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The intracoronary drug provocation test has been the gold standard for diagnosis of coronary artery spasm (CAS); however, it has been identified with severe complications. In this study, we investigated the sensitivity, specificity, and safety of radial artery provocation test at different doses of ergonovine in the diagnosis of CAS. This study enrolled 57 patients, which were then divided into CAS group (n = 24) and control group (n = 33) after intracoronary ergonovine provocation test. All patients underwent radial artery provocation test at different doses of ergonovine. The predictive values of radial artery provocation test for the diagnosis of CAS were analyzed using receiver operator characteristic curve. In the radial artery provocation test at different doses of ergonovine, radial artery stenosis degree was all found to be significantly higher in the CAS group than in the control group (all P < 0.001). In the control group, significant differences were noted in the radial artery stenosis degree between different doses of ergonovine (all P < 0.05). In the CAS group, the radial artery stenosis degree was significantly higher in 160 μg and 100 μg of ergonovine than in 60 μg of ergonovine (all P < 0.001). The radial artery provocation test at 60 μg and 100 μg of ergonovine did not cause CAS, chest pain, and ECG ischemic changes. In the radial artery provocation test at 160 μg of ergonovine, some patients had CAS, chest pain, and ECG ischemic changes. The specificity and sensitivity of radial artery provocation test were 90.91% and 50.00% at 60 μg of ergonovine, 96.97% and 66.67% at 100 μg of ergonovine, and 90.91% and 95.83% at 160 μg of ergonovine for the diagnosis of CAS. As per our findings, we can conclude that the basic tension of radial artery increases in the CAS group. With the increase of ergonovine doses, its sensitivity and specificity improve, but its safety decreases. We will explore the most optimal dose of ergonovine in future studies.

Background: An increase in blood flow in the forearm arteries has been reported after brachial plexus block (BPB). However, few studies have quantitatively analysed the blood flow of the forearm arteries after BPB or have studied only partial haemodynamic parameters. The purpose of the present study was to comprehensively assess blood flow changes in the distal radial artery (RA) and ulnar artery (UA) after BPB performed via a new costoclavicular space (CCS) approach using colour Doppler ultrasound., Methods: Thirty patients who underwent amputated finger replantation and received ultrasound-guided costoclavicular BPB were included in the study. The haemodynamic parameters of the RA and UA were recorded before the block and 10 min, 20 min, and 30 min after the block using colour Doppler ultrasound to determine the peak systolic velocity (PSV), end-diastolic velocity (EDV), mean velocity (V mean ), pulsatility index (PI), resistance index (RI) and area. The volumetric flow rate (VFR) was calculated using the formula Q = area×V mean . The aforementioned parameters were compared not only before and after the BPB but also between the RA and UA., Results: Compared with those of the respective baselines, there was a significant increase in the PSV, EDV, V mean , area, and VFR and a significant decrease in the PI and RI of the RA and UA 10 min, 20 min, and 30 min post-block. The increase 30 min post-block in EDV (258.68 % in the RA, 279.63 % in the UA) was the most notable, followed by that in the V mean (183.36 % in the RA, 235.24 % in the UA), and the PSV (139.11 % in the RA, 153.15 % in the UA) changed minimally. The V mean and VFR of the RA were significantly greater than those of the UA before the BPB; however, there was no significant difference in the VFR between the RA and UA after the BPB., Conclusions: A costoclavicular BPB can increase blood flow in the forearm arteries. The RA had a higher volumetric flow rate than the UA before the BPB; however, the potential blood supply capacity of the UA was similar to that of the RA after a BPB., Trial Registration: This study was registered at the Chinese Clinical Trial Registry (http://www.chictr.org.cn/searchproj.aspx, clinical trial number: ChiCTR 1900023796, date of registration: June 12, 2019).

We investigated the sensitivity, specificity and safety of ergonovine provocation test of radial artery in the diagnosis of coronary artery spasm (CAS). The patients who came to our hospital for chest pain from January to June 2020 as well as had coronary stenosis < 50% and no radial artery stenosis, were enrolled in this study. These patients were divided into CAS group and control group after intracoronary ergonovine provocation test. All patients underwent ergonovine provocation test of radial artery, the inner diameter (D 0 and D 1 ) and the peak systolic velocities (PSV 0 and PSV 1 ) of the radial artery were measured by ultrasound before and after ergonovine provocation. The predictive value of ergonovine provocation test of radial artery for the diagnosis of CAS was analyzed using receiver operator characteristic (ROC) curve. There were 19 patients in the CAS group and 28 patients in the control group. Low density lipoprotein cholesterol and smoking rate were significantly higher in the CAS group than in the control group (all P < 0.05), but there were no significant differences in other items (P > 0.05) between the two groups. In the ergonovine provocation test of radial artery, degree of radial artery stenosis was significantly higher in the CAS group [41.50% (35.60%, 50.00%)] than in the control group [11.25% (5.15%, 23.00%)] (P = 0.000), but there were no siginificant differences in D 0 , PSV 0 and PSV 1 between the two groups (P > 0.05). The area under ROC curve of ergonovine (120 µg) provocation test of radial artery for the diagnosis of CAS was 0.912 with 95%CI: 0.792-0.975, P = 0.001, cut-off of 31%, specificity of 92.86% and sensitivity of 84.21%. The ergonovine (120 µg) provocation test of radial artery did not cause any adverse reactions. We concluded that the ergonovine provocation test of radial artery has high sensitivity, specificity and safety in the diagnosis of CAS.

The aim of this study was to evaluate the clinical and blood flow changes associated with the use of a levonorgestrel-releasing intrauterine device (LNG-IUD) in patients with idiopathic heavy menstrual bleeding (HMB). LNG-IUD was inserted into a total of 91 patients (39.5 ± 5.4 years) who were diagnosed with HMB. Uterine volume, ovarian volume, uterine, radial and spiral artery blood flow, Pictorial Blood Loss Assessment Chart (PBAC) scores, and other clinical and laboratory parameters were evaluated before and 12 months after insertion of LNG-IUD. Compared to pre-insertion values, LNG-IUD dramatically improved haemoglobin, PBAC scores, and endometrial thickness. Mean resistance indices of radial and spiral arteries significantly increased 12 months after insertion. Our study results suggest that a significant increase in the resistance indices of the intra-myometrial arteries in LNG-IUD users one year after insertion may be due to its local progestational effects, indicating a possible mechanism of LNG-IUD in reducing menstrual blood flow.Impact Statements What is already known on this subject? The mechanisms of action of LNG-IUD on heavy menstrual bleeding include atrophy, decidualization and vascular changes of in the endometrium, resulting endometrial suppression. However, the exact mechanism to stop bleeding is not clear. What do the results of this study add? The present study suggests that one of the effects of the LNG-IUD on heavy menstrual bleeding is its ability to increase the resistance indexes of the intra-myometrial arteries. What are the implications of these findings for clinical practice and/or further research? These results will foster further studies on the effects of LNG-IUD on intra-myometrial arteries and will further assure clinicians on the vascular effect of LNG-IUD during management of heavy menstrual bleeding which includes hysterectomy as a final step.

The regulation of intracellular pH (pH i ) plays a vital role in various cellular functions. We previously demonstrated that three different acid extruders, the Na + -H + exchanger (NHE), Na + -HCO 3 - co-transporter (NBC) and H + -linked monocarboxylate transporter (MCT), functioned together in cultured human radial artery smooth muscle cells (HRASMCs). However, the functions of acid-loading transporters in HRASMCs remain poorly understood. Urotensin II (U-II), one of the most potent vasoconstrictors, is highly expressed in many cardiovascular diseases. The aim of this present study was to determine the concentration effect of U-II (3 pM∼100 nM) on the functional activity of pH i regulators in HRASMCs. Cultured HRASMCs were derived from segments of human radial arteries obtained from patients undergoing bypass grafting. Changes in pH i recovery due to intracellular acidification and alkalization induced by NH 4 Cl prepulse and Na-acetate prepulse, respectively, were detected by microspectrofluorimetry with the pH-sensitive fluorescent dye BCECF. Our present study showed that (a) U-II increased the activity of NHE in a concentration-dependent manner but did not change that of NBC or MCT or resting pH i , (b) the Cl - -OH - exchanger (CHE) facilitated base extrusion, and (c) U-II induced a concentration-dependent increase in the activity of CHE. In conclusion, for the first time, our results highlight a concentration-dependent increase in the activity of NHE and CHE, but not NBC and MCT, induced by U-II in HRASMCs., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2019. Published by Elsevier Inc.)

