Hypertension meets osteoarthritis - revisiting the vascular aetiology hypothesis.

Osteoarthritis (OA) is a whole-joint disease characterized by subchondral bone perfusion abnormalities and neovascular invasion into the synovium and articular cartilage. In addition to local vascular disturbance, mounting evidence suggests a pivotal role for systemic vascular pathology in the aetiology of OA. This Review outlines the current understanding of the close relationship between high blood pressure (hypertension) and OA at the crossroads of epidemiology and molecular biology. As one of the most common comorbidities in patients with OA, hypertension can disrupt joint homeostasis both biophysically and biochemically. High blood pressure can increase intraosseous pressure and cause hypoxia, which in turn triggers subchondral bone and osteochondral junction remodelling. Furthermore, systemic activation of the renin-angiotensin and endothelin systems can affect the Wnt-ß-catenin signalling pathway locally to govern joint disease. The intimate relationship between hypertension and OA indicates that endothelium-targeted strategies, including re-purposed FDA-approved antihypertensive drugs, could be useful in the treatment of OA.

Diversity of Vascular Niches in Bones and Joints During Homeostasis, Ageing, and Diseases.

The bones and joints in the skeletal system are composed of diverse cell types, including vascular niches, bone cells, connective tissue cells and mineral deposits and regulate whole-body homeostasis. The capacity of maintaining strength and generation of blood lineages lies within the skeletal system. Bone harbours blood and immune cells and their progenitors, and vascular cells provide several immune cell type niches. Blood vessels in bone are phenotypically and functionally diverse, with distinct capillary subtypes exhibiting striking changes with age. The bone vasculature has a special impact on osteogenesis and haematopoiesis, and dysregulation of the vasculature is associated with diverse blood and bone diseases. Ageing is associated with perturbed haematopoiesis, loss of osteogenesis, increased adipogenesis and diminished immune response and immune cell production. Endothelial and perivascular cells impact immune cell production and play a crucial role during inflammation. Here, we discuss normal and maladapted vascular niches in bone during development, homeostasis, ageing and bone diseases such as rheumatoid arthritis and osteoarthritis. Further, we discuss the role of vascular niches during bone malignancy.

Anti-IL-17A treatment reduces serum inflammatory, angiogenic and tissue remodeling biomarkers accompanied by less synovial high endothelial venules in peripheral spondyloarthritis.

Spondyloarthritis (SpA) is characterized by inflammation and new bone formation. The exact pathophysiology underlying these processes remains elusive. We propose that the extensive neoangiogenesis in SpA could play a role both in sustaining/enhancing inflammation and in new bone formation. While ample data is available on effects of anti-TNF on angiogenesis, effects of IL-17A blockade on serum markers are largely unknown. We aimed to assess the impact of secukinumab (anti-IL-17A) on synovial neoangiogenesis in peripheral SpA, and how this related to changes in inflammatory and tissue remodeling biomarkers. Serum samples from 20 active peripheral SpA patients included in a 12 week open-label trial with secukinumab were analyzed for several markers of angiogenesis and tissue remodeling. Synovial biopsies taken before and after treatment were stained for vascular markers. Serum levels of MMP-3, osteopontin, IL-6 (all P < 0.001), IL-31, S100A8, S100A9, Vascular Endothelial Growth Factor A (VEGF-A), IL-33, TNF-α (all P < 0.05) decreased significantly upon anti-IL17A treatment. Secukinumab treatment resulted in a decrease in the number of synovial high endothelial venules and lymphoid aggregate score. These results indicate that anti-IL-17A not only diminishes inflammation, but also impacts angiogenesis and tissue remodeling/new bone formation. This may have important implications for disease progression and/or structural damage.

[Transarterial Periarticular Embolization (TAPE): Indications and Initial Experience in Germany]. / Transarterielle periartikuläre Embolisation (TAPE): klinischer Einsatz und erste Erfahrungen in Deutschland.

