Limb Blood Flow Research Articles

Abstract 13886: Impaired Locomotor Muscle Blood Flow During Cycling Exercise in Heart Failure With Preserved Ejection Fraction

Introduction: Obesity and hypertension (HTN) are highly prevalent comorbid risk factors for heart failure with preserved ejection fraction (HFpEF). Obesity and HTN independently increase sympathetic nervous activity and impair muscle blood flow during exercise. Previous work has reported attenuated limb blood flow in patients with HFpEF; however, these findings were compared to controls with dissimilar comorbidities and during small muscle mass exercise. It is unclear if HFpEF alters muscle blood flow responses independent of the obesity- and HTN-mediated alterations. Hypothesis: We hypothesized the muscle blood flow response during cycling would be lower in HFpEF patients than age, sex, BMI, and HTN matched controls (CTL). Methods: HFpEF patients (n=14, 9M/5W, 71±7yrs, 32±4 kg/m 2 ) and CTL (n=12, 8M/4W, 69±7yrs, 31±4 kg/m 2 ) performed an incremental cycling test. Blood pressure was measured by manual sphygmomanometry, cardiac output (Q) by open-circuit acetylene wash-in technique, and systemic vascular resistance (SVR) was calculated. Vastus lateralis blood flow index (BFI) was measured by near-infrared spectroscopy and indocyanine green dye injections and venous norepinephrine concentration was measured. Changes from rest to 40 W of the incremental test are reported. Results: Resting Q, mean arterial pressure, SVR, and venous norepinephrine concentration were not statistically different between groups (p>0.18). From rest to 40 W, the increases in Q (CTL: 3.9±0.8 vs. HFpEF: 3.6±0.7 L/min), mean arterial pressure (CTL: 5.7±2.7 vs. HFpEF: 6.6±6.1 mmHg), and SVR (CTL: -7.3±2.1 vs. HFpEF: -6.0±2.0 mmHg/L/min) were not statistically different between groups (all, p>0.13). The HFpEF group had smaller increases in vastus lateralis BFI at 40 W compared to CTL (CTL: 7.2±3.6 vs. HFpEF: 4.2±2.6 fold-increase from rest) (p=0.02). The HFpEF group had greater increases in venous norepinephrine concentration from rest to 40 W than CTL (CTL: 164±216 vs. HFpEF: 377±247 pg/mL) (p=0.05). Conclusions: Our findings suggest that, compared to age, sex, BMI, and HTN matched controls, patients with HFpEF have an impaired locomotor muscle blood flow response during submaximal cycling exercise likely due to higher locomotor muscle vascular resistance.

Sex differences in muscle contraction-induced limb blood flow limitations.

To determined sex differences in absolute- and %-reductions in blood flow during intermittent muscular contractions as well as relationships between blood flow reductions and time to task failure (TTF). Thirteen males (25 ± 4 years) and 13 females (22 ± 5 years) completed intermittent isometric trapezoidal forearm flexion at 50% maximal voluntary contraction until task failure. Doppler ultrasound was used to measure brachial artery blood flow (BABF) during the 12-s plateau phase and 12-s relaxation phase. Target torque was less in females than males (24 ± 5 vs. 42 ± 7 Nm; p < 0.001); however, TTF was not different between sexes (F: 425 ± 187 vs. M: 401 ± 158s; p = 0.72). Relaxation-phase BABF at end-exercise was less in females than males (435 ± 161 vs. 937 ± 281mL/min; p < 0.001) but contraction-phase BABF was not different (127 ± 46 vs. 190 ± 99mL/min; p = 0.42). Absolute- and %-reductions in BABF by contraction were less in females than males (309 ± 146 vs. 747 ± 210mL/min and 69 ± 10 vs. 80% ± 6%, respectively; both p < 0.01) and were associated with target torque independent of sex (r = 0.78 and 0.56, respectively; both p < 0.01). Absolute BABF reduction per target torque (mL/min/Nm) and TTF were positively associated in males (r = 0.60; p = 0.031) but negatively associated in females (r = -0.61; p = 0.029). This study provides evidence that females incur less proportional reduction in limb blood flow from muscular contraction than males at a matched relative intensity suggesting females may maintain higher levels of muscle oxygen delivery and metabolite removal than males across the contraction-relaxation cycle of intermittent exercise.

Quantitative hemodynamic assessment of stenotic below-the-knee arteries using spatio-temporal bolus tracking on 4D-CT angiography.

