Altered bioavailability of epoxyeicosatrienoic acids is associated with conduit artery endothelial dysfunction in type 2 diabetic patients.

BACKGROUND: This pathophysiological study addressed the hypothesis that soluble epoxide hydrolase (sEH), which metabolizes the vasodilator and anti-inflammatory epoxyeicosatrienoic acids (EETs) to dihydroxyeicosatrienoic acids (DHETs), contributes to conduit artery endothelial dysfunction in type 2 diabetes. METHODS AND RESULTS: Radial artery endothelium-dependent flow-mediated dilatation in response to hand skin heating was reduced in essential hypertensive patients (n = 9) and type 2 diabetic subjects with (n = 19) or without hypertension (n = 10) compared to healthy subjects (n = 36), taking into consideration cardiovascular risk factors, flow stimulus and endothelium-independent dilatation to glyceryl trinitrate. Diabetic patients but not non-diabetic hypertensive subjects displayed elevated whole blood reactive oxygen species levels and loss of NO release during heating, assessed by measuring local plasma nitrite variation. Moreover, plasma levels of EET regioisomers increased during heating in healthy subjects, did not change in hypertensive patients and decreased in diabetic patients. Correlation analysis showed in the overall population that the less NO and EETs bioavailability increases during heating, the more flow-mediated dilatation is reduced. The expression and activity of sEH, measured in isolated peripheral blood mononuclear cells, was elevated in diabetic but not hypertensive patients, leading to increased EETs conversion to DHETs. Finally, hyperglycemic and hyperinsulinemic euglycemic clamps induced a decrease in flow-mediated dilatation in healthy subjects and this was associated with an altered EETs release during heating. CONCLUSIONS: These results demonstrate that an increased EETs degradation by sEH and altered NO bioavailability are associated with conduit artery endothelial dysfunction in type 2 diabetic patients independently from their hypertensive status. The hyperinsulinemic and hyperglycemic state in these patients may contribute to these alterations. Trial registration NCT02311075. Registered December 8, 2014.

Blood flow differences in cun-kou (radial) artery and anterior tibial artery: normal people vs patients with chronic gastritis.

OBJECTIVE: To explore the blood flow differences in cun-kou (radial) artery and anterior tibial artery between normal people and patients with chronic gastritis. METHODS: Using doppler ultrasonography, blood flow charts [peak systolic velocity (VP), maximum blood flow velocity in diastole (VD), mean blood flow velocity (VM), pulse index (PI), resistance index (RI), blood vessel diameter (D), vessel volume (SV), circulation blood flow periodic time (ET)] measured by at cun-kou (radial) artery and anterior tibial artery in normal group (n = 30) and chronic gastritis group (n = 30) in department of ultrasound, Beijing Anzhen hospital, capital medical university. RESULTS: In the doppler flow charts of the normal group, there were statistically significant differences in VD, VM, D, RI, SV, ET between cun-kou artery and anterior tibial artery (P < 0.05), and there were more statistically significant differences in PI between cun-kou artery and anterior tibial artery (P < 0.01). In the comparison of doppler flow charts in the chronic gastritis group, there were statistically significant differences in VD, VM, D, RI, SV, ET between cun-kou artery and anterior tibial artery (P < 0.05), and there were more statistically significant differences in PI between cun-kou artery and anterior tibial artery (P < 0.01). In the comparison of doppler flow charts between normal group and chronic gastritis group, there were statistically significant differences in SV, ET between normal group and chronic gastritis group (P < 0.05), and there were more statistically significant differences in PI between normal group and chronic gastritis group (P < 0.01). CONCLUSION: Based on the differences in doppler flow charts between the normal group and the chronic gastritis group, the doppler flow charts of cun-kou artery and anterior tibial artery were not only proved to be significantly different, but also provided quantitative objective indexes for the study of cun-kou artery and anterior tibial artery doppler flow charts of normal people and chronic gastritis patients. This study also proves that the doppler flow chart of the anterior tibial pulse is of great significance for the diagnosis of chronic gastritis.

General, regional or local anesthesia for successful radial cephalic arteriovenous fistula.

