may train patients to withstand higher levels of AA, and inflammatory signaling, resulting in longer walking times. Clinical Relevance: This manuscript describes the use of metabolomic techniques to measure the interindividual effects of SET in patients with peripheral artery disease (PAD). We identified high levels of AEA are linked to CB1 signaling and activation of inflammatory pathways. This alters energy expenditure in myoblasts by decreasing glucose uptake and may induce an acquired skeletal muscle myopathy. SET may also help participants tolerate increased levels of AA and inflammation produced during exercise, resulting in longer walking times. This data will enhance understanding of the pathophysiology of PAD and the mechanism by which SET improves walking intolerance.

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.

Impact of supervised exercise on skeletal muscle blood flow and vascular function measured with MRI in patients with peripheral artery disease.

Supervised exercise is a common therapeutic intervention for patients with peripheral artery disease (PAD), however, the mechanism underlying the improvement in claudication symptomatology is not completely understood. The hypothesis that exercise improves microvascular blood flow is herein tested via temporally resolved magnetic resonance imaging (MRI) measurement of blood flow and oxygenation dynamics during reactive hyperemia in the leg with the lower ankle-brachial index. One hundred and forty-eight subjects with PAD were prospectively assigned to standard medical care or 3 mo of supervised exercise therapy. Before and after the intervention period, subjects performed a graded treadmill walking test, and MRI data were collected with Perfusion, Intravascular Venous Oxygen saturation, and T2* (PIVOT), a method that simultaneously quantifies microvascular perfusion, as well as relative oxygenation changes in skeletal muscle and venous oxygen saturation in a large draining vein. The 3-mo exercise intervention was associated with an improvement in peak walking time (64% greater in those randomized to the exercise group at follow-up, P < 0.001). Significant differences were not observed in the MRI measures between the subjects randomized to exercise therapy versus standard medical care based on an intention-to-treat analysis. However, the peak postischemia perfusion averaged across the leg between baseline and follow-up visits increased by 10% (P = 0.021) in participants that were adherent to the exercise protocol (completed >80% of prescribed exercise visits). In this cohort of adherent exercisers, there was no difference in the time to peak perfusion or oxygenation metrics, suggesting that there was no improvement in microvascular function nor changes in tissue metabolism in response to the 3-mo exercise intervention.NEW & NOTEWORTHY Supervised exercise interventions can improve symptomatology in patients with peripheral artery disease, but the underlying mechanism remains unclear. Here, MRI was used to evaluate perfusion, relative tissue oxygenation, and venous oxygen saturation in response to cuff-induced ischemia. Reactive hyperemia responses were measured before and after 3 mo of randomized supervised exercise therapy or standard medical care. Those participants who were adherent to the exercise regimen had a significant improvement in peak perfusion.

Aged Mouse Hippocampus Exhibits Signs of Chronic Hypoxia and an Impaired HIF-Controlled Response to Acute Hypoxic Exposures.

Altered hypoxia-inducible factor-alpha (HIF-α) activity may have significant consequences in the hippocampus, which mediates declarative memory, has limited vascularization, and is vulnerable to hypoxic insults. Previous studies have reported that neurovascular coupling is reduced in aged brains and that diseases which cause hypoxia increase with age, which may render the hippocampus susceptible to acute hypoxia. Most studies have investigated the actions of HIF-α in aging cortical structures, but few have focused on the role of HIF-α within aged hippocampus. This study tests the hypothesis that aging is associated with impaired hippocampal HIF-α activity. Dorsal hippocampal sections from mice aged 3, 9, 18, and 24 months were probed for the presence of HIF-α isoforms or their associated gene products using immunohistochemistry and fluorescent in situ hybridization (fISH). A subset of each age was exposed to acute hypoxia (8% oxygen) for 3 h to investigate changes in the responsiveness of HIF-α to hypoxia. Basal mean intensity of fluorescently labeled HIF-1α protein increases with age in the hippocampus, whereas HIF-2α intensity only increases in the 24-month group. Acute hypoxic elevation of HIF-1α is lost with aging and is reversed in the 24-month group. fISH reveals that glycolytic genes induced by HIF-1α (lactose dehydrogenase-a, phosphoglycerate kinase 1, and pyruvate dehydrogenase kinase 1) are lower in aged hippocampus than in 3-month hippocampus, and mRNA for monocarboxylate transporter 1, a lactose transporter, increases. These results indicate that lactate, used in neurotransmission, may be limited in aged hippocampus, concurrent with impaired HIF-α response to hypoxic events. Therefore, impaired HIF-α may contribute to age-associated cognitive decline during hypoxic events.

Anesthesia and neurotoxicity study design, execution, and reporting in the nonhuman primate: A systematic review.

