The myth of pulmonary Raynaud's phenomenon: the contribution of pulmonary arterial vasospasm in patients with systemic sclerosis related pulmonary arterial hypertension

Abstract

Objective: To investigate the contribution of cold induced pulmonary vasospasm by peripheral and central cold stimulus in exacerbating pulmonary arterial hypertension (PAH) in patients with systemic sclerosis undergoing cardiac catheterisation. Methods: In a prospective pilot study, 21 patients with systemic sclerosis and catheter proven PAH had mean pulmonary artery pressure (mPAP), pulmonary vascular resistance (PVR), and cardiac output (CO) measured before and after peripheral (hand immersion into cold water at 10-15˚C for two minutes if tolerated) and central (direct cold water at 4˚C injected into the right atrium) cold pressor challenge. Markers of endothelial activation, platelet function, and nitric oxide degradation were measured in blood sampled from the pulmonary artery. Results: 19 of the patients (mean (SD) age, 56 (4) years; baseline mPAP, 34 (8) mm Hg; PVR, 420 (87) dyne.s.cm 25 ; CO, 6.4 (1.8) l/min) tolerated cold hand immersion for the maximum two minute duration. All 21 tolerated central cold pressor challenge (three to five injections of 10 ml saline boluses at 4˚C). There was no significant change in haemodynamics after cold challenge by either route of provocation. Levels of endothelin-1, von Willebrand factor, fibrinogen, and 3-nitrotyrosine were raised compared with control values in patients with systemic sclerosis but without PAH, but did not change significantly after peripheral cold challenge. Conclusions: Pulmonary vasospasm in response to peripheral and centrally administered cold pressor challenge is unlikely to contribute to persistence of pulmonary arterial hypertension in patients with systemic sclerosis.

Isolated right ventricular dysfunction in systemic sclerosis: latent pulmonary hypertension?

“…[9]. A Raynauds phenomenon of the pulmonary vasculature has been proposed as a potential mechanism in labile PH associated with systemic sclerosis [29], but a pulmonary pressor response has not been reported in these patients during central cold tests or by hand immersion cold challenges [30]. Exercise Doppler echocardiography has been used to reveal abnormal pulmonary vascular response in high-altitude pulmonary oedema-susceptible subjects or in asymptomatic carriers of the primary PH gene [12,13].…”

Pulmonary Vasospasm in Systemic Sclerosis: Noninvasive Techniques for Detection

“…Other measurement techniques, including krypton perfusion lung scan (demonstrating reduced pulmonary perfusion) 20 and RHC (demonstrating an increase in mPAP and PVR in a subgroup of patients), 21 have provided support for the notion of pulmonary vasospasm, in at least a subgroup of patients. More recently, in SSc patients with established pulmonary hypertension, Coghlan and colleagues 22 found no change in right heart catheter parameters or circulating markers of endothelial cell activation after cold-pressor testing. These conflicting results have created understandable confusion, and a major limitation in identifying pulmonary vasospasm remains the lack of a readily available, validated measure of PBF.…”

“…13 Various measurement techniques (including right heart catheterization [RHC], radioisotope lung perfusion scans, and diffusing capacity of the lung for carbon monoxide [DLCO]) have been evaluated for the detection of pulmonary vasospasm, with varying results. [14][15][16][17][18][19][20][21][22] Technological advances now allow for the assessment of pulmonary blood flow (PBF) with several noninvasive techniques, including inertgas rebreathing (IGR) and dual-energy computed-tomography pulmonary angiography (DE-CTPA).…”

Microcirculatory disturbances – relationship with peripheral vascular reactivity and structure-functional properties of endothelium in systemic sclerosis

“…Выраженность микроциркуляторных нарушений при ССД зависит от степе-ни изменения структурно-функционального состояния эндотелия как на перифе-рическом, так и на системном сосудистых уровнях. К л ю ч е в ы е с л о в а : системная склеродермия, нарушения микроциркуляции, перифе-рическая сосудистая реактивность клеток синтезировать и высвобождать NO в легоч-ной микроциркуляции [7].…”