Peripheral arterial disease (PAD) is a chronic occlusive disease that restricts blood flow in the lower limbs, causing partial or complete blockages of the blood flow. While digital subtraction angiography (DSA) has traditionally been the preferred method for assessing blood flow in the lower limbs, advancements in wide beam Computed Tomography (CT), allowing successive acquisition at high frame rate, might enable hemodynamic measurements. To quantify the arterial blood flow in stenotic below-the-knee (BTK) arteries. To this end, we propose a novel method for contrast bolus tracking and assessment of quantitative hemodynamic parameters in stenotic arteries using4D-CT. Fifty patients with suspected PAD underwent 4D-CT angiography in addition to the clinical run-off computed tomography angiography (CTA). From these dynamic acquisitions, the BTK arteries were segmented and the region of maximum blood flow was extracted. Time attenuation curves (TAC) were estimated using 2D spatio-temporal B-spline regression, enforcing both spatial and temporal smoothness. From these curves, quantitative hemodynamic parameters, describing the shape of the propagating contrast bolus were automatically extracted. We evaluated the robustness of the proposed TAC fitting method with respect to interphase delay and imaging noise and compared it to commonly used approaches. Finally, to illustrate the potential value of 4D-CT, we assessed the correlation between the obtained hemodynamic parameters and the presence ofPAD. 280 out of 292 arteries were successfully segmented, with failures mainly due to a delayed contrast arrival. The proposed method led to physiologically plausible hemodynamic parameters and was significantly more robust compared to 1D temporal regression. A significant correlation between the presence of proximal stenoses and several hemodynamic parameters was found. The proposed method based on spatio-temporal bolus tracking was shown to lead to stable and physiologically plausible estimation of quantitative hemodynamic parameters, even in the case of stenotic arteries. These parameters may provide valuable information in the evaluation of PAD and contribute to itsdiagnosis.

Acute upper and lower limb hemodynamic responses during single sessions of low- versus high-intensity inspiratory muscle strength training.

Inspiratory muscle strength training (IMST) has shown potential to improve both respiratory and cardiovascular function in health and disease. Less is known about acute hemodynamic responses to a single IMST session, therefore we assessed upper and lower limb blood flow via Doppler ultrasound in the brachial and popliteal arteries, respectively. Mean, anterograde, and retrograde blood flow (BF) and shear rate (SR) were assessed relative to baseline during low-intensity (15% maximal inspiratory pressure - PImax) and high-intensity (75% PImax) IMST. During low-intensity IMST, popliteal BF and SR were reduced by ∼10%, and brachial BF and SR were reduced by ∼40%. During high-intensity IMST, popliteal BF and SR were reduced by ∼20%, and brachial BF and SR were reduced by ∼35%. BF and SR responses were not statistically different between low-intensity and high-intensity training for either blood vessel (P > 0.05). In addition, anterograde BF and SR were significantly decreased in the brachial artery for both low-intensity and high-intensity training (P < 0.05), but not the popliteal artery (P > 0.05). Finally, during IMST retrograde BF and SR were significantly increased in both the upper and lower limbs during low-intensity and high-intensity training (P < 0.05). These data provide novel insight into the acute BF and SR responses to a single bout of IMST and may enhance our understanding of the mechanism(s) by which IMST imparts its beneficial chronic effects on cardiovascular function.NEW & NOTEWORTHY Herein, we demonstrate for the first time that upper and lower limb blood flow and shear rate patterns are altered during a single bout of IMST, at low- and high-intensity training. Specifically, anterograde blood flow and shear rate are significantly reduced in the brachial artery, whereas retrograde blood flow is significantly elevated in both the brachial and popliteal arteries. These findings provide insight into the vascular impact of IMST, which may inform future mechanistic studies.

