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Abstract Background Cytochrome P450 (CYP) enzyme 2J2, an epoxygenase predominantly expressed in the heart, metabolises arachidonic acid to biologically active eicosanoids. One of the CYP2J2 products, 11, 12-epoxyeicosatrienoic acid, has several vasoprotective effects. The CYP2J2-G-50T-promotor polymorphism decreases gene expression and is associated with coronary artery disease. This association supports the vascular protective role of CYP-derived eicosanoids in cardiovascular disease. In the present study, we investigated the influence of this polymorphism on survived myocardial infarction in two study groups of patients with on average high cardiovascular risk profile. Methods The CYP2J2 polymorphism was genotyped in two groups of patients that were collected with the same method of clinical data collection. Data from 512 patients with sleep apnoea (group: OSA) and on average high cardiovascular risk profile and from another 488 patients who were admitted for coronary angiography (CAR-group) were evaluated for a potential correlation of the CYP2J2 polymorphism G-50T and a history of myocardial infarction. The G-50T polymorphism of the CYP2J2 gene was genotyped by allele specific restriction and light cycler analysis. Results The T-allele of the polymorphism was found in 111 (11.1%; CAR-group: N = 65, 13.3%; OSA: N = 46, 9.0%). 146 patients had a history of myocardial infarction (CAR: N = 120, 24.6%; OSA: N = 26, 5.1%). Cardiovascular risk factors were equally distributed between the different genotypes of the CYP2J2 G-50T polymorphism. In the total group of 1000 individuals, carriers of the T-allele had significantly more myocardial infarctions compared to carriers of the wild type (T/T or G/T: 21.6%; G/G: 13.7%; p = 0.026, odds ratio 1.73, 95%-CI [1.06–2.83]). In the multivariate logistic regression analysis the odds ratio for a history of myocardial infarction in carriers of the T-allele was 1.611, 95%-CI [0.957–2.731] but this trend was not significant (p = 0.073). Conclusion In presence of other risk factors, the CYP2J2 G-50T failed to show a significant role in the development of myocardial infarction. However, since our result is close to the border of significance, this question should be clarified in larger, prospective studies in the future.

Abstract Background The increased sympathetic nervous activity in patients with obstructive sleep apnea (OSA) is largely responsible for the high prevalence of arterial hypertension, and it is suggested to adversely affect triglyceride and high-density lipoprotein (HDL) cholesterol levels in these patients. The functionally relevant polymorphisms of the β2-adrenergic receptor (Arg-47Cys/Arg16Gly and Gln27Glu) have been shown to exert modifying effects on these risk factors in previous studies, but results are inconsistent. Methods We investigated a group of 429 patients (55 ± 10.7 years; 361 men, 68 women) with moderate to severe obstructive sleep apnea (apnea/hypopnea index (AHI) 29.1 ± 23.1/h) and, on average, a high cardiovascular risk profile (body mass index 31.1 ± 5.6, with hypertension in 60.1%, dyslipidemia in 49.2%, and diabetes in 17.2% of patients). We typed the β2-adrenergic receptor polymorphisms and investigated the five most frequent haplotypes for their modifying effects on OSA-induced changes in blood pressure, heart rate, and lipid levels. The prevalence of cardiovascular risk factors and coronary heart disease (n = 55, 12.8%) and survived myocardial infarction (n = 27, 6.3%) were compared between the genotypes and haplotypes. Results Multivariate linear/logistic regressions revealed a significant and independent (from BMI, age, sex, presence of diabetes, use of antidiabetic, lipid-lowering, and antihypertensive medication) influence of AHI on daytime systolic and diastolic blood pressure, heart rate, prevalence of hypertension, and triglyceride and HDL levels. The β2-adrenergic receptor genotypes and haplotypes showed no modifying effects on these relationships or on the prevalence of dyslipidemia, diabetes, and coronary heart disease, yet, for all three polymorphisms, heterozygous carriers had a significantly lower relative risk for myocardial infarction (Arg-47Cys: n = 195, odds ratio (OR) = 0.32, P = 0.012; Arg16Gly: n = 197, OR = 0.39, P = 0.031; Gln27Glu: OR = 0.37, P = 0.023). Carriers of the most frequent haplotype (n = 113) (haplotype 1; heterozygous for all three polymorphisms) showed a five-fold lower prevalence of survived myocardial infarction (OR = 0.21, P = 0.023). Conclusion Our study showed no significant modifying effect of the functionally relevant β2-adrenergic receptor polymorphisms on OSA-induced blood pressure, heart rate, or lipid changes. Nevertheless, heterozygosity of these polymorphisms is associated with a lower prevalence of survived myocardial infarction in this group with, on average, a high cardiovascular risk profile.

