scholarly journals Thermotherapy reduces blood pressure and circulating endothelin-1 concentration and enhances leg blood flow in patients with symptomatic peripheral artery disease

2016 ◽  
Vol 311 (2) ◽  
pp. R392-R400 ◽  
Author(s):  
Dustin Neff ◽  
Alisha M. Kuhlenhoelter ◽  
Chen Lin ◽  
Brett J. Wong ◽  
Raghu L. Motaganahalli ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Blood Flow ◽  
Peripheral Artery Disease ◽  
Popliteal Artery ◽  
Peripheral Artery ◽  
Leg Blood Flow ◽  
Endothelin 1 ◽  
Control Intervention ◽  
Artery Disease ◽  
The Impact

Leg thermotherapy (TT) application reduces blood pressure (BP) and increases both limb blood flow and circulating levels of anti-inflammatory mediators in healthy, young humans and animals. The purpose of the present study was to determine the impact of TT application using a water-circulating garment on leg and systemic hemodynamics and on the concentrations of circulating cytokines and vasoactive mediators in patients with symptomatic peripheral artery disease (PAD). Sixteen patients with PAD and intermittent claudication (age: 63 ± 9 yr) completed three experimental sessions in a randomized order: TT, control intervention, and one exercise testing session. The garment was perfused with 48°C water for 90 min in the TT session and with 33°C water in the control intervention. A subset of 10 patients also underwent a protocol for the measurement of blood flow in the popliteal artery during 90 min of TT using phase-contrast MRI. Compared with the control intervention, TT promoted a significant reduction in systolic (∼11 mmHg) and diastolic (∼6 mmHg) BP ( P < 0.05) that persisted for nearly 2 h after the end of the treatment. The serum concentration of endothelin-1 (ET-1) was significantly lower 30 min after exposure to TT (Control: 2.3 ± 0.1 vs. TT: 1.9 ± 0.09 pg/ml, P = 0.026). In addition, TT induced a marked increase in peak blood flow velocity (∼68%), average velocity (∼76%), and average blood flow (∼102%) in the popliteal artery ( P < 0.01). These findings indicate that TT is a practical and effective strategy to reduce BP and circulating ET-1 concentration and enhance leg blood flow in patients with PAD.

scholarly journals Systemic and regional hemodynamic response to activation of the exercise pressor reflex in patients with peripheral artery disease

2020 ◽  
Vol 318 (4) ◽  
pp. H916-H924 ◽  
Author(s):  
Danielle Jin-Kwang Kim ◽  
Marcos Kuroki ◽  
Jian Cui ◽  
Zhaohui Gao ◽  
J. Carter Luck ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Blood Flow ◽  
Peripheral Artery Disease ◽  
Plantar Flexion ◽  
Peripheral Artery ◽  
Exercise Pressor Reflex ◽  
Femoral Blood Flow ◽  
Femoral Blood ◽  
Pressor Reflex ◽  
Artery Disease

Patients with peripheral artery disease (PAD) have an accentuated exercise pressor reflex (EPR) during exercise of the affected limb. The underlying hemodynamic changes responsible for this, and its effect on blood flow to the exercising extremity, are unclear. We tested the hypothesis that the exaggerated EPR in PAD is mediated by an increase in total peripheral resistance (TPR), which augments redistribution of blood flow to the exercising limb. Twelve patients with PAD and 12 age- and sex-matched subjects without PAD performed dynamic plantar flexion (PF) using the most symptomatic leg at progressive workloads of 2–12 kg (increased by 1 kg/min until onset of fatigue). We measured heart rate, beat-by-beat blood pressure, femoral blood flow velocity (FBV), and muscle oxygen saturation ([Formula: see text]) continuously during the exercise. Femoral blood flow (FBF) was calculated from FBV and baseline femoral artery diameter. Stroke volume (SV), cardiac output (CO), and TPR were derived from the blood pressure tracings. Mean arterial blood pressure and TPR were significantly augmented in PAD compared with control during PF. FBF increased during exercise to an equal extent in both groups. However, [Formula: see text] of the exercising limb remained significantly lower in PAD compared with control. We conclude that the exaggerated pressor response in PAD is mediated by an abnormal TPR response, which augments redistribution of blood flow to the exercising extremity, leading to an equal rise in FBF compared with controls. However, this increase in FBF is not sufficient to normalize the SmO2 response during exercise in patients with PAD. NEW & NOTEWORTHY In this study, peripheral artery disease (PAD) patients and healthy control subjects performed graded, dynamic plantar flexion exercise. Data from this study suggest that previously reported exaggerated exercise pressor reflex in patients with PAD is driven by greater vasoconstriction in nonexercising vascular territories which also results in a redistribution of blood flow to the exercising extremity. However, this rise in femoral blood flow does not fully correct the oxygen deficit due to changes in other mechanisms that require further investigation.

