Effects of polycythemia on systemic endothelial function in chronic hypoxic lung disease

2011 ◽  
Vol 110 (5) ◽  
pp. 1196-1203 ◽  
Author(s):  
Laurent Boyer ◽  
Vicky Chaar ◽  
Gabriel Pelle ◽  
Bernard Maitre ◽  
Christos Chouaid ◽  
...  

Chronic obstructive pulmonary disease (COPD) is a major risk factor for cardiovascular disease. Polycythemia, a common complication of hypoxic COPD, may affect systemic vascular function by altering blood viscosity, vessel wall shear stress (WSS), and endothelium-derived nitric oxide (NO) release. Here, we evaluated the effects of hypoxia-related polycythemia on systemic endothelial function in patients with COPD. We investigated blood viscosity, WSS, and endothelial function in 15 polycythemic and 13 normocythemic patients with COPD of equal severity, by recording brachial artery diameter variations in response to hyperemia and by using venous occlusion plethysmography (VOP) to measure forearm blood flow (FBF) responses to a brachial artery infusion of acetylcholine (ACh), bradykinin (BK), sodium nitroprusside (SNP), substance P (SP), isoptin, and N-monomethyl-l-arginine (l-NMMA). At baseline, polycythemic patients had higher blood viscosity and larger brachial artery diameter than normocythemic patients but similar calculated WSS. Flow-mediated brachial artery vasodilation was increased in the polycythemic patients, in proportion to the hemoglobin levels. ACh-induced vasodilation was markedly impaired in the polycythemic patients and negatively correlated with hemoglobin levels. FBF responses to endothelium- (BK, SP) and non-endothelium-dependent (SNP, isoptin) vasodilators were not significantly different between the two groups. l-NMMA infusion induced a similar vasoconstrictor response in both groups, in accordance with their similar baseline WSS. In conclusion, systemic arteries in polycythemic patients adjust appropriately to chronic or acute WSS elevations by appropriate basal and stimulated NO release. Overall, our results suggest that moderate polycythemia has no adverse effect on vascular function in COPD.

1997 ◽  
Vol 2 (2) ◽  
pp. 87-92 ◽  
Author(s):  
Akimi Uehata ◽  
Eric H Lieberman ◽  
Marie D Gerhard ◽  
Todd J Anderson ◽  
Peter Ganz ◽  
...  

Coronary atherosclerosis is characterized by an early loss of endothelium-dependent vasodilation. However, the methods of assessing coronary endothelial function are invasive and difficult to repeat over time. Recently, a noninvasive ultrasound method has been widely used to measure flow-mediated dilation in the brachial artery as a surrogate test for endothelial function. We seek to further validate this method of measuring vascular function. The brachial artery diameters and blood flow of 20 normal volunteers (10 males and 10 females) were measured using high resolution (7.5 MHz) ultrasound and strain gauge plethysmography. Flow-mediated endothelium-dependent vasodilation was measured in the brachial artery during reactive hyperemia after 5 minutes of cuff occlusion in the upper arm. The brachial artery diameter increased maximally by 9.7 ± 4.3% from baseline at 1 min after cuff release and blood flow increased by 1002 ± 376%. Five min of cuff occlusion was sufficient to achieve 97 ± 6% of maximal brachial artery dilation and degree of dilation was not different whether the cuff was inflated proximally or distally to the image site. The intraobserver variability in measuring brachial diameters was 2.9 % and the variability of the hyperemic response was 1.4%. In young, healthy men and women, the baseline brachial artery diameter was the only factor that was predictive of the flow-mediated vasodilation response. The brachial noninvasive technique has been further validated by the determination of flow-mediated dilation. This method of assessing endothelial function may help to determine the importance of vasodilator dysfunction as a risk factor in the development of atherosclerosis.


Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 984-984
Author(s):  
Sharon E. Cox ◽  
Julie Makani ◽  
Elizabeth Ellins ◽  
Gurishaeli Walter ◽  
Selemani Mtunguja ◽  
...  