Comparison Between the Efficacy of Spinal Cord Stimulation and of Endovascular Revascularization in the Treatment of Diabetic Foot Ulcers: A Retrospective Observational Study

ObjectiveWe aimed to compare the effects of spinal cord stimulation (SCS) with those of endovascular revascularization on the treatment of diabetic foot ulcers. Materials and MethodsA total of 104 patients with diabetic foot ulcers who met the inclusion criteria were retrospectively analyzed and classified to the SCS treatment group (n = 46) and endovascular revascularization treatment group (n = 46). The quality-of-life scores (Quality of Life Scale for Patients with Liver Cancer v2.0), visual pain analog scale score, lower limb skin temperature, lower limb arterial ultrasound results, and lower extremity electromyography results were analyzed to compare the efficacy of the two treatments for diabetic foot ulcers in the two groups before surgery and six months after surgery. ResultsA total of 92 patients (men: 73.9%, mean age: 66.51 ± 11.67 years) completed the six-month postoperative follow-up period. The patients in the SCS treatment group had a higher quality-of-life score (25.54% vs 13.77%, p < 0.05), a larger reduction in pain scores (69.18% vs 37.21%, p < 0.05), and a larger reduction in foot temperature (18.56% vs 7.24%, p < 0.05) than those of the endovascular revascularization treatment group at six months after surgery. The degree of vasodilation in the lower limbs on color Doppler arterial ultrasound and the nerve conduction velocity were higher in the SCS treatment group than in the endovascular revascularization treatment group at six months after surgery (p < 0.05). ConclusionSCS was more effective than endovascular revascularization in improving quality of life, relieving pain, improving lower limb skin temperature, increasing lower limb blood flow, and improving nerve conduction in patients with diabetic foot ulcers at six months after surgery.

Chinese expert consensus on the endovascular treatment of ischemic lesions in the diabetic foot

The arterial lesions in the lower limbs of diabetic foot patients are very complex, and restoring arterial blood flow in the lower limbs is the key to improving the quality of life and limb preservation rate of diabetic foot patients. The current endovascular treatment technique is the main choice in China because of its minimally invasive nature and rapid postoperative recovery. In order to provide better and more standardized treatment for diabetic foot and benefit patients, the Diabetic Foot Sub-Committee of the China Association for the Promotion of International Exchange of Healthcare and the Diabetic Foot Committee of the Chinese Chapter Congress of the International Union of Angiology have developed this consensus based on the literature and the clinical experience of various experts, including the objectives and principles of diabetic foot treatment and the selection of endovascular treatment methods for vascular lesions.

Spermidine improves angiogenic capacity of senescent endothelial cells, and enhances ischemia-induced neovascularization in aged mice

Aging is closely associated with the increased morbidity and mortality of ischemic cardiovascular disease, at least partially through impaired angiogenic capacity. Endothelial cells (ECs) play a crucial role in angiogenesis, and their angiogenic capacity declines during aging. Spermidine is a naturally occurring polyamine, and its dietary supplementation has exhibited distinct anti-aging and healthy lifespan-extending effects in various species such as yeast, worms, flies, and mice. Here, we explore the effects of spermidine supplementation on the age-related decline in angiogenesis both in vitro and in vivo. Intracellular polyamine contents were reduced in replicative senescent ECs, which were subsequently recovered by spermidine supplementation. Our findings reveal that spermidine supplementation improved the declined angiogenic capacity of senescent ECs, including migration and tube-formation, without affecting the senescence phenotypes. Mechanistically, spermidine enhanced both autophagy and mitophagy, and improved mitochondrial quality in senescent ECs. Ischemia-induced neovascularization was assessed using the hind-limb ischemia model in mice. Limb blood flow recovery and neovascularization in the ischemic muscle were considerably impaired in aged mice compared to young ones. Of note, dietary spermidine significantly enhanced ischemia-induced angiogenesis, and improved the blood flow recovery in the ischemic limb, especially in aged mice. Our results reveal novel proangiogenic functions of spermidine, suggesting its therapeutic potential against ischemic disease.

Effect of obesity on venous blood flow in the lower limbs.

Although obesity is a recognized risk factor for the development of lower limb venous disease, less attention has been paid to objectively measuring the effect of centripetal obesity on blood flow in the lower limbs. The diameter of lower limb veins and venous blood flow were measured in 44 patients (65.6 ±12.5 years, 25 females, 19 males) with centripetal obesity and chronic venous disease. The mean diameter of both common femoral veins (CFV) increased significantly in the semi-supine position following elevation of the panniculus (right: ∆0.73 ±1.21mm; p≤0.001, left: ∆1.16 ±1.42mm; p≤0.001). Moreover, there was a significant increase in venous flow volume in the left CFV (∆62.96 ±117.85ml/min; p = 0.001). Similarly, there was an increase in the diameter of left great saphenous vein (∆0.24 ±0.41mm; p = 0.002), measured at the mid-thigh, when the patient lifted their abdominal panniculus. Finally, the grade of obesity correlated with the extent of the venous disease. These data provide preliminary evidence that centripetal obesity results in both structural and hemodynamic changes in the lower limb veins, even in the absence of classical reflux.