Background: Cytochrome P450 (CYP) enzyme 2J2, an epoxygenase predominantly expressed in the heart, metabolizes arachidonic acid to biologically active eicosanoids. One of the CYP2J2 products, 11, 12-epoxyeicosatrienoic acid, has several vasoprotective effects. The CYP2J2-G-50T-promotor polymorphism decreases gene expression and is associated with coronary artery disease. This association supports the vascular protective role of CYP-derived eicosanoids in cardiovascular disease. In the present study, we investigated the influence of this polymorphism on survived myocardial infarction in two study groups of patients with on average high cardiovascular risk profile.Methods: The CYP2J2 polymorphism was genotyped in two groups of patients that were collected with the same method of clinical data collection. Data from 512 patients with sleep apnoea (group: OSA) and on average high cardiovascular risk profile and from another 488 patients who were admitted for coronary angiography (CAR-group) were evaluated for a potential correlation of the CYP2J2 polymorphism G-50T and a history of myocardial infarction. The G-50T polymorphism of the CYP2J2 gene was genotyped by allele specific restriction and light cycler analysis.Results: The T-allele of the polymorphism was found in 111 (11.1%; CAR-group: N = 65, 13.3%; OSA: N = 46, 9.0%). 146 patients had a history of myocardial infarction (CAR: N = 120, 24.6%; OSA: N = 26, 5.1%). Cardiovascular risk factors were equally distributed between the different genotypes of the CYP2J2 G-50T polymorphism. In the total group of 1000 individuals, carriers of the T-allele had significantly more myocardial infarctions compared to carriers of the wild type (T/T or G/T: 21.6%; G/G: 13.7%; p = 0.026, odds ratio 1.73, 95%-CI [1.06-2.83]). In the multivariate logistic regression analysis the odds ratio for a history of myocardial infarction in carriers of the T-allele was 1.611, 95%-CI [0.957-2.731] but this trend was not significant (p = 0.073).Conclusion: In presence of other risk factors, the CYP2J2 G-50T failed to show a significant role in the development of myocardial infarction. However, since our result is close to the border of significance, this question should be clarified in larger, prospective studies in the future. [ABSTRACT FROM AUTHOR]

Reports on the case of a boy who suffered from a typical clivus chordoma. Description of chordomas; Familial appearance of chordoma; Association between chordoma and tuberous sclerosis complex.

In nature, nonheme iron enzymes use dioxygen to generate high-spin iron(IV)=O species for a variety of oxygenation reactions. Although synthetic chemists have long sought to mimic this reactivity, the enzyme-like activation of O 2 to form high-spin iron(IV) = O species remains an unrealized goal. Here, we report a metal-organic framework featuring iron(II) sites with a local structure similar to that in α-ketoglutarate-dependent dioxygenases. The framework reacts with O 2 at low temperatures to form high-spin iron(IV) = O species that are characterized using in situ diffuse reflectance infrared Fourier transform, in situ and variable-field Mössbauer, Fe Kβ x-ray emission, and nuclear resonance vibrational spectroscopies. In the presence of O 2 , the framework is competent for catalytic oxygenation of cyclohexane and the stoichiometric conversion of ethane to ethanol.