PURPOSE: The purpose of this article is to demonstrate the potential indications, procedural technique and initial results of the transarterial periarticular embolization (TAPE). MATERIAL AND METHODS: TAPE was performed in three patients with chronic pain in different joints. In the first case the patient suffered from osteoarthritis of the shoulder, in the second case from epicondylitis humeri ulnaris ("golfer-elbow") and in the third case from patellar tendinitis ("jumpers-knee"). Clinical as well as pain assessment was performed pre and post-interventionally. RESULTS: TAPE was performed with technical success in all three patients. For vessel access, either a transradial or transfemoral access was chosen. The joint supplying vessels were catheterized superselectively with microcatheters and embolized with Imipenem/Cilastatin diluted in contrast medium. After embolization of the knee the patient demonstrated skin redness, which disappeared within one week. No further complications were noted. All patients reported significant pain relief within the first day after intervention. CONCLUSION: TAPE is a novel therapy for the treatment of persistent, chronic joint pain and tendinopathies, supported by publications from institutes outside of Europe. The initial experiences made in our institute are encouraging and suggest that TAPE may have the potential as an adjunct therapy option for patients with therapy-resistant chronic joint and tendinopathy-pain. KEY POINTS: · TAPE is a novel therapy for treatment of degenerative joint pain and tendinopathies. · TAPE is a technically challenging endovascular procedure and requires high interventional expertise. · TAPE may have the potential to develop to a minimally-invasive therapy option for patients with chronic joint pain. CITATION FORMAT: · Katoh M, Schott P, Freyhardt P et al. Transarterial Periarticular Embolization (TAPE): Indications and Initial Experience in Germany. Fortschr Röntgenstr 2020; 192: 1046 - 1052.

The clinical value of head-neck joint high-resolution vessel wall imaging in ischemic stroke.

BACKGROUND AND PURPOSE: To study the feasibility and clinical utility of head-neck joint high-resolution vessel wall imaging (HNJ-VWI) in the assessment of ischemic stroke. METHODS: We reviewed our institutional HNJ-VWI database. Patients with transient ischemic attack (TIA) or ischemic stroke were included. Abnormal findings of intracranial and/or extracranial artery were assessed on three-dimensional time-of-flight magnetic resonance angiography (3D TOF MRA) and HNJ-VWI modified from high-resolution 3D T1 sequence and classified into three groups including intracranial, extracranial and coexisting based on the locations. Etiologies of stroke were recorded according to Trial of Org 10172 in Acute Stroke Treatment criteria. RESULTS: One hundred and ten consecutive patients were studied. 3D TOF MRA displayed 71.8% (79/110, based on patients) abnormal arteries (stenosis or occlusion) , while HNJ-VWI displayed 96.3% (106/110) abnormal arteries (plaque,wall thickness and occlusion) including four isolated extracranial lesions and ten coexisting lesions. The etiologies of TIA/ischemic stroke included large artery atherosclerosis (80 cases), cerebral small vessel disease (6 cases), cardiogenic (2 cases), dissection (6 cases), vasculitis (4 cases), moyamoya disease (6 cases), others (2 cases) and undetermined (4 cases). For patients with atherosclerosis stroke, re-infarctions were more common in coexisting group than intracranial group (extracranial vs. intracranial vs coexisting: 0% vs. 9.1% vs. 43.7%, p = 0.001). CONCLUSIONS: HNJ-VWI is a feasible and valuable technique in assessment of ischemic stroke by detecting extracranial and intracranial artery abnormalities with one-step scan.

Acromegaly and joint pain: is there something more? A cross-sectional study to evaluate rheumatic disorders in growth hormone secreting tumor patients.

