Az endothelialis funkció non-invazív vizsgálata Melyik technika?
Jelen tanulmány célja az volt, hogy összehasonlítsunk három non-invazív, gyermekekben és
felnőttekben endothelialis funkciót vizsgáló technikát, és kiértékeljük hasznosságukat az akut
Háttér- Az endothelialis dysfunkció egy korai kulcsfontosságú állapot a pre-klinikai
atherosclerosisban. Az áramlás-mediált dilatáció (FMD), annak ellenére, hogy megalapozott
technika, költséges és technikai hozzáértést igényel. A belélegzett salbutamolra bekövetkező
vascularis változások pulzushullám analízissel (PWA) vagy pulzuskontúr analízissel (PCA)
történő vizsgálatai potenciális alternatívák.
Módszerek- 16 felnőttet (átlagéletkor: 28 év, 18-39 év) és 16 gyermeket (átlagéletkor: 13 év,
7-17 év) vizsgáltunk egyidejűleg a vascularis funkció tekintetében két alkalommal
ultrahanggal, PWA-val és PCA-val. 18 férfit is bevettünk a vizsgálatba, akiket typus
vakcináció előtt és után is megmértünk. Eredmények- Az FMD reprodukálhatósága felnőttekben és gyermekekben magas volt
(variációs koefficiens (CV)=7,1, illetőleg 6,3). A Salbutamolra adott válasz nagyobb
variabilitást mutatott PWA-val (felnőtt CV=11,5, gyermek CV=17,1) és PCA-val főként
gyermekekben (felnőtt CV=18,2, gyermek CV=36,3). Az áramlás-mediálta dilatáció
(p<0,001) és a PWA salbutamolra adott válasszal (p=0,03) a vakcináció után lecsökkent, míg
PCA-val (p=0,7) változatlan maradt. Következtetés- Akut gyulladásos folyamat során a vascularis dysfunkció FMD-vel és
salbutamolra adott válasz PWA-val mérhető. Az áramlás-mediálta dilatáció kevésbé
variábilis, mint a PWA. A PCA variabilitás ezt a technikát alkalmatlanná teszi az endothelialis
funkció mérésére gyermekekben. Az áramlás-mediálta dilatáció a legreprodukálhatóbb
módszer. (J Am Coll Cardiol 2006; 48:1845-50)
Endothelial Function Non-Invasive Assessment of Endothelial Function Which Technique? Ann E. Donald, AVS,* Marietta Charakida, MD,* Tim J. Cole, SCD,* Peter Friberg, MD, PHD,* Phil J. Chowienczyk, FRCP,† Sandrine C. Millasseau, PHD,† John E. Deanfield, MB, FRCP,* Julian P. Halcox, MD, MRCP* London, United Kingdom OBJECTIVES The purpose of this study was to compare 3 non-invasive techniques for assessment of endothelial function in adults and children and evaluate their utility in acute inflammation. BACKGROUND Endothelial dysfunction is a key early event in pre-clinical atherosclerosis. Flow-mediated dilation (FMD), although the established technique, is expensive and technically demanding. Measurements of vascular responses to inhaled salbutamol by pulse wave analysis (PWA) or pulse contour analysis (PCA) are potential alternatives. METHODS Sixteen adults (mean age 28 years, range 18 to 39) and 16 children (mean age 13 years, range 7 to 17) underwent concurrent vascular function testing on 2 occasions with ultrasound, PWA, and PCA. Eighteen men were also studied before and after typhoid vaccination. RESULTS Reproducibility of FMD was high in adults and children (coefficient of variation [CV] _ 7.1 and 6.3, respectively). Salbutamol responses were more variable with PWA (adults CV _ 11.5, children CV _ 17.1) and PCA particularly in children (adults CV _ 18.2, children CV _ 36.3). Flow-mediated dilation (p _ 0.001) and PWA with salbutamol (p _ 0.03) responses fell after typhoid vaccination, and PCA (p _ 0.7) was unchanged. CONCLUSIONS Vascular dysfunction during acute inflammation can be measured by FMD and by PWA with salbutamol. Flow-mediated dilation is less variable than PWA. Variability of PCA makes this technique currently unsuited to serial measures of endothelial function in children. Flowmediated dilation remains the most reproducible method. (J Am Coll Cardiol 2006;48: 1846–50) 2006 by the American College of Cardiology