Astrocytic activation increases blood flow in the adult olfactory bulb.

Activation of astrocytes after sensory stimulation has been reported to be involved in increased blood flow in the central nervous system. In the present study, using a chemogenetic method to induce astrocyte activation in mice without sensory stimulation, we found that astrocytic activation led to increased blood flow in the olfactory bulb, suggesting that astrocyte activation is sufficient for increasing blood flow in the olfactory bulb. The technique established here will be useful for studying the mechanisms underlying sensory input-dependent blood flow increases.

Association of choroidal thickness and blood flow features with asymmetric axial lengths in children with unilateral myopic anisometropia.

BACKGROUND: Considering that changes in the choroidal thickness are closely related to ocular growth, we studied the choroidal thickness (CT) and the blood flow features in children with unilateral myopic anisometropia (UMA) as well as investigating the relationship between choroidal changes and myopia. METHODS: Subjective refractive, axial length (AL), and biometric parameters were measured in 98 UMA children (age: 8-15 years). CT and choroidal blood-flow features, including the choroidal vessel volume (CVV), choroidal vascularity index (CVI), and choriocapillaris perfusion area (CCPA), were measured through swept-source optical coherence tomography angiography. The macular region was categorized into four concentric circles of diameters 0-1 mm (central fovea), 1-3 mm (parafovea), 3-6 mm (perifovea), and 6-9 mm (extended), and further categorized into superior (S), inferior (I), temporal (T), and nasal (N) quadrants. RESULTS: The aforementioned four regions of myopic eyes displayed significantly lower CT, CVV, and CVI than those of non-myopic eyes. CCPA changes differed across different regions of both the eyes (parts of N and T quadrants). There was an inverse association between CT and the interocular AL difference (central and other regions S, T quadrant). No correlation was noted between CVV and CVI with interocular AL difference. CT and CVV were positively correlated in the 0-6-mm macular region of myopic eyes (Spearman correlation coefficient = 0.763, P < 0.001). CONCLUSIONS: In UMA children, CCT and blood flow may be related to myopia progression. A robust correlation between CT and CVV in the 0-6-mm macular region and reduced CT and diminished blood flow indicated an association with myopia.

Acute effects of blood flow restricted aerobic exercise in type 2 diabetes mellitus.

BACKGROUND: This study aimed to compare the acute effects of aerobic exercise performed with blood flow restriction (BFR), a novel method to increase exercise gains, with blood free flow (BFF) conditions in type 2 diabetes mellitus (T2DM). METHODS: Fifteen individuals with T2DM performed BFF and BFR (40% of arterial occlusion pressure) cycling exercises 48 hours apart, at equal intensity (45% heart rate reserve) and duration (38 minutes). Systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), blood glucose, heart rate, and muscle oxygen saturation (SmO2) were assessed before-after and during exercise sessions. RESULTS: SBP, DBP, and MAP in the overload phase were higher in the BFR group than in the BFF group (P = .009, 0.031, and 0.013, respectively). Changes in blood pressure (∆SBP and ∆DBP) were similar between the BFF and BFR groups (P > .05), whereas ∆MAP differed (P = .016). Changes in blood glucose levels and heart rates were not significantly different between the groups. Although SmO2baseline was lower in the BFR group (P = .049), SmO2min and SmO2max did not differ significantly between the BFF and BFR groups. CONCLUSION: The similar decrease in blood glucose levels between the groups suggests that BFR exercise is favorable in terms of hypoglycemia. The higher blood pressure observed during the BFR exercise remained within safe limits. These results suggest that people with T2DM can safely perform BFR aerobic exercises; however, further studies are required.

Acute Sympathetic Blockade Improves Insulin-Mediated Microvascular Blood Flow in the Forearm of Adult Human Subjects With Obesity.