PURPOSE: The aim of the present study was to evaluate the rheumatic profile in acromegalic patients to better characterize joint pain. METHODS: The immunological pattern (rheumatoid factor; antinuclear antibodies-ANA, extractable nuclear antigens-ENA-Ab; anti-citrullinated protein antibodies; erythrocyte sedimentation rate) was evaluated in 20 acromegaly subjects (AS) and 20 control subjects (CS). Bilateral joint ultrasound of hands/wrists and nail capillaroscopy were also performed. RESULTS: Articular pain was more frequent in AS than in CS (p = 0.027). No difference was detected in immunological parameters. ANA and ENA-Ab were positive in only 10% of AS and in 5% of CS, while no difference was found in anti-citrullinated protein antibodies. No difference was detected between rheumatoid factor positivity, but threefold higher IgG were detected in AS compared to CS. The erythrocyte sedimentation rate was significantly higher in AS than CS (p = 0.040), while in AS, there was a trend in increased Power Doppler (PWD) articular uptake. The capillaroscopic evaluation showed a significant difference in almost each parameter (presence and number of tortuous capillaries, capillary enlargements, and hemorrhages), showing a moderate-to-severe microangiopathy in AS. CONCLUSION: The results of our study suggest that joint damage in acromegaly has not an autoimmune etiology. Increased erythrocyte sedimentation rate levels and PWD alteration in acromegalic population reflect a possible inflammatory nature, while the capillaroscopic findings suggest a moderate-to-severe microangiopathy that could help to identify patients with a greater macroangiopathic risk.

Inflammation and Hypervascularization in a Large Animal Model of Knee Osteoarthritis: Imaging with Pathohistologic Correlation.

PURPOSE: To evaluate if synovial inflammation and hypervascularization are present in a dog model of knee osteoarthritis and can be detected on conventional magnetic resonance imaging (MRI), dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), contrast-enhanced magnetic resonance imaging (CE-MRI), and quantitative digital subtraction angiography (Q-DSA) imaging. MATERIALS AND METHODS: Six dogs underwent MRI and angiography of both knees before and 12 weeks after right knee anterior cruciate ligament injury. Synovial vascularity was evaluated on CE-MRI, DCE-MRI, and Q-DSA by 2 independent observers. Synovial inflammation and vascularity were histologically scored independently. Cartilage lesions and osteophytes were analyzed macroscopically, and cartilage volumetry was analyzed by MRI. Vascularity and osteoarthritis markers on imaging were compared before and after osteoarthritis generation, and between the osteoarthritis model and the control knee, using linear mixed models accounting for within-dog correlation. RESULTS: In all knees, baseline imaging showed no abnormalities. Control knees did not develop significant osteoarthritis changes, synovial inflammation, or hypervascularization. In osteoarthritis knees, mean synovial enhancement score on CE-MR imaging increased by 13.1 ± 0.59 (P < .0001); mean synovial inflammation variable increased from 47.33 ± 18.61 to 407.97 ± 18.61 on DCE-MR imaging (P < .0001); and area under the curve on Q-DSA increased by 1058.58 ± 199.08 (P = .0043). Synovial inflammation, hypervascularization, and osteophyte formations were present in all osteoarthritis knees. Histology scores showed strong correlation with CE-MR imaging findings (Spearman correlation coefficient [SCC] = 0.742; P = .0002) and Q-DSA findings (SCC = 0.763; P < .0001) and weak correlation with DCE-MR imaging (SCC = -0.345; P = .329). Moderate correlation was found between CE-MR imaging and DSA findings (SCC = 0.536; P = .0004). CONCLUSIONS: In this early-stage knee osteoarthritis dog model, synovial inflammation and hypervascularization were found on imaging and confirmed by histology.

Musculoskeletal ultrasound for intra-articular bleed detection: a highly sensitive imaging modality compared with conventional magnetic resonance imaging.

