Coronary Endothelial Function Research Articles

Effects of maternal exercise during pregnancy on coronary artery vascular function in high fat fed swine offspring (886.2)

The purpose of this study was to test the hypothesis that maternal exercise during pregnancy would enhance coronary artery endothelial function in swine offspring that were fed a high fat diet. Pubertal gilts were divided into exercise (n =8) and sedentary (n =8) groups. Pregnant gilts in the exercise group performed treadmill exercise 5 days per week. Offspring were fed a high fat diet and endothelial (bradykinin; BK) and vascular smooth muscle (sodium nitroprusside; SNP) function were measured at 4 and 8 months of age in the left anterior descending (LAD) artery using in vitro wire myography. Exercise sows had a significantly lower resting heart rate at week 15 of pregnancy compared to their sedentary counterparts (EX: 94.43 ± 4.0; SED: 107.13 ± 3.6 bpm). There were no significant differences in litter characteristics at birth (i.e., number of piglets alive and litter weight). There were no significant differences in vasorelaxation dose response or maximal response to BK or SNP from offspring of exercise or sedentary sows at 4 months of age (BK: EX: 94.35 ± 3.8; SED: 104.1 ± 7.7 % relaxation; SNP: EX: 101.45 ± 2.3; SED: 100.44 ± 3.4 % relaxation) or 8 months of age (BK: EX: 82.75 ± 8.5; SED: 93.92 ± 7.4 % relaxation; SNP: EX: 95.44 ± 2.7; SED: 96.51 ± 1.5 % relaxation) for the LAD artery. Therefore, maternal exercise during pregnancy does not significantly alter LAD artery function at 4 or 8 months of age in swine offspring fed a high fat diet.Grant Funding Source: Supported by the American Heart Association Grant # 12FDG8540001 (S.C.N.)

0202: Deficiency in nitric oxide decreases the microcirculation reactivity in response to acetylcholine but is not always associated with a higher blood pressure in mice

Endothelial dysfunction is associated with cardiovascular diseases and can be evaluated in clinical setting for risk stratification in patients. Flow mediated dilation (FMD) or local acetylcholine (ACh) administration are used to assess endothelial dysfunction in arteries but also in microcirculation (MC) using Laser Doppler Flowmetry (LDF). In our study, we aim to investigate the role of nitric oxide (NO) in the endothelial response of microcirculation in vivo in mice. Two strains of mice (C57BL6 and BALBc mice; 20 weeks old) were treated with NO synthase inhibitor (L-NAME) in drinking water (1 g/L) and compared with their respective untreated controls. After 3 or 7 days of L-NAME, mice were anesthetized with isoflurane. Systolic blood pressure (SBP) was then measured by plethysmography and skin MC assessed by LDF. Blood flow was measured at baseline and in response to ACh administered by iontophoresis or during hyperemic response due to local heating at 44°C. At day 3, we observed a slight increase in SBP only in BALBc mice treated with L-NAME (+13 mmHg), not maintained at day 7. Conversely, at day 7, we observed an increase in SBP (+30 mmHg) only in L-NAME-treated C57BL6 mice. MC flow response to ACh was decreased by 65% and 58% in BALBc mice at day 3 and 7, respectively, and by 68% in C57BL6 mice only after 7 days of L-NAME treatment compared to untreated mice. No difference was observed in response to local heating, neither between strains nor after L-NAME treatment. In conclusion, skin microcirculation reactivity can be routinely assessed in vivo in mice. Our results show that a part of the transitory Ach-induced microcirculation flow increase is NO-mediated. Moreover, this decrease in NO bioavailability in microcirculation is not always associated with increase in systemic BP. Further studies are now required in order to determine if the microcirculation response to ACh could be a marker of coronary endothelial function in animal models as it is in human.