Background and Aim of the Study: In vitro studies have shown a reduction in radial artery spasm with the use of calcium antagonists. The purpose of this study was to evaluate the efficacy of topical treatment of the radial artery conduit using either verapamil or nicardipine before the anastomoses., Methods: This prospective randomized study included 131 patients, who underwent coronary artery bypass grafting surgery with the use of the radial artery as a conduit. In 65 patients, the harvested radial artery was topically treated with verapamil and in 66 patients with nicardipine. After harvesting the radial artery, the direct flow through the conduit was measured in vitro before 5-minute incubation in nicardipine or verapamil and measured again after incubation. The flow before and after incubation was compared. Postincubation flow was also compared in the two groups. After performing the anastomosis, the flow through the radial artery was measured in vivo., Results: The mean flow after NaCl incubation was 19.93 ± 12.66 mL/min and after incubation in the Ca+ channel blocker 47.16 ± 14.58 mL/min (P < .001). No significant difference in postincubation free flow was found between verapamil (46.29 ± 15.43 mL/min) and nicardipine (48.01 ± 13.77 mL/min; P = .503)., Conclusion: Topical treatment with Ca+ channel blockers reduces radial artery spasm and significantly increases the free flow through the radial artery conduit. Nicardipine is a safe and effective alternative of verapamil in preventing spasm of radial artery conduit., (© 2019 Wiley Periodicals, Inc.)

Sacral dural arteriovenous fistulas (SDAVFs) are rare, constituting no more than 10% of all spinal dural fistulas. They are most commonly fed by the lateral sacral artery (LSA), a branch of the internal iliac artery (IIA). Catheterization of this vessel requires either a crossover at the aortic bifurcation in cases of right femoral access or retrograde catheterization from the ipsilateral common femoral artery. We present the case of a 79-year-old man with tethered cord syndrome and a symptomatic SDAVF fed by two feeders from the left LSA. Spinal diagnostic angiography was made exceptionally challenging by an aorto-bi-iliac endograft, and selective catheterization of the left IIA was not possible. The patient could not undergo surgery due to multiple comorbidities, therefore embolization was considered the best approach. The procedure was carried out through a transradial access (TRA) with Onyx and n-butyl cyanoacrylate. The SDAVF was successfully treated and the patient made a full neurological recovery., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Few studies have evaluated the effect of chronic calcium-channel blocker therapy (CCB) on the angiographic and clinical outcome of radial artery (RA) grafts used for coronary bypass surgery., Objectives: The purpose of this study was to evaluate if CCB influences midterm clinical and angiographic outcomes of RA grafts., Methods: Patient-level data of 6 angiographic randomized trials evaluating RA graft status at midterm follow-up were joined in this observational analysis. Cox regression and propensity score methods were used to evaluate the effect of CCB on the incidence of a composite of major adverse cardiac events (MACE) (death, myocardial infarction, and repeat revascularization) and graft occlusion., Results: The study population included 732 patients (502 on CCB). The median clinical follow-up was 60 months. The cumulative incidence of MACE at 36, 72, and 108 months was 3.7% vs. 9.3%, 13.4% vs. 17.6%, and 16.8% vs. 20.5% in the CCB and no CCB groups, respectively (log-rank p = 0.003). Protocol-driven angiographic follow-up was available in 243 patients in the CCB group and 200 in the no CCB group. The median angiographic follow-up was 55 months. The cumulative incidence of RA occlusion at 36, 72, and 108 months was 0.9% vs. 8.6%, 9.6% vs. 21.4%, and 14.3% vs. 38.9% in the CCB and no CCB groups, respectively (log-rank p < 0.001). After controlling for known confounding, CCB therapy was found to be consistently associated with a significantly lower risk of MACE (multivariate Cox hazard ratio: 0.52; 95% confidence interval: 0.31 to 0.89; p = 0.02) and RA graft occlusion (multivariate Cox hazard ratio: 0.20; 95% confidence interval: 0.08 to 0.49; p < 0.001)., Conclusions: In patients with RA grafts CCB is associated with significantly better midterm clinical and angiographic RA outcomes., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to evaluate the safety of calcium-channel blockers (CCBs) during radial artery catheterization in two populations with a contraindication to their use., Background: Cardiac catheterization performed via the radial approach has become increasingly common worldwide, but adoption has been slow in the United States. One possible explanation is concern over radial artery vasospasm, which can complicate procedures. Spasmolytic drugs, typically intra-arterial CCBs, are used to prevent spasm, but their safety is not well established in high-risk populations, such as those with ST-segment elevation myocardial infarction (STEMI) or systolic heart failure (HF), in which CCB may be contraindicated., Methods: Consecutive STEMI and HF patients undergoing cardiac catheterization over a 1-year period were prospectively evaluated. All operators in our laboratory use the radial approach unless contraindicated. All patients received CCB immediately after sheath insertion. The primary outcome of interest was change in blood pressure immediately after CCB. Procedural outcomes were also evaluated., Results: A total of 184 patients were included in the study (54 with STEMI and 129 with HF). There was a significant drop in systolic blood pressure (SBP) and diastolic blood pressure (DBP) following verapamil administration (P<.001 for both), but no change in HR (P>.99). SBP decreased more than 20 mm Hg in 15.7% of patients, none of whom required initiation of vasopressors. In regression analysis, only baseline SBP correlated significantly with the change in blood pressure., Conclusions: Patients with STEMI or HF can safely tolerate intra-arterial CCB during radial catheterization.

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.

Objectives: Upper extremity arterial access is often required for endovascular procedures, especially for antegrade access to the visceral aortic branches. Radial arterial access has been shown previously to have low complication rates, and patients tolerate the procedure well and are able to recover quickly. However, transradial access remains relatively uncommon amongst vascular surgeons., Methods: The radial artery was evaluated by ultrasound to evaluate for adequate caliber, and to identify any aberrant anatomy or arterial loops. A modified Barbeau test was performed to ensure sufficient collateral circulation. A cocktail of nitroglycerin, verapamil and heparin was administered intra-arterially to combat vasospasm. Sheaths up to 6 French were utilized for interventions. On completion of the procedure, a compression band was used for hemostasis in all cases., Results: Twenty-five interventions were performed in 24 patients. The left radial artery was used in 23/25 cases (92.0%). Procedures included visceral and renal artery interventions; stent graft repair of a renal artery aneurysm; embolization of splenic, pancreaticoduodenal and internal mammary aneurysms; embolization of bilateral hypogastric arteries following blunt pelvic trauma; interventions for peripheral arterial disease; delivery of a renal snorkel graft during endovascular aortic aneurysm repair, and access for diagnostic catheters during thoracic endovascular aortic aneurysm repair. Technical success was 92.0%. There was one post-operative radial artery occlusion (4.3%) which led to paresthesias but resolved with anticoagulation. There were no instances of arterial rupture, hematoma, or hand ischemia requiring intervention., Conclusions: Using the transradial approach, we have demonstrated a high technical success rate over a range of clinical contexts with minimal morbidity and no significant complications such as bleeding or hand ischemia. The safety profile compares favorably to historical complication rates from brachial access. Radial access is a safe and useful skill for vascular surgeons to master.

Background: Radial artery (RA) is widely used in coronary artery bypass (CABG) surgery and the prevention of spasm is crucial for graft patency. Botulinum toxin A (BTX-A) and B are commonly used for aesthetic reasons and neuromuscular disorders. They are proven to raise blood flow and increase survival of ischemic skin flaps. In this study we evaluated and compared the vasodilator effects of BTX-A and papaverine on human RA grafts., Methods: After resting 60 min in isolated organ baths, human RA grafts were examined. Contraction responses for different doses of serotonin (5-HT) and endothelin-1 (ET-1) were evaluated as a percent of maximum contraction response elicited by 80 mM potassium chloride (KCl). The inhibitory effects of BTX-A and papaverine on contraction responses taken at the 0th hour were compared with the 1st and 2nd hour responses. Inhibitory effects of BTX-A and papaverine against the contractile agent were evaluated by comparing the results of the first and last (0th and 2nd hour) application., Results: In low concentrations, when we compared the effects of BTX-A (10 - 8  M) and papaverine (10 - 6  M) on 5-HT, papaverine was found to be more effective at both the 0th and 2nd hour (p < 0.05). Both BTX-A and papaverine inhibited the maximum contractile effect of ET-1 to the same extent at the 0th hour; but, the inhibitory effect of BTX-A was significantly stronger at the 2nd hour (p < 0.05). In high concentrations, when we compared the effects of BTX-A (10 - 6  M) and papaverine (10 - 4  M) on 5-HT, papaverine showed stronger inhibition (p < 0.05), whereas both agents had similar action of inhibition on ET-1 mediated maximum contraction responses., Conclusion: BTX-A inhibits both ET-1 and 5-HT induced contractions and its effectiveness does not decrease over time as observed with papaverine. This study is the first in the literature using human RA for prevention of vasospasm by BTX-A.