Essentials The best imaging modality for joint blood detection in hemophilia is unknown. Blood appearance and detection thresholds were studied with ultrasound and conventional MRI. Ultrasound is sensitive to low volume and concentration of blood, whereas conventional MRI is not. The findings establish the validity of ultrasound for rapid bleed detection in hemophilia care. SUMMARY: Background There is increasing demand for musculoskeletal ultrasound (MSKUS) to detect hemophilic joint bleeding, but there is uncertainty regarding blood detection concentration thresholds or if magnetic resonance imaging (MRI) is more accurate. Aims Compare the sensitivity of blood detection by MSKUS and MRI. Methods Increasing blood concentrations in plasma were imaged with MSKUS and MRI 1-2 h, 3-4 days and 7 days after blood withdrawal in vitro, and after injection into cadaveric pig joints. Additionally, effusions in the joints of two patients with hemophilia joints were imaged, followed by aspiration. MSKUS was performed using an 8-18-MHz linear transducer; MRI was performed at 3T using T1-weighted and T2-weighted fat-suppressed sequences. Images were reviewed by a hematologist certified in MSKUS and a musculoskeletal radiologist. Results MSKUS permitted the detection of blood in vitro and in pig joint spaces at concentrations as low as 5%, demonstrated by the presence of echogenic signals that were absent with plasma alone. In contrast, no differences between fluids were discernible on the T1-weighted or T2-weighted MRI images. Results were confirmed in the two patients with hemophilia. Blood clots demonstrated varying and dynamic echogenicity patterns over time and, using MRI, were visualized best with T2 sequences. Conclusion MSKUS is extremely sensitive in detecting low concentrations of intra-articular blood and in discriminating between bloody and non-bloody fluid, whereas conventional MRI is not. These observations demonstrate the advantages of MSKUS over MRI in detecting intra-articular blood, and show that MSKUS is ideal for rapid bleed detection in the clinic.

Microflow imaging: New Doppler technology to detect low-grade inflammation in patients with arthritis.

AIM: To assess the efficacy of microvascular imaging in detecting low-grade inflammation in arthritis compared with Power Doppler ultrasound (PDUS). METHOD AND MATERIALS: Patients presenting for ultrasound with arthralgia were assessed with grey-scale, PDUS and Superb Microvascular Imaging (SMI). Videoclips were stored for analysis at a later date. Three musculoskeletal radiologists scored grey-scale changes, signal on PDUS and/or SMI within these joints. If a signal was detected on both PDUS and SMI, the readers graded the conspicuity of vascular signal from the two Doppler techniques using a visual analogue scale. RESULTS: Eighty-three patients were recruited with 134 small joints assessed. Eighty-nine of these demonstrated vascular flow with both PD and SMI, whilst in five no flow was detected. In 40 joints, vascularity was detected with SMI but not with PDUS (p = 0.007). Out of the 89 joints with vascularity on both SMI and PDUS, 23 were rated as being equal; while SMI scored moderately or markedly better in 45 cases (p <0.001). CONCLUSION: SMI is a new Doppler technique that increases conspicuity of Doppler vascularity in symptomatic joints when compared to PDUS. This allows detection of low grade inflammation not visualised with Power Doppler in patients with arthritis. KEY POINTS: • SMI detects vascularity with improved resolution and sensitivity compared to Power Doppler. • SMI can detect low-grade inflammation not seen with Power Doppler. • Earlier detection of active inflammation could have significant impact on treatment paradigms.

Effect of Tranexamic Acid on Hematologic Values and Blood Loss in Reverse Total Shoulder Arthroplasty.

PURPOSE: Use of tranexamic acid (TXA) in the setting of arthroplasty of the lower extremity has been previously described. The aim of this study was to evaluate the benefit of a single dose of TXA (500 mg vial) administered intravenously just prior to RTSA in an Asian population. METHODS: The records of 48 patients (no TXA, n = 24, versus TXA, n = 24) that underwent RTSA for cuff tear arthropathy were retrospectively reviewed. All patients had a Hemovac drain positioned for 2 days after surgery. Hemoglobin (Hb) and hematocrit (Hct) were checked on postoperative day 2 and compared with preoperative levels. RESULTS: Hematologic change on postoperative day 2 as determined by Hb level after surgery was statistically lower in the TXA group (2.8 ± 0.8 versus 2.1 ± 0.8 (mg/dL), P = 0.006). Mean fall in Hct level was also significantly less in the TXA group (8.0 ± 2.5 versus 6.1 ± 2.6 (L/L), P = 0.012). Total Hemovac drainage tended to be lower in the TXA group (263.4 ± 129.3 versus 203.5 ± 84.2 (ml), P = 0.064). TXA was found to have no noticeable side effects. CONCLUSION: The use of a single intravenous dose of TXA immediately prior to RTSA reduces hematologic deterioration postoperatively and the amount of Hemovac drainage. TXA could avoid unnecessary transfusion and its associated medical side effects and cost.