Coordinatively unsaturated metal sites within certain zeolites and metal-organic frameworks can strongly adsorb a wide array of substrates. While many classical examples involve electron-poor metal cations that interact with adsorbates largely through physical interactions, unsaturated electron-rich metal centers housed within porous frameworks can often chemisorb guests amenable to redox activity or covalent bond formation. Despite the promise that materials bearing such sites hold in addressing myriad challenges in gas separations and storage, very few studies have directly interrogated mechanisms of chemisorption at open metal sites within porous frameworks. Here, we show that nondissociative chemisorption of H 2 at the trigonal pyramidal Cu + sites in the metal-organic framework Cu I -MFU-4 l occurs via the intermediacy of a metastable physisorbed precursor species. In situ powder neutron diffraction experiments enable crystallographic characterization of this intermediate, the first time that this has been accomplished for any material. Evidence for a precursor intermediate is also afforded from temperature-programmed desorption and density functional theory calculations. The activation barrier separating the precursor species from the chemisorbed state is shown to correlate with a change in the Cu + coordination environment that enhances π-backbonding with H 2 . Ultimately, these findings demonstrate that adsorption at framework metal sites does not always follow a concerted pathway and underscore the importance of probing kinetics in the design of next-generation adsorbents.

Iodoarenes are versatile intermediates and common synthetic targets in organic synthesis. Here, we present a strategy for selective C-H iodination of (hetero)arenes with a broad functional group tolerance. We demonstrate the utility and differentiation to other iodination methods of supposed sulfonyl hypoiodites for a set of carboarenes and heteroarenes.

Selective methylene C-H oxidation for the synthesis of alcohols with a broad scope and functional group tolerance is challenging due to the high proclivity for further oxidation of alcohols to ketones. Here, we report the selective synthesis of benzylic alcohols employing bis(methanesulfonyl) peroxide as an oxidant. We attempt to provide a rationale for the selectivity for monooxygenation, which is distinct from previous work; a proton-coupled electron transfer mechanism (PCET) may account for the difference in reactivity. We envision that our method will be useful for applications in the discovery of drugs and agrochemicals.

Incorporation of the CF 3 group into arenes has found increasing importance in drug discovery. Herein, we report the first photoredox-catalyzed cross-coupling of aryl thianthrenium salts with a copper-based trifluoromethyl reagent, which enables a site-selective late-stage trifluoromethylation of arenes. The reaction proceeds with broad functional group tolerance, even for complex small molecules on gram scale. The method was further extended to produce pentafluoroethylated derivatives., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

We report a direct radical aromatic amination reaction that provides unprotected anilines with an improvement in the substrate scope compared to prior art. Hydrogen bonding by the solvent hexafluoroisopropanol to anions of cationic species is responsible for increased reactivity and can rationalize the enhancement in substrate scope. Our findings may have bearings on radical additions to arenes for direct C-H functionalization in general.

Synthetic methods for oxidative aromatic C-O bond formation are sparse, despite their demand in metabolite synthesis for drug discovery and development. We report a novel methodology for late-stage C-O bond formation of arenes. The reaction proceeds with excellent functional group tolerance even for highly functionalized substrates. The resulting aryl mesylates provide access to potential human metabolites of pharmaceuticals, and may be used directly to install a C-F bond to block metabolic hotspots. A charge-transfer interaction between the reagent bis(methanesulfonyl) peroxide and the substrate arenes may be relevant for the chemoselective functionalization of arenes over other functional groups.

Cholesterol is an essential component of most biological membranes and serves important functions in controlling membrane integrity, organization, and signaling. However, probes to follow the dynamic distribution of cholesterol in live cells are scarce and so far show only limited applicability. Herein, we addressed this problem by synthesizing and characterizing a class of versatile and clickable cholesterol-based imidazolium salts. We show that these cholesterol analogs faithfully mimic the biophysical properties of natural cholesterol in phospholipid mono- and bilayers, and that they integrate into the plasma membrane of cultured and primary human cells. The membrane-incorporated cholesterol analogs can be specifically labeled by click chemistry and visualized in live-cell imaging experiments that show a distribution and behavior comparable with that of endogenous membrane cholesterol. These results indicate that the cholesterol analogs can be used to reveal the dynamic distribution of cholesterol in live cells., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