Autogenous fistulas and in particular radiocephalic fistulas are recommended as the first vascular access for hemodialysis. Unfortunately, the rates of early failure and non-maturation are very high. For more than a decade, brachial plexus block has been proposed as the anesthesia of choice for fistula creation due to its beneficial sympathectomy-like effect, causing vasodilation and attenuation of spasm. Until recently, there was not a single randomized clinical study supporting this proposition. Because performing regional anesthesia is time-consuming and requires expertise, many surgeons prefer local or general anesthesia for vascular access surgery. However, in August 2016 a randomized clinical trial was published showing that regional anesthesia significantly reduces early failure and improves primary and functional patency at 3 months compared to local anesthesia. The aging of the dialysis population, with their attendant morbidity and increased risk for general anesthesia, makes it clear that regional anesthesia is the recommended approach for fistula creation. The excess time required for this approach will decrease with increasing expertise along the learning curve, and will be compensated by a reduction in time that would otherwise be needed for new access construction due to failure of fistulas constructed under local anesthesia.

Morphological analysis of pressure wave in the arterial tree with stenosis - a modeling approach.

This paper describes the morphological changes in peripheral signals due to arterial diseases with various severity conditions and site of stenosis using modeling approaches, and its effect in the morphological parameters of radial artery. As stenosis induces abrupt change in geometry and elastic properties of arterial tree (constitutes major reflection sites), hybrid model is well suited for studying the changes in shape of the pressure and flow wave transmitted through the stenosis. These morphological changes in wave shape of peripheral signal have significant diagnostic value in both modern and traditional medicine systems. It can be used for the quantitative assessment of the severity of the arterial diseases.

Effect of pulsatile perfusion during cardiopulmonary bypass in terms of radial artery sphygmogram.

OBJECTIVE: To investigate a quantitative method for using radial artery pulse waveforms to assess the effect of pulsatile flow during cardiopulmonary bypass (CPB). METHODS: A total of 34 adults with heart disease who underwent open-heart surgery between April 2010 and January 2011 were randomized into a pulsatile perfusion group (n = 17) and a non-pulsatile perfusion group (n = 17). Radial arterial pulse waveforms of pulsatile and non-pulsatile perfusion patients were observed and compared before and during CDB. RESULTS: No pulse waveform could be detected at patients' radial artery in both groups when the aorta was cross-clamped. Pulse waveforms could be detected at pulsatile perfusion patients' radial artery, but could not be detected at non-pulsatile perfusion patients' radial artery during CPB. Additionally, patients' pulse waveforms during pulsatile perfusion were lower than those before the operation. CONCLUSION: Our findings indicate that radial artery sphygmogram can be used as a valid indicator to evaluate the effectiveness of pulsatile perfusion during CPB.

Relationships among the serum omega fatty acid levels, serum C-reactive protein levels and arterial stiffness/wave reflection in Japanese men.

OBJECTIVE: We examined the relationship among the serum omega-3 and omega-6 fatty acid (O3FA and O6FA) levels, serum C-reactive protein (CRP) levels, and arterial stiffness/wave reflection (AS/WR) in healthy Japanese men. METHODS: In 2206 Japanese healthy men, parameters related to the AS/WR (i.e., brachial-ankle pulse wave velocity and radial arterial pulse wave analysis) were measured. RESULTS: No significant inverse relationships were observed between the serum O3FA levels and the AS/WR-related parameters. Adjusted values of the AS/WR-related parameters and serum CRP levels were higher in the subjects with serum O6FA levels in the highest tertile than in those with serum O6FA levels in the lowest tertile. CONCLUSIONS: In healthy Japanese men with known high dietary intakes of O3FAs, the serum O3FA levels may not reflect the pathophysiological abnormalities related to AS/WR. Increased serum O6FA levels appeared to be independently associated with the unfavorable conditions related to AS/WR and inflammation.

Ultrasound-guided infraclavicular brachial plexus block enhances postoperative blood flow in arteriovenous fistulas.

OBJECTIVE: Brachial plexus block offers several advantages when creating vascular access for hemodialysis. However, no controlled studies have directly evaluated arteriovenous fistula (AVF) blood flow in patients anesthetized by this method. We compared the effects of ultrasound-guided, infraclavicular brachial plexus block and local infiltration anesthesia on blood flow in the radial artery and AVF during the early and late postoperative periods. METHODS: Sixty patients were randomly assigned to an experimental group, which received infraclavicular brachial plexus block (IB), or to a control (C) group that received local infiltration anesthesia. Blood flow in the distal radial artery was measured before and after IB or infiltration anesthesia. AVF flow during the early and late postoperative period was evaluated using duplex ultrasound imaging. The rates of primary fistula failure were also compared. RESULTS: After anesthesia, preoperative radial arterial flow was 56 ± 8.6 mL/min in group IB vs 40.7 ± 6.11 mL/min in group C (P < .0001). Blood flow in the fistula, measured in mL/min at 3 hours, 7 days, and 8 weeks postoperatively, was also greater in group 1B vs group C, respectively, at 69.6 ± 7.9 vs 44.8 ± 13.8 (P < .001), 210.6 ± 30.9 vs 129 ± 36.1 (P < .001), and 680.6 ± 96.7 vs 405.3 ± 76.2 (P < 0.001). CONCLUSION: When used for AVF access surgery, infraclavicular brachial plexus block provides higher blood flow in the radial artery and AVF than is achieved with infiltration anesthesia.