BACKGROUND: Concern for a role of anesthesia in neurotoxicity in children originated from neonatal rodent and nonhuman primate (NHP) models, yet prospective clinical studies have largely not supported this concern. The goal of this study was to conduct an objective assessment of published NHP study rigor in design, execution, and reporting. METHODS: A MEDLINE search from 2005 to December 2021 was performed. Inclusion criteria included full-length original studies published in English under peer-reviewed journals. We documented experimental parameters on anesthetic dosing, monitoring, vitals, and experimental outcomes. RESULTS: Twenty-three manuscripts were included. Critical issues identified in study design included: lack of blinding in data acquisition (57%) and analysis (100%), supratherapeutic (4-12 fold) maintenance dosing in 22% of studies, lack of sample size justification (91%) resulting in a mean (SD) sample size of 6 (3) animals per group. Critical items identified in the conduct and reporting of studies included: documentation of anesthesia provider (0%), electrocardiogram monitoring (35%), arterial monitoring (4%), spontaneous ventilation employed (35%), failed intubations resulting in comingling ventilated and unventilated animals in data analysis, inaccurate reporting of failed intubation, and only 50% reporting on survival. Inconsistencies were noted in drug-related induction of neuroapoptosis and region of occurrence. Further, 67%-100% of behavior outcomes were not significantly different from controls. CONCLUSIONS: Important deficits in study design, execution, and reporting were identified in neonatal NHP studies. These results raise concern for the validity and reliability of these studies and may explain in part the divergence from results obtained in human neonates.

Exercise Training Increases Resting Calf Muscle Oxygen Metabolism in Patients with Peripheral Artery Disease.

Exercise training can mitigate symptoms of claudication (walking-induced muscle pain) in patients with peripheral artery disease (PAD). One adaptive response enabling this improvement is enhanced muscle oxygen metabolism. To explore this issue, we used arterial-occlusion diffuse optical spectroscopy (AO-DOS) to measure the effects of exercise training on the metabolic rate of oxygen (MRO2) in resting calf muscle. Additionally, venous-occlusion DOS (VO-DOS) and frequency-domain DOS (FD-DOS) were used to measure muscle blood flow (F) and tissue oxygen saturation (StO2), and resting calf muscle oxygen extraction fraction (OEF) was calculated from MRO2, F, and blood hemoglobin. Lastly, the venous/arterial ratio (γ) of blood monitored by FD-DOS was calculated from OEF and StO2. PAD patients who experience claudication (n = 28) were randomly assigned to exercise and control groups. Patients in the exercise group received 3 months of supervised exercise training. Optical measurements were obtained at baseline and at 3 months in both groups. Resting MRO2, OEF, and F, respectively, increased by 30% (12%, 44%) (p < 0.001), 17% (6%, 45%) (p = 0.003), and 7% (0%, 16%) (p = 0.11), after exercise training (median (interquartile range)). The pre-exercise γ was 0.76 (0.61, 0.89); it decreased by 12% (35%, 6%) after exercise training (p = 0.011). Improvement in exercise performance was associated with a correlative increase in resting OEF (R = 0.45, p = 0.02).

Towards rapid intraoperative axial localization of spinal cord ischemia with epidural diffuse correlation monitoring.

Spinal cord ischemia leads to iatrogenic injury in multiple surgical fields, and the ability to immediately identify onset and anatomic origin of ischemia is critical to its management. Current clinical monitoring, however, does not directly measure spinal cord blood flow, resulting in poor sensitivity/specificity, delayed alerts, and delayed intervention. We have developed an epidural device employing diffuse correlation spectroscopy (DCS) to monitor spinal cord ischemia continuously at multiple positions. We investigate the ability of this device to localize spinal cord ischemia in a porcine model and validate DCS versus Laser Doppler Flowmetry (LDF). Specifically, we demonstrate continuous (>0.1Hz) spatially resolved (3 locations) monitoring of spinal cord blood flow in a purely ischemic model with an epidural DCS probe. Changes in blood flow measured by DCS and LDF were highly correlated (r = 0.83). Spinal cord blood flow measured by DCS caudal to aortic occlusion decreased 62%. This monitor demonstrated a sensitivity of 0.87 and specificity of 0.91 for detection of a 25% decrease in flow. This technology may enable early identification and critically important localization of spinal cord ischemia.

Cerebral Hypoxia: Its Role in Age-Related Chronic and Acute Cognitive Dysfunction.