Understanding lower limb blood flow occlusion parameters for use in field-based settings

ABSTRACT Reduction of blood flow to the limb using cuffs before or during exercise has become increasingly popular for training and rehabilitation. Our study tested the effects of cuff brand/width on pressures required to reach limb occlusion pressure (LOP) and developed, cross-validated, and compared accuracy of two LOP prediction equations to previously created methods. Supine LOP was determined in the distal popliteal artery using four different cuff brands/widths in 23 adult participants. Participants then had demographic and resting variables assessed, and two LOP prediction equations were developed from these variables and were compared to five previously developed models and a method using posterior tibial artery palpation for LOP assessment in an independent sample (n = 14 adult runners). For cuff comparison, the widest two cuffs had significantly lower LOP (mean ~149 mmHg) than the narrowest cuffs (mean ~176 mmHg), with the narrowest cuff unable to reach LOP. The eight methods used to predict LOP ranged in accuracy (mean absolute percent errors 3.9–23.0%), with highest accuracy in equations using mean arterial pressure (MAP) and BMI. Practitioners using blood flow reduction methods should be consistent with cuff use due to demonstrated differences across brands/widths. Equations using MAP and BMI appear best for prediction of leg LOP.

Abstract 648: Divergent Roles For Endothelial Cell Marcks In Endothelial Cell Regeneration And Signaling After Arterial Injury And Ischemia

Cardiovascular interventions cause endothelial injury and trigger re-establishment of intact endothelium. After ischemia, endothelial signaling is essential for capillary angiogenesis as well as flow-mediated collateral artery enlargement to restore perfusion. We studied the role of the signaling protein MARCKS (myristoylated alanine-rich C kinase substrate) in the endothelial response to injury and ischemia-induced angiogenesis. Methods: Targeted deletion of MARCKS in endothelial cells was done with Cadherin 5-driven Cre/Lox recombination and confirmed with immunohistochemistry. All controls were Cre(-) littermates. Re-endothelialization after femoral artery wire injury was measured by arterial area quantitation after Evan’s Blue exclusion. After femoral artery ligation, limb blood flow was determined by serial laser Doppler scanning, and angiogenesis by counting CD31-positive cells in the gastrocnemius muscle on day 28. Results: Endothelial cell-specific deletion of MARCKS was confirmed in Cre (+) animals. Deletion of MARCKS did not affect endothelial regeneration on post operative day 6 after denuding femoral wire injury (68.2% versus 68.7% recovery, n=5-6, p&gt;.05). Ischemia-induced capillary angiogenesis was not affected by deletion of MARCKS (Capillary Count, Cre(+): 602 versus Cre(-): 511, n=6, p&gt;.05), however animals lacking endothelial MARCKS had worsened limb perfusion on days 1, 3, 7 and 21 after ischemia (ABI Range Cre(+) versus Cre(-): 0.04-0.22 versus 0.07-0.41, respectively, n=6-9, p&lt;.05). Conclusions: These studies demonstrate distinct and divergent roles for MARCKS in the endothelial cell response to injury and ischemia. MARCKS is not essential for endothelial regeneration after denuding large vessel injury, or for capillary angiogenesis induced by ischemia. Surprisingly, endothelial MARCKS appears to be a novel endogenous promotor of ischemia-induced limb revascularization. This suggests that endothelial cell MARCKS promotes flow-mediated endothelial cell signaling essential for ischemia-induced arterial enlargement. MARCKS activity could be a possible therapeutic target to enhance collateral artery formation in limb ischemia.

Purinergic 2X Receptors Contribute to the Exaggerated Mechanoreflex in Rats with Heart Failure