The hypertension of hemophilia is associated with vascular remodeling in the joint.

OBJECTIVE: Hemophilic arthropathy is associated with pronounced vascular joint remodeling. Also, compared to the general population, PWH have a higher prevalence of hypertension not explained by usual risk factors. As vascular remodeling in various vascular beds is a hallmark of hypertension, we hypothesized that vascular joint remodeling is associated with elevated blood pressures and hypertension. METHODS: Elbows, knees, and ankles of 28 adult PWH were evaluated for vascular abnormalities with MSKUS/PD, as well as for radiographic and clinical status and pain. Logistic and linear regression models were fitted to examine associations between hypertension, blood pressure, and PD score. RESULTS: The extent of vascular abnormalities was associated with hypertension and blood pressures. Hypertensive patients had a higher PD score compared to nonhypertensive patients, and the risk of hypertension increased steeply with PD score. SBP was also strongly associated with PD score, while DBP was only weakly associated. CONCLUSIONS: Vascular remodeling in hemophilic joints is associated with hypertension and elevated blood pressures. As hypertension is a grave risk factor for intracranial hemorrhage, a prominent cause of mortality in hemophilia patients, future studies are needed to address the causal pathways between vascular joint remodeling and blood pressure.

Articular Ultrasound in Asymptomatic Volunteers: Identification of the Worst Measures of Synovial Hypertrophy, Synovial Blood Flow and Joint Damage Among Small-, Medium- and Large-Sized Joints.

Articular ultrasound of 6500 joint recesses was performed for the purpose of identifying which joint had the highest measurements among small-sized (SSJ), medium-sized (MSJ) and large-sized (LSJ) joints. Quantitative measurements of synovial hypertrophy (QSR) and semiquantitative measurements of synovial hypertrophy (SSH), power Doppler (SPD) and bone erosion (SBE) (score: 0-3) were made. Higher measurements (p < 0.01) of QSR were obtained in the second metatarsophalangeal joint (MTP), talonavicular joint, and hip. The highest SSH scores (2/3) were obtained in the second MTP, talonavicular joint, hip and knee; the highest SPD scores (1/2/3) in the first MTP, second MTP, dorsal second metacarpophalangeal (MCP) and radiocarpal recesses; and the highest SBE scores (2/3) in the radiocarpal, ulnocarpal and posterior recesses of the glenohumeral joint. In conclusion, higher measurements of synovial hypertrophy were found in the first and second MTPs (SSJ), talonavicular recess (MSJ) and hip (LSJ). Synovial blood flow was frequent in the first MTP and radiocarpal recess. Bone erosion stood out only in the glenohumeral joint.

Insights into cryotherapy and joint bleeding: cryotherapy and hemophilia.

: There is some controversy over the use of cryotherapy. Low temperatures (Temp) could interfere with coagulation and increase the risk of bleeding. We sought to examine the effect of cryotherapy on joint swelling, temperature, friction, and inflammatory condition after experimental hemarthrosis. The left knee of 23 albino rabbits, 10 in heparin Ice, five in citrate Ice, four in heparin control, and four in citrate control were injected intraarticularly with 1 ml of blood. In total, four animals were considered to be in normal control group. Joint diameter, Temp, and ultrasonography were assessed before the blood injection. One day after the intraarticular blood injection, cryotherapy was applied 4 times per day for 4 consecutive days. Joint diameter and Temp were measured twice a day. After cessation of the protocol, joint diameter and Temp were assessed and sonography performed, animals euthanized, the friction test was performed and the synovial membrane collected, respectively. Joint diameter and Temp were increased after the intraarticular blood injection. Cryotherapy was capable of reducing the swelling and Temp. Ultrasonography findings approved the positive effect of cryotherapy on joint swelling. The proinflammatory tumor necrosis factor (TNF-α) reduced by cryotherapy in both cryotherapy groups but Interleukin 1ß was only reduced in heparin group. Interleukin-4 increased in heparin Ice group that was in comparison with TNF-α reduction. Cryotherapy reduced joint swelling and has a positive effect on controlling joint inflammation and Temp.

