An exercise stress test for contrast-enhanced duplex ultrasound assessment of lower limb muscle perfusion in patients with peripheral arterial disease.

OBJECTIVE: The aim of the present study was to develop a standardized contrast-enhanced duplex ultrasound (CE-DUS) protocol to assess lower-extremity muscle perfusion before and after exercise and determine relationships of perfusion with clinical and functional measures. METHODS: CE-DUS (EPIQ 5G, Philips) was used before and immediately after a 10-minute, standardized bout of treadmill walking to compare microvascular perfusion of the gastrocnemius muscle in older (55-82 years) patients with peripheral arterial disease (PAD) (n = 15, mean ankle-brachial index, 0.78 ± 0.04) and controls (n = 13). Microvascular blood volume (MBV) and microvascular flow velocity (MFV) were measured at rest and immediately following treadmill exercise, and the Modified Physical Performance Test (MPPT) was used to assess mobility function. RESULTS: In the resting state (pre-exercise), MBV in patients with PAD was not significantly different than normal controls (5.17 ± 0.71 vs 6.20 ± 0.83 arbitrary units (AU) respectively; P = .36); however, after exercise, MBV was ∼40% lower in patients with PAD compared with normal controls (5.85 ± 1.13 vs 9.53 ± 1.31 AU, respectively; P = .04). Conversely, MFV was ∼60% higher in patients with PAD compared with normal controls after exercise (0.180 ± 0.016 vs 0.113 ± 0.018 AU, respectively; P = .01). There was a significant between-group difference in the exercise-induced changes in both MBV and MFV (P ≤ .05). Both basal and exercise MBV directly correlated with MPPT score in the patients with PAD (r = 0.56-0.62; P < .05). CONCLUSIONS: This standardized protocol for exercise stress testing of the lower extremities quantifies calf muscle perfusion and elicits perfusion deficits in patients with PAD. This technique objectively quantifies microvascular perfusion deficits that are related to reduced mobility function and could be used to assess therapeutic efficacy in patients with PAD.

Thermographic assessment of the immediate and short term-effects of blood flow restriction exercise on Achilles tendon skin temperature.

OBJECTIVES: To determine the thermal patterning of the Achilles tendon following bodyweight resistance exercise with and without blood-flow restriction (BFR). DESIGN: Cross-sectional. SETTING: Research laboratory. PARTICIPANTS: Twelve asymptomatic recreational runners (Age: 37 ± 10, Height: 169 ± 20, Mass: 73.8 ± 13.4). MAIN OUTCOME MEASURES: Thermograms were taken pre and post exercise with and without a BFR cuff on separate legs. BFR cuff pressure was set at 80% maximal arterial occlusion pressure determined using doppler via the tibial artery. Linear mixed-effects models were used to assess the effect of BFR and time post-exercise on skin-temperature (Tskin). RESULTS: A lower Tskin was seen following BFR exercise at the tendon insertion (P = 0.002), but not at the free tendon (P = 0.234), or the musculotendinous junction (P = 0.933). A significant effect of time upon changes in Tskin was observed in both BFR and non-BFR groups (P = 0.002). No interaction of time and BFR were observed on changes in Tskin (P = 0.726). CONCLUSION: Region specific changes in Tskin were found, with greater and longer reductions observed at the insertion of the Achilles following BFR exercise before returning to baseline. These findings could have implications for the programming of BFR exercise on tendon health. Future research should observe for differences between symptomatic and healthy tendons.

Quantifiable Contrast-Enhanced Ultrasound Explores the Role of Protection, Rest, Ice (Cryotherapy), Compression and Elevation (PRICE) Therapy on Microvascular Blood Flow.