Radial artery occlusion (RAO) occurs in 2% to 18% of patients after transradial access (TRA) cardiac catheterization. Using a kaolin-filled pad (QuikClot) reduces compression time during TRA and might reduce RAO. We examined the RAO risk with the kaolin-filled pad after TRA cardiac catheterization.This was a prospective cross-sectional study of 260 patients who underwent TRA cardiac catheterization in a cardiac ward of a Medical Center from 2012 to 2016. Patients were randomly assigned to 1 of 2 groups: the case group (n = 130) was postoperatively treated with a kaolin-filled pad, and the control group (n = 130) was treated with conventional hemostasis. Color duplex ultrasound was used to evaluate the 24-hour and 1-month postoperative radial artery flow velocity, diameter, patency, and RAO risk.RAO risk was not significantly different between the case and control groups after 24 hours (4.6% vs 5.4%, P = .776) or after 1 month (5.4% vs 6.1%, P = .789), regardless of whether it was a first TRA cardiac catheterization (after 24 hours [P = .153] or after 1month [P = .617], respectively) or a repeated TRA cardiac catheterization (after 24 hours [P = .754] or after 1month [P = .753], respectively).Using a kaolin-filled pad after TRA cardiac catheterization did not significantly reduce RAO risk compared with conventional hemostasis.

Objective: The aim of this study was to compare the efficacy of two different papaverine concentrations (0.5 mg/ml and 2 mg/ml) for vasospasm prevention and their impact on endothelium integrity., Methods: We have studied distal segments of radial arteries obtained by no-touch technique from coronary artery bypass graft (CABG) patients (n=10). The vasodilatory effect of papaverine (concentrations of 0.5 mg/ml and 2 mg/ml) was assessed in vitro, in isometric tension studies using ex vivo myography (organ bath technique) and arterial rings precontracted with potassium chloride (KCl) and phenylephrine. The impact of papaverine on endothelial integrity was studied by measurement of the percentage of vessel's circumference revealing CD34 endothelial marker., Results: 2 mg/ml papaverine concentration showed stronger vasodilatatory effect than 0.5 mg/ml, but it caused significantly higher endothelial damage. Response to KCl was 7.35±3.33 mN for vessels protected with papaverine 0.5 mg/ml and 2.66±1.96 mN when papaverine in concentration of 2 mg/ml was used. The histological examination revealed a significant difference in the presence of undamaged endothelium between vessels incubated in papaverine 0.5 mg/ml (72.86±9.3%) and 2 mg/ml (50.23±13.42%), P=0.002., Conclusion: Papaverine 2 mg/ml caused the higher endothelial damage. Concentration of 0.5 mg/ml caused better preservation of the endothelial lining.

Background and Aims: The mechanisms involved in endothelial dysfunction in humans during aging are largely unknown at the level of conduit arteries. We aimed to asses the role of NO and CYP450 epoxygenases-derived epoxyeicosatrienoic acids (EETs) in the regulation of endothelium-dependent flow-mediated dilatation of conduit arteries during aging., Methods: Radial artery diameter and mean wall shear stress were determined by echotracking coupled with Doppler in 83 subjects (19-71 years old) during a sustained flow increase induced by hand skin heating, with the brachial infusion of saline or NO-synthase and cytochrome P450 epoxygenase inhibitors (L-NNMA and fluconazole respectively). Local blood sampling was performed for the quantification of NO metabolite nitrite and EETs., Results: The magnitude of flow-mediated dilatation was independently and negatively correlated with age, baseline artery diameter and systolic blood pressure, and positively correlated with the increase in shear stress induced by heating. There was an increase in nitrite level during heating until the age of 35-40 years, which declined thereafter. However, the inhibitory effect of L-NMMA on flow-mediated dilatation progressively decreased during aging, demonstrating a decrease in functional NO availability. Moreover, aging progressively reduced the increase in EET level during heating as well as the inhibitory effect of fluconazole on flow-mediated dilatation., Conclusions: These results show that aging impairs the availability of EETs and NO and epoxyeicosatrienoic acids in peripheral conduit arteries, contributing to the development of endothelial dysfunction., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Facemasks are increasingly worn during air pollution episodes in China, but their protective effects are poorly understood. We aimed to evaluate the filtration efficiencies of N95 facemasks and the cardiopulmonary benefits associated with wearing facemasks during episodes of pollution., Results: We measured the filtration efficiencies of particles in ambient air of six types of N95 facemasks with a manikin headform. The most effective one was used in a double-blind, randomized, controlled crossover study, involving 15 healthy young adults, conducted during 2 days of severe pollution in Beijing, China. Subjects were asked to walk along a busy-traffic road for 2 h wearing authentic or sham N95 facemasks. Clinical tests were performed four times to determine changes in the levels of biomarkers of airway inflammation, endothelial dysfunction, and oxidative stress within 24 h after exposure. The facemasks removed 48-75% of number concentrations of ambient air particles between 5.6 and 560 nm in diameter. After adjustments for multiple comparison, the exhaled nitric oxide level and the levels of interleukin-1α, interleukin-1β, and interleukin-6 in exhaled breath condensate increased significantly in all subjects; however, the increases in those wearing authentic facemasks were statistically significantly lower than in the sham group. No significant between-group difference was evident in the urinary creatinine-corrected malondialdehyde level. In arterial stiffness indicators, the ejection duration of subjects wearing authentic facemasks was higher after exposure compared to the sham group; no significant between-group difference was found in augmentation pressure or the augmentation index., Conclusions: In young healthy adults, N95 facemasks partially reduced acute particle-associated airway inflammation, but neither systemic oxidative stress nor endothelial dysfunction improved significantly. The clinical significance of these findings long-term remains to be determined., Trial Registration: The trial registration number (TRN) for this study is ChiCTR1800016099 , which was retrospectively registered on May 11, 2018.

Vascular endothelial dysfunction plays an important role in the process of atherosclerosis up to the final stage of plaque rupture. Vascular endothelial dysfunction is reversible, and can be recovered by medications and life-style changes. Improvement in endothelial function may reduce cardiovascular events and improve long-term prognosis. A total of 50 patients with stable angina and dyslipidemia were enrolled, including patients who had not received prior treatment with statins and had serum LDL-C levels ≥ 100 mg/dL, and patients who had previously received statin treatment. All agreed to register regardless of their LDL-C level. Rosuvastatin was initially administered at a dose of 2.5 mg and appropriately titrated up to the maximum dose of 20 mg or until LDL-C levels lower than 80 mg/dL were achieved, for 24 weeks. Endothelial function was assessed by the reactive hyperemia peripheral arterial tonometry (RH-PAT) index in the radial artery by Endo-PAT ® 2000 (Endo-PAT ® 2000, software version 3.0.4, Itamar Medical Ltd., Caesarea, Israel). RH-PAT data were digitally analyzed online by Endo-PAT ® 2000 at baseline and at 24 weeks. LDL-C and MDA-LDL-C decreased from 112.6 ± 23.3 to 85.5 ± 20.2 mg/dL and from 135.1 ± 36.4 to 113.9 ± 23.5 mg/dL respectively (p < 0.0001). However, HDL-C, hs-CRP and TG did not change significantly after treatment. RH-PAT index levels significantly improved, from 1.60 ± 0.31 to 1.77 ± 0.57 (p = 0.04) after treatment, and the percent change of the RH-PAT index was 12.8 ± 36.9%. Results of multivariate analysis show that serum LDL-C levels over 24 weeks did not act as a predictor of improvement of the RH-PAT index. However, HbA1c at baseline was an independent predictor which influenced the 24-week RH-PAT index level. The RH-PAT index of patients with high HbA1c at baseline did not improve after administration of rosuvastatin but it did improve in patients with low HbA1c at baseline. Aggressive lowering of LDL-C with rosuvastatin significantly improved the RH-PAT index, suggesting that it may improve endothelial function in patients with coronary artery disease.Clinical Trial Registration No: UMIN-CTR, UMIN000010040.