Abstract 11611: Muscle Superoxide Dismutase and Augmented Autonomic Responsiveness in Rats With Peripheral Artery Disease

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Jihong Xing ◽  
Jian Lu ◽  
Jiahao Liu ◽  
Jianhua Li
Keyword(s):  
Blood Pressure ◽  
Blood Flow ◽  
Muscle Contraction ◽  
Peripheral Artery Disease ◽  
Optical Density ◽  
Blood Pressure Response ◽  
Pressure Response ◽  
Static Exercise ◽  
Peripheral Artery ◽  
Artery Disease

Background: During exercise, responses of sympathetic nerve and blood pressure are amplified in patients with peripheral artery disease (PAD). This worsens the restricted blood flow directed to the limbs in this disease. The purpose of this study was to determine the role played by muscle oxidative stress in regulating the augmented autonomic responses to static exercise in PAD. Superoxide dismutases (SOD) is a class of enzymes to catalyze the dismutation of superoxide into oxygen and hydrogen peroxide, and considered as an important antioxidant. Thus, our specific hypothesis was that limb ischemia impairs muscle SOD and thereby leads to abnormal autonomic responsiveness observed in PAD. Methods and Results: We used a rat model of femoral artery ligation to study PAD. Note that all data are presented as mean ± SE. First, western blot analysis shows that 72 hours of femoral occlusion significantly decreased the protein levels of SOD in the oxidative muscle (optical density: 1.02±0.03 in control vs. 0.21±0.02 after ligation, P< 0.05; n = 6 in each group) and glycolytic muscle (optical density: 1.03±0.03 in control vs. 0.65±0.04 after ligation, P< 0.05; n = 6 in each group). Additional immunofluorescence study demonstrates down-regulation of SOD in the ischemic hindlimb muscles. Second, the reflex blood pressure response to static muscle contraction was examined in control rats (n=5) and rats with 72 hours of femoral occlusion (n=6). The data show that the augmented reflex pressor response to muscle contraction was significantly attenuated after compensating SOD in ischemic muscles by chronic administration of tempol (a mimetic of SOD, 30 mg over a period of 72 hours) into the hindlimb. In the ligated rats, mean arterial pressure response was 26±3 mmHg with no tempol (n=6) and 12±2 mmHg with tempol application ( P< 0.05 vs. group with no tempol; n =5). Conclusions: Muscle SOD is blunted in the ischemic limbs and supplement of SOD mimetic for anti-oxidation improves the augmented blood pressure response during static exercise, which is beneficial to the restricted blood flow to the limbs in PAD patients.

Abstract 17075: Impact of Peripheral Artery Disease on Outcomes Following Admission for Cardiogenic Shock

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Nino Mihatov ◽  
Robert W Yeh ◽  
Eunhee Choi ◽  
Changyu Shen ◽  
Sahil A Parikh ◽  
...  
Keyword(s):  
Hospital Mortality ◽  
Cardiogenic Shock ◽  
Peripheral Artery Disease ◽  
Circulatory Support ◽  
Complication Rates ◽  
Medicare Beneficiaries ◽  
Peripheral Artery ◽  
Adjusted Risk ◽  
Artery Disease ◽  
The Impact