The aim of this randomized controlled laboratory study was to evaluate the role of standardized protection, rest, ice (cryotherapy), compression and elevation (PRICE) therapy on microvascular blood flow in human skeletal muscle. Quantifiable contrast-enhanced ultrasound was used to analyze intramuscular tissue perfusion (ITP) of the rectus femoris (RF) and vastus intermedius (VI) muscles in 20 healthy athletes who were randomly assigned to PRICE or control groups. Baseline perfusion measurements (resting conditions, T0) were compared with cycling exercise (T1), intervention (PRICE or control, T2) and follow-up at 60 min post-intervention (T3). The 20 min PRICE intervention included rest, cryotherapy (3°C), compression (35 mm Hg) and elevation. After intervention, PRICE demonstrated a decrease of ITP in VI (-47%, p = 0.01) and RF (-50%, p = 0.037) muscles. At T3, an ongoing decreased ITP for the RF (p = 0.003) and no significant changes for the VI were observed. In contrast, the control group showed an increased ITP at T2 and no significant differences at T3. PRICE applied after exercise led to a down-regulation of ITP, and the termination of PRICE does not appear to be associated with a reactive hyperemia for at least 60 min after treatment.

A novel MRI analysis for assessment of microvascular vasomodulation in low-perfusion skeletal muscle.

Compromised microvascular reactivity underlies many conditions and injuries, but its assessment remains difficult, particularly in low perfusion tissues. In this paper, we develop a new mathematical model for the assessment of vasomodulation in low perfusion settings. A first-order model was developed to approximate changes in T1 relaxation times as a result of vasomodulation. Healthy adult rats (N = 6) were imaged on a 3-Tesla clinical MRI scanner, and vasoactive response was probed on gadofosveset using hypercapnic gases at 20% and 5% CO2 to induce vasoconstriction and vasodilation, respectively. MRI included dynamic 3D T1 mapping and T1-weighted images during gas challenge; heart rate was continuously monitored. Laser Doppler perfusion measurements were performed to corroborate MRI findings. The model was able to identify hypercapnia-mediated vasoconstriction and vasodilation through the partial derivative [Formula: see text]. MRI on animals revealed gradual vasoconstriction in the skeletal muscle bed in response to 20% CO2 followed by gradual vasodilation on transitioning to 5% CO2. These trends were confirmed on laser Doppler perfusion measurements. Our new mathematical model has the potential for detecting microvascular dysfunction that manifests in the early stages across multiple metabolic and ischemic pathologies.

Assessment of resistance vessel function in human skeletal muscle: guidelines for experimental design, Doppler ultrasound, and pharmacology.

The introduction of duplex Doppler ultrasound almost half a century ago signified a revolutionary advance in the ability to assess limb blood flow in humans. It is now widely used to assess blood flow under a variety of experimental conditions to study skeletal muscle resistance vessel function. Despite its pervasive adoption, there is substantial variability between studies in relation to experimental protocols, procedures for data analysis, and interpretation of findings. This guideline results from a collegial discussion among physiologists and pharmacologists, with the goal of providing general as well as specific recommendations regarding the conduct of human studies involving Doppler ultrasound-based measures of resistance vessel function in skeletal muscle. Indeed, the focus is on methods used to assess resistance vessel function and not upstream conduit artery function (i.e., macrovasculature), which has been expertly reviewed elsewhere. In particular, we address topics related to experimental design, data collection, and signal processing as well as review common procedures used to assess resistance vessel function, including postocclusive reactive hyperemia, passive limb movement, acute single limb exercise, and pharmacological interventions.

The association between near-infrared spectroscopy-derived and flow-mediated dilation assessment of vascular responsiveness in the arm.