0211 Prevention of cardiovascular, renal and metabolic abnormalities by soluble epoxide hydrolase inhibition in a murine model of type 2 diabetes

Epoxyeicosatrienoic acids (EETs) are synthesized from arachidonic acid, notably in endothelial cells, and display attractive metabolic, vasodilatory and anti-inflammatory properties. We demonstrated previously that inhibiting EET degradation mediated by soluble epoxide hydrolase (sEH) reduces hypertension and heart failure, and others reported that it improves glucose homeostasis in type 2 diabetes. However, the impact of such strategy on target organ damage in diabetes remains to be clarified. The pharmacological sEH inhibitor t -AUCB (10 mg/l in drinking water) was administered for 8 weeks in mice subjected to a high-fat diet (HFD, 60% fat) for 16 weeks. Mice on control chow diet (10% fat), non-treated HFD mice and HFD mice treated with glibenclamide (80 mg/l) served as controls. Glibenclamide and t -AUCB similarly prevented the increased fasting glycemia in HFD mice (Control: 5.4±0.2; HFD: 8.0±0.8; HFD+GLI: 5.1±0.3; HFD+ t -AUCB: 5.6±0.2 mmol/L; p<0.05). However, only t -AUCB improved glucose tolerance and decreased gluconeogenesis. In parallel, t -AUCB prevented adipose tissue activation and dyslipidemia. Moreover, t -AUCB improved coronary endothelial function and prevented diastolic dysfunction, as shown by echocardiography (E/A ratio; Control: 1.25±0.02; HFD: 1.05±0.03; HFD+GLI: 1.07±0.04; HFD+ t -AUCB: 1.23±0.04; p<0.05) and invasive hemodynamics (LVEDPVR; Control: 1.9±0.55; HFD: 3.8±0.61; HFD+GLI: 3.1±0.8; HFD+ t - AUCB: 1.88±0.2 mmHg/RVU; p<0.05). Finally, t -AUCB prevented the increased urinary albumine-to-creatinine ratio and decreased renal inflammation. These results demonstrate that beyond its glucose-lowering effects sEH inhibition improves coronary endothelial function, diastolic dysfunction and prevents early kidney damage in a murine model of type 2 diabetes. This positive impact on target organ damage and metabolic homeostasis prompts sEH inhibition as a promising therapeutic perspective in type 2 diabetes.

Coronary flow velocity reserve is impaired in hypertensive patients with hyperhomocysteinemia

Hyperhomocysteinemia (HHcy) is an independent risk factor for coronary artery disease. Chronic HHcy induces coronary endothelial injury, and homocysteine (Hcy) inhibits insulin sensitivity by inducing endoplasmic reticulum stress in adipose tissue. However, the combined effects of chronic HHcy and hypertension on coronary artery endothelial function have still remained unclear. Fifty-one patients with essential hypertension (HT) were recruited, and were divided into nHT group (without HHcy) and H-type HT group (with HHcy). Forty healthy subjects were enrolled as controls. We assessed coronary artery endothelial function by coronary flow velocity reserve (CFVR). Hcy levels were significantly higher (15.60±6.58 vs 13.08±4.13 μmol l(-1), P<0.05), whereas CFVR values were significantly lower in the HT patients than in the control group (2.88±0.70 vs 3.23±0.54, P<0.05). Hcy levels were negatively correlated with CFVR value (r=-0.578, P<0.01, 95% confidence interval -0.085 to -0.046). The homeostasis model assessment-insulin resistance values were significantly higher (3.92±2.16 vs 2.72±1.50, P<0.05) , whereas CFVR values were significantly lower in H-type HT group than in nHT group (2.31±0.31 vs 3.25±0.62, P<0.01). Coronary artery endothelial function may be impaired in essential hypertensive patients with HHcy, and insulin resistance induced by HHcy may contribute to this damage.