Foundation The vascular endothelium is a key signal transducer in atherogenesis (1). Study of preclinical vascular disease has been facilitated by use of non-invasive ultrasound techniques (2). The vasodilator response to increased conduit arterial flow (flow-mediated dilation [FMD]) is dependent on local nitric oxide (NO) bioavailability, and measurement of this response has been widely used in clinical studies (3,4). Recently, alternative non-invasive techniques have been developed with beta2 adrenoceptor agonist-mediated endothelial NO release, using measurement of the response with radial artery applanation tonometry (pulse wave analysis [PWA]) or digital photoplethysmography (pulse contour analysis [PCA]) (5–7). Although the equipment is small, portable, and easy to use, the comparative reproducibility of PWA and PCA and their ability to detect acute vascular changes have not been determined. We designed this study to assess the reproducibility of PWA, PCA, and FMD in children and adults and compared their ability to detect inflammation-induced changes in vascular function. METHODS Study population. We studied 16 children (11 boys, mean age 13 years, range 7 to 17) and 16 adults (9 men, mean age 28 years, range 18 to 39) to determine reproducibility and 18 men (mean age 26 years, range 18 to 39) to study vascular responses during acute inflammation. All were healthy and free from cardiovascular risk factors. All adults and parents gave written consent; children gave verbal assent. The study was approved by the local ethics committee. Study protocol. All investigations were performed by 2 experienced investigators. Subjects refrained from caffeine-containing drinks and food for 4 h before study and from vigorous exercise on the day of study. All studies were undertaken in a warm, temperaturecontrolled room by the same operator at the same time of
day on both occasions. STUDY 1—REPRODUCIBILITY: ADULTS. Adults attended on consecutive days (Fig. 1A). Brachial FMD was assessed. The effect of a 25-_g sublingual dose of glyceryl trinitrate (GTN) was then assessed simultaneously by ultrasound, PWA, and PCA for _15 min after administration, until the brachial artery diameter (D) had returned to baseline. The PWA and PCA were assessed before and at 2.5-min intervals From the *Institute of Child Health, University College London, London, United Kingdom; and †King’s College London, Cardiovascular Division, Department of Clinical Pharmacology, St. Thomas’ Hospital, London, United Kingdom. Support was provided by the Coronary Artery Disease Research Association (to Ms. Donald), the Greek State Scholarship Foundation (to Dr. Charakida), the UK Medical Research Council (to Prof. Cole), the British Heart Foundation (to Prof. Deanfield and Dr. Halcox), and the Swedish Medical Research Council (to Prof. Friberg). Dr. Chowienzyck was a director of Micromedical until March 2005. Dr. Millasseau is supported by Micromedical. Ms. Donald and Dr. Charakida contributed equally to this study. Manuscript received March 20, 2006; revised manuscript received June 26, 2006, accepted July 3, 2006. Journal of the American College of Cardiology Vol. 48, No. 9, 2006 2006 by the American College of Cardiology Foundation ISSN 0735-1097/06/$32.00 Published by Elsevier Inc. doi:10.1016/j.jacc.2006.07.039
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Co-Promotion von Takeda und Pfizer: gemeinsamer Vertrieb von actos® in China Takeda Pharmaceutical Company Limited (Takeda) hat Pfizer Inc. (Pfizer) als Co-Promotionpartner für den Vertrieb von actos® (Pioglitazon HCI) in China gewonnen. Diese exklusive Vereinbarung berücksichtigt das Umsatzpotenzial von actos® und erhöht entsprechend den medizinischen Außendienst zur Unterst