BACKGROUND: Obesity is associated with resistance to the metabolic (glucose uptake) and vascular (nitric-oxide mediated dilation and microvascular recruitment) actions of insulin. These vascular effects contribute to insulin sensitivity by increasing tissue delivery of glucose. Studies by us and others suggest that sympathetic activation contributes to insulin resistance to glucose uptake. Here we tested the hypothesis that sympathetic activation contributes to impaired insulin-mediated vasodilation in adult subjects with obesity. METHODS AND RESULTS: In a randomized crossover study, we used a euglycemic hyperinsulinemic clamp in 12 subjects with obesity to induce forearm arterial vasodilation (forearm blood flow) and microvascular recruitment (contrast-enhanced ultrasonography) during an intrabrachial infusion of saline (control) or phentolamine (sympathetic blockade). Insulin increased forearm blood flow on both study days (from 2.21±1.22 to 4.89±4.21 mL/100 mL per min, P=0.003 and from 2.42±0.89 to 7.19±3.35 mL/100 mL per min, P=0.002 for the intact and blocked day, respectively). Sympathetic blockade with phentolamine resulted in a significantly greater increase in microvascular flow velocity (∆microvascular flow velocity: 0.23±0.65 versus 2.51±3.01 arbitrary intensity units (AIU/s) for saline and phentolamine respectively, P=0.005), microvascular blood volume (∆microvascular blood volume: 1.69±2.45 versus 3.76±2.93 AIU, respectively, P=0.05), and microvascular blood flow (∆microvascular blood flow: 0.28±0.653 versus 2.51±3.01 AIU2/s, respectively, P=0.0161). To evaluate if this effect was not due to nonspecific vasodilation, we replicated the study in 6 subjects with obesity comparing intrabrachial infusion of phentolamine to sodium nitroprusside. At doses that produced similar increases in forearm blood flow, insulin-induced changes in microvascular flow velocity were greater during phentolamine than sodium nitroprusside (%microvascular flow velocity=58% versus 29%, respectively, P=0.031). CONCLUSIONS: We conclude that sympathetic activation impairs insulin-mediated microvascular recruitment in adult subjects with obesity.

The hemodynamic response to nitrite is acute and dependent upon tissue perfusion.

In the vasculature, nitric oxide (NO) is produced in the endothelium by endothelial nitric oxide synthase (eNOS) and is critical for the regulation of blood flow and blood pressure. Blood flow may also be regulated by the formation of nitrite-derived NO catalyzed by hemoproteins under hypoxic conditions. We sought to investigate whether nitrite administration may affect tissue perfusion and systemic hemodynamics in WT and eNOS knockout mice. We found that global eNOS KO mice show decreased tissue perfusion compared to WT mice by using laser speckle contrast imaging. To study both the acute and long-term effects of sodium nitrite (0, 0.1, 1, and 10 mg/kg) on peripheral blood flow and systemic blood pressure, a bolus of nitrite was delivered intraperitoneally every 24 h over 4 consecutive days. We found that nitrite administration resulted in a dose-dependent and acute increase in peripheral blood flow in eNOS KO mice but had no effects in WT mice. The nitrite induced changes in tissue perfusion were transient, as determined by intraindividual comparisons of tissue perfusion 24-h after injection. Accordingly, 10 mg/kg sodium nitrite acutely decreased blood pressure in eNOS KO mice but not in WT mice as determined by invasive Millar catheterization. Interestingly, we found the vasodilatory effects of nitrite to be inversely correlated to baseline tissue perfusion. These results demonstrate the nitrite acutely recovers hypoperfusion and hypertension in global eNOS KO mice and suggest the vasodilatory actions of nitrite are dependent upon tissue hypoperfusion.

Individuals Can be Taught to Sense the Degree of Vascular Occlusion: Implications for Practical Blood Flow Restriction.