DIAGNOSTIC ACCURACY OF MRI ASSESSMENT OF CORONARY ENDOTHELIAL FUNCTION COMPARED WITH INVASIVE ANGIOGRAPHY

The diagnostic accuracy of MRI assessment of coronary endothelial function has not been well defined. vWe recruited patients with chest pain and non-obstructive coronary artery disease (CAD) who have undergone elective coronary angiography and invasive coronary physiologic testing. Patients

Aldosterone inhibition and coronary endothelial function in women without obstructive coronary artery disease: An ancillary study of the National Heart, Lung, and Blood Institute–sponsored Women's Ischemia Syndrome Evaluation

Endothelial dysfunction is highly prevalent and associated with adverse outcomes among patients without obstructive coronary artery disease (CAD). Angiotensin II inhibition may improve endothelial function, but with continued treatment, "aldosterone escape" may occur. Thus, it is unknown if adding aldosterone blockade further improves endothelial function. In a double-blind, parallel-group, repeated-measures study, women with symptoms and signs of ischemia, no significant CAD, and coronary endothelial dysfunction receiving an angiotensin-converting enzyme inhibitor or receptor blocker were randomized to aldosterone blockade or placebo. The primary outcome at 16 weeks was percent change in coronary diameter to acetylcholine, and secondary outcome, coronary flow reserve to adenosine, both adjusted for baseline reactivity. Forty-one women completed the treatment period with repeat coronary reactivity testing. Their mean age was 54 ± 10 years; body mass index, 30 ± 7.4 kg/m2; 12% had diabetes; and 15% had metabolic syndrome. There were no significant differences between treatment groups. At baseline, the percent change in reference vessel coronary diameter to acetylcholine was -5.0% in the aldosterone blockade group and -3.4% in the placebo group and, at 16 weeks, -7.2% in the aldosterone blockade group versus -14.3% in the placebo group (P = .15). At 16 weeks, the change in coronary flow reserve to intracoronary adenosine was -0.13 in the aldosterone blockade group versus -0.25 in the placebo group (P = .66). Adding aldosterone receptor blockade to angiotensin II inhibition did not improve coronary endothelial or microvascular function among women with signs and symptoms of ischemia in the setting of nonobstructive CAD.

Altered coronary endothelial function in young smokers detected by magnetic resonance assessment of myocardial blood flow during the cold pressor test

Endothelial dysfunction is a key element in early atherogenesis. The purposes of this study were to evaluate the feasibility of magnetic resonance (MR) assessment of altered myocardial blood flow (MBF) in response to the cold pressor test (CPT) and to determine if coronary endothelial dysfunction in young smokers can be detected with this noninvasive approach. Fourteen healthy non-smokers (31±6years) and 12 smokers (34±8years) were studied. Breath-hold phase-contrast cine MR imaging (PC-MRI) of the coronary sinus (CS) were obtained at rest and during the CPT. MBF was measured as CS flow divided by left ventricle mass and the rate pressure product. In non-smokers, MBF was 0.88±0.19ml/min/g at rest and significantly increased to 1.13±0.26ml/min/g during the CPT (P=0.0001). In smokers, MBF was 0.94±0.26ml/min/g at rest and 0.96±0.30ml/min/g during the CPT (P=0.73). ΔMBF (MBF during the CPT-MBF at rest) was significantly reduced in smokers compared with non-smokers (0.02±0.20 vs. 0.26±0.18ml/min/g, P=0.005). The intra-class correlation coefficient between measurements by two observers was 0.90 for ΔMBF. A significant reduction in MBF response to CPT was demonstrated in young smokers with PC-MRI at 1.5T. This noninvasive method has great potential for assessment of coronary endothelial function.