We report a C-F reductive elimination from a characterized first-row aryl metal fluoride complex. Reductive elimination from the presented nickel(III) complexes is faster than C-F bond formation from any other characterized aryl metal fluoride complex., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A family of practical, liquid trifluoromethylation and pentafluoroethylation reagents is described. We show how halogen bonding can be used to obtain easily handled liquid reagents from gaseous CF3I and CF3CF2I. The synthetic utility of the new reagents is exemplified by a novel direct arene trifluoromethylation reaction as well as adaptations of other perfluoroalkylation reactions., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: The aim of the study was to characterize RV adaptation to varying loading conditions in patients with chronic thromboembolic hypertension (CTEPH) before and after pulmonary endarterectomy (PEA). Nearly 4% of patients with pulmonary embolism develop CTEPH. PEA offers a cure with excellent outcome. By use of cardiovascular magnetic resonance (CMR) combined with hemodynamic measurements pulmonary arterial elastance (Ea-pulm_i), end-systolic right ventricular elastance (Ees-RV_i) and ventriculo-arterial coupling (Ea-pulm_i/Ees-RV_i) can be studied before and after PEA., Methods: Sixty-five patients (mean age 41±12 years, 28 female) underwent CMR pre- and post-PEA. Ejection fraction (EF), end-diastolic (EDVi), end-systolic (ESVi), and stroke (SVi) volumes were indexed for body surface area. Ea-pulm_i was calculated as pulmonary artery mean pressure (mPAP)/SVi, and Ees-RV_i as mPAP/ESVi., Results: mPAP decreased from 47±12 to 25±9 mmHg, p=0.0001. Ea-pulm_i was increased before PEA and normalized afterwards (2.8±2.1 vs. 0.85±0.4 mmHg/ml/m2, p=0.0001). Ees-RV_i was depressed before and after PEA (0.72±0.27 vs. 0.66±0.3 mmHg/ml/m2, p=0.13). EF improved from 25±12% to 46±10%, p=0.0001, because ventriculo-arterial coupling was restored (4.2±3 vs. 1.4±0.6, p=0.0001). EDVi and ESVi mproved significantly (EDVi 92±32 to 72±23 ml, p=0.0001; ESVi 69±31 to 41±18 ml, p=0.0001)., Conclusion: RV function is largely determined by afterload and returns to normal once afterload is normalized. This is paralleled by a significant improvement of CMR indices of right ventricular remodelling.

Selective 1,2-hydrosilylation of 1,3-dienes is a challenging problem in transition metal catalysis. Butadiene, specifically, would be a useful substrate because 3-butenylsilane products have promise as superior coupling reagents for hybrid organic/inorganic materials synthesis. We report the first selective 1,2-hydrosilylation of conjugated dienes including butadiene. Hydrosilylation proceeds through a Pt(II/IV) cycle, and selectivity is generated at a hexacoordinate Pt(IV) complex that favors η(2)-diene coordination and prevents π-allyl complex formation.

Background: Immunoadsorption (IA) is used in patients with inflammatory dilative cardiomyopathy (iDCM) to remove cardiotoxic autoantibodies, and to improve myocardial function. Even if IA is used only once, the level of anti-cardiac antibodies remains low over time. Changes in cell-mediated immunity after IA may contribute to this observation. The aim of this study is to investigate the effect of IA on cell-mediated immunity especially on regulatory and early activated T cells., Methods: Ten patients (50.1 ± 9.3 years) with chronic iDCM (with signs of myocardial inflammation in biopsies, but without persistence of virus genome), reduced left ventricular ejection fraction (EF < 35%) underwent IA. Blood samples were drawn before and after an IA course of 5 days, and 1, 3, and 6 months after IA. Leukocyte subpopulations were quantified by FACS analysis., Results: Left ventricular systolic function improved on average at 6 months from 25.6 ± 4.9 to 37.3 ± 10.1% (p < 0.05). The left ventricular end-diastolic diameter was reduced after 6 months (63.3 ± 3.1 vs. 57.1 ± 4.1 mm; p < 0.05). IA therapy led to an increase of regulatory T cells (CD4(+), CD25(+) and CD127(low)) over time (up to 6 months). This was associated with a decrease of activated T cells (CD4(+)/CD69(+) and CD8(+)/CD69(+) cells) and CD28(+) T cells (co-stimulatory cells), which was detectable for at least 6 months after IA., Conclusion: It is suggested that changes in cell-mediated immunity contribute to the beneficial effect of IA on myocardial function, and on maintenance of reduced blood levels of cardiotoxic autoantibodies.