Background: Radial artery access is the primary approach for coronary interventions due to higher safety profile in comparison to femoral access. Radial artery occlusion (RAO) is the main complication of transradial catheterization that can lead to severe symptoms and a permanent artery occlusion. The incidence of RAO after transradial access ranges from 5 to 38% and data regarding treatment is scarce. Whether anticoagulation and vasoactive medication provides an additional benefit in recovery of radial artery patency (RAP) after catheterization has not been investigated in detail., Aim: The objective was to investigate the impact of anticoagulation and vasoactive medication on regained patency after documented RAO following transradial catheterization., Patients and Methods: Overall 2635 patients were screened. 2215 (84%) catheterizations were performed by femoral and 420 (16%) by radial access. In 30 patients RAO was observed. In case of RAO patients were classified in three groups: Anticoagulation, anticoagulation added with alprostadil and controls. Follow-up was conducted after 3 months with ultrasound and clinical examination., Results: Eight patients received anticoagulation and 11 patients anticoagulation together with alprostadil. Eleven patients served as controls. Recovery of RAP after catheterization was higher following either treatment (79.5%) compared to controls (0%, p = 0.006). Subgroup analysis yielded a higher RAP recovery in patients treated with anticoagulation (62.5%) as compared to controls (0%, p = 0.002). No effect on regained RAP was found with additional alprostadil therapy (33.3%) compared to anticoagulation therapy (62.5%, p = 0.229)., Conclusion: RAO should be treated with anticoagulation to regain patency. Addition of vasoactive medication does not lead to further beneficial effects. Further research is needed regarding preventive and therapeutic strategies following RAO.

Objective: The objective of this review was to identify the effectiveness of topical medications on radial artery spasm (RAS) in patients undergoing transradial percutaneous coronary procedures., Introduction: Percutaneous coronary procedures were traditionally carried out via the femoral artery; however, over the last 20 years there has been a global increase in the number of proceduralists carrying out percutaneous coronary procedures via the transradial approach. Radial artery spasm remains an issue for the transradial approach, potentially leading to procedural failure. Topical medications have been suggested to reduce the occurrence of RAS during transradial percutaneous coronary procedures., Inclusion Criteria: This review considered papers that included participants aged 18 years and over undergoing non-emergency transradial percutaneous coronary procedures. This review considered papers on the utilization of topical medications prior to commencing the transradial approach for percutaneous coronary procedures to reduce RAS. Topical medications were compared to other medications. The primary outcome was the incidence of RAS as assessed by angiography or ultrasound or resistance felt by the operator while manipulating the catheter. Other outcomes of interest included change in radial artery diameter, measured by angiography or ultrasound, change in radial artery patency and side effects of medications administered. Randomized and quasi-randomized controlled trials were considered., Methods: A three-step search strategy was utilized in this review. A search of various databases was carried out followed by a search for unpublished literature between 1989 to January 2017. Only papers published in English were included in the review. Papers selected for retrieval were assessed by two independent reviewers for methodological validity prior to inclusion in the review using standardized critical appraisal instrument from the Joanna Briggs Institute (JBI). There was no need for a third reviewer. Quantitative data was extracted from papers included in the review using the JBI data extraction instrument and entered in to RevMan5 (Copenhagen: The Nordic Cochrane Centre, Cochrane). All results were subject to double data entry. Effect sizes were expressed as odds ratio (for categorical data) and weighted mean differences (for continuous data) and their 95% confidence intervals were calculated for analysis., Results: Only three studies involving 697 participants met the inclusion criteria. There was a statistically significant reduction in the incidence of RAS in patients treated with a eutectic mixture of local anesthetics compared to subcutaneous lidocaine (OR 0.26; 95%CI 0.07,0.96). However there were no significant differences in RAS in studies that compared eutectic mixture of local anesthetics and placebo or a combinations of lidocaine with nitroglycerine compared to placebo., Conclusions: It is difficult to draw a valid conclusion, given the low number of studies, small sample sizes and heterogeneity between the studies.

Background: The radial artery is increasingly used for cardiac procedures, but is a relatively small vessel that is prone to spasm when instrumented. Intra-arterial nitroglycerine has been shown to reduce radial spasm but first requires arterial access. We investigated the effect of pre-procedure sublingual nitroglycerin (NTG) on the diameter of the radial artery in a large cohort of patients., Methods: 305 subjects underwent ultrasound measurement of their radial and ulnar arteries in both arms before and after the administration of 800μg of sublingual NTG. The Allen's test was also performed in the subjects prior to and after NTG., Results: Radial artery diameter in this Caucasian study group is larger than that reported for other populations. The administration of sublingual NTG significantly increased the size of the right radial artery from 2.88±0.36mm to 3.36±0.40mm in men and from 2.23±0.37 up to 2.74±0.36mm in women. There were also significant increases in left radial, right and left ulnar artery diameters in males and females with NTG. There was no significant effect of NTG on blood pressure. In all patients with an unfavourable Allen's test, retesting following sublingual NTG resulted in transition to a favourable Allen's., Conclusion: Caucasian populations have larger calibre radial arteries compared to other geographic areas. Sublingual NTG is effective at dilating the radial artery in both men and women. This may make radial artery puncture and cannulation less challenging and should be considered in all patients in the absence of contraindications. The results of Allen's testing are dynamic and its usefulness for screening prior to transradial access is undetermined., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Aim: Transradial access (TRA) for coronary intervention is increasingly used in current clinical practice. The aim of the present study was to evaluate the hypothesis that cutaneous analgesia before TRA for coronary intervention at a puncture site 30 minutes before puncture can reduce patient discomfort and the incidence of radial artery spasm (RAS)., Methods: Patients (n=104) undergoing planned coronary interventions using TRA were prospectively randomized to receive either 1 mL of 1% lidocaine subcutaneously (n=52) (control group) or subcutaneous lidocaine plus 5% lidocaine cream (n=52) cutaneously 30 minutes before puncture (treatment group). The primary endpoint was angiographically or clinically confirmed RAS. Secondary endpoints were the occurrence of patient discomfort in the forearm during the procedure and access-site crossover to the femoral artery. Patient discomfort was quantified with a visual analogue scale (VAS) score., Results: Fifty-two patients in the treatment group (60.5±9.4 years of age and 16 female) and 52 patients in the control group (60.4±9.7 years of age and 16 female) were included in the final analysis. Radial artery spasm occurrence decreased in the treatment group compared to the control group (26.9% vs 9.6%; p=0.04) accompanied by a VAS score of 3.7±1.8 in the treatment group and 4.9±2.0 in the control group; p=0.02. The access site crossover rate did not differ between the groups (7.6% vs 21.1%; p=0.09)., Conclusion: Cutaneous analgesia before TRA for coronary interventions is associated with a substantial reduction in the RAS and the procedure-related level of patient discomfort.