Morphology variability analysis of wrist pulse waveform for assessment of arteriosclerosis status.

In this paper, approximate entropy (ApEn) is applied to study the variability of pulse waveform for assessing coronary arteriosclerosis status. Having analyzed the wrist pulse waveforms taken from both normal subjects and the patients suffering from coronary arteriosclerosis (CA) disorders, we find that pulse morphology variability (PMV) is more efficient than pulse interval variability (PIV) in assessing the conditions of human coronary artery. Usually, the PMVs of the healthy are higher than those of the patients with CA diseases, and the PMVs of patients with CA diseases have more high frequency components than those of the healthy subjects. That is to say, the CA disease also has influence on vascular tone. The effect of changes in cardiac performance due to CA disease can be reflected through the PMV. The experiment demonstrates that the specificity and sensitivity of the PMV's spectral energy ratio for clinical diagnosis of cardiovascular system is 80% and 97%, respectively.

Arterial stiffness and the response to carotid sinus massage in older adults.

BACKGROUND AND AIMS: Carotid sinus hypersensitivity (CSH) is a common cause of fainting and falls in the older adult population and is diagnosed by carotid sinus massage (CSM). Previous work has suggested that age-related stiffening of blood vessels reduces afferent input from the carotid sinus leading to central upregulation of the overall arterial baroreflex response. We examined the differences in arterial stiffness and baroreflex function in older adults at high cardiovascular risk (advanced age, Type 2 diabetes, hypertension and hyperlipidemia) with and without CSH. METHODS: Forty-three older adults (mean age 71.4+/-0.7) with Type 2 diabetes, hyperlipidemia and hypertension were recruited. After resting supine for 45 minutes prior to the start of data collection, each subject had arterial stiffness measured by pulse wave velocity (PWV, Complior SD), followed by spontaneous baroreflex measures (Baroreflex sensitivity, BRS) and CSM. RESULTS: Of the 43 subjects tested, 10 subjects met the criteria for CSH (8 pure vasodepressor and 2 mixed CSH). CSH subjects had higher measures of arterial stiffness when compared to normal subjects for both radial PWV (11.5+/-0.6 vs 9.6+/-0.4 m/s, p=0.043) and femoral PWV (13.4+/-0.9 vs 11.0+/-0.5 m/s, p=0.036). The CSH group demonstrated significantly lower BRS as compared to the normal group (BRS, 6.73+/-0.58 vs 10.41+/-0.85 ms/mmHg, p=0.038). These results were unchanged when the analysis was repeated with only the VD subjects. CONCLUSIONS: Older adults with CSH have higher arterial stiffness and reduced arterial baroreflex sensitivity. There was no evidence to support upregulation of the arterial baroreflex in patients with CSH.

Serum phosphorus concentrations and arterial stiffness among individuals with normal kidney function to moderate kidney disease in MESA.

BACKGROUND AND OBJECTIVES: Higher phosphorus levels are associated with cardiovascular disease (CVD) events and mortality. Whether vascular stiffness may be responsible is unknown. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This study examined the cross-sectional associations of serum phosphorus with ankle brachial index (ABI), pulse pressure, and large and small artery elasticity by radial artery waveform analysis among 1370 individuals (440 with moderate chronic kidney disease) who did not have clinical CVD and participated in the Multi-Ethnic Study of Atherosclerosis. RESULTS: Fifty-nine (4%) individuals had high ABI (>1.30), a marker of peripheral arterial stiffness. Participants with phosphorus levels >4 mg/dl had greater than four-fold risk for high ABI compared with participants with phosphate levels <3 mg/dl (relative risk 4.6; 95% confidence interval 1.6 to 13.2; P = 0.01) after adjustment for demographics, traditional CVD risk factors, and kidney function. Higher phosphorus levels were also associated with greater pulse pressure and lesser large and small artery elasticity in unadjusted models, but these associations were attenuated after adjustment. CONCLUSIONS: Higher phosphorus levels are strongly associated with high ABI but not pulse pressure or large or small artery elasticity. If confirmed in future studies, then the association of higher phosphorus concentrations with CVD events may be partially mediated through peripheral arterial stiffness.