Introduction: Contemporary in-hospital mortality rates for patients presenting with acute myocardial infarction (AMI) and cardiogenic shock (CS) remain as high as 50%. The impact of comorbid lower extremity peripheral artery disease (LE-PAD) is unknown. Hypothesis: LE-PAD is associated with higher morbidity and mortality in patients presenting with CS and AMI. Methods: Medicare beneficiaries hospitalized with CS related to AMI from 10/2015-6/2017 were identified. PAD status was defined by the inpatient billing codes present in the year prior to presentation. Outcomes included in-hospital mortality, amputation, peripheral revascularization, and 6-month mortality. Adjusted regression models were used to evaluate outcomes. A subgroup analysis included patients requiring mechanical circulatory support (MCS). Results: Among 45,144 patients, 5.9% (N=2,651) had LE-PAD. The average age was 77.8±7.9, 59.8% were male and 83.0% were white. Cumulative in-hospital mortality was 46.8%, with greater risk among LE-PAD patients (55.2% vs 46.3%; adjusted OR 1.52, 95% CI 1.39-1.65). LE-PAD patients also had greater adjusted risk of in-hospital amputation (1.5% vs 0.2%; OR 3.23, 95% CI: 2.16-4.83), peripheral revascularization rates (1.4% vs 0.4%; OR 1.54, 95% CI: 1.06-2.23), and 6-month mortality (43.2% vs 23.7%; HR 2.06, 95% CI: 1.80-2.35). MCS was less frequently utilized in LE-PAD (20.1% vs. 38.1%, p<0.01). Adjusted in-hospital mortality, amputation and peripheral revascularization rates were comparable between LE-PAD and non-LE-PAD patients who received MCS. Non-MCS LE-PAD patients had a 2.28 fold higher adjusted 6-month mortality compared with MCS LE-PAD patients (95% CI 1.60-3.11; Figure). Conclusions: Comorbid PAD is associated with worse limb outcomes and mortality among patients with AMI and CS. Although MCS was less likely to be used in LE-PAD patients, in-hospital mortality and limb complication rates were comparable to non-LE-PAD MCS patients.

scholarly journals Chronic femoral artery ligation exaggerates the pressor and sympathetic nerve responses during dynamic skeletal muscle stretch in decerebrate rats

2018 ◽  
Vol 314 (2) ◽  
pp. H246-H254 ◽  
Author(s):  
Evan A. Kempf ◽  
Korynne S. Rollins ◽  
Tyler D. Hopkins ◽  
Alec L. Butenas ◽  
Joseph M. Santin ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Peripheral Artery Disease ◽  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Peripheral Artery ◽  
Nerve Activity ◽  
Exercise Pressor Reflex ◽  
Pressor Reflex ◽  
Artery Disease ◽  
Dynamic Stretch

Mechanical and metabolic signals arising during skeletal muscle contraction reflexly increase sympathetic nerve activity and blood pressure (i.e., the exercise pressor reflex). In a rat model of simulated peripheral artery disease in which a femoral artery is chronically (~72 h) ligated, the mechanically sensitive component of the exercise pressor reflex during 1-Hz dynamic contraction is exaggerated compared with that found in normal rats. Whether this is due to an enhanced acute sensitization of mechanoreceptors by metabolites produced during contraction or involves a chronic sensitization of mechanoreceptors is unknown. To investigate this issue, in decerebrate, unanesthetized rats, we tested the hypothesis that the increases in mean arterial blood pressure and renal sympathetic nerve activity during 1-Hz dynamic stretch are larger when evoked from a previously “ligated” hindlimb compared with those evoked from the contralateral “freely perfused” hindlimb. Dynamic stretch provided a mechanical stimulus in the absence of contraction-induced metabolite production that closely replicated the pattern of the mechanical stimulus present during dynamic contraction. We found that the increases in mean arterial blood pressure (freely perfused: 14 ± 1 and ligated: 23 ± 3 mmHg, P = 0.02) and renal sympathetic nerve activity were significantly greater during dynamic stretch of the ligated hindlimb compared with the increases during dynamic stretch of the freely perfused hindlimb. These findings suggest that the exaggerated mechanically sensitive component of the exercise pressor reflex found during dynamic muscle contraction in this rat model of simulated peripheral artery disease involves a chronic sensitizing effect of ligation on muscle mechanoreceptors and cannot be attributed solely to acute contraction-induced metabolite sensitization. NEW & NOTEWORTHY We found that the pressor and sympathetic nerve responses during dynamic stretch were exaggerated in rats with a ligated femoral artery (a model of peripheral artery disease). Our findings provide mechanistic insights into the exaggerated exercise pressor reflex in this model and may have important implications for peripheral artery disease patients.

scholarly journals Genetic Variation in Blood Pressure and Lifetime Risk of Peripheral Artery Disease: A Mendelian Randomization Study