Skeletal muscle contraction stimulates mechanically activated channels on the sensory endings of thin fiber muscle afferents which evokes reflex increases in sympathetic nerve activity and blood pressure. This reflex is termed the mechanoreflex and its activation in healthy populations plays a key role in facilitating oxygen delivery to contracting muscles and exercise performance. However, mechanoreflex activation in patients with heart failure with reduced ejection fraction (HF-rEF) results in excessive peripheral vasoconstriction and impaired limb blood flow during exercise. Recent evidence in a rat model of HF-rEF demonstrated that hindlimb arterial injection of PPADS, an antagonist for ATP-sensitive purinergic 2X (P2X) receptors, reduced thin fiber muscle afferent responsiveness to static hindlimb muscle stretch (a model of mechanoreflex activation isolated from contraction-induced metabolite production) to a greater extent in HF-rEF rats than in healthy counterparts. Those data suggest that, in HF-rEF, P2X receptor stimulation results in the sensitization of co-localized mechanically activated channels on the sensory endings of muscle afferents. To date, however, those electrophysiological findings have not been extended to reflex experiments investigating the cardiovascular consequences of mechanoreflex activation. Accordingly, we sought to determine the role played by P2X receptors in evoking the exaggerated blood pressure response to isolated mechanoreflex activation in HF-rEF rats. We hypothesized that hindlimb arterial injection of the P2X receptor antagonist PPADS (5mg) would reduce the integrated area under the blood pressure signal (the blood pressure index: BPI) evoked during 30 seconds of static hindlimb skeletal muscle stretch in decerebrate, unanesthetized HF-rEF rats to a greater extent than in healthy rats. Experiments were performed six to eight weeks following either a coronary artery ligation surgery to induce myocardial infarction and HF-rEF ( n=8M/2F; ejection fraction 37±6%) or a sham procedure ( n=1M/4F; ejection fraction 84±4; P&lt;0.01versus HF-rEF). In sham rats, P2X receptor blockade had no effect on the BPI response to hindlimb muscle stretch (control: 197±67, PPADS: 211±159mmHg⋅s; p=0.46). Conversely, in HF-rEF rats P2X receptor blockade reduced the BPI response to hindlimb muscle stretch (control: 425±60, PPADS: 257±83mmHg⋅s; p=0.01). The integrated area of the muscle tension signal during the stretch maneuver (tension-time-index; TTI) was not different between control and P2X receptor blockade conditions in either sham (control: 20±2, PPADS: 21±2kg·s; P=0.31) or HF-rEF (control: 24±2, PPADS: 25±2kg·s; P=0.09) rats. The data suggest that P2X receptors on the sensory endings of thin fiber muscle afferents do not play a role in the cardiovascular responses to mechanoreflex activation in health, but contribute importantly to the cardiovascular responses to mechanoreflex activation in HF-rEF. This work was supported by the National Institutes of Health (NIH) R01HL142877 to S.W.C. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Abstract 553: Loss Of Endothelial Bag3 Does Not Worsen Ischemia Induced Myopathy

Chronic limb threatening ischemia (CLTI), the most severe manifestation of peripheral artery disease, isaccompanied by high rates of limb amputation and death. There is a pressing need for novel therapydevelopment in these patients, which will require a thorough understanding of the individual cellularcontributions to ischemic limb pathology. BAG3 is a multifunctional adaptor protein that regulatesdiverse cellular functions. Mutations in BAG3 now appear to be one of the most common to causedisease in the clinical setting, including predisposing Black patients to cardiovascular disease. Wepreviously identified a coding variant in Bag3 that contributes to ischemic muscle necrosis after murinehindlimb ischemia (HLI) that was rescued by gene therapy, although we do not know which cell typesrequire Bag3 individually to mount efficient responses to ischemia. We hypothesized that vascularendothelial cell Bag3 would be required for both the restoration of blood flow and muscle function afterHLI. To test this hypothesis, we generated an inducible genetic model of endothelial cell Bag3 deletion(Cdh5(PAC)-CreERT2;Bag3 -/- ). At 20 weeks of age, mice were administered either tamoxifen (KO; n =20) orvehicle (CON, n =28) and evaluated at baseline or subjected to HLI for 7-days. Endothelial cell specific Bag3 deletion was validated first by genotyping and then by qRT-PCR in flow sorted cells. KO did notalter animal body weights, heart or skeletal muscle wet weights, physiologic muscle function (extensordigitorum longus absolute or specific force) or muscle histology (no regression of limb muscle tissuevascular cells) at baseline when compared with CON. After HLI, KO did not cause limb tissue necrosis,reduce limb blood flow recovery (laser doppler perfusion imaging) or physiologic muscle function, anddid not worsen histological damage to the limb muscle when compared with CON. Our study providesevidence for the first time that loss of endothelial cell Bag3 does not exacerbate myopathy and delaylimb blood flow recovery after hindlimb ischemia and suggests that the benefits of Bag3 gene therapymay be driven by the muscle cell compartment of the ischemic limb.

Sympathetic and hemodynamic responses to exercise in heart failure with preserved ejection fraction.