Coronary endothelial function in patients with obstructive sleep apnea

Obstructive sleep apnea (OSA) has been associated with increased risk for cardiovascular events, possibly mediated by endothelial dysfunction. The current study evaluates the association between invasive coronary endothelial dysfunction and OSA in patients with nonobstructive coronary atherosclerosis. All patients who had undergone both polysomnography and an invasive coronary vasomotor study at the Mayo Clinic, Rochester, Minnesota, from January 1997 to August 2011 were identified (n=143). OSA was defined as an apnea-hypopnea index of 5 or higher. Three endpoints of coronary endothelial function - percentage change in coronary artery diameter at the mid and distal left anterior descending artery to intracoronary acetylcholine and percentage change in coronary blood flow to intracoronary acetylcholine - were assessed. Differences between patients with OSA (n=102) and those without OSA (n=41) were evaluated using multivariate analysis of variance. Follow-up mortality data were collected and Kaplan-Meier curves were plotted to evaluate differences in mortality between patients with and without OSA. Patients with OSA were more likely to have hypertension compared with patients without OSA. OSA was not significantly associated with coronary endothelial dysfunction on univariate analysis (P=0.23) and after adjustment for hypertension (P=0.19). Similarly, there was no significant difference in coronary endothelial function in patients who had oxygen desaturation of less than 90% during polysomnography (P=0.42). There was a trend toward higher mortality in patients with OSA compared with those without OSA, but this did not reach statistical significance (5 vs. 0% at 10 years, P=0.25). The current study suggests that OSA is not an independent risk factor for coronary endothelial dysfunction in patients with early coronary atherosclerosis. Adverse coronary outcomes in patients with OSA may be independent of coronary endothelial dysfunction.

Fractional Flow Reserve With Dobutamine Challenge and Coronary Microvascular Endothelial Dysfunction in Symptomatic Myocardial Bridging

Myocardial bridging (MB) results in compression of the coronary artery lumen in systole, extending into diastole with resultant hemodynamic alternation as reflected by fractional flow reserve (FFR). MB has also been associated with coronary endothelial dysfunction. The objective of this study was to investigate relationship between FFR with dobutamine challenge and coronary microvascular endothelial dysfunction in symptomatic MB. Seventeen consecutive patients who had cardiac catheterization assessment of MB were enrolled. The patients were divided into 2 groups according to normal (% increase in coronary blood flow [%CBF] ≥50%, n=7) or impaired (%CBF <50%, n=10) coronary microvascular endothelial function assessed on vasoreactivity in the coronary artery with intracoronary infusion of acetylcholine (Ach). Myocardial ischemia was then assessed using FFR at rest and during i.v. dobutamine infusion challenge across the MB with intracoronary pressure wires. FFR was significantly decreased at peak dobutamine infusion compared to at rest in the impaired group (0.85±0.06 vs. 0.91±0.05, P=0.001), but not in the normal group (0.93±0.05 vs. 0.91±0.07, P=0.618). Both FFR at rest and at peak dobutamine infusion had a positive correlation with %CBF by Ach in the impaired group (r(2)=0.46, P=0.030; r(2)=0.52, P=0.018, respectively). Microvascular endothelial dysfunction was associated with decreased FFR at peak dobutamine stress in patients with symptomatic MB.

Protection of coronary endothelial function during cardiac surgery: potential of targeting endothelial ion channels in cardioprotection.

Vascular endothelium plays a critical role in the control of blood flow by producing vasoactive factors to regulate vascular tone. Ion channels, in particular, K+ channels and Ca2+-permeable channels in endothelial cells, are essential to the production and function of endothelium-derived vasoactive factors. Impairment of coronary endothelial function occurs in open heart surgery that may result in reduction of coronary blood flow and thus in an inadequate myocardial perfusion. Hyperkalemic exposure and concurrent ischemia-reperfusion during cardioplegic intervention compromise NO and EDHF-mediated function and the impairment involves alterations of K+ channels, that is, KATP and KCa, and Ca2+-permeable TRP channels in endothelial cells. Pharmacological modulation of these channels during ischemia-reperfusion and hyperkalemic exposure show promising results on the preservation of NO and EDHF-mediated endothelial function, which suggests the potential of targeting endothelial K+ and TRP channels for myocardial protection during cardiac surgery.

Antioxidant Therapy: Is it your Gateway to Improved Cardiovascular Health?

General use and popularity of over-the-counter supplemental antioxidants have rapidly spread all over the world and are believed to promote cardiovascular health and wellbeing. However, there is a paucity of information and lack of proof that physiological and above-physiological levels of oxidants do harm at the cellular and organismal levels. Instead, several reports demonstrated that reduction in Reactive Oxygen Species (ROS) did not improve vascular function. Interestingly, recent studies show that increased ROS levels play protective role in vascular endothelium and may improve coronary endothelial function. In the current review, we introduce the concept that increased ROS levels, often seen in association with cardiovascular disease, probably is an endothelial-way or ‘oxidative response’ to cope with vascular pathology.

