Objective-We explored the potential role of the endogenous NO synthase inhibitor asymmetrical dimethylarginine (ADMA) in patients with idiopathic pulmonary arterial hypertension (IPAH). Method and Results-We correlated plasma ADMA levels and cardiovascular indices from right heart catheterization in 57 patients with IPAH. Predictors of survival in patients with IPAH were studied. Furthermore, the effect of systemic ADMA infusion on pulmonary ventricular resistance and stroke volume was investigated in healthy volunteers using right heart catheterization. Mean plasma ADMA concentrations were significantly higher in patients with IPAH than in control subjects (0. Key Words: idiopathic pulmonary arterial hypertension Ⅲ ADMA Ⅲ nitric oxide I diopathic pulmonary arterial hypertension (IPAH) is a disease of unknown etiology that is characterized by progressive obliteration of small and medium-size pulmonary arteries, elevation in pulmonary arterial pressure, and increase in pulmonary vascular resistance, eventually leading to right heart failure and death. 1 Without appropriate medical treatment, mean survival of patients experiencing IPAH is Ͻ3 years. 2 In the current understanding of the pathogenesis of IPAH, it is thought that a combination of genetically determined predisposition coupled with ill-defined exogenous factors may contribute to damage of the pulmonary vessels, resulting in endothelial dysfunction with proliferation of vascular endothelial and smooth muscle cells. [3][4][5] Endothelial dysfunction attributable to reduced bioavailability of endogenous vasodilator substances such as NO is thought to play an important role in the development of pulmonary hypertension. 6,7 NO is synthesized in the endothelium from the amino acid L-arginine by the action of NO synthase (NOS). Endogenous guanidino-substituted analogues of L-arginine that can selectively inhibit NOS have been implicated in the pathogenesis of various cardiovascular diseases. The most potent of these endogenous NOS inhibitors is asymmetrical dimethylarginine (ADMA). Elevated ADMA levels and low L-arginine/ADMA ratios not only correlate with the severity of atherosclerotic disease 8 -11 but also predict cardiovascular outcome and overall mortality. 12, 13 We demonstrated recently that pathophysiologically relevant ADMA blood concentrations inhibited NO production and reduced cardiac output and renal perfusion in healthy subjects. 14 Experimental data from a rat model of chronic hypoxia-induced pulmonary hypertension revealed that increased pulmonary concentrations of ADMA contributes to pulmonary hypertension. 15 On the basis of these observations, it seems possible that increased plasma ADMA concentrations may also contribute to endothelial dysfunction in patients with pulmonary vascular disease. 16 The present study was undertaken to evaluate a potential role of ADMA in IPAH.53Ϯ0 Subjects and Methods Participants and ProtocolsThe study protocol was approved by the local Ethics committee, and all participants gave informed consent. 17 For comp...

Procedure-related pulmonary hypertension in patients undergoing PEI is multifactorial. Plasma concentrations of the NO precursor l-arginine are reduced by arginase released from lysed erythrocytes, a condition further exacerbated by the increased concentrations of symmetric dimethylarginine, which may compete with the cellular uptake of l-arginine. The result would be reduced synthesis of NO, the concentration of which would be further decreased extracellularly through free hemoglobin. Predictably, the result would be severe endothelial dysfunction and pulmonary hypertension in patients undergoing PEI. These mechanisms might also be relevant in other states of (sudden) hemolysis.

The diagnostic uses of high-resolution ultrasonography (7.5-20 MHZ) have dramatically advanced in the past 20 years. We present representative examples of ultrasound diagnosis, based on our experience with over 15,000 examinations. For example, peripheral arterial disease was identified in 30% of older patients with venous diseases, while peripheral emboli and vasculitis can lead to widespread skin disease. Ultrasonographic diagnosis is required for appropriate interdisciplinary treatment. In addition, regular evaluation of the supra-aortic vessels and coronary arteries as well as arteries and veins of the limbs is needed in some forms of vasculitis. The causes of peripheral venous disease can be subdivided into four groups based on sonographic findings: Primary or secondary epi- and/or subfascial venous insufficiency, thrombotic venous occlusion, venous compression syndrome and arteriovenous-lymphatic malformations. The diagnosis and therapeutic approach to lymphedema and soft tissue diseases, with or without lymphadenopathy, requires careful sonographic evaluation. Ultrasonography is an essential part of dermatologic oncology, both for planning primary therapy and for follow-up. A sound command of ultrasonography is today an essential aspect of dermatologic diagnosis and therapy.