Abstract Introduction Endothelial function is impaired in adults with sickle cell anaemia (SCA), but limited data exists in children. Endothelial damage occurs from chronic inflammation, oxidant damage, immune cell activation and ischemia-reperfusion injury. In addition, availability of nitric oxide (NO) as the major vasodilator may be reduced as a result of scavenging by plasma haemoglobin and reduced arginine substrate for endothelial nitric oxide synthase. Methods Tanzanian children (N=119) with SCA (HbSS) aged 8-11.9 years enrolled in the Vascular Function Intervention Trial (ISRCTN74331412/NCT01718054) underwent baseline assessment of endothelium-dependent and -independent vasodilatation. All children were determined clinically well at assessment, hydroxyurea naive, on no long-term medication and not receiving chronic blood transfusions. Blood pressure and vasomotion were assessed after 10 minutes recumbent rest in a temperature controlled room between 08-13:00 hrs. An identical protocol as published in children (Donald & Charakida et al. Eur Heart J; 2010: 31; 1502-10) was used. In brief, brachial arterial endothelium dependent dilatation was assessed by 1 of 3 trained technicians using ultrasound imaging (Ultrasonix SonixTouch with a 12Mz probe & stereotactic holder) to assess flow-mediated dilatation (FMD) in response to reactive hyperaemia induced after release of transient blood pressure cuff occlusion (5 min, 200 mmHg, Hokanson, USA) using an automated air regulator (Logan Research, UK). Automated B-mode image edge detection was used to measure maximum change in arterial diameter (Brachial Tools) expressed as a percentage of resting baseline diameter (FMDmax). Endothelium-independent responses to 2.5µg sub-lingual glyceryl-trinitrate (GTN) were also assessed. All recordings were over-read by an experienced researcher in the UK. Venepuncture for full blood count, clinical chemistry and amino acids was conducted after FMD assessment. Results Patient characteristics are described in Table 1. Mean brachial artery diameter at baseline was 2.61mm (95% CI 2.55 – 2.67mm). Mean FMDmax was 7.70% (95% CI 7.09 – 8.32%). Endothelium-independent vasodilation (GTNmax) was 4.15% (95% CI 3.83 – 4.47%). The FMDmax response was on greater than the GTNmax response (Figure 1). No effect of room or skin temperature on FMDmax or GTNmax was observed. There was a strong inverse association between baseline artery diameter and FMDmax (-3.46, P<0.001) (Figure 2). The time to peak brachial artery diameter in response to hyperaemia was positively skewed (median 55s (IQR: 43-79s)) and was not associated with FMDmax. The only patient characteristic associated with FMDmax was age with a non-significant inverse correlation (-0.52, P=0.06) but was reduced when adjusting for baseline diameter. Baseline heart rate was positively associated with FMDmax and GTNmax (P=0.01 & 0.025). Discussion We have characterised peripheral vascular function in a large cohort of children with SCA. Mean FMDmax was slightly lower than that observed in predominantly Caucasian non-SCA British children of similar age (8.1% [SD3.4]) (Donald & Charakida et al. Eur Heart J 2010: 31; 1502-10), but higher than reported in 21 older French children with SCA (5.6 +/- 0.2) (Montalembert et al. Haematol 2007: 92; 1709-10) which might reflect deterioration of endothelial function with age. There was no apparent association between FMDmax and hemolytic markers or with nutritional status at baseline. Recruitment and assessment of appropriate local non-SCA controls for comparison is planned. Amino acid analyses are ongoing. Disclosures: No relevant conflicts of interest to declare.


2006 ◽  
Vol 110 (4) ◽  
pp. 475-482 ◽  
Author(s):  
Mikko J. Järvisalo ◽  
Laura Jartti ◽  
Jukka Marniemi ◽  
Tapani Rönnemaa ◽  
Jorma S. A. Viikari ◽  
...  