Effects of atorvastatin loading prior to primary percutaneous coronary intervention on endothelial function and inflammatory factors in patients with ST-segment elevation myocardial infarction.

Previous studies have demonstrated the beneficial effect of statin loading prior to elective and early percutaneous coronary intervention (PCI), in which the ‘pleiotropic effects’ of statins may contribute to these clinical benefits. The aim of the present study was to examine the potential effects of atorvastatin loading prior to primary PCI on coronary endothelial function and inflammatory factors in patients with acute ST-segment elevation myocardial infarction (STEMI). A total of 60 patients with STEMI were randomized into three groups: Loading dose (80 mg atorvastatin prior to PCI; n=20), regular dose (20 mg atorvastatin prior to PCI; n=20) and control (without atorvastatin prior to PCI; n=20). The plasma samples were collected prior to, and immediately, 6 and 24 h after PCI in all the patients. The plasma concentrations of endothelial nitric oxide synthase (eNOS), nitric oxide (NO), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and intercellular adhesion molecule-1 (ICAM-1) were examined using ELISA. The plasma eNOS levels immediately and 24 h after PCI were significantly higher in the regular dose group compared with the other groups. However, there were no significant differences in the plasma eNOS concentration prior to and 6 h after PCI, or in the plasma NO concentration at any of the time-points among the three groups. The plasma IL-6 levels prior to PCI were significantly lower in the loading dose group compared with the other groups; however, there were no significant differences in the plasma concentration of IL-6 following PCI or in the concentrations of TNF-α and ICAM-1 at any of the time-points among the three groups. In conclusion, atorvastatin loading in patients with STEMI undergoing primary PCI may not have protective effects on endothelial function and the inflammatory reaction.

Abstract 18473: Oxidative Stress Improves Coronary Endothelial Function Through Activation of the Pro-Survival Kinase AMPK

Introduction: Failure of several multi-center clinical trials using antioxidants to improve outcomes in patients with cardiovascular disease, and the recent findings showing paradoxical role for NADPH oxidase-derived reactive oxygen species (ROS) in endothelial function challenge a long-held notion that higher ROS levels are harmful for vascular function. Hypothesis: We examined the hypothesis that endothelium-specific conditional increase in NADPH oxidase-derived ROS will induce stress-signal-mediated activation of eNOS and thus improve coronary endothelial function. Methods: We have generated a novel binary (Tet-ON/OFF) conditional transgenic mouse (Tet-Nox2:VE-Cad-tTA) that induces endothelial cell (EC)-specific overexpression of Nox2/gp91 (NADPH oxidase) and 1.8±0.42-fold increase in EC-ROS upon tetracycline withdrawal (Tet-OFF). We examined the effects of increased ROS on EC signaling and coronary endothelial function using eight animals in each group (Tet-ON and Tet-OFF). Results: First, we demonstrate that endothelium-dependent coronary vasodilation was significantly improved in Tet-OFF Nox2 compared to Tet-ON (control) littermates. Using EC isolated from mouse heart (MHEC), we demonstrate that Nox2-derived ROS increased eNOS activation and nitric oxide (NO) synthesis through activation of the survival kinase AMPK. We also show that endothelium-dependent coronary vasodilation in Tet-OFF Nox2 animals was CaMKKβ-AMPK-dependent. Finally, we demonstrate that AMPK activation induced autophagy and thus, protected ECs from oxidant-induced cell death in these animals. Together, these results suggest that activation of AMPK plays an important role in EC survival and endothelial function during oxidative stress. Conclusion: These findings suggest that increased ROS levels, often associated with pathophysiological conditions, play a protective role in endothelial homeostasis by inducing AMPK-eNOS axis.