Excessive sympathetic activity during exercise causes heightened peripheral vasoconstriction, which can reduce oxygen delivery to active muscles, resulting in exercise intolerance. Although both patients suffering from heart failure with preserved and reduced ejection fraction (HFpEF and HFrEF, respectively) exhibit reduced exercise capacity, accumulating evidence suggests that the underlying pathophysiology may be different between these two conditions. Unlike HFrEF, which is characterized by cardiac dysfunction with lower peak oxygen uptake, exercise intolerance in HFpEF appears to be predominantly attributed to peripheral limitations involving inadequate vasoconstriction rather than cardiac limitations. However, the relationship between systemic hemodynamics and the sympathetic neural response during exercise in HFpEF is less clear. This mini review summarizes the current knowledge on the sympathetic (i.e., muscle sympathetic nerve activity, plasma norepinephrine concentration) and hemodynamic (i.e., blood pressure, limb blood flow) responses to dynamic and static exercise in HFpEF compared to HFrEF, as well as non-HF controls. We also discuss the potential of a relationship between sympathetic over-activation and vasoconstriction leading to exercise intolerance in HFpEF. The limited body of literature indicates that higher peripheral vascular resistance, perhaps secondary to excessive sympathetically mediated vasoconstrictor discharge compared to non-HF and HFrEF, drives exercise in HFpEF. Excessive vasoconstriction also may primarily account for over elevations in blood pressure and concomitant limitations in skeletal muscle blood flow during dynamic exercise, resulting in exercise intolerance. Conversely, during static exercise, HFpEF exhibit relatively normal sympathetic neural reactivity compared to non-HF, suggesting that other mechanisms beyond sympathetic vasoconstriction dictate exercise intolerance in HFpEF.

Protective Effects and Potential Mechanism of Tongxinluo on Mice with Thromboangiitis Obliterans Induced by Sodium Laurate.

To investigate the effects of Tongxinluo (TXL) on thromboangiitis obliterans (TAO) and the underlying mechanisms. Ninety male C57/BL6J mice were randomly divided into 6 groups according to a random number table: the sham group, TAO model group, Compound Danshen Tablet (CDT) group, and the high-, medium-, and low-dose TXL groups. All mice except the sham group were injected with sodium laurate (0.1 mL, 5 mg/mL) in the femoral artery to establish TAO mouse model. After modeling, mice in the sham and TAO model groups were intragastrically administered 0.5% (w/v) sodium carboxymethylcellulose, mice in the CDT group were intragastrically administered 0.52 g/kg CDT, and mice in the TXL-H, TXL-M, and TXL-L groups were intragastrically administered 1.5, 0.75, and 0.38 g/kg TXL, respectively. After 4 weeks of gavage, the recovery of blood flow in the lower limbs of mice was detected by Laser Doppler Imaging. The pathological changes and thrombosis of the femoral artery were observed by morphological examination. The expressions of tumor necrosis factor α (TNF-α) and inducible nitric oxide synthase (iNOS) in the femoral artery wall were detected by HE staining. Levels of thromboxane B2 (TXB2), 6-keto-prostaglandin F1α (6-keto-PGF1α), endothelin-1 (ET-1), interleukin (IL)-1β and IL-6 were measured using enzyme-linked immunosorbent assay (ELISA). Levels of activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT) and fibrinogen (FIB) were detected by a fully automated biochemical analyzer. TXL promoted the restoration of blood flow in the lower limbs, reduced the area of thrombosis in the femoral artery, and alleviated the pathological changes in the femoral artery wall. Moreover, the levels of TXB2, ET-1, IL-6, IL-1β, TNF-α and iNOS were significantly lower in the TXL groups compared with the model group (P<0.05 or P<0.01), while the level of 6-keto-PGF1α was significantly higher (P<0.01). In addition, APTT, PT, and TT were significantly prolonged in TXL groups compared with the model group (P<0.05 or P<0.01), and FIB levels were significantly decreased compared with the model group (P<0.01). TXL had a protective effect on TAO mice, and the mechanism may involve inhibition of thrombosis and inflammatory responses. TXL may be a potential drug for the treatment of TAO.

Exaggerated pressor responses, but unaltered blood flow regulation and functional sympatholysis during lower limb exercise in young, non-Hispanic black males.