INTRODUCTION: Following a period of blood flow occlusion, the near-infrared spectroscopy (NIRS)-derived reperfusion slope of the oxygen saturation signal (StO2) is a measure of microvascular responsiveness that has been shown to be positively correlated with flow-mediated dilation (FMD) assessment of conduit artery function in the lower limb vasculature. Given that previously established differences in structure and function of the vessels in the upper compared to the lower limbs may change this relationship, investigating whether this correlation between the reperfusion slope of the StO2 and the FMD response is maintained in upper limbs is important. Accordingly, this study investigated the correlation between the reperfusion slope of the StO2 and FMD in the arm vasculature. METHODS: 18 physically active individuals were submitted to a vascular occlusion test (VOT). Microvascular responsiveness was calculated as the NIRS-derived reperfusion slope assessed in a forearm muscle. Macrovascular responsiveness was assessed at the brachial artery and calculated as a percent of change in FMD (%FMD). RESULTS: A statistically significant correlation (r = 0.66; P = 0.001) was found between the reperfusion slope and %FMD response. CONCLUSION: The significant correlation between the reperfusion slope in the forearm muscle and %FMD in the brachial artery, reinforces the relationship between downstream and upstream vascular reactivity in healthy human limbs.

Effects of ischemic preconditioning on economy, VO2 kinetics and cycling performance in endurance athletes.

The aim of this study was to determine the effect of ischemic preconditioning (IPC) on several measures of aerobic function and 4-km cycling time-trial performance. An acute cross-over design was adopted involving eight well-trained cyclists (age 27.0 ± 7.0 years) who completed incremental and square-wave exercise tests for determination of peak O2 uptake (VO2peak), ventilatory threshold (VT) and moderate- and heavy-intensity domain VO2 kinetics, as well as 4-km time trials. All were preceded by IPC, or sham-IPC, involving repeated bouts of thigh blood flow occlusion, interspersed with reperfusion. There was no significant difference between IPC and sham-IPC with respect to VO2peak (4.4 ± 0.6 L min-1 vs 4.4 ± 0.5 L min-1, effect size - 0.01 ± 0.09), VT (3.4 ± 0.6 L min-1 vs 3.5 ± 0.5 L min-1, effect size 0.07 ± 0.28), cycling economy (4.9 ± 4.9%, ES 0.24 ± - 0.24, P > 0.05) or any moderate-domain VO2 kinetic parameter. During heavy-intensity exercise, a reduced end-exercise VO2, slow component amplitude and overall gain was observed following IPC compared to sham-IPC. Though not statistically significant, there was a possibly beneficial effect of IPC on 4-km time-trial mean power output (2.2 ± 2.0%; effect size: 0.18 ± 0.15, P > 0.05). The observed reduction in VO2 slow component and tendency for improved economy and 4-km time-trial performance, albeit small, suggests that acute IPC shows some potential as a performance-enhancing priming strategy for well-trained cyclists prior to high-intensity exercise.

Reliability of forearm oxygen uptake during handgrip exercise: assessment by ultrasonography and venous blood gas.

Assessment of forearm oxygen uptake (V˙O2 ) during handgrip exercise is a keenly investigated concept for observing small muscle mass metabolism. Although a combination of Doppler ultrasound measurements of brachial artery blood flow (Q˙) and blood gas drawn from a deep forearm vein has been utilized to calculate forearm V˙O2 for more than two decades, the applicability of this experimental design may benefit from a thorough evaluation of its reliability during graded exercise. Therefore, we evaluated the reliability of this technique during incremental handgrip exercise in ten healthy young (24 ± 3(SD) years.) males. V˙O2 and work rate (WR) exhibited a linear relationship (1.0 W: 43.8 ± 10.1 mL·min-1 ; 1.5 W: 53.8 ± 14.1 mL·min-1 ; 2.0 W: 63.4 ± 16.3 mL·min-1 ; 2.5 W: 72.2 ± 17.6 mL·min-1 ; 3.0 W: 79.2 ± 18.6 mL·min-1 ; r = 0.65, P < 0.01). In turn, V˙O2 was strongly associated with Q˙ (1.0 W: 359 ± 86 mL·min-1 ; 1.5 W: 431 ± 112 mL·min-1 ; 2.0 W: 490 ± 123 mL·min-1 ; 2.5 W: 556 ± 112 mL·min-1 ; 3.0 W: 622 ± 131 mL·min-1 ; r = 0.96; P < 0.01), whereas arteriovenous oxygen difference (a-vO2diff ) remained constant following all WRs (123 ± 11-130 ± 10 mL·L-1 ). Average V˙O2 test-retest difference was -0.4 mL·min-1 with ±2SD limits of agreement (LOA) of 8.4 and -9.2 mL·min-1 , respectively, whereas coefficients of variation (CVs) ranged from 4-7%. Accordingly, test-retest Q˙ difference was 11.9 mL·min-1 (LOA: 84.1 mL·min-1 ; -60.4 mL·min-1 ) with CVs between 4 and 7%. Test-retest difference for a-vO2diff was -0.28 mL·dL-1 (LOA: 1.26mL·dL-1 ; -1.82 mL·dL-1 ) with 3-5% CVs. In conclusion, our results revealed that forearm V˙O2 determination by Doppler ultrasound and direct venous sampling is linearly related to WR, and a reliable experimental design across a range of exercise intensities.