Vascular calcification (VC) is a very common phenomenon in patients with chronic kidney disease(CKD) and it increases the incidence of cardiovascular disease and leads to high mortality in CKD patients. It has been reported that some microRNAs (miRs) play roles in vascular calcification as an epigenetic regulator. Indoxyl sulfate (IS) is a protein-bound uremic toxin which has been proven as one of the major risk factors of cardiovascular disease in CKD. Here we investigated whether microRNA-29b (miR-29b) is involved in IS-induced vascular calcification. We found that vascular miR-29b was down-regulated in radial arteries of patients with end-stage renal disease. Consistently, IS also decreased miR-29b expression in human aortic smooth muscle cells (HASMCs) and potentiated their calcification. MiR-29b mimics significantly suppressed, while miR-29b anti-miR markedly enhanced, IS-induced runt-related transcription factor 2 and osteopontin expression. The expression of Wnt7b/β-catenin in radial arteries was higher in end stage renal disease than in control group, and IS increased Wnt7b/β-catenin expression in HASMCs as early as 3days after stimulation. Furthermore, miR-29b mimics potently repressed Wnt7b/β-catenin protein expression in HASMCs, whereas miR-29b anti-miR increased their expression, indicating miR-29b indeed negatively regulates Wnt7b/β-catenin signaling. Dickkopf-1 protein, the Wnt/β-catenin signaling inhibitor, suppressed anti-miR-29b-enhanced HASMCs calcification. Our data thus indicate that miR-29b downregulation and Wnt/β-catenin signaling activation may be the key mechanism of IS induced vascular calcification in chronic kidney disease., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: We sought to demonstrate that the combination of a local vasodilator (verapamil), modern materials, patent hemostasis, and intravenous anticoagulant only in the case of percutaneous coronary intervention, as compared to default heparin administration after sheath insertion, may optimize a combined endpoint, including radial artery oc-clusion (RAO), radial artery spasm (RAS), and access site complication., Methods: This is a prospective, single-center, double-blind randomized trial. Overall, 418 patients undergoing a transradial approach (TRA) for coronary procedures were randomized 1: 1 to receive intraradial verapamil (5 mg) or heparin (5,000 IU) after a 6-Fr sheath insertion. The primary outcome was the 24-h occurrence of RAO (ultrasound confirmation), access site complication, and RAS requiring the bailout administration of vasodilators., Results: The combined primary outcome occurred in 127 (30%) patients. It was significantly lower in patients randomized to verapamil as compared to others (26 vs. 35%, p = 0.03). This was mainly due to a significant reduction in RAS (3 vs. 10%, p = 0.006). The 24-h and 30-day occurrence of RAO did not differ between the study groups., Conclusion: Local administration of verapamil versus heparin reduces RAS, without increasing RAO, which appears to be strictly related to radial artery diameter and hemostasis time., (© 2018 S. Karger AG, Basel.)

Radial artery graft spasm in the perioperative or postoperative period of coronary bypass surgery necessitates urgent treatment due to risk of graft failure and mortality. Herein, we evaluated the effect of iloprost, a prostacyclin (PGI 2 ) analogue, against the contractions produced by noradrenaline and potassium chloride on isolated human radial artery. Following the determination of endothelial and vascular relaxing capacities of the arteries, iloprost (10 -9 M-10 -6 M) was cumulatively applied on rings precontracted submaximally with the spasmogens. In some rings, the response to iloprost was assessed following pretreatment with nitric oxide (NO) synthase inhibitor, l-NAME (3×10 -4 M,30min). Iloprost produced complete relaxations on radial artery rings precontracted with noradrenaline whereas, only moderate relaxations against the contractions induced by potassium chloride. Notably, the relaxation to iloprost was remarkably blunted in radial arteries with impaired endothelial function. Moreover, the relaxation to iloprost was unchanged in rings pretreated with l-NAME. Our results demonstrated that iloprost could be a potent relaxant agent in reversing radial artery spasm, particularly initiated by noradrenaline, possibly acting via an endothelium-mediated mechanism unrelated to NO., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Arterial stiffness and cardiac function are important predictors of cardiovascular events in patients with hypertension, even with adequate blood pressure (BP) control. We evaluated whether a direct renin inhibitor, aliskiren, reduces arterial stiffness and modulates left ventricular function compared with a diuretic, hydrochlorothiazide, in elderly hypertensive patients. Twenty-one hypertensive patients [67 ± 14 (SD) yr] were randomly assigned to receive 6-mo aliskiren ( n = 11) or hydrochlorothiazide ( n = 10)-based therapy. We assessed β-stiffness of the local arteries, arterial elastance ( E a ), and echocardiographic variables, including early ( E ) and late ( A ) mitral inflow velocity, deceleration time of E, early ( E ') and late ( A ') diastolic mitral annular velocity, and left ventricular end-systolic elastance ( E es ) before and after treatment. BP decreased similarly ( P < 0.001) after both therapies. β-Stiffness of the carotid artery decreased after aliskiren but increased after hydrochlorothiazide treatment (aliskiren: 6.42 ± 2.34 pre vs. 5.07 ± 1.29 post; hydrochlorothiazide: 5.05 ± 1.78 vs. 7.25 ± 2.68, P = 0.001 for interaction). β-Stiffness of the femoral and radial arteries were not different after either treatment. Different from aliskiren, E decreased (73 ± 16 vs. 67 ± 14 cm/s, P = 0.026), and the deceleration time was prolonged (218 ± 40 vs. 236 ± 35 ms, P = 0.032) after hydrochlorothiazide therapy, whereas the E / A , and E ' remained unchanged after both treatments. E a and E es decreased after aliskiren therapy (both P < 0.05), whereas the E a / E es (ventricular-arterial coupling) was maintained after both treatments. Thus, aliskiren decreased the stiffness of carotid artery and left ventricular end-systolic elastance with maintenance of ventricular-arterial coupling without any effects on diastolic filling, while hydrochlorothiazide increased carotid arterial stiffness and slowed early diastolic filling in elderly hypertensive patients., (Copyright © 2017 the American Physiological Society.)

A detailed description of intraoperative prevention of radial artery graft spasm using a solution of the calmodulin inhibitor chlorpromazine is presented. This method is used in direct myocardial revascularization and can reliably prevent perioperative spasm of radial artery grafts, as confirmed by intraoperative flow measurement, bypass angiography in the postoperative period, and in vitro experimental data., (© The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

We evaluated the effect of long-term administration of nicorandil on endothelial function of the radial artery in patients with angina undergoing elective transradial coronary intervention (TRI). A total of 127 patients were randomly assigned to nicorandil (standard medication plus nicorandil 5 mg twice daily, n = 64) or control group (standard medication except nicorandil, n = 63) immediately after TRI procedure. Radial artery diameter (RAD), flow-mediated dilation (FMD), and nitroglycerin-mediated dilation (NMD) of radial artery were measured 1 day before TRI as well as 1 day and 3 months after TRI by Ultrasound-Doppler. No significant difference was observed in the baseline RAD, FMD, and NMD between the 2 groups (all P > .05). In cannulated arm, at 3-month follow-up, RAD in nicorandil group was much larger than that in the control group (2.78 ± 0.27 mm vs 2.61 ± 0.30 mm, P = .001). Besides, FMD and NMD were much higher in nicorandil group than those in the control group (10.38% ± 2.43% vs 6.81% ± 1.86%; 15.94% ± 6.28% vs 10.46% ± 5.37%, respectively, all Ps < .001). In conclusion, long-term administration of nicorandil after TRI could improve the endothelial function of the cannulated radial artery.

Reperfusion in the setting of acute ischemia is essential in limiting tissue necrosis. However, reperfusion itself is associated with significant adverse effects. There is animal evidence that platelets play a role in the adverse effects of ischemia and reperfusion (IR) injury. We examined whether clopidogrel would have favorable effects on endothelial dysfunction induced by an episode of IR. Using a parallel design, we administered clopidogrel 600 mg or matching placebo to normal volunteers (n = 20) 24 hours before an episode of IR. Flow-mediated dilatation (FMD, radial artery) was assessed before and after 20 minutes of upper arm ischemia. Following IR, there was a highly significant decrease in FMD in the placebo group (7.6% ± 1.3% vs 3.4% ± 0.1%; P < .001). In the clopidogrel group, there was no change in FMD post-IR (8.3% ± 0.8% vs 7.1% ± 1.2%; P = not significant). Following IR, FMD in the placebo group was significantly smaller than that observed in the clopidogrel group ( P < .01). Ischemia and reperfusion caused no change in plasma levels of biomarkers of inflammation (intercellular adhesion molecule 1, chemokine ligand 5, and interleukin 6) in either group. Therefore, a single dose of clopidogrel given 24 hours prior to an episode of IR had protective effects, limiting the adverse effects of ischemia on endothelial function.