Background: Hypertensive urgency/emergency occurs frequently, yet no prospective data on common secondary causes, including sleep apnea (SA), renal artery stenosis (RAS), and hyperaldosteronism, are available., Methods: Patients presenting to the emergency room for over 1 year with systolic blood pressure > or =180 mmHg and/or diastolic blood pressure > or =100 mmHg and typical symptoms were included. RAS was diagnosed by direct duplex/Doppler ultrasound of the renal artery, resistance index, and imaging. The aldosterone/renin ratio (ARR) was determined from morning blood samples taken with the patients supine after > or =2 h of rest. A positive ARR (>50) was followed by saline infusion to exclude primary hyperaldosteronism. SA was evaluated by nasal breathing flow screening; when positive [apnea/hypopnea index (AHI) >5/h], complete polysomnography was performed., Results: Of 161 patients (age, 66.0 +/- 13.1 years; BMI, 28.6 +/- 5.1 kg), 131 had previously identified hypertension (duration, 12.7 +/- 11.5 years; 1.9 +/- 1.5 antihypertensive medications). SA was found in 114 (70.8%) patients [18% mild (AHI: 5-15/h), 26.8% moderate (15.1-30/h), and 24.2% severe (>30/h)]. Aldosterone levels exceeded 160 pg/ml in 22 of 23 patients with hyperaldosteronism; 4 had primary and 12 had secondary hyperaldosteronism. Thirteen (8.1%) patients had RAS. Three secondary causes were found in 1 patient (0.6%), > or =2 in 25 (15.5%), and > or =1 in 124 patients (77.0%). Of 150 detected secondary causes, only 5 were recognized previously., Conclusions: Secondary causes of hypertension are common and predominantly unrecognized in patients with hypertensive urgency/emergency. Co-prevalence of secondary causes occurs in about 15% and should be considered before therapeutic intervention.

Recent attention has been drawn to a potential drug-drug interaction observed between clopidogrel and proton pump inhibitors (PPIs). However, this potential interaction may not be a class effect of PPIs. We investigated if pantoprazole, which has a different metabolism than omeprazole, diminishes the effectiveness of clopidogrel. Our study included 336 patients (mean age 64.6 years; 106 women) 48 hours after percutaneous coronary stent implantation with a loading dose of 600 mg clopidogrel hydrogensulfate and 500 mg aspirin, followed by 75 mg clopidogrel and 100 mg aspirin daily. Whereas 188 patients (59 women) were not given any PPI comedication, 122 patients received pantoprazole and 26 either omeprazole or esomeprazole. The platelet aggregation followed by impedance aggregometry (in Ohm) was induced by 5 mmol/L adenosine diphosphate. The percentage of clopidogrel low-response (CLR) was similar between the non-PPI group [2.75 Ohm (confidence interval, CI: 2.25-3.26); 21.9% CLR] and the pantoprazole group [2.33 Ohm (CI: 1.79-2.87); 16.4% CLR] but higher in patients treated with omeprazole/esomeprazole (3.00 Ohm (CI: 1.49-4.51); 30.8% CLR). Multivariate regression analysis reveals that the risk of CLR in the pantoprazole comedication group was not increased compared with the group without any PPI [odds ratio 0.59 (CI: 0.31-1.13) 0.11]. Our data suggest that pantoprazole does not diminish the antiplatelet effectiveness of clopidogrel early after coronary stenting. Therefore, the use of pantoprazole seems preferable in patients treated with clopidogrel when a concomitant medication with a PPI is indicated.