Voxel-based measurement sensitivity of spatially resolved near-infrared spectroscopy in layered tissues.

We quantitatively investigated the measurement sensitivity of spatially resolved spectroscopy (SRS) across six tissue models: cerebral tissue, a small animal brain, the forehead of a fetus, an adult brain, forearm muscle, and thigh muscle. The optical path length in the voxel of the model was analyzed using Monte Carlo simulations. It was found that the measurement sensitivity can be represented as the product of the change in the absorption coefficient and the difference in optical path length in two states with different source-detector distances. The results clarified the sensitivity ratio between the surface layer and the deep layer at each source-detector distance for each model and identified changes in the deep measurement area when one of the detectors was close to the light source. A comparison was made with the results from continuous-wave spectroscopy. The study also identified measurement challenges that arise when the surface layer is inhomogeneous. Findings on the measurement sensitivity of SRS at each voxel and in each layer can support the correct interpretation of measured values when near-infrared oximetry or functional near-infrared spectroscopy is used to investigate different tissue structures.

Near-infrared spectroscopy assessment of microvasculature detects difference in lower limb vascular responsiveness in obese compared to lean individuals.

BACKGROUND: Microvascular dysfunction is an early complication in obesity-related cardiovascular disease (CVD) that can lead to changes in hemodynamic function and endothelial cell expression throughout the vasculature that is vessel specific. This study aimed to evaluate whether the near-infrared spectroscopy (NIRS) combined with a vascular occlusion (VOT) assessment was capable of detecting differences in vascular responsiveness within the microvasculature of the lower limb between lean and obese individuals. METHODS AND RESULTS: Twenty lean (BMI = 21.6 ±â€¯1.3) and 17 obese individuals (BMI = 33.9 ±â€¯1.1) participated in the study. Individuals underwent a VOT (5 min of baseline, 5 min of occlusion, and 8 min following cuff release) and vascular responsiveness was evaluated by the Slope 2 (Slope 2 StO2) and the area under the curve (StO2AUC) of oxygen saturation (StO2) signal during reperfusion. The difference between the minimal and the maximal value of StO2 was calculated as the Amplitude of the StO2 response. The Slope 2 StO2 of the obese individuals was smaller (0.68 ±â€¯0.07%·s-1) than the Slope 2 StO2 of the lean individuals (1.08 ±â€¯0.13%·s-1;P < 0.05). The StO2AUC of the obese was smaller (978 ±â€¯169%·s-1) than the StO2AUC of the lean individuals (1708 ±â€¯168%·s-1; P < 0.001). The amplitude of StO2 was smaller in obese individuals than the lean ones (30.4 ±â€¯2.9 vs 21.6 ±â€¯1.3 StO2 (%), respectively; P < 0.05). There was a significant correlation between Slope 2 StO2 and StO2AUC for lean individuals (r = 0.745; P < 0.001). CONCLUSION: This study demonstrated differences in vascular responses within the microvasculature of the lower limb between lean and obese individuals.