Background: The uptake of percutaneous coronary procedures via the radial artery has increased internationally due to the decreased risk of complications and increased patient satisfaction. The increased susceptibility of the radial artery to spasm however presents a potential risk for procedural failure. Although most experts agree on the need for prophylactic medications to reduce radial artery spasm, currently there is inconsistency in literature regarding the most effective vasodilatory medication or combination of medications., Review Objective: The objective of this study is to identify the effectiveness of vasodilatory medications on radial artery spasm in patients undergoing transradial coronary artery procedures., Inclusion Criteria Types of Participants: This review considered studies that included participants aged 18 years and over undergoing non-emergent transradial percutaneous coronary artery procedures., Types of Intervention(s): This review considered studies that used vasodilating intravenous and intra-arterial medications or combinations of medications prior to commencing and during transradial coronary approaches to reduce radial artery spasm., Outcomes: The outcomes of interest were the incidence of radial artery spasm during percutaneous coronary procedure using objective and/or subjective measures and its effect on the successful completion of the procedure., Types of Studies: Randomized controlled trials published in the English language between 1989 to date were considered for inclusion., Search Strategy: The search strategy aimed to find both published and unpublished studies. A three-step search strategy was utilized in this review. An initial search of MEDLINE, CINAHL and Scopus was undertaken, followed by a search for unpublished studies., Assessment of Methodological Quality: Papers selected for retrieval were assessed by two independent reviewers for methodological validity prior to inclusion in the review using standardized critical appraisal instruments. Any disagreements that arose between the reviewers were resolved through discussion., Data Extraction: Quantitative data was extracted from papers included in the review using the standardized data extraction tool from RevMan5 (Copenhagen: The Nordic Cochrane Centre, Cochrane)., Data Synthesis: Quantitative data, where possible, was pooled in statistical meta-analysis using RevMan5. All results were subject to double data entry. Effect sizes expressed as risk ratio (for categorical data) and weighted mean differences (for continuous data) and their 95% confidence intervals were calculated for analysis., Results: Nine trials involving 3614 patients were included in the final review. Pooled data involving 992 patients on the effect of calcium channel blockers demonstrated a statistically significant reduction in the incidence of vasospasm in patients who received verapamil 5 mg compared to those who received a placebo (OR 0.33; 95%CI 0.19, 0.58). Similarly patients who received verapamil 2.5 mg or 1.25 mg had significantly fewer incidences of vasospasm when compared to those who received a placebo. Nitroglycerine 100mcg was demonstrated to be associated with a statistically significant reduction in the incidence of vasospasm., Conclusion: The evidence demonstrates a benefit in the use of vasodilatory medications for the reduction of vasospasm in patients having radial coronary procedures. Further large-scale multi-center trials are needed to determine the preferred medication.

Background: Endothelin receptor antagonists are approved for pulmonary arterial hypertension. Development of selective ET A -receptor antagonists over mixed or dual receptor antagonists has depended on a range of receptor binding assays, second messenger assays and functional blood vessel assays. This study compared the 3 clinically-approved endothelin receptor antagonists in assays of human isolated pulmonary and radial arteries in vitro., Methods: Human isolated pulmonary (i.d. 5.5mm) and human radial (i.d. 3.23mm) artery ring segments were mounted in organ baths for isometric force measurement. Single concentration-contraction curves to endothelin-1 were constructed in the absence or presence of bosentan (1-10µM), macitentan (0.03-0.3µM) or ambrisentan (0.1-1µM)., Results: All 3 endothelin antagonists caused competitive rightward shifts in the endothelin-1 concentration-response curves in both arteries. The Clark plot and analysis gave the following pK B values: bosentan, pulmonary artery 6.28±0.13 and radial artery 6.04±0.10; macitentan, pulmonary artery 8.02±0.13 and radial artery 7.49±0.08; and ambrisentan, pulmonary artery 7.38±0.13 and radial artery 6.96±0.10., Conclusions: Noting the maximum plasma levels attained from recommended oral doses of each antagonist in volunteers, the pK B findings here show that there would be significant antagonism of endothelin-1 contraction in the pulmonary and radial arteries at therapeutic plasma levels. This functional assay confirms in human tissue that much higher plasma concentrations of endothelin-1 receptor antagonists are required to be effective than those predicted from binding or other biochemical assays., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Context: Perivascular adipose tissue (PVAT) is suggested to impact on vascular cells via humoral factors, possibly contributing to endothelial dysfunction and atherosclerosis., Objective: To address whether the hepatokine fibroblast growth factor (FGF) 21 affects the PVAT secretome., Methods: Human perivascular (pre)adipocytes were subjected to targeted proteomics and whole-genome gene expression analysis., Results: Preadipocytes, as compared to adipocytes, secreted higher amounts of inflammatory cytokines and chemokines. Adipocytes released higher amounts of adipokines [e.g. adipisin, visfatin, dipeptidyl peptidase 4 (DPP4), leptin; p < 0.05, all]. In preadipocytes, omentin 1 release was 1.28-fold increased by FGF-21 (p < 0.05). In adipocytes, FGF-21 reduced chemerin release by 5% and enhanced DPP4 release by 1.15-fold (p < 0.05, both). FGF-21 altered the expression of four secretory genes in preadipocytes and of 18 in adipocytes (p < 0.01, all)., Conclusion: The hepatokine FGF-21 exerts secretome-modulating effects in human perivascular (pre)adipocytes establishing a new liver-PVAT-blood vessel axis that possibly contributes to vascular inflammation and atherosclerosis.

Objectives: Many reports exist of the cardiovascular toxicity of smoked cannabis but none of arterial stiffness measures or vascular age (VA). In view of its diverse toxicology, the possibility that cannabis-exposed patients may be ageing more quickly requires investigation., Design: Cross-sectional and longitudinal, observational. Prospective., Setting: Single primary care addiction clinic in Brisbane, Australia., Participants: 11 cannabis-only smokers, 504 tobacco-only smokers, 114 tobacco and cannabis smokers and 534 non-smokers., Exclusions: known cardiovascular disease or therapy or acute exposure to alcohol, amphetamine, heroin or methadone., Intervention: Radial arterial pulse wave tonometry (AtCor, SphygmoCor, Sydney) performed opportunistically and sequentially on patients between 2006 and 2011., Main Outcome Measure: Algorithmically calculated VA., Secondary Outcomes: other central haemodynamic variables., Results: Differences between group chronological ages (CA, 30.47±0.48 to 40.36±2.44, mean±SEM) were controlled with linear regression. Between-group sex differences were controlled by single-sex analysis. Mean cannabis exposure among patients was 37.67±7.16 g-years. In regression models controlling for CA, Body Mass Index (BMI), time and inhalant group, the effect of cannabis use on VA was significant in males (p=0.0156) and females (p=0.0084). The effect size in males was 11.84%. A dose-response relationship was demonstrated with lifetime exposure (p<0.002) additional to that of tobacco and opioids. In both sexes, the effect of cannabis was robust to adjustment and was unrelated to its acute effects. Significant power interactions between cannabis exposure and the square and cube of CA were demonstrated (from p<0.002)., Conclusions: Cannabis is an interactive cardiovascular risk factor (additional to tobacco and opioids), shows a prominent dose-response effect and is robust to adjustment. Cannabis use is associated with an acceleration of the cardiovascular age, which is a powerful surrogate for the organismal-biological age. This likely underlies and bi-directionally interacts with its diverse toxicological profile and is of considerable public health and regulatory importance., Competing Interests: Conflicts of Interest: None declared., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Review Objective: The objective is to identify the effectiveness of topical medications in reducing radial artery spasm in patients undergoing transradial coronary procedures.

Vascular calcification (VC) is an independent risk factor for cardiovascular disease and mortality in uremia. Post-translational core fucosylation is implicated in a number of pathological processes. First, we investigated the role of core fucosylation and key TGF-β1 pathway receptors in calcified arteries in vivo. To determine whether blocking core fucosylation effectively inhibited VC and TGF-β/Smad signaling pathway, we established an in vitro model of phosphate-induced calcification in rat vascular smooth muscle cells (VSMCs) to assess the role of core fucosylation in VC. Core fucose could be detected at markedly higher levels in calcified VSMCs than control cells. Fut8 (α-1,6 fucosyltransferase), the only enzyme responsible for core fucosylation in humans, was significantly upregulated by high phosphate. Exposed to high phosphate media and blocking core fucosylation in VSMCs by knocking down Fut8 using a siRNA markedly reduced calcium and phosphorus deposition and Cbfα1 expression (osteoblast-specific transcription factor), and increased α-Sma expression (smooth muscle cell marker). Fut8 siRNA significantly inhibited TGF-β/Smad2/3 signaling activation in VSMCs cultured in high phosphate media. In conclusion, this study provides evidence to suggest core fucosylation plays a major role in the process of VC and appropriate blockade of core fucosylation may represent a potential therapeutic strategy for treating VC in end-stage renal disease., (Copyright © 2016. Published by Elsevier Ltd.)