ABSTRACT: Song, JS, Hammert, WB, Kataoka, R, Yamada, Y, Kang, A, and Loenneke, JP. Individuals can be taught to sense the degree of vascular occlusion: Implications for practical blood flow restriction. J Strength Cond Res 38(8): 1413-1418, 2024-It is currently unknown if individuals can be conditioned to a relative arterial occlusion pressure (AOP) and replicate that pressure at a later time point. The purpose of this study was to determine whether individuals can be taught to sense a certain relative pressure (i.e., target pressure) by comparing a conditioning method with a time-matched non-conditioning control. Fifty-eight subjects completed 2 visits in a randomized order: (a) conditioning condition and (b) time-matched control condition. The conditioning involved 11 series of inflations to 40% AOP for 12 seconds followed by cuff deflation for 22 seconds. The pressure estimations were taken at 5 and 30 minutes after each condition. Data are presented as mean differences (95% credible interval). The absolute error at 5 minutes was greater for the control compared with conditioning condition (7.1 [2.0-12.1] mm Hg). However, this difference in absolute error between conditioning and control was reduced at 30 minutes (2.9 [-1.3 to 7.1] mm Hg). The mean difference and 95% limits of agreement for the control were 8.2 (-42.4 to 58.5) mm Hg at 5 minutes and 0.02 (-43.5 to 43.5) at 30 minutes. The agreements for the conditioning were -6.2 (-32.4 to 20.0) mm Hg at 5 minutes and -11.2 (-36.6 to 14.3) mm Hg at 30 minutes. The results suggest that the individuals can be taught to sense the target pressure, but this effect only lasts a short amount of time. Future work is necessary to refine the conditioning method to extend the duration of this conditioning effect.

The effect of individualised post-exercise blood flow restriction on recovery following strenuous resistance exercise: A randomised controlled trial.

The purpose was to clarify the effect of individualised post-exercise blood flow restriction (PE-BFR) on measures of recovery following strenuous resistance exercise. Twenty resistance-trained adults were randomised to a PE-BFR or control (CON) group and completed a fatigue protocol of five sets of 10 repetitions of maximal intensity concentric and eccentric seated knee extension exercise. Participants then lied supine with cuffs applied to the upper thigh and intermittently inflated to 80% limb occlusion pressure (PE-BFR) or 20 mmHg (CON) for 30 min (3 × 5 min per leg). Peak torque (PT), time-to-peak torque (TTP), countermovement jump height (CMJ), muscle soreness (DOMS) and perceived recovery (PR) were measured pre-fatigue, immediately post-fatigue and at 1, 24, 48 and 72 h post-fatigue. Using a linear mixed-effect model, PE-BFR was found to have greater recovery of CMJ at 48 h (mean difference [MD]=-2.8, 95% confidence interval [CI] -5.1, 0.5, p = 0.019), lower DOMS at 48 (MD = 3.0, 95% CI 1.2, 4.9, p = 0.001) and 72 h (MD = 1.95, 95% CI -1.2, 1.5, p = 0.038) and higher PR scores at 24 (MD = -1.7, 95% CI -3.4, -0.1, p = 0.038), 48 (MD = -3.1, 95% CI -4.8, -1.5, p < 0.001) and 72 h (MD = -2.2, 95% CI -3.8, -0.5, p = 0.011). These findings suggest that individualised PE-BFR accelerates recovery after strenuous exercise.

Robust analysis of microcirculatory flowmotion during post-occlusive reactive hyperemia.

BACKGROUND: Flowmotion analysis of the microcirculatory blood flow is a method to extract information about the vessel regulatory function. It has previously shown promise when applied to measurements during a post-occlusive reactive hyperemia. However, the reperfusion peak and the following monotonic decline introduces false low frequencies that should not be interpreted as rhythmic vasomotion effect. AIM: To develop and validate a robust method for flowmotion analysis of post-occlusive reactive hyperemia signals. METHOD: The occlusion-induced reperfusion response contains a typical rapid increase followed by a monotonic decline to baseline. A mathematical model is proposed to detrend this transient part of the signal to enable further flowmotion analysis. The model is validated in 96 measurements on healthy volunteers. RESULTS: Applying the proposed model corrects the flowmotion signal without adding any substantial new false flowmotion components. CONCLUSION: Future studies should use the proposed method or equivalent when analyzing flowmotion during post-occlusive reactive hyperemia to ensure valid results.

Comparison of Adaptations in the Gastrocnemius Muscle from an Exercise Program with and without Low-Intensity Blood Flow Restriction Banding in 18 Male Amateur Basketball Players Aged 16-45 Years.