Cigarette smoking is a well known risk factor for cardiovascular disease with a great impact on mortality. Studies have linked smoking to inflammation, platelet activation and enhanced atherosclerosis. The present study investigated the activation and expression of proinflammatory markers on platelets obtained from smokers. The expression of P-selectin (CD62P) (as a marker of activation) and CD40/CD40L (as a marker for proinflammatory processes) were quantified in platelets by flow cytometry. Platelet-rich plasma was obtained from 34 apparent healthy volunteers (19 cigarette smokers, 15 age-matched control persons). Basal measurements and the response to stimulation with ADP and TRAP (10, 30, 100 micromol/l) were evaluated. Values given (mean fluorescence index, MFI) are mean +/- standard deviation. The basal values of platelet bound CD40 (3.20 +/- 0.50 vs. 2.71 +/- 0.28; P = 0.002), CD40L (1.10 +/- 0.12 vs. 0.95 +/- 0.12; P = 0.005) and P-selectin (0.70 +/- 0.21 vs. 0.55 +/- 0.11; P = 0.012) were significantly elevated in smokers as compared to controls. In addition, higher values were noted on stimulation with ADP or TRAP in smokers, although these different values were without statistical significance. According to our data cigarette smoking activates platelets (P-selectin expression) and stimulates the CD40-CD40L-pathway in otherwise healthy volunteers. These findings emphasize that cigarette smoking leads to a proinflammatory and prothrombotic state thus contributing to accelerated atherosclerosis.

Background: Bone-marrow derived endothelial progenitor cells (CD34+ and VEGFR2+ KDR+ EPC) and endothelial-derived microparticles (CD 31+Annexin V+, EMP; indicator for endothelial apoptosis) were examined in the peripheral blood of 35 male, clinically stable patients with 3-vessel coronary artery disease (CAD). The patients were divided in 2 groups, those with preserved or normal function (n = 17; EF 65 +/- 6%) and those with reduced left ventricular (LV) function (n = 18; EF 36 +/- 11%)., Methods and Results: The number of circulating EPCs was decreased by 25% (P = .07) and the number of EMPs was increased by 109 % (P < .05) in patients with LV dysfunction compared with those with normal or preserved LV function. EPCs were positively correlated (r = 0.24 for patients with LV dysfunction and r = 0.28 for patients with preserved LV function) with endothelial function as assessed by flow-mediated vasodilatation. In contrast, EMPs were inversely correlated (r = -0.42 for patients with LV dysfunction and r = -0.49 for patients with preserved LV function)., Conclusions: CAD patients with significant LV dysfunction show an increased index of endothelial cell damage. This decrease (or lack of compensatory elevation) of EPCs may result in a reduced potential for repair and thus contribute at least in part to the pathogenesis of endothelial dysfunction.

Studies from the USA have reported that sleep apnoea is common in congestive heart failure (CHF), with Cheyne-Stokes respiration (CSR) being the most frequent type of sleep-disordered breathing (SDB) in these patients. Within the present study, the authors sought to assess the prevalence and type of SDB among CHF patients in Germany. A total of 203 CHF patients participated in this prospective multicentre study. All patients were stable in New York Heart Association classes II and III and had a left ventricular ejection fraction (LVEF)<40%. The patients were investigated by polygraphy and all data were centrally analysed. Patient enrolment was irrespective of sleep-related symptoms. The majority of patients were male with a mean age of 65 yrs and hospitalised. Of the 203 patients, 145 (71%) had an apnoea/hypopnoea index>10.h(-1), obstructive sleep apnoea (OSA) occurred in 43% (n=88) and CSR in 28% (n=57) of patients. The prevalence of sleep-disordered breathing is high in patients with stable severe congestive heart failure from a European population. As sleep-disordered breathing may have a negative impact on the prognosis of congestive heart failure, a sleep study should be performed in every patient with congestive heart failure and a left ventricular ejection fraction of <40%. This diagnostic approach should probably be adopted for all of these patients irrespective of the presence of sleep-related symptoms.

Objective: Endothelial progenitor cells (EPCs) may have an important role in vascular homeostasis and repair., Methods: We examined the level of circulating EPCs in pre- (n = 22; mean age 28.7 years), and postmenopausal healthy females without (n = 30; mean age 61.6 years) or under current hormone replacement therapy (HRT) (n = 19; mean age 59.8 years)., Results: Premenopausal females had the highest level of circulating EPCs (0.147 +/- 0.076 per thousand of polymorphnuclear cells). The level of EPCs was lowest in postmenopausal females (0.094 +/- 0.058 per thousand), and increased significantly with HRT on average by 25.5%. In addition, the proliferative capacity of circulating EPCs was assessed under cell culture conditions. This capacity was significantly increased in EPCs isolated from postmenopausal subjects under current HRT as compared to corresponding samples obtained from postmenopausal females without HRT., Conclusions: This observation is in line with the hypothesis that the hormonal status in females modulates the cardiovascular risk and that circulating EPCs could be involved in this phenomenon.