Young non-Hispanic black (BL) males have displayed lower blood flow (BF) and vascular conductance (VC), but intact functional sympatholysis, during upper limb exercise when compared to non-Hispanic white (WH) males. This study sought to explore if similar differences were also present in the lower limbs. Thirteen young BL males and thirteen WH males completed one visit comprised of rhythmic lower limb (plantar flexion) exercise as well as upper limb (handgrip) exercise for a limb-specific comparison. Limb BF, mean arterial pressure (MAP), and VC were evaluated at three submaximal workloads (8, 16, and 24kg). To determine potential limb differences in functional sympatholysis, the impact of sympathetic nervous system activation (via cold-pressor test (CPT)) was evaluated at rest and during steady state exercise (30% of maximal voluntary contraction) on a subsequent visit. MAP responses to lower and upper limb exercise were elevated in young BL males (vs WH males), resulting in significantly lower VC responses in the upper limb, but not the lower limb. Further, BL males, when compared to WH males, revealed no differences in functional sympatholysis, evident by similar responses in both the exercising leg and arm VC during CPT. The findings of the current study indicate that although elevated MAP responses were observed during both lower and upper limb exercise in young BL males, vascular conductance was only hindered in the upper limbs. This may potentially highlight enhanced compensatory mechanisms in the lower limb (vs upper limb) to maintain perfusion in young BL males.

The quality and quantity media-cultured mononuclear cell transplantation is safe and effective in ischemic hindlimb mouse model

ObjectiveThis study was conducted to investigate in vitro proangiogenic and anti-inflammatory phenotypes and functions and the in vivo efficacy and safety of quality and quantity (QQ) media-cultured mononuclear cells (MNCs) compared with standard cultured MNCs from the peripheral blood of patients with chronic limb-threatening ischemia (CLTI) with atherosclerotic risk factors. MethodsPeripheral blood MNCs (PBMNCs) from patients with CLTI were cultured in QQ culture media or standard culture media. Phenotypic analysis of progenitor cells (CD34+CD133+), M2 macrophages (CD206+), and inactivated T regulatory cells (CD4+CD25+CD127+), colony-forming assay, and tube formation assay of QQ media-cultured MNCs (QQMNCs) and PBMNCs, were conducted. Intramuscular transplantation of QQMNCs or PBMNCs was performed in the ischemic hindlimb model. The clinical appearance of ischemic limbs was observed, and blood flow in ischemic limbs was measured using a laser Doppler perfusion imager. Outcomes were compared between the QQMNC and PBMNC groups. ResultsTwenty patients with CLTI were included. The mean percentages of CD34+ cells, CD133+ cells, CD34+CD133+ progenitor cells, CD206+ cells, colony-forming cells, and tube formation were significantly higher in the QQMNCs. The mean percentage of CD4+CD25+CD127+ cells was significantly lower in QQMNC. The colony-forming unit count and Dil-acetylated low-density lipoprotein uptake were significantly greater in QQMNCs. The clinical appearance of post-QQMNC-injected limbs was less severe than the appearance of post-PBMNC-injected limbs. Limb perfusion was significantly better in the QQMNCs. ConclusionsProangiogenic and anti-inflammatory phenotypes of MNCs cultured in QQ culture media were reproducible. Intramuscular QQMNC transplantation was safe and resulted in better reperfusion of ischemic hindlimbs compared with PBMNCs.

Utility of thermographic evaluation in spinal cord stimulation therapy DTM workflow for thoracolumbar compression fracture and lumbar spinal canal stenosis

Among the orthopedic conditions that cause low back pain, many patients with thoracolumbar compression fractures and lumbar spinal canal stenosis caused by osteoporosis visit orthopedic surgeons. However, many patients do not respond to analgesics or nerve block injections, and many are at risk or unwilling to undergo surgery due to age or underlying disease. We believe that spinal cord stimulation therapy is a new treatment option for orthopedic low back and leg pain. We have performed spinal cord stimulation for chronic intractable pain in patients with thoracolumbar spine compression fractures and lumbar spinal canal stenosis who had lower limb pain and back pain. There are few reports of spinal cord stimulation therapy treatment by orthopedic surgeons. In many cases, medical medications and nerve blocks do not improve the pain, and surgical treatment may be performed. We evaluated whether minimally invasive spinal cord stimulation therapy for orthopedic diseases improves pain by altering blood flow to the lower extremities using thermography. Methods: Thermography and NRS of both lower extremities were measured before and after spinal cord stimulation therapy in 27 patients (15 women and 12 men) with back and leg pain due to thoracolumbar spine compression fracture and lumbar spinal canal stenosis. Results: Thermography showed an increase in body surface temperature of approximately 6°C. NRS showed an average improvement of 6.4. Discussion: Spinal cord stimulation therapy may improve blood flow in both lower limbs and lower back and leg pain, especially for back and leg pain caused by thoracolumbar vertebral compression fracture and lumbar spinal canal stenosis, among other orthopedic diseases. Thermography is likely to be useful as an evaluation tool.