BACKGROUND Basketball is a sport with a global impact and recognized major leagues, and is one of the most studied and analyzed sports for improvement at the level of the high-performance athlete. Increasing the jump height of basketball players is an essential factor for high athletic performance. MATERIAL AND METHODS This study aimed to identify the effect of low-intensity training with flow restriction versus the eccentric exercise protocol on amateur athletes. Eighteen amateur basketball players aged 16-45 years were divided into 2 groups: Group A consisted of 9 participants with low-intensity training with flow restriction (40% intensity) with 200 mmHg occlusion applying flow restriction bands in the popliteal area, while Group B consisted of 9 participants who performed an eccentric exercises protocol on the gastrocnemius. An anthropometric evaluation was applied, which consisted of perception of effort, range of movement (ROM), muscle strength intensity, and the power of the jump measured with a jump platform. RESULTS Notable changes were observed in favor of Group A for the right dorsiflexion, with mean difference (MD)=-2.444 (P=0.018); left dorsiflexion with MD=-2.778 (P=0.027) and left foot perimeter variable with MD=-0.667 (P=0.026) at 95% confidence interval (CI); while the vertical jump was in favor of Group B, with MD=-2.899 (P=0.006). CONCLUSIONS Low-intensity training with flow restriction and eccentric exercise protocol were both effective in improving jumping performance. A significant improvement was shown in the jump height and ROM of the 2 study groups.

Muscle activity and hypoalgesia in blood flow restricted versus unrestricted effort-matched resistance exercise in healthy adults.

This study assessed muscle activity (root mean square, RMS, and median frequency, MDF) to evaluate the acute response to blood flow restriction (BFR) resistance exercise (RE) and conventional moderate intensity (MI) RE. We also performed exploratory analyses of differences based on sex and exercise-induced hypoalgesia (EIH). Fourteen asymptomatic individuals performed four sets of unilateral leg press with their dominant leg to volitional fatigue under two exercise conditions: BFR RE and MI RE. Dominant side rectus femoris (RF) and vastus lateralis (VL) muscle activity were measured using surface electromyography (sEMG) through exercise. RMS and MDF were calculated and compared between conditions and timepoints using a linear mixed model. Pressure pain thresholds (PPT) were tested before and immediately after exercise and used to quantify EIH. Participants were then divided into EIH responders and nonresponders, and the differences on RMS and MDF were compared between the two groups using Hedges' g. RMS significantly increased over time (RF: p = 0.0039; VL: p = 0.001) but not between conditions (RF: p = 0.4; VL: p = 0.67). MDF decreased over time (RF: p = 0.042; VL: p < 0.001) but not between conditions (RF: p = 0.74; VL: p = 0.77). Consistently lower muscle activation was found in females compared with males (BRF, RF: g = 0.63; VL, g = 0.5. MI, RF: g = 0.72; VL: g = 1.56), with more heterogeneous findings in MDF changes. For BFR, EIH responders showed greater RMS changes (Δ RMS) (RF: g = 0.90; VL: g = 1.21) but similar MDF changes (Δ MDF) (RF: g = 0.45; VL: g = 0.28) compared to nonresponders. For MI, EIH responders demonstrated greater increase on Δ RMS (g = 0.61) and decrease on Δ MDF (g = 0.68) in RF but similar changes in VL (Δ RMS: g = 0.40; Δ MDF: g = 0.39). These results indicate that when exercising to fatigue, no statistically significant difference was observed between BFR RE and conventional MI RE in Δ RMS and Δ MDF. Lower muscle activity was noticed in females. While exercising to volitional fatigue, muscle activity may contribute to EIH.

Optical coherence tomography angiography in thyroid associated ophthalmopathy: a systematic review.

