The present investigation demonstrates that NO, but not prostacyclin, is essential for flow-mediated dilatation of large human arteries. Hence, this response can be used as a test for the L-arginine/NO pathway in clinical studies.

In vivo arterial stiffness is a dynamic property based on vascular function and structure. It is influenced by confounding factors like blood pressure (BP), age, gender, body mass index, heart rate, and treatment. As a consequence, standardization of the measurement conditions is imperative. General and method/device-specific user procedures are discussed. The subject's conditions should be standardized before starting measurements. These conditions include a minimal resting period of 10 min in a quiet room. It also includes prohibitions on smoking, meals, alcohol, and beverages containing caffeine before measurements. The position of the subject and time of measurements should be standardized. In comparative studies, corrections should be made for confounding factors. Repeated measurements are done preferably by the same investigator, and if available validated with user-independent automated procedures. As it is not feasible to discuss all methods or devices measuring arterial stiffness in one article, more attention is given to user procedures of commercially available devices, because these devices are of interest for a wider group of investigators. User procedures of methods/devices are discussed according to the nature of arterial stiffness measured: systemic, regional, or local arterial stiffness. Each section discusses general or method/device-specific user procedures and is followed by recommendations. Each recommendation discussed during the First International Consensus Conference on the Clinical Applications of Arterial Stiffness is quoted with the level of agreement reached during the conference. Also proposals for future research are made.

Background-The lymphatic system regulates interstitial tissue fluid balance, and lymphatic malfunction causes edema.The heart has an extensive lymphatic network displaying a dynamic range of lymph flow in physiology. Myocardial edema occurs in many cardiovascular diseases, eg, myocardial infarction (MI) and chronic heart failure, suggesting that cardiac lymphatic transport may be insufficient in pathology. Here, we investigate in rats the impact of MI and subsequent chronic heart failure on the cardiac lymphatic network. Further, we evaluate for the first time the functional effects of selective therapeutic stimulation of cardiac lymphangiogenesis post-MI. Methods and Results-We investigated cardiac lymphatic structure and function in rats with MI induced by either temporary occlusion (n=160) or permanent ligation (n=100) of the left coronary artery. Although MI induced robust, intramyocardial capillary lymphangiogenesis, adverse remodeling of epicardial precollector and collector lymphatics occurred, leading to reduced cardiac lymphatic transport capacity. Consequently, myocardial edema persisted for several months post-MI, extending from the infarct to noninfarcted myocardium. Intramyocardial-targeted delivery of the vascular endothelial growth factor receptor 3-selective designer protein VEGF-C C152S , using albumin-alginate microparticles, accelerated cardiac lymphangiogenesis in a dose-dependent manner and limited precollector remodeling post-MI. As a result, myocardial fluid balance was improved, and cardiac inflammation, fibrosis, and dysfunction were attenuated. Conclusions-We show that, despite the endogenous cardiac lymphangiogenic response post-MI, the remodeling and dysfunction of collecting ducts contribute to the development of chronic myocardial edema and inflammationaggravating cardiac fibrosis and dysfunction. Moreover, our data reveal that therapeutic lymphangiogenesis may be a promising new approach for the treatment of cardiovascular diseases. deleterious effects, including induction of blood vascular rarefaction and dysfunction and stimulation of cardiac fibrosis, contributing to the development of chronic heart failure . 14 Furthermore, many inflammatory mediators, and oxygen radicals generated during inflammation, as well, negatively affect lymphatic function, causing impairment of lymph flow and initiation of lymph edema and chronic inflammation. 15,16 It is noteworthy that clinically detectable myocardial edema, extending beyond the infarct zone, may persist for up to 6 to 12 months post-myocardial infarction (MI) in humans, which is suggestive of lymphatic insufficiency. 17,18Whether cardiac lymphatic dysfunction occurs after myocardial injury, and the impact this may have on myocardial fluid balance and cardiac inflammation, remains to be investigated. Moreover, although the advent of molecular lymphatic markers has fueled investigations into lymphatic anatomy, function, and growth in many organs, 19-21 only a handful of articles have assessed lymphangiogenesis in the heart. It was rec...