Study of ankle–Brachial index among the patients of metabolic syndrome

Background: Metabolic syndrome (MetS) refers to a group of conditions that are associated with increased cardiovascular risk. Ankle–brachial index (ABI) is a noninvasive, inexpensive way of assessing the blood flow in the lower limbs and may be useful as an indirect marker of subclinical atherosclerosis. Aim and Objective: To study and compare ABI values between patients with MetS and patients without MetS. Materials and Methods: A total of 98 patients attending the outpatient department between October 2018 and September 2020 were included in the study. They were categorized as MetS and non-MetS as per the National Cholesterol Education Program Adult Treatment Panel III guidelines. They were tested for ABI with a handheld Doppler. The ABI values were compared between the two groups. Results: Among 98 patients, 49 were cases and 49 as controls. ABI values were found to be 1.09 ± 0.12 among the cases and 1.22 ± 0.05 among the controls and were found to be statistically significant (P < 0.001). Conclusion: The patients with MetS had lower ABI compared with the patients who did not have MetS. ABI can be used as an indirect marker of atherosclerosis and can be used in routine clinical assessment for identifying patients at a higher cardiovascular risk.

Chopart amputation with tendon balancing.

When foot necrosis occurs due to lower limb blood flow disorder caused by diabetes or peripheral arterial occlusion, many patients require lower limb amputation. The functional prognosis after lower limb amputation largely depends on whether the heel can be preserved. However, there are many reports that Chopart amputation causes varus and equinus deformity, and is functionally unfavorable. We herein report a case of Chopart amputation performed with muscle balancing. Postoperatively, the foot was not deformed and the patient was able to walk independently with a foot prosthesis. A 78-year-old man presented with ischemic necrosis of his right forefoot. The range of necrosis extended to the central part of the sole, so Chopart amputation was performed. In the operation, to prevent varus and equinus deformity, the Achilles tendon was lengthened, the tibialis anterior tendon was transferred through a tunnel created in the neck of talus, and the peroneus brevis tendon was transferred through a tunnel created in the anterior part of the calcaneus. At the final follow-up 7 years after the operation, no varus or equinus deformity was observed. The patient became able to stand up and walk on his heel without a prosthesis. In addition, step motion was possible by wearing a foot prosthesis.

Comprehensive analysis of the efficacy of personalized rehabilitation programs in patients with breast cancer

To perform the comprehensive analysis of the efficacy of personalized rehabilitation programs in patients with BC. The combined comparative multi-centre randomised trial of rehabilitation program efficacy in patients with breast cancer was done. The study included 219 patients aged from 30 to 45 years (median 39.4 year), who were divided into 2 groups. The rehabilitation by programs, that included current personalized rehabilitative techniques (RT) with proved efficiency, based on scientometrical analysis of evidential research was performed in the first group patients. In the second group aftercare was done according to the standard programs. The comprehensive evaluation of treatment efficacy was conducted in several stages: 1) performance analysis of rehabilitative programs; 2) verification of the effectiveness' determinant of rehabilitation; 3) factor analysis to assess the mechanisms of therapeutic effects in experimental groups; 4) comparative analysis of alternative strategies for selecting rehabilitation programs. The use of rehabilitative programs, based on recommended RT, changes the rehabilitation structure, significantly increasing its efficacy by 17%. Furthermore, the percentage of high-efficiency usage of this type programs increases by 17% compared with standard programs. The main determinants, affecting the efficacy of rehabilitation programs, based on selected RT, are anamnestic data, parameters of exercise tolerance and physical activity and ultrasound parameters of upper limb blood flow. The therapeutic effects of personalized rehabilitation programs are realized by correction of clinical rates, increasing exercise tolerance and physical activity, as well as psychophysiological parameters. The use of the evaluation system of anamnestic, clinical, functional and psychophysiological features of patient (the effectiveness' determinant) in realization of personalized rehabilitation programs for women with BC, allows to predict and manage the efficacy of RT applying.