Background: Cardioversion for atrial fibrillation (AF) is associated with impairment of left atrial mechanical function and increased risk of thrombus formation with subsequent embolisation. Measuring atrial mechanical function is of interest to determine the individual risk of thromboembolism and the risk of recurrent AF., Methods: We included 112 consecutive patients with AF and planned cardioversion. Serial echocardiographic measurements of left atrial size and Doppler measurement of mitral valve peak A wave velocities were obtained at days 0, 1, 2, 3, and 28 following cardioversion. These measurements and clinical parameters were related to clinical events and recurrent AF within 4 weeks following cardioversion. Cardioversion was achieved in 100 patients., Results: AF-recurrence within 4 weeks was 23.9% and 45.8% for patients with < or = and > 6 weeks AF-duration, respectively (p=0.04). Peak A wave velocities were significantly lower up to 2 days following cardioversion in patients with AF-recurrence. A peak A wave velocity < 52 cm/s at day 1 resulted in an odds ratio of 5.0 (95% CI: 1.4-18.6) for recurrence of AF. In multiple logistic regression analysis, peak A wave velocity at day 1 remained the only independent predictor of recurrent AF. Left atrial diameter did not correlate with recurrence of AF., Conclusions: A single measurement of mitral peak A wave velocity 1 day following cardioversion is predictive of AF recurrence. This method is feasible for risk estimation with potential therapeutic implications.

OSA (obstructive sleep apnoea) stimulates sympathetic nervous activity and elevates resting HR (heart rate) and BP (blood pressure). In the present study in a cohort of 309 untreated OSA patients, the resting HR and BP during the daytime were correlated with AHI (apnoea/hypopnea index) and compared with patients with R389R (n = 162), R389G (n = 125) and G389G (n = 22) genotypes of the beta1-adrenoreceptor R389G polymorphism. We analysed the impact of the genotype on the decline of HR and BP in a subgroup of 148 patients (R389R, n = 86; R389G, n = 54; G389G, n = 8) during a 6-month follow-up period under CPAP (continuous positive airway pressure) therapy during which cardiovascular medication remained unchanged. In untreated OSA patients, we found an independent relationship between AHI and resting HR (beta = 0.096, P < 0.001), systolic BP (beta = 0.09, P = 0.021) and diastolic BP (beta = 0.059, P = 0.016). The resting HR/BP, however, did not differ among carriers with the R389R, R389G and G389G genotypes. CPAP therapy significantly reduced HR [-2.5 (-1.1 to -4.0) beats/min; values are mean difference (95% confidence intervals)] and diastolic BP [-3.2 (-1.5 to -5.0) mmHg]. The decline in HR was more significantly pronounced in the R389R group compared with the Gly(389) carriers [-4.1 (-2.3 to -5.9) beats/min (P < 0.001) compared with -0.2 (2.1 to -2.6) beats/min (P = 0.854) respectively; Student's t test between groups, P = 0.008]. Diastolic BP was decreased significantly (P < 0.001) only in Gly389 carriers (R389G or G389G) compared with R389R carriers [-5.0 (-2.3 to -7.6) mmHg compared with -2.0 (0.4 to -4.3) mmHg respectively]. ANOVA revealed a significant difference (P = 0.023) in HR reduction between the three genotypes [-4.1 (+/-8.4) beats/min for R389R, -0.5 (+/-9.3) beats/min for R389G and +1.9 (+/-7.2) beats/min for G389G]. In conclusion, although the R389G polymorphism of the beta1-adrenoceptor gene did not influence resting HR or BP in untreated OSA patients, it may modify the beneficial effects of CPAP therapy on these parameters.