PURPOSE: To evaluate the evidence for alterations of blood flow, vascular and perfusion densities in the choroid, macula, peripapillary region, and the area surrounding the optic nerve head (ONH) in patients with thyroid-associated ophthalmopathy (TAO) based on changes of OCTA parameters. METHODS: A systematic review of Pubmed, Google Scholar, Scopus, WOS, Cochrane, and Embase databases, including quality assessment of published studies, investigating the alterations of OCTA parameters in TAO patients was conducted. The outcomes of interest comprised changes of perfusion and vascular densities in radial peripapillary capillary (RPC), ONH, superficial and deep retinal layers (SRL and DRL), choriocapillaris (CC) flow, and the extent of the foveal avascular zone (FAZ). RESULTS: From the total of 1253 articles obtained from the databases, the pool of papers was narrowed down to studies published until March 20th, 2024. Lastly, 42 studies were taken into consideration which contained the data regarding the alterations of OCTA parameters including choriocapillary vascular flow, vascular and perfusion densities of retinal microvasculature, SRL, and DRL, changes in macular all grid sessions, changes of foveal, perifoveal and parafoveal densities, macular whole image vessel density (m-wiVD) and FAZ, in addition to alterations of ONH and RPC whole image vessel densities (onh-wiVD and rpc-wiVD) among TAO patients. The correlation of these parameters with visual field-associated parameters, such as Best-corrected visual acuity (BCVA), Visual field mean defect (VF-MD), axial length (AL), P100 amplitude, and latency, was also evaluated among TAO patients. CONCLUSION: The application of OCTA has proven helpful in distinguishing active and inactive TAO patients, as well as differentiation of patients with or without DON, indicating the potential promising role of some OCTA measures for early detection of TAO with high sensitivity and specificity in addition to preventing the irreversible outcomes of TAO. OCTA assessments have also been applied to evaluate the effectiveness of TAO treatment approaches, including systemic corticosteroid therapy and surgical decompression.

Caffeine Abstinence in Habituated Users: Cardiovascular Responses to Exercise With Blood Flow Restriction.

CONTEXT: Blood flow restriction resistance exercise studies often require caffeine abstinence to avoid cardiovascular effects that could change the blood flow restriction stimulus. However, effects may be attenuated for habituated users. OBJECTIVE: To compare cardiovascular responses to blood flow restriction resistance exercise when habituated users consume or abstain from caffeine. DESIGN: Thirty participants completed a 3-visit within-subject study beginning with familiarization and caffeine intake questionnaire. METHODS: Visits 2 and 3 consisted of blood flow restriction resistance exercise (3 sets bicep curls to failure, 30% 1-repetition max, 40% arterial occlusion pressure [AOP]), following participants' normal caffeine consumption (CAFF) or abstaining (ABS). AOP, systolic (SBP) and diastolic (DBP) blood pressure, and heart rate were measured preexercise and postexercise. Prevalues and preexercise to postexercise change scores for SBP, DBP, AOP (all millimeters of mercury), heart rate (in beats per minute), and repetitions were compared between conditions. Results are represented as mean (SD). RESULTS: Preexercise AOP was similar for CAFF (137.8 [14.4]) and ABS (137.1 [14.9], BF10 = 0.2), although pre-SBP was higher for CAFF (115.4 [9.8]) than ABS (112.3 [9.4], BF10 = 1.9). Pre-DBP was similar between conditions. The exercise-induced change in AOP was greater for CAFF (18.4 [11.2]) than ABS (13.2 [14.9]), though evidence was anecdotal (BF10 = 0.7). Exercise-induced changes in SBP, DBP, and heart rate were similar between conditions (all BF10 ≤ 0.40). More repetitions were completed for CAFF (63 [26]) than ABS (57 [17], BF10 = 2.1). CONCLUSIONS: The findings of this study suggest that for habituated users, maintaining daily caffeine habits will not have substantial effects on common cardiovascular variables relevant to blood flow restriction.

Endurance Training Improves Leg Proton Release and Decreases Potassium Release During High-Intensity Exercise in Normoxia and Hypobaric Hypoxia.