Venous occlusion plethysmography vs. Doppler ultrasound in the assessment of leg blood flow kinetics during different intensities of calf exercise.

PURPOSE: It has recently been shown that venous occlusion plethysmography (VOP) can successfully assess the rate of increase in leg blood flow (LBF) (LBF kinetics) responses during calf exercise, but there is lack of data supporting its validity. METHODS: Using Doppler ultrasound (DU) as a criterion standard technique, we tested the hypothesis that VOP would provide similar estimates of LBF kinetics responses as DU during calf plantar-flexion exercise at a range of different intensities. Ten healthy men performed repeated intermittent calf plantar-flexion contractions (3 s duty cycles, 1 s contraction/2 s relaxation) at 30, 50 and 70% maximum voluntary contraction (MVC) on different days. RESULTS: Resting LBF values were significantly (P < 0.05) larger for DU than VOP but the overall mean LBF responses during exercise were not different (P > 0.05) between DU and VOP (30% MVC: 330 ± 78 vs. 313 ± 92 ml/min; 50% MVC: 515 ± 145 vs. 483 ± 164 ml/min; 70% MVC: 733 ± 218 vs. 616 ± 229 ml/min). LBF kinetics analyses revealed that the end-amplitude at the highest intensity (70% MVC) was significantly higher when measured by DU compared with VOP, but all other kinetics parameters were not different between VOP and DU. CONCLUSIONS: Given that these slight differences in amplitude observed during exercise can be explained by differences in vascular regions which the two techniques assess, our results suggest that VOP can accurately assess LBF kinetics responses during calf plantar-flexion exercise at intensities between 30 and 70% MVC.

Exercise versus vasodilator stress limb perfusion imaging for the assessment of peripheral artery disease.

PURPOSE: Our aim was to determine whether pharmacologic vasodilation is an alternative to exercise stress during limb perfusion imaging for peripheral artery disease (PAD). METHODS: Quantitative contrast-enhanced ultrasound (CEU) perfusion imaging of the bilateral anterior thigh and calf was performed in nine control subjects and nine patients with moderate to severe PAD at rest and during vasodilator stress with dipyridamole. For those who were able, CEU of the calf was then performed during modest plantar flexion exercise (20 watts). CEU time-intensity data were analyzed to quantify microvascular blood flow (MBF) and its parametric components of microvascular blood volume and flux rate. RESULTS: Thigh and calf skeletal muscle MBF at rest was similar between control and PAD patients. During dipyridamole, MBF increased minimally (

[Diabetic foot syndrome: importance of calf muscles MR spectroscopy in the assessment of limb ischemia and effect of revascularization]. / Syndrom diabetické nohy: význam MR spektroskopie lýtkových svalu pro hodnocení koncetinové ischemie a efektu revaskularizace.