2020 ◽  
Author(s):  
Michael G Levin ◽  
Derek Klarin ◽  
Venexia M Walker ◽  
Dipender Gill ◽  
Julie Lynch ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Calcium Channel ◽  
Peripheral Artery Disease ◽  
Genetic Correlations ◽  
Channel Blockers ◽  
Peripheral Artery ◽  
Antihypertensive Medications ◽  
Increased Risk ◽  
Genes Encoding ◽  
Artery Disease

Aims: We aimed to estimate the effect of blood pressure and blood pressure lowering medications (via genetic proxies) on peripheral artery disease. Methods and Results: GWAS summary statistics were obtained for BP (International Consortium for Blood Pressure + UK Biobank GWAS; N = up to 757,601 individuals), peripheral artery disease (PAD; VA Million Veteran Program; N = 24,009 cases, 150,983 controls), and coronary artery disease (CAD; CARDIoGRAMplusC4D 1000 Genomes; N = 60,801 cases, 123,504 controls). Genetic correlations between systolic BP (SBP), diastolic BP (DBP), pulse pressure (PP) and CAD and PAD were estimated using LD score regression. The strongest correlation was between SBP and CAD (rg = 0.36; p = 3.9 x 10-18). Causal effects were estimated by two-sample MR using a range of pleiotropy-robust methods. Increased SBP, DBP, and PP increased risk of both PAD (SBP OR 1.25 [1.19-1.31] per 10mmHg increase, p = 3 x 10-18; DBP OR 1.27 [1.17-1.39], p = 4 x 10-8; PP OR 1.51 [1.38-1.64], p = 1 x 10-20) and CAD (SBP OR 1.37 [1.29-1.45], p = 2 x 10-24; DBP OR 1.6 [1.45-1.76], p = 7 x 10-22; PP OR 1.56 [1.4-1.75], p = 1 x 10-15). The effects of SBP and DBP were greater for CAD than PAD (pdiff = 0.024 for SBP, pdiff = 4.9 x 10-4 for DBP). Increased liability to PAD increased PP (beta = 1.04 [0.62-1.45] mmHg per 1 unit increase in log-odds in liability to PAD, p = 1 x 10-6). MR was also used to estimate the effect of BP lowering through different classes of antihypertensive medications using genetic instruments containing BP-trait associated variants located within genes encoding protein targets of each medication. SBP lowering via calcium channel blocker-associated variants was protective of CAD (OR 0.38 per 10mmHg decrease in SBP; 95% CI 0.19-0.77; p = 0.007). Conclusions: Higher BP is likely to cause both PAD and CAD but may have a larger effect on CAD risk. BP-lowering through calcium-channel blockers (as proxied by genetic variants) decreased risk of CAD.

scholarly journals Eight weeks of nitrate supplementation improves blood flow and reduces the exaggerated pressor response during forearm exercise in peripheral artery disease

2018 ◽  
Vol 315 (1) ◽  
pp. H101-H108 ◽  
Author(s):  
Nicholas T. Kruse ◽  
Kenichi Ueda ◽  
William E. Hughes ◽  
Darren P. Casey
Keyword(s):  
Blood Flow ◽  
Peripheral Artery Disease ◽  
Pressor Response ◽  
Treated Group ◽  
Moderate Intensity ◽  
Peripheral Artery ◽  
Pressor Responses ◽  
Nitrate Supplementation ◽  
Artery Disease ◽  
Forearm Exercise