AIM: To assess the impact of endurance training on skeletal muscle release of H+ and K+. METHODS: Nine participants performed one-legged knee extension endurance training at moderate and high intensities (70%-85% of Wpeak), three to four sessions·week-1 for 6 weeks. Post-training, the trained and untrained (control) leg performed two-legged knee extension at low, moderate, and high intensities (40%, 62%, and 83% of Wpeak) in normoxia and hypoxia (~4000 m). The legs were exercised simultaneously to ensure identical arterial inflow concentrations of ions and metabolites, and identical power output was controlled by visual feedback. Leg blood flow was measured (ultrasound Doppler), and acid-base variables, lactate- and K+ concentrations were assessed in arterial and femoral venous blood to study K+ and H+ release. Ion transporter abundances were assessed in muscle biopsies. RESULTS: Lactate-dependent H+ release was similar in hypoxia to normoxia (p = 0.168) and was lower in the trained than the control leg at low-moderate intensities (p = 0.060-0.006) but similar during high-intensity exercise. Lactate-independent and total H+ releases were higher in hypoxia (p < 0.05) and increased more with power output in the trained leg (leg-by-power output interactions: p = 0.02). K+ release was similar at low intensity but lower in the trained leg during high-intensity exercise in normoxia (p = 0.024) and hypoxia (p = 0.007). The trained leg had higher abundances of Na+/H+ exchanger 1 (p = 0.047) and Na+/K+ pump subunit α (p = 0.036). CONCLUSION: Moderate- to high-intensity endurance training increases lactate-independent H+ release and reduces K+ release during high-intensity exercise, coinciding with increased Na+/H+ exchanger 1 and Na+/K+ pump subunit α muscle abundances.

Assessing Leg Blood Flow and Cardiac Output During Running Using Thermodilution.

Cardiac output (Q̇C) and leg blood flow (Q̇LEG) can be measured simultaneously with high accuracy using transpulmonary and femoral vein thermodilution with a single-bolus injection. The invasive measure has offered important insight into leg hemodynamics and blood flow distribution during exercise. Despite being the natural modality of exercise in humans, there has been no direct measure of Q̇LEG while running in humans. We sought to determine the feasibility of the thermodilution technique for measuring Q̇LEG and conductance during high-intensity running, in an exploratory case study. A trained runner (30 years male) completed two maximal incremental tests on a cycle ergometer and motorized treadmill. Q̇LEG and Q̇C were determined using the single-bolus thermodilution technique. Arterial and venous blood were sampled throughout exercise, with continuous monitoring of metabolism, intra-arterial and venous pressure, and temperature. The participant reached a greater peak oxygen uptake (V̇O2peak) during running relative to cycling (74 vs. 68 mL/kg/min) with comparable Q̇LEG (19.0 vs. 19.5 L/min) and Q̇C (27.4 vs. 26.2 L/min). Leg vascular conductance was greater during high-intensity running relative to cycling (82 vs. 70 mL/min/mmHg @ ~80% V̇O2peak). The "beat phenomenon" was apparent in femoral flow while running, producing large gradients in conductance (62-90 mL/min/mmHg @ 70% V̇O2peak). In summary, we present the first direct measure of Q̇LEG and conductance in a running human. Our findings corroborate several assumptions about Q̇LEG during running compared with cycling. Importantly, we demonstrate that using thermodilution in running exercise can be completed effectively and safely.

Dual-task improvement of older adults after treadmill walking combined with blood flow restriction of low occlusion pressure: the effect on the heart-brain axis.

OBJECTIVE: This study explored the impact of one session of low-pressure leg blood flow restriction (BFR) during treadmill walking on dual-task performance in older adults using the neurovisceral integration model framework. METHODS: Twenty-seven older adults participated in 20-min treadmill sessions, either with BFR (100 mmHg cuff pressure on both thighs) or without it (NBFR). Dual-task performance, measured through light-pod tapping while standing on foam, and heart rate variability during treadmill walking were compared. RESULTS: Following BFR treadmill walking, the reaction time (p = 0.002) and sway area (p = 0.012) of the posture dual-task were significantly reduced. Participants exhibited a lower mean heart rate (p < 0.001) and higher heart rate variability (p = 0.038) during BFR treadmill walking. Notably, BFR also led to band-specific reductions in regional brain activities (theta, alpha, and beta bands, p < 0.05). The topology of the EEG network in the theta and alpha bands became more star-like in the post-test after BFR treadmill walking (p < 0.005). CONCLUSION: BFR treadmill walking improves dual-task performance in older adults via vagally-mediated network integration with superior neural economy. This approach has the potential to prevent age-related falls by promoting cognitive reserves.