Aim: Radial artery spasm is common during transradial procedures and is the most common cause of procedural failure. The objectives of this study were to assess whether the routine administration of sedation at the beginning of transradial coronary angiography with the use of hydrophilic-coated and smaller sheaths/catheters would reduce the incidence of radial artery spasm., Patients and Methods: Patients undergoing transradial coronary angiography were prospectively randomized to receive midazolam during the procedure or no sedative treatment. The primary endpoint was angiographically confirmed radial artery spasm. Stenosis of the radial artery was measured with a computer-assisted quantification method., Results: In all, 150 patients were randomized into a treatment group and a control group. Spasm occurred in 15 patients of the treatment group (20 %) versus 16 in the control group (21.3 %). There were no differences between the two groups regarding the incidence of spasm and the distribution of spasm severity (p > 0.05). No significant differences were observed between the two groups in terms of 30-day mortality or repeat hospitalization for any cause (p > 0.05)., Conclusion: Routine use of midazolam could not reduce the occurrence of radial artery spasm during transradial coronary angiography.

Arterial grafts have long-term patency superior to vein grafts but have a tendency to develop spasm that can lead to potentially life-threatening complications. A perfect antispastic protocol should include advanced surgical technique and adequate pharmacologic methods. All pharmacologic vasodilator drugs relax the vessel through specific mechanisms, and therefore, there is no perfect, single best vasodilator to prevent or treat spasm of the arterial graft against all mechanisms of contraction. One of the choices is to use a combination of pharmacologic vasodilators targeting different mechanisms of spasm to obtain the reliable and best effect., (Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Recent studies have shown that arterial stiffness is reduced after meal intake. We evaluated the acute response of central hemodynamics to glucose loading and the variation in their responses among normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and diabetes mellitus (DM)., Methods: The study enrolled 85 patients with known or suspected coronary artery disease who underwent a 75-g oral glucose tolerance test. Central hemodynamic measurements were assessed using radial applanation tonometry at fasting, 60, and 120 minutes after glucose loading., Results: Glucose loading decreased the augmentation index normalized to a heart rate of 75 bpm (AIx@75) (81.6±13.9 to 74.5±14.1%, P < 0.01) and central systolic blood pressure (SBP) (115±22 to 109±21mm Hg, P < 0.01) at 120 minutes without a significant change in brachial SBP (126±25 to 125±25mm Hg, P = 0.93). Glucose loading decreased central SBP in NGT and IGT groups but did not affect the DM group. Change in AIx@75 at 120 minutes after glucose loading was blunted in IGT and DM groups compared with the NGT group (-5.7±4.4 vs. -3.6±4.1 vs. -9.3±6.2%, P < 0.01). Multivariate logistic regression analysis identified DM as an independent factor associated with the presence of blunted response of AIx to glucose loading., Conclusions: Oral glucose loading decreased central SBP and AIx@75 without a significant change in brachial SBP, and these central hemodynamic responses were blunted in patients with DM., (© American Journal of Hypertension, Ltd 2015. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: The dorsalis pedis artery (DPA) is a good alternative to the radial artery (RA) for invasive blood pressure monitoring when the upper limb is burned or injured, or if the RA is not available. Understanding the pattern of pressure difference between DPA and the commonly used RA during inhalational anaesthesia is helpful for haemodynamic management and therapeutic decisions., Objectives: The objective of this study was to investigate the time-dependent variation of DPA-to-RA pressure gradient during sevoflurane anaesthesia and the overall difference between the two pressures during neurosurgery, together with the causes of the pressure gradient change., Design: A prospective, self-control, single-centre study., Setting: The operating room of a teaching hospital from 1 January 2013 to 1 September 2013., Patients: Thirty-seven patients between 18 and 60 years of age, American Society of Anesthesiologists' physical status 1-3, scheduled for neurosurgery in the supine position and requiring invasive arterial pressure monitoring., Main Outcome Measures: The time-dependent change of DPA-to-RA pressure gradient and skin temperature gradient, the difference between absolute values and average values of SBP, DBP and mean blood pressure (MBP) between RA and DPA during surgery, and the internal cross-sections and systolic blood flow velocities of RA and DPA at the baseline and at the end of surgery., Results: Data from 30 patients were analysed. The mean ± standard deviation DPA-to-RA pressure gradient gradually decreased with time from 9.7 ± 8.8 to -1.8 ± 7.6 mmHg for systolic pressure, -2.3 ± 2.7 to -3.7 ± 2.8 mmHg for diastolic pressure and -2.1 ± 3.2 to -5.4 ± 3.4 mmHg for MBP. Biases during the entire procedure were 2.2 ± 10.1, -3.1 ± 3.4 and -4.3 ± 4.2 mmHg for SBP, DBP and MBP, respectively. The DPA-to-RA skin temperature gradient gradually reduced from -3.6 ± 2.4 to -1.1 ± 1.3°C. A greater increase in the inner cross-sectional area and blood flow from the baseline was observed at DPA compared with RA., Conclusion: The blood pressure, temperature and inner cross-sectional area differences between DPA and RA reduced gradually during sevoflurane anaesthesia in patients undergoing neurosurgery. Therapeutic decisions may rely on DPA pressure as long as the anaesthetists are aware of the pattern of change in DPA pressure during surgery., Trial Registration: www.chictr.org with registry number ChiCTR-RNRC-13003853.

Background: Vasodilatory function of radial artery (RA) declines following the transradial catheterization. However, it is uncertain whether impaired vasodilatory function develops in every patient. The aim of this study was to investigate the incidence and predictive factors of impaired vasodilatory function following transradial procedures., Methods: Consecutive patients undergoing elective transradial procedures were prospectively enrolled. Ultrasound examination of RA was recorded just before and 1 week after the procedure. RA diameters and flow velocities were measured at baseline, after flow mediated vasodilation (FMD) and after nitrate mediated vasodilation (NMD)., Results: Fifty-one patients were included (62 ± 11 years, 55% male, 41% hypertensive, 20% diabetic, 65% with coronary artery disease). Overall FMD and NMD were significantly impaired after 1 week. However, deterioration of FMD and NMD was observed in 67% and 71% of patients, respectively. Absolute change in FMD was significantly different in patients using a renin- angiotensin system (RAS) inhibitor compared to those who were not (1.9 ± 12.9 vs. -7.7 ± ± 12.7%, respectively, p = 0.025). Additionally, there was a moderate but significant correlation between baseline RA diameter and absolute change in NMD (r = 0.419, p < 0.001). RAS blockade was independently associated with protection against FMD deterioration (OR 0.241, 95% CI 0.066-0.883, p = 0.032), whereas RA diameter (OR 0.079, 95% CI 0.009-0.720, p = 0.024) and procedure time (OR 1.156, 95% CI 0.989-1.350, p = 0.068) were associated with NMD deterioration, although the latter had borderline significance., Conclusions: Vasodilatory function of RA gets impaired in most patients following transradial procedures. RAS blockade seems to exert a protective role against deteriorating endothelium- dependent vasodilation, whereas smaller RA diameter and potentially longer procedure time are associated with impaired endothelium-independent vasodilation.