AIM: The standard method for assessment of effect of revascularization in patients with diabetic foot (DF) and critical limb ischemia (CLI) is transcutaneous oxygen pressure (TcPO2). Phosphorus magnetic resonance spectroscopy (31P MRS) enables to evaluate oxidative muscle metabolism that could be impaired in patients with diabetes and its complications. The aim of our study was to compare MRS of calf muscle between patients with DF and CLI and healthy controls and to evaluate the contribution of MRS in the assessment of the effect of revascularization. METHODS: Thirty-four diabetic patients with DF and CLI treated either by autologous cell therapy (ACT; 15 patients) or percutaneous transluminal angioplasty (PTA; 12 patients) in our foot clinic during 2013-2016 and 19 healthy controls were included into the study. TcPO2 measurement was used as a standard method of non-invasive evaluation of limb ischemia. MRS examinations were performed using the whole-body 3T MR system 1 day before and 3 months after the procedure. Subjects were examined in a supine position with the coil fixed under the m. gastrocnemius. MRS parameters were obtained at rest and during the exercise period. Rest MRS parameters of oxidative muscle metabolism such as phosphocreatine (PCr), inorganic phosphate (Pi), phosphodiesters (PDE), adenosine triphosphate (ATP), dynamic MRS parameters such as recovery constant PCr (τPCr) and mitochondrial capacity (Qmax), and pH were compared between patients and healthy controls, and also before and 3 months after revascularization. RESULTS: Patients with CLI had significantly lower PCr/Pi (p < 0.001), significantly higher Pi and pH (both p < 0.01), significantly lower Qmax and prolonged τPCr (both p < 0.001) in comparison with healthy controls. We observed a significant improvement in TcPO2 at 3 months after revascularization (from 26.4 ± 11.7 to 39.7 ± 17.7 mm Hg, p < 0.005). However, the rest MRS parameters did not change significantly after revascularization. In individual cases we observed improvement of dynamic MRS parameters. There was no correlation between MRS parameters and TcPO2 values. CONCLUSION: Results of our study show impaired oxidative metabolism of calf muscles in patients with CLI in comparison with healthy controls. We observed an improvement in dynamic MRS parameters in individual cases; this finding should be verified in a large number of patients during longer follow-up.Key words: autologous cell therapy - critical limb ischemia - diabetic foot - MR spectroscopy.

Dietary supplementation of branched-chain amino acids increases muscle net amino acid fluxes through elevating their substrate availability and intramuscular catabolism in young pigs.

Branched-chain amino acids (BCAA) have been clearly demonstrated to have anabolic effects on muscle protein synthesis. However, little is known about their roles in the regulation of net AA fluxes across skeletal muscle in vivo. This study was aimed to investigate the effect and related mechanisms of dietary supplementation of BCAA on muscle net amino acid (AA) fluxes using the hindlimb flux model. In all fourteen 4-week-old barrows were fed reduced-protein diets with or without supplemental BCAA for 28 d. Pigs were implanted with carotid arterial, femoral arterial and venous catheters, and fed once hourly with intraarterial infusion of p-amino hippurate. Arterial and venous plasma and muscle samples were obtained for the measurement of AA, branched-chain α-keto acids (BCKA) and 3-methylhistidine (3-MH). Metabolomes of venous plasma were determined by HPLC-quadrupole time-of-flight-MS. BCAA-supplemented group showed elevated muscle net fluxes of total essential AA, non-essential AA and AA. As for individual AA, muscle net fluxes of each BCAA and their metabolites (alanine, glutamate and glutamine), along with those of histidine, methionine and several functional non-essential AA (glycine, proline and serine), were increased by BCAA supplementation. The elevated muscle net AA fluxes were associated with the increase in arterial and intramuscular concentrations of BCAA and venous metabolites including BCKA and free fatty acids, and were also related to the decrease in the intramuscular concentration of 3-MH. Correlation analysis indicated that muscle net AA fluxes are highly and positively correlated with arterial BCAA concentrations and muscle net BCKA production. In conclusion, supplementing BCAA to reduced-protein diet increases the arterial concentrations and intramuscular catabolism of BCAA, both of which would contribute to an increase of muscle net AA fluxes in young pigs.

The value of near-infrared spectroscopy for the assessment of calf muscle function in venous patients.