Postoperative cognitive dysfunction (POCD) has been reported with widely varying frequency but appears to be strongly associated with aging. Outside of the surgical arena, chronic and acute cerebral hypoxia may exist as a result of respiratory, cardiovascular, or anemic conditions. Hypoxia has been extensively implicated in cognitive impairment. Furthermore, disease states associated with hypoxia both accompany and progress with aging. Perioperative cerebral hypoxia is likely underdiagnosed, and its contribution to POCD is underappreciated. Herein, we discuss the various disease processes and forms in which hypoxia may contribute to POCD. Furthermore, we outline hypoxia-related mechanisms, such as hypoxia-inducible factor activation, cerebral ischemia, cerebrovascular reserve, excitotoxicity, and neuroinflammation, which may contribute to cognitive impairment and how these mechanisms interact with aging. Finally, we discuss opportunities to prevent and manage POCD related to hypoxia.

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.

Hypoxia, hypercarbia, and mortality reporting in studies of anaesthesia-related neonatal neurodevelopmental delay in rodent models: A systematic review.

BACKGROUND: The concept of anaesthesia-related neonatal neurotoxicity originated in neonatal rodent models, yet prospective clinical studies have largely not supported this concern. OBJECTIVES: To determine the frequency and magnitude of hypercarbia, hypoxia and death in rodent models of neonatal anaesthetic toxicity and neurodevelopmental delay. DESIGN: Systematic review of published rodent studies of neonatal anaesthesia neurotoxicity. We documented anaesthetic, route, dose, frequency and duration of exposures. We further report ventilation method, documentation of adequacy of ventilation [arterial blood gas (ABG), other], mortality and the reporting of mortality. DATA SOURCES: A PubMed literature search from 2003 to 2017 was conducted to identify studies on neurotoxicity in neonatal rodent models. ELIGIBILITY: Studies were included when at least one group of animals fell within the postnatal age range of 3 to 15 days. Only English language original studies published as full-length articles in peer reviewed journals were included in the final analysis. RESULTS: One hundred and three manuscripts were included. Ninety-eight percent of studies were conducted using spontaneous ventilation (101/103), with ABG monitoring used in only 33% of studies and visual monitoring alone for respiratory distress or cyanosis was employed in 60%. Of the 33% who reported ABG results, there were widely divergent values, with most reporting modest-to-severe hypercarbia. Mortality (median 11%, range of 0 to 40%), which infers severe hypoxia, was documented in only 36/103 (35%) reports. CONCLUSION: Hypoxia and hypercarbia have known apoptotic effects on developing brains. Hence, the inadequate control of hypercarbia and hypoxia in neonatal rodent models of anaesthetic exposure during spontaneous ventilation suggests that the evidence for developmental delay and neurotoxicity attributed to anaesthesia may not be valid in humans.

Diffuse Correlation Spectroscopy Analysis Implemented on a Field Programmable Gate Array.

Diffusive correlation spectroscopy (DCS) is an emerging optical technique that measures blood perfusion in deep tissue. In a DCS measurement, temporal changes in the interference pattern of light, which has passed through tissue, are quantified by an autocorrelation function. This autocorrelation function is further parameterized through a non-linear curve fit to a solution to the diffusion equation for coherence transport. The computational load for this non-linear curve fitting is a barrier for deployment of DCS for clinical use, where real-time results, as well as instrument size and simplicity, are important considerations. We have mitigated this computational bottleneck through development of a hardware analyzer for DCS. This analyzer implements the DCS curving fitting algorithm on digital logic circuit using Field Programmable Gate Array (FPGA) technology. The FPGA analyzer is more efficient than a typical software analysis solution. The analyzer module can be easily duplicated for processing multiple channels of DCS data in real-time. We have demonstrated the utility of this analyzer in pre-clinical large animal studies of spinal cord ischemia. In combination with previously described FPGA implementations of auto-correlators, this hardware analyzer can provide a complete device-on-a-chip solution for DCS signal processing. Such a component will enable new DCS applications demanding mobility and real-time processing.

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.

Astrocyte HIF-2α supports learning in a passive avoidance paradigm under hypoxic stress.