Peripheral artery disease (PAD) is characterized by a reduced blood flow (BF) and an elevated blood pressure (pressor) response during lower extremity exercise. Although PAD is evident in the upper extremities, no studies have determined BF and pressor responses during upper extremity exercise in PAD. Emerging evidence suggests that inorganic nitrate supplementation may serve as an alternative dietary strategy to boost nitric oxide bioavailability, improving exercising BF and pressor responses during exercise. The present study investigated 1) BF and pressor responses to forearm exercise in patients with PAD ( n = 21) relative to healthy age-matched control subjects ( n = 16) and 2) whether 8 wk of NaNO3 supplementation influenced BF and pressor responses to forearm exercise in patients with PAD. Patients with moderate to severe PAD were randomly assigned to a NaNO3 (1 g/day, n = 13)-treated group or a placebo (microcrystalline cellulose, n = 8)-treated group. Brachial artery forearm BF (FBF; via Doppler) and blood pressure (via finger plethysmography) were measured during mild-intensity (~3.5-kg) and moderate-intensity (~7-kg) handgrip exercise. The absolute change (from baseline) in FBF was reduced (except in the 3.5-kg condition) and BP responses were increased in patients with PAD compared with healthy control subjects in 3.5- and 7-kg conditions (all P < 0.05). Plasma nitrate and nitrite were elevated, exercising (7-kg) ΔFBF was improved (from 141 ± 17 to 172 ± 20 ml/min), and mean arterial pressure response was reduced (from 13 ± 1 to 9 ± 1 mmHg, P < 0.05) in patients with PAD that received NaNO3 supplementation for 8 wk relative to those that received placebo. These results suggest that the BF limitation and exaggerated pressor response to moderate-intensity forearm exercise in patients with PAD are improved with 8 wk of NaNO3 supplementation. NEW & NOTEWORTHY Peripheral artery disease (PAD) results in an exaggerated pressor response and reduced blood flow during lower limb exercise; however, the effect of PAD in the upper limbs has remained unknown. These results suggest that 8 wk of inorganic nitrate supplementation improves the blood flow limitation and exaggerated pressor response to moderate-intensity forearm exercise in PAD.

461Modulation of ischemic and bleeding risk by peripheral artery disease after an acute coronary syndrome

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M Cespon Fernandez ◽  
S Raposeiras Roubin ◽  
E Abu-Assi ◽  
S Manzano-Fernandez ◽  
F Dascenzo ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Peripheral Artery Disease ◽  
Cumulative Incidence ◽  
Bleeding Risk ◽  
Peripheral Artery ◽  
Data Set ◽  
Coronary Syndrome ◽  
Artery Disease ◽  
The Impact

Abstract Introduction Peripheral artery disease (PAD) is associated with heightened ischemic and bleeding risk in patients with acute coronary syndrome (ACS). With this study from real-life patients, we try to analyze the balance between ischemic and bleeding risk during treatment with dual antiplatelet therapy (DAPT) after an ACS according to the presence or not of PAD. Methods The data analyzed in this study were obtained from the fusion of 3 clinical registries of ACS patients: BleeMACS (2004–2013), CardioCHUVI/ARRITXACA (2010–2016) and RENAMI (2013–2016). All 3 registries include consecutive patients discharged after an ACS with DAPT and undergoing PCI. The merged data set contain 26,076 patients. A propensity-matched analysis was performed to match the baseline characteristics of patients with and without PAD. The impact of prior PAD in the ischemic and bleeding risk was assessed by a competitive risk analysis, using a Fine and Gray regression model, with death being the competitive event. For ischemic risk we have considered a new acute myocardial infarction (AMI), whereas for bleeding risk we have considered major bleeding (MB) defined as bleeding requiring hospital admission. Follow-up time was censored by DAPT suspension/withdrawal. Results From the 26,076 ACS patients, 1,600 have PAD (6.1%). Patients with PAD were older, and with more cardiovascular risk factors. DAPT with prasugrel/ticagrelor was less frequently prescribed in patients with PAD in comparison with the rest of the population (8.2% vs 22.8%, p<0.001). During a mean follow-up of 12.2±4.8 months, 964 patients died (3.7%), and 640 AMI (2.5%) and 685 MB (2.6%) were reported. After propensity-score matching, we obtained two matched groups of 1,591 patients. Patients with PAD showed a significant higher risk of both AMI (sHR 2.17, 95% CI 1.51–3.10, p<0.001) and MB (sHR 1.51, 95% CI 1.07–2.12, p=0.018), in comparison with those without PAD. The cumulative incidence of AMI was 63.9 and 29.8 per 1,000 patients/year in patients with and without PAD, respectively. The cumulative incidence of MB was 55.9 and 37.6 per 1,000 patients/year in patients with and without PAD, respectively. The rate difference per 1,000 patient-years for AMI between patients with and without PAD was +34.1 (95% CI 30.1–38.1), and for MB +18.3 (16.1–20.4). The net balance between ischemic and bleeding events comparing patients with and without PAD was positive (+15.8 per 1,000 patients/year, 95% CI 9.7–22.0). Conclusions PAD was associated with higher ischemic and bleeding risk after hospital discharge for ACS treated with DAPT. However, the balance between ischemic and bleeding risk was positive for patients with PAD in comparison with patients without PAD. As summary, ACS patients with PAD had an ischemic risk greater than the bleeding risk.

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