[The value of complior method for studying the endothelial dysfunction in hypertensive patients]. / Valoarea metodei complior in studiul disfunctiei endoteliale la pacientii hipertensivi.

OBJECTIVE: Non-invasive methods that measure the arterial stiffness and wave reflection have recently been used for assessing the endothelial dysfunction. Despite this fact, Complior method, which can study the relation between nitric oxide (NO) and pulse wave velocity as a measure of arterial stiffness, is not currently used. Our study evaluates the potential of Complior technique for a global assessing of the endothelial dysfunction. MATERIAL AND METHODS: Endothelial dysfunction was prospectively studied before and after 6 and 12 months of antihypertensive treatment in 92 hypertensive patients, strictly selected and 50 matched normotensives. The studied parameters were pulse wave velocity (PWV) and its variation under pharmacodynamic stimulation. NO-dependent/ independent vasodilatation were assessed with 400 microg Ventolin spray (deltaPWV% = BR) and 0.5 mg sublingual NTG (deltaPWV% = NR1), respectively. RESULTS: 1. The endothelial dysfunction has a large interindividual variability, irrespective the blood pressure values. 2. The endothelial dysfunction is a heterogenous condition, being more affected in peripheral arterial territory and in NO-dependent component. 3. Therapeutic effect depends on vascular structure and antihypertensive regimen. ACE inhibitors and calcium channel blockers have complementary intervention, so the combination can be useful for a better therapeutic control of the endothelial dysfunction. CONCLUSION: Complior is a very useful method for studying the complex profile of endothelial dysfunction and can complete the vascular ultrasound data for peripheral arterial site.

Folic Acid does not limit endothelial dysfunction induced by ischemia and reperfusion: a human study.

Nitric oxide synthase (NOS) uncoupling is a condition of increased production of superoxide anion associated with a decreased production of nitric oxide (NO) by this enzyme. Folic acid can prevent and/or reverse NOS uncoupling in the setting of diabetes, smoking, hypercholesterolemia, and nitrate tolerance. Whereas animal studies showed a protective effect of folic acid in ischemia and reperfusion (IR) injury, no study tested whether folic acid administration limits IR-induced endothelial dysfunction in humans. In a double-blind, parallel study, 20 healthy young male volunteers were randomized to receive folic acid, 10 mg/d for 7 days, or matching placebo. At the end of the treatment period, endothelium-dependent, flow-mediated dilation (FMD) of the radial artery was measured before and after IR injury (15 minutes of ischemia at the level of the brachial artery followed by 15 minutes of reperfusion). There was no difference at baseline between groups in any variable. In the placebo group, IR significantly blunted FMD (before IR, 6.7+/-1.0%; after IR, 1.5+/-1.3%, P<0.01). A similar effect was observed in the folic acid group (before IR, 6.3+/-1.1%; after IR, 2.1+/-1.0%, P=ns compared with placebo). As opposed to animal studies, high-dose folic acid does not protect the vascular endothelium from IR injury in humans.

Protective effects of ascorbic acid on arterial hemodynamics during acute hyperglycemia.

Mortality increases when acute coronary syndromes are complicated by stress-induced hyperglycemia. Early pulse wave reflection can augment central aortic systolic blood pressure and increase left ventricular strain. Altered pulse wave reflection may contribute to the increase in cardiac risk during acute hyperglycemia. Chronic ascorbic acid (AA) supplementation has recently been shown to reduce pulse wave reflection in diabetes. We investigated the in vivo effects of acute hyperglycemia, with and without AA pretreatment, on pulse wave reflection and arterial hemodynamics. Healthy male volunteers were studied. Peripheral blood pressure (BP) was measured at the brachial artery, and the SphygmoCor pulse wave analysis system was used to derive central BP, the aortic augmentation index (AIx; measure of systemic arterial stiffness), and the time to pulse wave refection (Tr; measure of aortic distensibility) from noninvasively obtained radial artery pulse pressure (PP) waveforms. Hemodynamics were recorded at baseline and then every 30 min during a 120-min systemic hyperglycemic clamp (14 mmol/l). The subjects, studied on two separate occasions, were randomized in a double-blind, crossover manner to placebo or 2 g intravenous AA before the initiation of hyperglycemia. During hyperglycemia, AIx increased and Tr decreased. Hyperglycemia did not change peripheral PP but did magnify central aortic PP and diminished the normal physiological amplification of PP from the aorta to the periphery. Pulse wave reflection, as assessed from peripheral pulse wave analysis, is enhanced during acute hyperglycemia. Pretreatment with AA prevented the hyperglycemia-induced hemodynamic changes. By protecting hemodynamics during acute hyperglycemia, AA may have therapeutic use.