BACKGROUND: The brain is extensively vascularized, uses20% of the body's oxygen, and is highly sensitive to changes in oxygen. While synaptic plasticity and memory are impaired in healthy individuals by exposure to mild hypoxia, aged individuals appear to be even more sensitive. Aging is associated with progressive failure in pulmonary and cardiovascular systems, exposing the aged to both chronic and superimposed acute hypoxia. The HIF proteins, the "master regulators" of the cellular response to hypoxia, are robustly expressed in neurons and astrocytes. Astrocytes support neurons and synaptic plasticity via complex metabolic and trophic mechanisms. The activity of HIF proteins in the brain is diminished with aging, and the increased exposure to chronic and acute hypoxia with aging combined with diminished HIF activity may impair synaptic plasticity. PURPOSE: Herein, we test the hypothesis that astrocyte HIF supports synaptic plasticity and learning upon hypoxia. MATERIALS AND METHODS: An Astrocyte-specific HIF loss-of-function model was employed, where knock-out of HIF-1α or HIF-2α in GFAP expressing cells was accomplished by cre-mediated recombination. Animals were tested for behavioral (open field and rotarod), learning (passive avoidance paradigm), and electrophysiological (long term potentiation) responses to mild hypoxic challenge. RESULTS: In an astrocyte-specific HIF loss-of-function model followed by mild hypoxia, we identified that the depletion of HIF-2α resulted in an impaired passive avoidance learning performance. This was accompanied by an attenuated response to induction in long-term potentiation (LTP), suggesting that the hippocampal circuitry was perturbed upon hypoxic exposure following HIF-2α loss in astrocytes, and not due to hippocampal cell death. We investigated HIF-regulated trophic and metabolic target genes and found that they were not regulated by HIF-2α, suggesting that these specific targets may not be involved in mediating the phenotypes observed. CONCLUSION: Together, these results point to a role for HIF-2α in the astrocyte's regulatory role in synaptic plasticity and learning under hypoxia and suggest that even mild, acute hypoxic challenges can impair cognitive performance in the aged population who harbor impaired HIF function.

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.

Simultaneous measurement of macro- and microvascular blood flow and oxygen saturation for quantification of muscle oxygen consumption.

PURPOSE: To investigate the relationship between blood flow and oxygen consumption in skeletal muscle, a technique called "Velocity and Perfusion, Intravascular Venous Oxygen saturation and T2*" (vPIVOT) is presented. vPIVOT allows the quantification of feeding artery blood flow velocity, perfusion, draining vein oxygen saturation, and muscle T2*, all at 4-s temporal resolution. Together, the measurement of blood flow and oxygen extraction can yield muscle oxygen consumption ( V˙O2) via the Fick principle. METHODS: In five subjects, vPIVOT-derived results were compared with those obtained from stand-alone sequences during separate ischemia-reperfusion paradigms to investigate the presence of measurement bias. Subsequently, in 10 subjects, vPIVOT was applied to assess muscle hemodynamics and V˙O2 following a bout of dynamic plantar flexion contractions. RESULTS: From the ischemia-reperfusion paradigm, no significant differences were observed between data from vPIVOT and comparison sequences. After exercise, the macrovascular flow response reached a maximum 8 ± 3 s after relaxation; however, perfusion in the gastrocnemius muscle continued to rise for 101 ± 53 s. Peak V˙O2 calculated based on mass-normalized arterial blood flow or perfusion was 15.2 ± 6.7 mL O2 /min/100 g or 6.0 ± 1.9 mL O2 /min/100 g, respectively. CONCLUSIONS: vPIVOT is a new method to measure blood flow and oxygen saturation, and therefore to quantify muscle oxygen consumption. Magn Reson Med 79:846-855, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Effects of exercise training on calf muscle oxygen extraction and blood flow in patients with peripheral artery disease.

We employed near-infrared optical techniques, diffuse correlation spectroscopy (DCS), and frequency-domain near-infrared spectroscopy (FD-NIRS) to test the hypothesis that supervised exercise training increases skeletal muscle microvascular blood flow and oxygen extraction in patients with peripheral artery disease (PAD) who experience claudication. PAD patients ( n = 64) were randomly assigned to exercise and control groups. Patients in the exercise group received 3 mo of supervised exercise training. Calf muscle blood flow and oxygen extraction were optically monitored before, during, and after performance of a graded treadmill protocol at baseline and at 3 mo in both groups. Additionally, measurements of the ankle-brachial index (ABI) and peak walking time (PWT) to maximal claudication were made during each patient visit. Supervised exercise training was found to increase the maximal calf muscle blood flow and oxygen extraction levels during treadmill exercise by 29% (13%, 50%) and 8% (1%, 12%), respectively [ P < 0.001; median (25th percentile, 75th percentile)]. These improvements across the exercise group population were significantly higher than corresponding changes in the control group ( P < 0.004). Exercise training also increased PWT by 49% (18%, 101%) ( P = 0.01). However, within statistical error, the ABI, resting calf muscle blood flow and oxygen extraction, and the recovery half-time for hemoglobin\myoglobin desaturation following cessation of maximal exercise were not altered by exercise training. The concurrent monitoring of both blood flow and oxygen extraction with the hybrid DCS/FD-NIRS instrument revealed enhanced muscle oxidative metabolism during physical activity from exercise training, which could be an underlying mechanism for the observed improvement in PWT. NEW & NOTEWORTHY We report on noninvasive optical measurements of skeletal muscle blood flow and oxygen extraction dynamics before/during/after treadmill exercise in peripheral artery disease patients who experience claudication. The measurements tracked the effects of a 3-mo supervised exercise training protocol and revealed that supervised exercise training improved patient ability to increase microvascular calf muscle blood flow and oxygen extraction during physical activity.

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.