scholarly journals Evaluation of the EndoPAT as a Tool to Assess Endothelial Function

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
M. Moerland ◽  
A. J. Kales ◽  
L. Schrier ◽  
M. G. J. van Dongen ◽  
D. Bradnock ◽  
...  

Endothelial dysfunction is a potential target for (pharmaceutical) intervention of several systemic pathological conditions. We investigated the feasibility of the EndoPAT to evaluate acute changes in endothelial function with repeated noninvasive measurements and assessed its discriminating power in different populations. Endothelial function was stable over a longer period of time in renally impaired patients (coefficient of variation 13%). Endothelial function in renally impaired and type 2 diabetic patients was not decreased compared to healthy volunteers (2.9±1.4and1.8±0.3, resp., versus1.8±0.5,P>0.05). The EndoPAT did not detect an effect of robust interventions on endothelial function in healthy volunteers (glucose load: change from baseline0.08±0.50, 95% confidence interval −0.44 to 0.60; smoking: change from baseline0.49±0.92, 95% confidence interval −0.47 to 1.46). This suggests that at present the EndoPAT might not be suitable to assess (changes in) endothelial function in early-phase clinical pharmacology studies. Endothelial function as measured by the EndoPAT could be physiologically different from endothelial function as measured by conventional techniques. This should be investigated carefully before the EndoPAT can be considered a useful tool in drug development or clinical practice.

2010 ◽  
Vol 118 (10) ◽  
pp. 607-615 ◽  
Author(s):  
Sandra J. Hamilton ◽  
Gerard T. Chew ◽  
Timothy M.E. Davis ◽  
Gerald F. Watts

Dyslipidaemia contributes to endothelial dysfunction and CVD (cardiovascular disease) in Type 2 diabetes mellitus. While statin therapy reduces CVD in these patients, residual risk remains high. Fenofibrate corrects atherogenic dyslipidaemia, but it is unclear whether adding fenofibrate to statin therapy lowers CVD risk. We investigated whether fenofibrate improves endothelial dysfunction in statin-treated Type 2 diabetic patients. In a cross-over study, 15 statin-treated Type 2 diabetic patients, with LDL (low-density lipoprotein)-cholesterol <2.6 mmol/l and endothelial dysfunction [brachial artery FMD (flow-mediated dilatation) <6.0%] were randomized, double-blind, to fenofibrate 145 mg/day or matching placebo for 12 weeks, with 4 weeks washout between treatment periods. Brachial artery FMD and endothelium-independent NMD (nitrate-mediated dilatation) were measured by ultrasonography at the start and end of each treatment period. PIFBF (post-ischaemic forearm blood flow), a measure of microcirculatory endothelial function, and serum lipids, lipoproteins and apo (apolipoprotein) concentrations were also measured. Compared with placebo, fenofibrate increased FMD (mean absolute 2.1±0.6 compared with −0.3±0.6%, P=0.04), but did not alter NMD (P=0.75). Fenofibrate also increased maximal PIFBF {median 3.5 [IQR (interquartile range) 5.8] compared with 0.3 (2.1) ml/100 ml/min, P=0.001} and flow debt repayment [median 1.0 (IQR 3.5) compared with −1.5 (3.0) ml/100 ml, P=0.01]. Fenofibrate lowered serum cholesterol, triacylgycerols (triglycerides), LDL-cholesterol, apoB-100 and apoC-III (P≤0.03), but did not alter HDL (high-density lipoprotein)-cholesterol or apoA-I. Improvement in FMD was inversely associated with on-treatment LDL-cholesterol (r=−0.61, P=0.02) and apoB-100 (r=−0.54, P=0.04) concentrations. Fenofibrate improves endothelial dysfunction in statin-treated Type 2 diabetic patients. This may relate partly to enhanced reduction in LDL-cholesterol and apoB-100 concentrations.


Metabolism ◽  
2006 ◽  
Vol 55 (11) ◽  
pp. 1508-1515 ◽  
Author(s):  
Torben Østergård ◽  
Birgit Nyholm ◽  
Troels K. Hansen ◽  
Lars M. Rasmussen ◽  
Jørgen Ingerslev ◽  
...  

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Zhongjian Cheng ◽  
Xiaohua Jiang ◽  
Xinggui Shen ◽  
Pu Fang ◽  
Raj Kishore ◽  
...  

Background: Cumulative evidence indicates that plasma homocysteine (Hcy) level is positively correlated with cardiovascular mortality in Type 2 diabetic patients. Aims: To explore the effects and mechanisms of elevated plasma Hcy level[[Unable to Display Character: &#8213;]] hyperhomocysteinemia (HHcy) on endothelial function in db/db mice. Methods and Results: HHcy was induced in diabetic db/db and non-diabetic db/+ mice fed with a high methionine diet (HM, 2% methionine) for 8 weeks (plasma tHcy=54.31±5.4 and 34.21±4.15 μM). Endothelial function was examined in small mesenteric arteries (SMA) using myographs. In non-diabetic mice, HHcy did not change vascular relaxation to acetylcholine (Ach); whereas, nitric oxide (NO)- and prostacyclin (PGI2)-mediated relaxation to Ach were impaired. Interestingly, endothelium-derived hyperpolarization factor (EDHF)-mediated relaxation to Ach was improved. In diabetic mice, HHcy potentiated the impairment of NO-, PGI2- and EDHF-mediated relaxation to Ach. Moreover, sodium hydrogen sulfide (NaHS), a donor of hydrogen sulfide (H2S), induced EDHF-mediated relaxation which was impaired in diabetic mice and potentiated by HHcy. NS309, a non-specific calcium-activated potassium channel (Kca) activator, significantly improved H2S- and Ach-induced EDHF-mediated relaxation in diabetic mice with HHcy. Tram-34, an intermediate conductance Kca (IK) blocker, but not small conductance Kca blocker apamin, diminished HHcy-induced impairment of EDHF-mediated relaxation in diabetic mice, suggesting that IK inactivation plays a major role. Free sulfide was decreased in plasma and SMA of diabetic mice which was potentiated with HHcy. Superoxide generation was increased and potentiated by HHcy in lung ECs from diabetic mice. Moreover, PEG-SOD improved vascular relaxation in diabetic mice with HHcy. Finally, tyrosine nitration of IK was increased in human cardiac microvascular endothelial cells (ECs) treated with either D-glucose (25 mM) or DL-Hcy (500 μM) for 48h, which was potentiated by a combination of D-glucose and DL-Hcy. Conclusions: H2S is a major EDHF in resistant arteries in mouse. H2S-contributed EDHF-mediated vascular relaxation was impaired in diabetes and was potentiated by HHcy via oxidative stress and IK inactivation.


2014 ◽  
Vol 29 (2) ◽  
pp. 303-309 ◽  
Author(s):  
W. J. A. Banukie N. Jayasuriya ◽  
Chandanie A. Wanigatunge ◽  
Gita H. Fernando ◽  
D. Thusitha U. Abeytunga ◽  
T. Sugandhika Suresh

2015 ◽  
Vol 239 (1) ◽  
pp. 131-136
Author(s):  
Guangda Xiang ◽  
Lin Xiang ◽  
Honglin He ◽  
Junxia Zhang ◽  
Jing Dong

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