Ascorbic acid reduces blood pressure and arterial stiffness in type 2 diabetes.

Experimental evidence suggests that acute parenteral administration of high-dose ascorbic acid has beneficial vascular effects in type 2 diabetes. We studied the hemodynamic effects of chronic oral supplementation in this condition. Thirty patients, 45 to 70 years of age, with type 2 diabetes, were randomly assigned in a double-blind manner to receive 500 mg ascorbic acid daily by mouth or placebo. Patients were studied at baseline and after 4 weeks of assigned treatment. The central aortic augmentation index (AgIx) and the time to wave reflection (Tr) were derived from radial artery pulse wave analysis data. AgIx and Tr were used as measures of systemic arterial stiffness and aortic stiffness, respectively. Ascorbic acid decreased brachial systolic blood pressure from 142.1+/-12.6 (SD) to 132.3+/-12.1 mm Hg (difference [95% CI] 9.9 [4.7, 15.0]; P<0.01), brachial diastolic pressure from 83.9+/-4.8 to 79.5+/-6.0 mm Hg (4.4 [1.8, 7.0]; P<0.01), and AgIx from 26.8+/-5.5% to 22.5+/-6.8% (4.3 [1.5, 7.1]; P<0.01). Tr increased from 137.1+/-12.6 to 143.4+/-9.2 ms (-6.3 [-10.1, -2.5]; P<0.01). Placebo had no hemodynamic effects, and this difference between treatments was significant (P<0.01 for blood pressure and Tr, P=0.03 for AgIx). We have therefore shown that after 1 month, oral ascorbic acid lowered arterial blood pressure and improved arterial stiffness in patients with type 2 diabetes. As strict control of blood pressure reduces cardiovascular risk in diabetes, ascorbic acid supplementation may potentially be a useful and inexpensive adjunctive therapy. Larger and longer studies now need to be performed.

Correction of endothelial dysfunction in chronic heart failure: additional effects of exercise training and oral L-arginine supplementation.

OBJECTIVES: The aim of this study was to analyze whether L-arginine (L-arg.) has comparable or additive effects to physical exercise regarding endothelium-dependent vasodilation in patients with chronic heart failure (CHF). BACKGROUND: Endothelial dysfunction in patients with CHF can be corrected by both dietary supplementation with L-arg. and regular physical exercise. METHODS: Forty patients with severe CHF (left ventricular ejection fraction 19 +/- 9%) were randomized to an L-arg. group (8 g/day), a training group (T) with daily handgrip training, L-arg. and T (L-arg. + T) or an inactive control group (C). The mean internal radial artery diameter was determined at the beginning and after four weeks in response to brachial arterial administration of acetylcholine (ACh) (7.5, 15, 30 microg/min) and nitroglycerin (0.2 mg/min) with a transcutaneous high-resolution 10 MHz A-mode echo tracking system coupled with a Doppler device. The power of the study to detect clinically significant differences in endothelium-dependent vasodilation was 96.6%. RESULTS: At the beginning, the mean endothelium-dependent vasodilation in response to ACh, 30 microg/min was 2.54 +/- 0.09% (p = NS between groups). After four weeks, internal radial artery diameter increased by 8.8 +/- 0.9% after ACh 30 microg/min in L-arg. (p < 0.001 vs. C), by 8.6 +/- 0.9% in T (p < 0.001 vs. C) and by 12.0 +/- 0.3% in L-arg. +/- T (p < 0.005 vs. C, L-arg. and T). Endothelium-independent vasodilation as assessed by infusion of nitroglycerin was similar in all groups at the beginning and at the end of the study. CONCLUSIONS: Dietary supplementation of L-arg. as well as regular physical exercise improved agonist-mediated, endothelium-dependent vasodilation to a similar extent. Both interventions together seem to produce additive effects with respect to endothelium-dependent vasodilation.