Prophylaxis usage, bleeding rates, and joint outcomes of hemophilia, 1999 to 2010: a surveillance project.

This analysis of the US Hemophilia Treatment Center Network and the Centers for Disease Control and Prevention surveillance registry assessed trends in prophylaxis use and its impact on key indicators of arthropathy across the life-span among participants with severe hemophilia A. Data on demographics, clinical characteristics, and outcomes were collected prospectively between 1999 and 2010 at annual clinical visits to 134 hemophilia treatment centers. Trends in treatment and outcomes were evaluated using cross-sectional and longitudinal analyses. Data analyzed included 26 614 visits for 6196 males; mean age at first registry visit was 17.7 years; and median was 14 (range, 2 to 69). During this time, prophylaxis use increased from 31% to 59% overall, and by 2010, 75% of children and youths <20 years were on prophylaxis. On cross-sectional analysis, bleeding rates decreased dramatically for the entire population (P < .001) in parallel with increased prophylaxis usage, possibly because frequent bleeders adopted prophylaxis. Joint bleeding decreased proportionately with prophylaxis (22%) and nonprophylaxis (23%), and target joints decreased more with prophylaxis (80% vs 61%). Joint, total, and target joint bleeding on prophylaxis were 33%, 41%, and 27%, respectively, compared with nonprophylaxis. On longitudinal analysis of individuals over time, prophylaxis predicted decreased bleeding at any age (P < .001), but only prophylaxis initiation prior to age 4 years and nonobesity predicted preservation of joint motion (P < .001 for each). Using a national registry, care providers in a specialized health care network for a rare disorder were able to detect and track trends in outcomes over time.

The choice of a constitutive formulation for modeling limb flexion-induced deformations and stresses in the human femoropopliteal arteries of different ages.

Open and endovascular treatments for peripheral arterial disease are notorious for high failure rates. Severe mechanical deformations experienced by the femoropopliteal artery (FPA) during limb flexion and interactions between the artery and repair materials play important roles and may contribute to poor clinical outcomes. Computational modeling can help optimize FPA repair, but these simulations heavily depend on the choice of constitutive model describing the arterial behavior. In this study finite element model of the FPA in the standing (straight) and gardening (acutely bent) postures was built using computed tomography data, longitudinal pre-stretch and biaxially determined mechanical properties. Springs and dashpots were used to represent surrounding tissue forces associated with limb flexion-induced deformations. These forces were then used with age-specific longitudinal pre-stretch and mechanical properties to obtain deformed FPA configurations for seven age groups. Four commonly used invariant-based constitutive models were compared to determine the accuracy of capturing deformations and stresses in each age group. The four-fiber FPA model most accurately portrayed arterial behavior in all ages, but in subjects younger than 40 years, the performance of all constitutive formulations was similar. In older subjects, Demiray (Delfino) and classic two-fiber Holzapfel-Gasser-Ogden formulations were better than the Neo-Hookean model for predicting deformations due to limb flexion, but both significantly overestimated principal stresses compared to the FPA or Neo-Hookean models.

The Role of Angiogenesis in Haemophilic Arthropathy: Where Do We Stand and Where Are We Going?