OBJECTIVE: Near-infrared spectroscopy (NIRS) is a noninvasive technique with the potential to determine the degree of tissue oxygenation. The aim of the current study was to investigate the use of NIRS as a reliable method of detecting calf muscle pump dysfunction in groups of patients with venous disease. METHODS: Patients with superficial venous insufficiency (SVI) or history of deep venous thrombosis (DVT) were classified according to the comprehensive classification system for chronic venous disorders (clinical class, etiology, anatomy, and pathophysiology) and compared with controls (GROUP variable). A 10-stage evaluation of ambulatory venous function was performed, and corresponding values of calf regional oxygen saturation (crSaO2, %) at each phase were recorded (TIME variable). Thereafter, the percentage changes of crSaO2 values (Δ scores, %) between a given phase and the reference phase were estimated. Differences among groups and phases were evaluated using analysis of variance. Subgroup analysis between C0-C2 and C3-C6 patients was performed. The receiver operating characteristic curve analysis was used to detect the best predictive capability for SVI and DVT. RESULTS: A total of 30 patients with SVI, 31 patients with DVT, and 34 controls were included in the study. A statistically significant effect of TIME (F = 382.4; P < .001) and TIME × GROUP interaction (F = 6.3; P < .001) was recorded. Concerning prediction, we found a statistically significant area under the curve (AUC) for SVI (AUC = 0.72; 95% confidence interval, 0.58-0.83; P = .003) and for DVT (AUC = 0.83; 95% confidence interval, 0.71-0.92; P < .0001) patients. CONCLUSIONS: The measurement of crSaO2 using NIRS detected alterations in calf muscle pump oxygenation during exercise and differences in tissue oxygenation among SVI patients, DVT patients, and controls. NIRS may represent a reliable noninvasive tool for the study of calf muscle dysfunction in venous disease and a useful vehicle for generating testable hypotheses in the laboratory setting.

Non-invasive assessment of muscle oxygenation may aid in optimising transfusion threshold decisions in ambulatory paediatric patients.

OBJECTIVE: To assess the potential utility of a novel non-invasive muscle oxygen measurement to determine the presence of muscle hypoxia in patients with anaemia. BACKGROUND: Recent assessment of the risk/benefit ratio of blood transfusion has led to clinical strategies optimising transfusion decisions. These decisions are primarily based on haematocrit (Hct) but not oxygen delivery, the primary function of red blood cells (RBCs). We hypothesised that muscle oxygenation (MOx) would correlate with Hct in patients with anaemia and may be a physiologically relevant determinant of the transfusion threshold. METHODS/MATERIALS: MOx was non-invasively determined in children in the Cancer and Blood Disorders Center ambulatory clinic at Seattle Children's Hospital using a custom-designed optical probe and spectrometer. MOx was compared with contemporaneous Hct. In subjects receiving RBCs, MOx and Hct were also determined following transfusion. RESULTS: MOx ranged from 36·7 to 100%, and Hct ranged from 17·0 to 38·6% in 27 measurements from 16 patients. High MOx values were associated with high Hct. Mean MOx for patients with normal Hct for age (n = 5) was 95·9 ± 2·9%. RBC transfusion increased mean Hct from 19·1 ± 1·5% to 29·3 ± 2·0 and mean MOx from 67·9 ± 21·1% to 89·9 ± 9·8%. Among six transfusion episodes (in five patients) with initial Hct < 22, only three had a pre-transfusion MOx of <70%. Patients with the lowest pre-transfusion MOx had the largest increase in MOx after transfusion. CONCLUSIONS: These preliminary data suggest that MOx may aid in making transfusion decisions when used in combination with Hct.

Baseline assessment and comparison of arterial anatomy, hyperemic flow, and skeletal muscle perfusion in peripheral artery disease: The Cardiovascular Cell Therapy Research Network "Patients with Intermittent Claudication Injected with ALDH Bright Cells" (CCTRN PACE) study.