Impact of Darunavir, Atazanavir and Lopinavir Boosted with Ritonavir on Cultured Human Endothelial Cells: Beneficial Effect of Pravastatin

HIV-infected patients administered long-term ritonavir-boosted protease inhibitors (PIs) are at a greater risk for developing cardiovascular diseases. Endothelial dysfunction is an initiating event in HIV-associated atherosclerosis. Cultured endothelial cells can be used as a model to compare the endothelial toxicity of different PIs. We compared the effect of darunavir (DRV), darunavir/ritonavir (DRV/r), lopinavir/ritonavir (LPV/r) and atazanavir/ritonavir (ATV/r), used at clinically relevant concentrations, on human coronary artery endothelial cell vascular function, oxidative stress, inflammation and senescence, and studied the effect of pravastatin on PI-induced alterations. Vascular endothelial cell function, evaluated by the expression of endothelial nitric oxide synthase and the production of nitric oxide and endothelin-1, was unaffected by DRV or DRV/r, but altered by LPV/r or ATV/r. DRV or DRV/r did not alter, or mildly induced oxidative stress and inflammation (phosphorylation of p65/RelA-NFκB, secretion of IL-6 and IL-8), while ATV/r and LPV/r induced a marked increase. Secretion of sICAM or sVCAM, indicative of altered cell integrity, was not or weakly altered by DRV or DRV/r, but increased by 2-3-fold by LPV/r or ATV/r. Similar results were observed regarding senescence markers: SA-β-galactosidase activation and overexpression of phospho-p53, p16(ink4), p21(WAF-1) and prelamin A. Pravastatin could, in part, reverse PI-induced adverse effects. Ritonavir-boosted PIs differentially induced vascular endothelial cell dysfunction, reactive oxygen species production, inflammation and senescence with no effect or a mild effect of DRV/r, an intermediate effect of ATV/r, and a stronger effect of LPV/r. Statins could, in part, protect the cells from PI-induced endothelial dysfunction.

Usefulness of Brachial Artery Flow-Mediated Dilation to Predict Long-Term Cardiovascular Events in Subjects Without Heart Disease

Endothelial dysfunction is considered an important prognostic factor in atherosclerosis. To determine the long-term association of brachial artery flow-mediated dilation (FMD) and adverse cardiovascular (CV) events in healthy subjects, we prospectively assessed brachial FMD in 618 consecutive healthy subjects with no apparent heart disease, 387 men (63%), and mean age 54 ± 11 years. After overnight fasting and discontinuation of all medications for ≥12 hours, FMD was assessed using high-resolution linear array ultrasound. Subjects were divided into 2 groups: FMD ≤11.3% (n = 309) and >11.3% (n = 309), where 11.3% is the median FMD, and were comparable regarding CV risk factors, lipoproteins, fasting glucose, C-reactive protein, concomitant medications, and Framingham 10-year risk score. In a mean clinical follow-up of 4.6 ± 1.8 years, the composite CV events (all-cause mortality, nonfatal myocardial infarction, hospitalization for heart failure or angina pectoris, stroke, coronary artery bypass grafting, and percutaneous coronary interventions) were significantly more common in subjects with FMD ≤11.3% rather than >11.3% (15.2% vs 1.2%, p = 0.0001, respectively). Univariate analysis demonstrated that the median FMD significantly predicted CV events (odds ratio 2.78, 95% CI 1.35 to 5.71, p <0.001). Multivariate analysis, controlling for traditional CV risk factors, demonstrated that median FMD was the best independent predictor of long-term CV adverse events (odds ratio 2.93, 95% CI 1.28 to 6.68, p <0.001). In conclusion, brachial artery median FMD independently predicts long-term adverse CV events in healthy subjects with no apparent heart disease in addition to those derived from traditional risk factor assessment.