Recent studies suggest an association of obstructive sleep apnoea (OSA) with cardiovascular risk factors, such as dyslipidaemia. The present study analyses the effects of OSA and its therapy on serum lipid concentrations in 470 OSA patients in a single centre study. Multivariate regression showed a significant association between the apnoea-hypopnoea index and high-density lipoprotein cholesterol (HDL-C) serum levels (n = 366), independent of age, sex, body mass index, diabetes and lipid lowering medication. There were no independent associations with total cholesterol, triglyceride and low-density lipoprotein cholesterol serum levels. During follow-up (6 months) with effective bilevel or continuous positive airway pressure therapy in 127 patients (lipoproteins: n = 86) without change in their lipid lowering therapy, the mean HDL-C serum level increased significantly by 5.8% from 46.9+/-15.8 to 49.6+/-15.3 mg x dL(-1) (mean+/-SD). An independent relationship was found between the change of apnoea-hypopnoea index and the change of high-density lipoprotein cholesterol or triglycerides, respectively. All patients with abnormal serum lipid/lipoprotein levels improved significantly under bilevel or continuous positive airway pressure therapy. This study demonstrates an influence of obstructive sleep apnoea and its therapy on high-density lipoprotein cholesterol levels.

Background: There is increasing evidence that obstructive sleep apnea is an independent risk factor for arterial hypertension. Previous studies on the antihypertensive effects of positive airway pressure therapy on daytime blood pressure (BP) revealed inconsistent results., Methods: The relations between the apnea/hypopnea index (AHI) and BP or heart rate (HR) were investigated in a cohort of 540 consecutive patients (age, 55.4 +/-11.1 years) with moderate or severe obstructive sleep apnea (OSA). The mean AHI was 28.2 +/- 22.0 events/h before OSA therapy. A group of 196 patients in whom antihypertensive medication was kept unchanged was followed for 6 months during bilevel or continuous positive airway pressure (Bi-/CPAP) therapy., Results: Significant associations were found between AHI and systolic BP (beta = 0.078, P = .014), diastolic BP (beta = 0.056, P = .003), HR (beta = 0.096, P < .001), and the prevalence of arterial hypertension (odds ratio = 0.015, P = .003), independent of age, body mass index, and gender. During the follow-up period with effective Bi-/CPAP therapy, the mean daytime systolic BP decreased from 130.7 +/- 15.5 mm Hg to 128.6 +/- 15.9 mm Hg (P = .051), diastolic BP from 80.2 +/- 9.3 mm Hg to 77.5 +/- 9.5 mm Hg (P = .001), and HR from 77.7 +/- 8.8 to 75.7 +/- 8.1 beats/min (P = .001). Multiple linear regression analysis revealed that the absence of antihypertensive drugs and the level of the initial BP are significant and independent predictors for the lowering effect of Bi-/CPAP therapy on systolic and diastolic BP., Conclusions: This study confirms an independent relationship between the severity of OSA and BP/HR. Absence of BP-lowering medication and BP values before treatment are independent predictors for the reduction of BP with Bi-/CPAP therapy.

1. The activation of various purinoceptors in rat renal vasculature by P1,P2-diadenosine pyrophosphate (Ap2A), P1,P3-diadenosine triphosphate (Ap3A), P1,P4-diadenosine tetraphosphate (Ap4A), P1,P5-diadenosine pentaphosphate (Ap5A), P1,P6-diadenosine hexaphosphate (Ap6A) was studied by measuring their effects of perfusion pressure of a rat isolated perfused kidney. 2. The vasoconstrictive response to Ap5A was completely due to P2x purinoceptor activation, that to Ap4A and Ap6 was P2x purinoceptor mediated to a large extent, as evidenced by the inhibitory effects of suramin and pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid tetrasodium (PPADS). 3. The vasoconstrictive effects of Ap2A and Ap3A were mostly due to stimulation of A1-receptors, as shown by the inhibitory effect of 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). 4. The vasoconstrictive response to Ap6A was partially insensitive to A1 and P2x purinoceptor blockers. 5. In raised tone preparations Ap2A and Ap3A evoked vasodilatation, which was blocked by the A2 receptor blocker, 3,7-dimethyl-1-propargylxanthine (DMPX). 6. In raised tone preparations Ap4A evoked vasodilatation when the P2-purinoceptors were blocked by suramin. 7. The activation of different purinoceptor subtypes by diadenosine phosphates critically depends on the number of phosphate groups.