BACKGROUND: Peripheral artery disease (PAD) is important to public health as a major contributor to cardiovascular morbidity and mortality. Recent developments in magnetic resonance imaging (MRI) techniques permit improved assessment of PAD anatomy and physiology, and may serve as surrogate end points after proangiogenic therapies. METHODS: The PACE study is a randomized, double-blind, placebo-controlled clinical trial designed to assess the physiologic impact and potential clinical efficacy of autologous bone marrow-derived ALDHbr stem cells. The primary MRI end points of the study are as follows: (1) total collateral count, (2) calf muscle plasma volume (a measure of capillary perfusion) by dynamic contrast-enhanced MRI, and (3) peak hyperemic popliteal flow by phase-contrast MRI (PC-MRI). RESULTS: The interreader and intrareader and test-retest results demonstrated good-to-excellent reproducibility (interclass correlation coefficient range 0.61-0.98) for all magnetic resonance measures. The PAD participants (n=82) had lower capillary perfusion measured by calf muscle plasma volume (3.8% vs 5.6%) and peak hyperemic popliteal flow (4.1 vs 13.5mL/s) as compared with the healthy participants (n=16), with a significant level of collateralization. CONCLUSIONS: Reproducibility of the MRI primary end points in PACE was very good to excellent. The PAD participants exhibited decreased calf muscle capillary perfusion as well as arterial flow reserve when compared with healthy participants. The MRI tools used in PACE may advance PAD science by enabling accurate measurement of PAD microvascular anatomy and perfusion before and after stem cell or other PAD therapies.

Bedside Assessment of the Microvascular Venous Compartment in Cardiac Surgery Patients With Valvular Diseases Undergoing Cardiopulmonary Bypass.

OBJECTIVE: Blood volume reserve for venous return and the effects of cardiopulmonary bypass (CPB) on microvascular bed partitioning and blood flow were examined in patients with valvular diseases. DESIGN: Prospective, consecutive, case-control study. SETTING: Single university hospital. PARTICIPANTS: The study comprised 20 adult cardiac surgery patients and 20 healthy volunteers. INTERVENTIONS: Cardiovascular and microvascular variables were collected soon after the induction of anesthesia, after commencement of CPB, 20 minutes after separation from CPB, and in the intensive care unit. MEASUREMENTS AND MAIN RESULTS: The unstressed and stressed volumes (Vu, Vs) and pressures therein (Pit, Ps) were measured in the brachioradial muscle with near-infrared spectroscopy, applying incremental venous occlusions. At the first time point, Vs and Pit showed lower and higher values, respectively, than those of control patients, but Vs increased with Vu during the study, whereas Pit remained unchanged. Fluid balance correlated with Pit (r = 0.83, p<0.001) and hemoglobin (r = 0.78, p = 0.004). A nonlinear regression was found between fluid balance and ΔVu (r = 0.90, p<0.001) [y = 1.85+37.43(-0.01×x)]. The Vu/Pit and Vs/Ps ratios were lower than those of the control patients. Blood flow correlated to Vs/Ps (r = 0.75, p<0.001). The time constant was lower than reference (p = 0.005) and increased 10 times after CPB. CONCLUSIONS: Cardiac surgery patients have a limited blood volume reserve for venous return due to a reduced microvascular bed capacitance. This study demonstrated that during CPB a positive fluid balance induced an extravascular pressure increase and further reduced blood volume reserve.

Assessment of PTEN-associated vascular malformations in a patient with Bannayan-Riley-Ruvalcaba syndrome.

Misdiagnosis of phosphatase and tensin homologue hamartoma syndromes is common. Correct diagnosis has a relevant impact on patients, as the risk of malignancies is high and treatment options are limited. We report the case of a 24-year-old man who presented with symptomatic vascular intramuscular lesions of the left forearm and right calf, macrocephaly, post Hashimoto thyroiditis, a multicystic intracranial paratrigonal lesion, lentiginous hyperpigmented maculae on the foreskin and multiple skin lesions. MRI showed extended fibrofatty changes and malformed vessels in the forearm and calf lesions, also, arteriovenous shunting was present in these lesions. The patient had been treated by embolisation and surgically in the past, with limited results. A multidisciplinary assessment and genetic counselling were undertaken and a surveillance programme was initiated. Treatment options of the symptomatic vascular lesions include excision or possibly cryoablation. Physiotherapy to prevent progression of the contractures should be initiated meanwhile.