Influence of a paclitaxel coated balloon in combination with a bare metal stent on restenosis and endothelial function: Comparison with a drug eluting stent and a bare metal stent

Different approaches of local intravascular drug delivery may influence endothelial and microvascular function. The aim of this trial was to study the influence of a paclitaxel coated balloon in combination with a bare metal stent (DCB + BMS) versus a bare metal stent (BMS) or a sirolimus-eluting stent (DES) on coronary restenosis and endothelial function. This prospective trial included 77 patients with coronary de novo lesions. The patients were assigned to either one of the treatment groups. After 9 months, patients underwent angiographic follow-up including invasive measurement of coronary endothelial function. After 9 months, late lumen loss in-stent was highest in the BMS group (0.85 ± 0.73 mm), lower in DCB + BMS (0.36 ± 0.46 mm); and lowest in the DES group (0.25 ± 0.34 mm; P = 0.001 [ANOVA]). When compared to the BMS group, in-segment late lumen loss was significantly reduced in the DCB + BMS group (0.27 ± 0.43 mm vs. 0.60 ± 0.55 mm, P = 0.029) and the DES group (0.28 ± 0.40 mm, P = 0.045). Coronary flow reserve was significantly higher with the DCB + BMS treatment (3.16 ± 0.97 vs. 2.42 ± 0.99 [BMS], P = 0.036) whereas the increase in the DES group did not reach the significance level (3.06 ± 1.39, P = 0.144 vs. BMS). Parameters of endothelial function like intracoronary flow velocity and vessel diameter distal to the stented area showed similar patterns of response to adenosine, acetylcholine, and nitro in all groups. DES and the combination of DCB + BMS showed a significant reduction of late lumen loss as compared to a BMS alone. Furthermore, both types of local drug delivery were not associated with a deterioration of microvascular function at 9 months [ClinicalTrials.gov Identifier: NCT00473499].

Nocturnal Hemodialysis Restores Impaired Coronary Endothelial Function in End-Stage Renal Patients Receiving Conventional Hemodialysis

Nocturnal Hemodialysis Restores Impaired Coronary Endothelial Function in End-Stage Renal Patients Receiving Conventional Hemodialysis

Comparison of the effect of carvedilol and metoprolol in the treatment of dilated cardiomyopathy patients with heart failure

Objective To compare the clinical efficacy of carvedilol and metoprolol in the treatment of dilated cardiomyopathy patients with heart failure (DCM).Methods According to the different treatment method,90 DCM patients with heart failure patients were divided into the observation group and the control group,45 cases in each group.Both groups were given a diuretic,vasodilator,cardiac and other drug treatment,and the control group were added with metoprolol,and the observation group were added with carvedilol.The treatment lasted 4 to 6 months.Before and after treatment,the levels of left ventricular ejection fraction(LVEF),left ventricular end-systolic diameter (LVESVI),left ventricular diastolic diameter (LVEDVI),left ventricular fractional shorteningrate (FS),largest peak velocity (hCFV),coronary flow reserve (CFR),simultaneous detection of serum levels of endothelin (ET) and nitric oxide(NO) content were observed and compared betweon the two groups.Results After the treatment,the levels of LVEF,LVESVI,LVEDVI,FS,hCFV,CFR,ET,NO of the observation group were (44.0 ± 3.4) ml/m2,(45.2 ±6.9)mm,(20.9 ±5.4)mm,(30.4 ±5.3),(78.2 ±31.6) cm/s,(3.12 ±0.36),(52.2 ±5.6) ng/L,(5.2 ± 0.67) μmol/L,respectively,which were better than those of the control group[(37.9 ± 3.5)mL/m2,(51.1 ± 7.6)mm,(20.7 ±6.3) mm,(25.2 ±7.3),(70.5 ± 31.8)cm/s,(2.85 ±0.23),(63.5 ± 1.8)ng/L,(2.55 ± 0.33) μmoL/L] (t =8.386,-3.856,-4.487,3.867,-1.152,-4.239,12.887,-23.802,all P ＜ 0.05).Conclusion Carvedilol is an effective drug for the treatment of DCM consolidated psychological failure,which can improve heart function and coronary flow reserve capacity and endothelial function in patients,which is worth in the clinical with satisfactory results. Key words: Cardiomyopathy, dilated ; Heart failure, congestive; Carvedilol ; Metoprolol

Abstract 299: Remodeling of Endothelial Function in Atherosclerotic Mice Overexpressing Endothelin-1 Restricted to Endothelium