Brachial artery FMD (flow-mediated dilatation) is widely used as a marker of systemic arterial endothelial function. FMD, however, shows considerable 25% day-to-day variation that hinders its clinical use. The reasons for this variability are poorly characterized. Therefore the present study was designed to clarify factors responsible for the hourly variation in endothelial function, including consuming a low-fat meal and circadian rhythms in endogenous hormonal levels. Brachial artery FMD, along with serum glucose, triacylglycerols (triglycerides) and levels of several hormones were measured six times per day on two separate days 1 week apart. On one day, the subjects (healthy males: n=12, mean age, 24 years) ate a light breakfast and a standardized lunch (23.5% fat, 48.7% carbohydrate and 27.8% protein). On the other day, they had a similar breakfast after which they fasted. Postprandial FMD values (both after breakfast and after lunch) were similar to baseline FMD. FMD showed a 28% hourly variation and 27% weekly variation. Variation in plasma levels of insulin (P=0.02) associated negatively and DHPG (3,4-dihydroxyphenylglycol) (P=0.001), a marker of sympathetic nervous activation, associated positively with variation in FMD. The effects of DHPG and insulin on FMD were independent of changes in baseline brachial artery diameter, although DHPG was also inversely associated with baseline diameter. Eating a regular low-fat meal does not have any measurable effects on brachial artery endothelial function. These data suggest that strict requirements for fasting conditions may be unnecessary when measuring peripheral endothelial function using the ultrasound technique. Circadian variation in serum insulin and sympathetic tone are physiological determinants of endothelial function.


2018 ◽  
Vol 19 (12) ◽  
pp. 3942 ◽  
Author(s):  
Ali Mahdi ◽  
Tong Jiao ◽  
Yahor Tratsiakovich ◽  
Jiangning Yang ◽  
Claes-Göran Östenson ◽  
...  

Purinergic signaling may be altered in diabetes accounting for endothelial dysfunction. Uridine adenosine tetraphosphate (Up4A), a novel dinucleotide substance, regulates vascular function via both purinergic P1 and P2 receptors (PR). Up4A enhances vascular contraction in isolated arteries of diabetic rats likely through P2R. However, the precise involvement of PRs in endothelial dysfunction and the vasoconstrictor response to Up4A in diabetes has not been fully elucidated. We tested whether inhibition of PRs improved endothelial function and attenuated Up4A-mediated vascular contraction using both aortas and mesenteric arteries of type 2 diabetic (T2D) Goto Kakizaki (GK) rats vs. control Wistar (WT) rats. Endothelium-dependent (EDR) but not endothelium-independent relaxation was significantly impaired in both aortas and mesenteric arteries from GK vs. WT rats. Non-selective inhibition of P1R or P2R significantly improved EDR in aortas but not mesenteric arteries from GK rats. Inhibition of A1R, P2X7R, or P2Y6R significantly improved EDR in aortas. Vasoconstrictor response to Up4A was enhanced in aortas but not mesenteric arteries of GK vs. WT rats via involvement of A1R and P2X7R but not P2Y6R. Depletion of major endothelial component nitric oxide enhanced Up4A-induced aortic contraction to a similar extent between WT and GK rats. No significant differences in protein levels of A1R, P2X7R, and P2Y6R in aortas from GK and WT rats were observed. These data suggest that altered PR sensitivity accounts for endothelial dysfunction in aortas in diabetes. Modulating PRs may represent a potential therapy for improving endothelial function.


Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Keiichiro Yoshinaga ◽  
Yuuki Tomiyama ◽  
Satoshi Fujii ◽  
Saori Nishio ◽  
Noriki Ochi ◽  
...  

Introduction: Simple vascular function measurements are desirable for atherosclerosis risk assessments. Recently, we developed a novel modality of automated oscillometric method to measure a brachial artery’s vascular elastic modulus (V E ) and reported that V E is uninfluenced by blood pressure. Galectin-3 (Gal-3) expressed in endothelial cells regulates vascular fibrosis and is a molecular determinant of vascular stiffness. Hypothesis: We aimed to clarify whether V E selectively correlates with marker of vascular stiffness in chronic kidney disease (CKD). Methods: 12 moderate-to-severe CKD pts (mean eGFR 25.9±23.5 mL/min/1.73m 2 ) and 15 controls were studied. Rest V E in brachial artery was measured by new automated oscillometric detector. V E was defined as follows [VE =ΔPressure/ (100XΔarea/Area) mmHg/%]. Using ultrasound, the brachial artery diameter at rest and during reactive hyperemia [flow mediated dilatation (FMD) with endothelial-dependent dilatation] was measured. Gal-3 and interleukin-6 (IL-6), a representative inflammatory marker, were measured by enzyme-linked immune assay. Results: CKD had lower FMD (4.86±3.37 vs 9.05±2.98 %, P=0.003) and had attenuated V E than control (1.08±0.26 vs 0.83±0.17 mmHg/%, P=0.002). CKD had higher IL-6 (0.67±0.29 vs 0.29±0.33 pg/mL, P=0.003) and higher Gal-3 (20.0±12.4 vs. 5.84±2.83 pg/mL, P<0.001). V E was negatively correlated with %FMD (r=-0.46, P=0.015) and correlated with Gal-3 (r=0.40, P=0.036) but not in IL-6 (r=0.21, P=0.28). Conclusions: Attenuated vascular elasticity detected by this novel approach closely correlated with increase in Gal-3 and reduced FMD in CKD. This may indicate that the attenuated vascular elasticity selectively reflects vascular fibrosis as evidenced by Gal-3 and subsequent endothelial responses to vascular stiffness. Thus, this oscillometric measurement may be useful for detecting vascular fibrosis information and dysfunction in endothelium level.


Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Daniela K Andaku ◽  
Bruno Archiza ◽  
Flavia C Caruso ◽  
Katiany T Zangrando ◽  
Humberto Lanzotti ◽  
...  

Background: Recent evidence has indicated a ceiling to the benefits of exercise training that, if chronically surpassed, may have a negative effect on cardiac function. Conversely, improvements in peripheral arterial function may respond positively to chronic high volume training. Recent studies have shown that flow-mediated dilation (FMD) is decreased immediately after maximal exercise in sedentary subjects and is unaltered in subjects who participate in moderate volume exercise. We investigated the acute effects of maximal exercise on vascular function of elite female athletes with a high-volume training history. Methods: Fifteen elite female soccer players (mean age: 22.1 ± 4.4 years; BMI: 20.76 ± 1.75 kg/m2), with a high volume/intensity training history (4-6 hours per day) were evaluated. Subjects underwent maximal cardiopulmonary exercise testing (CPX) on a treadmill (VO2max 41.1 ± 3.9 mLO2•kg-1•min-1). Brachial artery FMD was determined using high-resolution ultrasound before and immediately after CPX. Flow velocity were measured at baseline (BSL) and during reactive hyperemia (RH) both prior to and following exercise. Results: Brachial artery diameter increased during RH before (3.42 ± 0.38mm vs. 3.03 ± 0.28mm, p<0.001) and after CPX (3.61 ± 0.44mm vs. 3.10 ± 0.37mm, p<0.001). Importantly, FMD was increased following CPX compared to BSL (16.86 ± 9.04% vs. 12.95 ± 7.03%, p=0.027). There was significant increase in peak flow velocity during RH before (135.28 ± 42.19cm/s vs. 79.19 ± 28.14cm/s, p=0.001) and after CPX (139.15 ± 41.07cm/s vs. 87.64 ± 21.23cm/s, p<0.001) (Table). Conclusion: The results of the current study indicate that arterial function is improved following acute aerobic exercise in elite female athletes with a chronic high volume training history. These findings deviate from the emerging literature suggesting chronic high volume training may be detrimental to cardiovascular function in the long term.


Author(s):  
Nidhi Pandey ◽  
Poonam Goel ◽  
Anita Malhotra ◽  
Reeti Mehra ◽  
Navjot Kaur

Background: The objective of the study was to assess vascular function in normal pregnant women and women with gestational diabetes and to study its temporal relationship with gestational age at 24-28-week POG and at 36-38-week POG and changes in FMD in postpartum period.Methods: Assessment of vascular function was done at 24-28-week POG, 36-38-week POG and at 6-12-week postpartum by flow mediated dilation of brachial artery in 37 healthy pregnant women and 37 pregnant women with GDM.Results: In GDM group mean FMD at 24-28 weeks of POG, at 36-38 weeks POG was lower as compared to the control group (11.225±6.20,8.464±6.09 versus 14.49±5.21, 10.898±4.12) although the difference in mean FMD in two groups was not statistically significant. It was found that the decrease in FMD at 36-38-week POG as compared to 24-28 weeks POG was statistically significant in both the groups (p<0.001).Conclusions: This study revealed that when endothelial function as assessed by FMD was compared at different period of gestation, the mean decrease in FMD at 36-38-week POG as compared to 24-28-week POG and 6-week post-partum was statistically significant in patients with GDM and as well as the control group, however this trend of change was same in both the groups and was not statistically significant when compared between the two group (GDM versus control). A negative correlation of FMD was found with BMI, and HBA1c, that was stronger in GDM group.


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