Haemophilia is an inherited bleeding disorder that can lead to degenerative joint arthropathy due to recurrent bleeding episodes affecting the musculoskeletal system of the patient. The cause of bleeding can be either traumatic or spontaneous. The pathogenesis of haemophilic arthropathy is unclear as many factors like iron, inflammatory cytokines, and angiogenic factors contribute to this process. Blood into joints can deteriorate the bone to such an extent that the patient experiences pain, reduction of the range of movement, and deformity of the joint, conditions that could have a great impact on quality of life. Over the years, management of haemophilic arthropathy has changed. Nowadays, early diagnosis with high resolution imaging like magnetic resonance imaging along with application of prophylaxis regimens can reduce the extent of damage to the joints. However, not all haemophilia patients have access to these interventions as cost may be prohibitive for some of them. The need for new, easy, and cost-effective strategies with the ability to identify early changes could be beneficial and could make a difference in the management of haemophilic arthropathy. Understanding the mechanism of processes like angiogenesis in the mechanism of developing arthropathy could be innovative for these patients and could help in the detection of new early diagnostic and therapeutic markers.

Development of Four Dimensional Human Model that Enables Deformation of Skin, Organs and Blood Vessel System During Body Movement - Visualizing Movements of the Musculoskeletal System.

We constructed a four dimensional human model that is able to visualize the structure of a whole human body, including the inner structures, in real-time to allow us to analyze human dynamic changes in the temporal, spatial and quantitative domains. To verify whether our model was generating changes according to real human body dynamics, we measured a participant's skin expansion and compared it to that of the model conducted under the same body movement. We also made a contribution to the field of orthopedics, as we were able to devise a display method that enables the observer to more easily observe the changes made in the complex skeletal muscle system during body movements, which in the past were difficult to visualize.

The cardiovascular response to passive movement is joint dependent.

The cardiovascular responses to passive limb movement (PLM) at the knee are well established, however, responses to PLM at other joints involving smaller muscle volume are unknown. To compare the cardiovascular responses to passive movement at other joints, 10 participants underwent a PLM protocol in which the wrist, elbow, ankle, and knee joints were passively extended and flexed at 1 Hz for 1 min. Heart rate (HR), mean arterial blood pressure (MAP), and arterial blood flow to that limb segment (BF) were measured and vascular conductance (VC) was calculated for a 30-sec baseline period and for 3-sec intervals throughout PLM protocols. PLM of the knee and elbow resulted in significant increases in BF and VC from baseline values with peak values 180% (P < 0.001) greater than baseline. PLM of the elbow resulted in significant increases in BF and VC from baseline values with peak values 109% and 115% (P < 0.001) greater than baseline, respectively. No changes in BF and VC were observed in the ankle and wrist. Furthermore, the greater increase in blood flow per limb segment volume in the thigh and upper arm (62.8 ± 36.5 and 55.5 ± 30.3 mL min(-1) L(-1), respectively) compared to the forearm and lower leg (23.6 ± 16.7 and 19.1 ± 10.3 mL min(-1) L(-1), respectively) indicates the limb volume is not solely responsible for the differences in the hyperemic responses. These data indicate that the use of PLM to assess vascular function or as a rehabilitation modality to maintain vascular health may be most appropriate for the muscles that span the elbow and knee.

The role of the prolactin/vasoinhibin axis in rheumatoid arthritis: an integrative overview.

Rheumatoid arthritis (RA) is a chronic, autoimmune, inflammatory disease destroying articular cartilage and bone. The female preponderance and the influence of reproductive states in RA have long linked this disease to sexually dimorphic, reproductive hormones such as prolactin (PRL). PRL has immune-enhancing properties and increases in the circulation of some patients with RA. However, PRL also suppresses the immune system, stimulates the formation and survival of joint tissues, acquires antiangiogenic properties upon its cleavage to vasoinhibins, and protects against joint destruction and inflammation in the adjuvant-induced model of RA. This review addresses risk factors for RA linked to PRL, the effects of PRL and vasoinhibins on joint tissues, blood vessels, and immune cells, and the clinical and experimental data associating PRL with RA. This information provides important insights into the pathophysiology of RA and highlights protective actions of the PRL/vasoinhibin axis that could lead to therapeutic benefits.