Background: In human atherosclerosis , which is associated with elevated plasma and coronary endothelin (ET)-1 levels, ET type A receptor antagonists improved coronary endothelial function. Mice overexpressing ET-1 specifically in the endothelium (eET-1) crossed with apolipoprotein E knockout mice (Apoe-/-) exhibited exaggerated high-fat diet (HFD)-induced atherosclerosis. Since endothelial dysfunction often precedes development of atherosclerosis, we investigated whether endothelium-specific ET-1 overexpression causes endothelial dysfunction in Apoe-/- mice. Methods: Eight-week male old eET-1, Apoe-/-, eET-1/Apoe-/- and wild-type (WT) mice were fed a regular diet or HFD for 8 weeks. Endothelial function was assessed in mesenteric arteries by pressurized myography. Results: In HFD-fed mice, acetylcholine-induced endothelium-dependent relaxation (EDR) was reduced in Apoe-/- and eET-1 compared to WT (Emax: 29.2±2.9% and 51.8±7.9%, respectively, vs. 88.0±2.6%, P&lt;0.05). Surprisingly, EDR was not impaired in eET-1/Apoe-/- (70.9±9.8%) compared to WT. Endothelium-independent relaxation to the nitric oxide (NO) donor sodium nitroprusside and contractile responses to norepinephrine were unaffected. Similar results were observed in regular diet-fed mice. In the presence of inhibitors of either NO synthase (NOS)-mediated relaxation, Nω-nitro-L-arginine methyl ester, or endothelium-dependent hyperpolarization (EDH)-mediated relaxation, apamin plus Tram34, EDR was blunted in WT (Emax: 2.8±0.4% and 35.7±8.4 respectively, P&lt;0.01), whereas relaxation was weakly reduced or unaffected in eET-1/Apoe-/- (Emax: 68.6±9.9, P&lt;0.05 and 80.6±8.0, respectively). However, the concomitant inhibition of NOS- and EDH-mediated relaxation strongly reduced EDR in eET-1/Apoe-/- (Emax: 43.0±8.2%, P&lt;0.05). Conclusions: These results show an interdependence of NOS and EDH pathways in EDR in WT mice. ET-1 overexpression induced development of compensatory mechanisms in pre-atherosclerotic arteries of Apoe-/- mice, which permits either NOS or EDH pathway to mediate independently EDR. Investigation of mechanisms involved in the remodeling of EDR in eET-1/Apoe-/- mice will allow a better understanding of the ET-1 role in atherosclerosis.

Coronary endothelial dysfunction is associated with increased risk of osteoporosis in postmenopausal women

Background: A growing body of evidence links coronary artery atherosclerosis and calcification to osteoporosis in women. Coronary endothelial dysfunction (CED) is regarded as an early stage of coronary atherosclerosis. We aimed to study the association of CED and development of osteoporosis. Methods: Coronary endothelial function was evaluated in 194 postmenopausal women, greater than age 50, with non-obstructive coronary arteries, by administration of intracoronary acetylcholine during diagnostic angiography. CED was defined as <50% increase in coronary blood flow (CBF) from baseline in response to maximal dose. After a median follow-up of 7 years, patients were assessed by a questionnaire for development of osteoporosis. Results: The average age of the cohort was 60.9 years + 7.4 years. Of 194 women, 119 (61.3%) had CED. 20.1% (39/194) developed osteoporosis during median follow-up period of seven years. Women who developed osteoporosis had a markedly lower response (% change) in CBF to acetylcholine administration when compared to women who did not develop osteoporosis: median (IQR) [-4.3 (-29.4, 47.6) vs. 39.9 (-7.3, 100.1) p=0.008.] In univariate analysis, coronary endothelial dysfunction was significantly associated with the development of osteoporosis (p=0.025; relative risk 2.1, 95% CI: 1.06, 4.12). Multivariate analysis adjusting for confounders revealed a similar association (p=0.024). ![Figure][1] Discussion: The current study demonstrates that coronary endothelial dysfunction is associated with and predictive of osteoporosis in postmenopausal women. This provides a potential common mechanism for the increased risk of osteoporosis in patients with coronary artery disease. [1]: pending:yes