Free Flap Perfusion in Microvascular Head and Neck Reconstruction: Influence of the Number of Ischemia Intervals and Ischemia Duration-A Retrospective Study.

BACKGROUND: In microvascular head and neck reconstruction, ischemia of the free flap tissue is inevitable during microsurgical anastomosis and may affect microvascular free flap perfusion, which is a prerequisite for flap viability and a parameter commonly used for flap monitoring. The aim of this study was to investigate the influence of the number of ischemia intervals and ischemia duration on flap perfusion. METHODS: Intraoperative and postoperative flap blood flow, hemoglobin concentration, and hemoglobin oxygen saturation at 2 and 8 mm tissue depths, as measured with the O2C tissue oxygen analysis system, were retrospectively analyzed for 330 patients who underwent microvascular head and neck reconstruction between 2011 and 2020. Perfusion values were compared between patients without (control patients) and with a second ischemia interval (early or late) and examined with regard to ischemia duration. RESULTS: Intraoperative and postoperative flap blood flow at 8 mm tissue depth were lower in patients with early second ischemia intervals than in control patients [102.0 arbitrary units (AU) vs 122.0 AU, P = .030; 107.0 AU vs 128.0 AU, P = .023]. Both differences persisted in multivariable analysis. Intraoperative and postoperative flap blood flow at 8 mm tissue depth correlated weakly negatively with ischemia duration in control patients (r = -.145, P = .020; r = -.124, P = .048). Both associations did not persist in multivariable analysis. CONCLUSIONS: The observed decrease in microvascular flap blood flow after early second ischemia intervals may reflect ischemia-related vascular flap tissue damage and should be considered as a confounding variable in flap perfusion monitoring.

Identifying the Mechanisms of a Peripherally Limited Exercise Phenotype in Patients With Heart Failure With Preserved Ejection Fraction.

BACKGROUND: We identified peripherally limited patients using cardiopulmonary exercise testing and measured skeletal muscle oxygen transport and utilization during invasive single leg exercise testing to identify the mechanisms of the peripheral limitation. METHODS: Forty-five patients with heart failure with preserved ejection fraction (70±7 years, 27 females) completed seated upright cardiopulmonary exercise testing and were defined as having a (1) peripheral limitation to exercise if cardiac output/oxygen consumption (VO2) was elevated (≥6) or 5 to 6 with a stroke volume reserve >50% (n=31) or (2) a central limitation to exercise if cardiac output/VO2 slope was ≤5 or 5 to 6 with stroke volume reserve <50% (n=14). Single leg knee extension exercise was used to quantify peak leg blood flow (Doppler ultrasound), arterial-to-venous oxygen content difference (femoral venous catheter), leg VO2, and muscle oxygen diffusive conductance. In a subset of participants (n=36), phosphocreatine recovery time was measured by magnetic resonance spectroscopy to determine skeletal muscle oxidative capacity. RESULTS: Peak VO2 during cardiopulmonary exercise testing was not different between groups (central: 13.9±5.7 versus peripheral: 12.0±3.1 mL/min per kg; P=0.135); however, the peripheral group had a lower peak arterial-to-venous oxygen content difference (central: 13.5±2.0 versus peripheral: 11.1±1.6 mLO2/dL blood; P<0.001). During single leg knee extension, there was no difference in peak leg VO2 (P=0.306), but the peripherally limited group had greater blood flow/VO2 ratio (P=0.024), lower arterial-to-venous oxygen content difference (central: 12.3±2.5 versus peripheral: 10.3±2.2 mLO2/dL blood; P=0.013), and lower muscle oxygen diffusive conductance (P=0.021). A difference in magnetic resonance spectroscopy-derived phosphocreatine recovery time was not detected (P=0.199). CONCLUSIONS: Peripherally limited patients with heart failure with preserved ejection fraction identified by cardiopulmonary exercise testing have impairments in oxygen transport and utilization at the level of the skeletal muscle quantified by invasive knee extension exercise testing, which includes an increased blood flow/V̇O2 ratio and poor muscle diffusive capacity. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04068844.