Objectives: The aim of this study is to review the available literature on the efficacy and safety of agents used for prevention of RAS., Background: Different vasodilator agents have been used to prevent radial artery spasm (RAS) in patients undergoing transradial cardiac catheterization., Methods: We included studies that evaluated any intra-arterial drug administered in the setting cardiac catheterization that was undertaken through the transradial access site (TRA). We also compared studies for secondary outcomes of major bleeding, procedure time, and procedure failure rate in setting of RAS prevention, patent hemostasis and radial artery occlusion., Results: 22 clinical studies met the inclusion criteria. For placebo, RAS rate was 12% (4 studies, 638 participants), which was similar to 2.5mg of verapamil 12% (3 studies, 768 participants) but greater than 5mg of verapamil (4%, 2 studies, 497 participants). For nicorandil, there was a much higher RAS rate compared to placebo (16%, 3 studies, 447 participants). The lowest rates of RAS was found for nitroglycerin at both 100 μg (4%) and 200 μg (2%) doses, isosorbide mononitrate (4%) and nicardipine (3%). We found no information regarding the procedure failure rates, patent hemostasis, and radial artery occlusion in these studies., Conclusions: In this largest and up-to-date review on intra-arterial vasodilators use to reduce RAS, we have found that the verapamil at a dose of 5mg or verapamil in combination with nitroglycerine are the best combinations to reduce RAS., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Aim: Sublingual (SL) nitroglycerin administered before radial artery puncture can improve cannulation success and decrease the incidence of radial artery spasm (RAS) compared with intra-arterial (IA) nitroglycerin in transradial procedures., Methods: Patients undergoing diagnostic transradial angiography were randomized to IA (200 mcg) or SL (400 mcg) nitroglycerin. Primary endpoints were puncture time and puncture attempts. Secondary endpoint was the incidence of RAS., Results: Total of 101 participants (mean age 60±11years, 53% male) were randomized (51 in IA and 50 in SL groups). Puncture time (50 [36-75] vs 50 [35-90] sec), puncture attempts (1.18±0.48 vs 1.20±0.49), multiple punctures (13.7 vs 16.0%) and RAS (19.6 vs 24.0%) were not statistically different between IA vs SL groups respectively. A composite endpoint of all adverse events related to transradial angiography (multiple punctures, RAS, access site crossover, hypotension/bradycardia associated with nitroglycerin and radial artery occlusion) was very similar in IA vs SL groups (39 vs 40%, respectively). However puncture time was significantly longer with SL nitroglycerin in patients <1.65m height (47 [36-66] vs 63 [41-110] sec, p=0.042). Multiple punctures seemed higher with SL nitroglycerin in patients with diabetes (0 vs 30%, p=0.028) or in patients <1.65m height (7.4 vs 25%, p=0.085). Likewise, RAS with SL nitroglycerin seemed more frequent in smokers compared to IA nitroglycerin (0 vs 27%, p=0.089)., Conclusions: SL nitroglycerin was not different from IA nitroglycerin in terms of efficiency and safety in overall study population. However it may be inferior to IA nitroglycerin in certain subgroups (shorter individuals, diabetics and smokers)., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objectives: In both low- and high-risk patients undergoing coronary artery bypass grafting, the internal mammary artery is the first choice of arterial graft, and the second choice is the radial artery (RA). Unfortunately, RA spasms are a significant problem for a surgical team to overcome in the perioperative and postoperative period. In current surgical practice, the use of vasodilator agents perioperatively in the pending graft preparation is generally accepted and these may be implemented topically, endoluminally or both ways. Moxonidine is the latest second-generation, centrally acting antihypertensive agent, and the intention in this paper is to investigate its direct vasorelaxant effects and relaxation mechanisms on the human radial artery in vitro., Methods: RA rings were mounted in an organ bath and tested for changes in isometric tension in its relaxation response to moxonidine in the presence and absence of NG-nitro-L-arginine methyl ester (L-NAME, non-specific inhibitor of nitric oxide synthase), idazoxan (non-selective I1 and α2-antagonist) and yohimbine (selective α2-antagonist)., Results: Moxonidine induced concentration-dependent relaxations on the RA rings precontracted with phenylephrine (P < 0.05). L-NAME and idazoxan significantly reduced the relaxation caused by moxonidine (P < 0.05), while yohimbine significantly increased the relaxation by moxonidine (P < 0.05). In the presence of L-NAME + idazoxan, the relaxation by moxonidine was eliminated completely (P < 0.05)., Conclusions: We speculate that the relaxant effect of moxonidine may be attributed partly to the synthesis and/or release of nitric oxide, and partly to the stimulation of imidazoline I1 receptors. We suggest that moxonidine may help to prevent RA spasms during the preparation period in operation when used topically or/and endoluminally., (© The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Pre-clinical studies have identified nitroxyl (HNO), the reduced congener of nitric oxide (NO•), as a potent vasodilator which is resistant to tolerance development. The present study explores the efficacy of HNO in human blood vessels and describes, for the first time, a vasodilator for humans that is not susceptible to tolerance. Human radial arteries and saphenous veins were obtained from patients undergoing coronary artery graft surgery and mounted in organ baths. Repeated vasodilator responses to the HNO donor Angeli's salt (AS) and NO• donor glyceryl trinitrate (GTN) were determined. AS- and GTN-induced concentration-dependent vasorelaxation of both human radial arteries (AS pEC50: 6.5 ± 0.2; -log M) and saphenous veins (pEC50: 6.7 ± 0.1) with similar potency. In human radial arteries, GTN-induced relaxation was reduced by the NO• scavenger hydroxocobalamin (HXC; P<0.05) but was unaffected by the HNO scavenger L-cysteine. Alternately, AS was unaffected by HXC but was reduced by L-cysteine (5-fold shift, P<0.05). The sGC (soluble guanylate cyclase) inhibitor ODQ abolished responses to both AS and GTN in arteries and veins (P<0.05). Inhibition of voltage-dependent potassium channels (Kv channels) with 4-AP also significantly reduced responses to AS (pEC50: 5.5) and GTN, suggesting that the relaxation to both redox congeners is cGMP- and Kv channel-dependent. Critically, a concentration-dependent development of tolerance to GTN (1 and 10 μM; P<0.05), but not to AS, was observed in both saphenous veins and radial arteries. Like GTN, the HNO donor AS causes vasorelaxation of human blood vessels via activation of a cGMP-dependent pathway. Unlike GTN, however, it does not develop tolerance in human blood vessels.

Objective: Beta-blockers are a heterogeneous class of agents that are used in the treatment of many cardiovascular diseases, especially hypertension and atherosclerosis, and that are commonly prescribed after cardiac surgery. In the present study, the aim is to investigate the vasorelaxant effects of some common beta-adrenoceptor blockers on the human radial artery in vitro, as well as their relaxation mechanisms., Methods: Radial artery rings sourced from human patients were mounted in an organ bath and tested for changes in isometric tension in relaxation response to labetalol, nebivolol, and propranolol in the presence and absence of NG-nitro-L-arginine methyl ester (3 × 10(-5) mol/L) and tetraethyl ammonium (3 × 10(-4) mol/L)., Results: The labetalol (10(-8) to 10(-4) mol/L), nebivolol (10(-8) to 10(-4) mol/L), and propranolol (10(-8) to 10(-4) mol/L) induced concentration-dependent relaxations on the radial artery rings, which had been precontracted with phenylephrine (10(-6) mol/L). The relaxation response induced by labetalol in the isolated radial artery rings was significantly higher when compared with the nebivolol and propranolol samples (P < .05). NG-nitro-L-arginine methyl ester significantly reduced the relaxation of nebivolol (P < .05), and tetraethyl ammonium significantly reduced the relaxation of labetalol, nebivolol, and propranolol (P < .05)., Conclusions: We speculated that the relaxant effect of labetalol, nebivolol, and propranolol was due partly to the Ca(2+)-activated K(+) channels. In addition, the relaxation induced by nebivolol was largely related with nitric oxide release. Nebivolol, and partly propranolol, may provide significant therapeutic benefit, but labetalol can be a good alternative for coronary artery bypass grafting with radial artery use., (Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Inorganic nitrite dilates small resistance arterioles via hypoxia-facilitated reduction to vasodilating nitric oxide. The effects of nitrite in human conduit arteries have not been investigated. In contrast to nitrite, organic nitrates are established selective dilators of conduit arteries., Methods and Results: We examined the effects of local and systemic administration of sodium nitrite on the radial artery (a muscular conduit artery), forearm resistance vessels (forearm blood flow), and systemic hemodynamics in healthy male volunteers (n=43). Intrabrachial sodium nitrite (8.7 μmol/min) increased radial artery diameter by a median of 28.0% (25th and 75th percentiles, 25.7% and 40.1%; P<0.001). Nitrite (0.087-87 μmol/min) displayed conduit artery selectivity similar to that of glyceryl trinitrate (0.013-4.4 nmol/min) over resistance arterioles. Nitrite dose-dependently increased local cGMP production at the dose of 2.6 μmol/min by 1.1 pmol·min(-1)·100 mL(-1) tissue (95% confidence interval, 0.5-1.8). Nitrite-induced radial artery dilation was enhanced by administration of acetazolamide (oral or intra-arterial) and oral raloxifene (P=0.0248, P<0.0001, and P=0.0006, respectively) but was inhibited under hypoxia (P<0.0001) and hyperoxia (P=0.0006) compared with normoxia. Systemic intravenous administration of sodium nitrite (8.7 μmol/min) dilated the radial artery by 10.7% (95% confidence interval, 6.8-14.7) and reduced central systolic blood pressure by 11.6 mm Hg (95% confidence interval, 2.4-20.7), augmentation index, and pulse wave velocity without changing peripheral blood pressure., Conclusions: Nitrite selectively dilates conduit arteries at supraphysiological and near-physiological concentrations via a normoxia-dependent mechanism that is associated with cGMP production and is enhanced by acetazolamide and raloxifene. The selective central blood pressure-lowering effects of nitrite have therapeutic potential to reduce cardiovascular events., (© 2014 American Heart Association, Inc.)