Proximal heat stress up-regulates angiopoietin-1 in fingers and reduces the severity of Raynaud’s phenomenon in systemic sclerosis: a single-centre pilot study

ABSTRACT Objectives Raynaud’s phenomenon (RP) is a peripheral vascular disorder that frequently occurs in systemic sclerosis (SSc). Although therapeutic heating seems reasonable given that RP is elicited by cold stimuli, the effects of heating are still unclear. We examined the effects of heating applied on various body parts in SSc patients with RP of fingers. Methods Fourteen SSc patients heated their neck, elbows, and wrists with disposable heating pads for 1 week each. The visual analogue scale (VAS) for RP during each heating period was compared with that of each 1-week pre-treatment interval. On the day after the expiration of each heating period, their finger temperature, the finger blood flow, and angiogenesis-related factors (vascular endothelial growth factor, endostatin, angiopoietin-1, and angiopoietin-2) obtained from the cubital vein and fingertip were measured. Results The mean VAS was significantly reduced during the heating of the neck and elbows. Fingertip blood samples showed significantly increased angiopoietin-1 after each of the heating periods and increased endostatin after wrist heating. After the termination of heating, changes in finger temperature or blood flow could not be detected. Conclusions Heating the neck or elbows can alleviate RP in SSc. The heat up-regulates angiopoietin-1 in the fingers.

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Methods for assessment of microcirculation

Revmatologiia (Bulgaria) ◽

10.35465/29.1.2021.pp73-84 ◽

2021 ◽

Vol 29 (1) ◽

pp. 73-84

Author(s):

Vladimira Boyadzhieva ◽

Nikolay Stoilov

Keyword(s):

Blood Flow ◽

Systemic Sclerosis ◽

Vascular Function ◽

Raynaud’S Phenomenon ◽

Connective Tissue Diseases ◽

Raynaud's Phenomenon ◽

Systemic Autoimmune Disease ◽

Discriminative Ability ◽

Limited Application ◽

Secondary Raynaud’S Phenomenon

To date, many methods have entered rheumatological practice in order to evaluate more accurately the microcirculation. Most of them are non-invasive or minimally invasive, easily accessible, providing different information depending on the specifics of the study. Over the years, some of them (such as chromametry and volumetry) have lost their routine application and have acquired rather historical significance, while others have become an integral part of the rheumatological armentarium. An example of this is video capillaroscopy, which, through its dynamic development over the last 20 years, has evolved in the knowledge of changes in microcirculation in systemic sclerosis, as well as in other systemic connective tissue diseases. The expansion of knowledge in this area has led to the updating of the classification criteria for systemic sclerosis, allowing the addition of capillaroscopic changes as recognized by the European League against Rheumatism (EULAR). Another important indication for performing video capillaroscopy is the differentiation of primary from secondary Raynaud's phenomenon. Laser Doppler perfusion imaging is also used to detect secondary Raynaud's phenomenon in order to distinguish whether reduced blood flow is due to systemic autoimmune disease. Thermography also has a helpful role in diagnosing Raynaud's phenomenon, but unlike the other two methods, it has a much more limited application due to the lack of discriminative ability to distinguish nutritional from thermoregulatory blood flow, which leads to erroneous conclusions in pathological conditions. Venous occlusive plethysmography is one of the "gold standards" in the assessment of vascular function in health and disease and is an accurate, reproducible and convenient method to assess the effect of new vasoactive drugs. However, its application in everyday rheumatological practice is quite limited.

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Blood flow changes with naftidrofuryl in systemic sclerosis and Raynaud's phenomenon

British Journal of Dermatology ◽

10.1111/j.1365-2133.1980.tb05665.x ◽

1980 ◽

Vol 102 (1) ◽

pp. 7-10 ◽

Cited By ~ 3

Author(s):

P. M. GAYLARDE ◽

O. T. TAN ◽

I. SARKANY

Keyword(s):

Blood Flow ◽

Systemic Sclerosis ◽

Raynaud’S Phenomenon ◽

Raynaud's Phenomenon ◽

Flow Changes

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Ascorbic Acid does not Improve Endothelium-Dependent Flow-mediated Dilatation of the Brachial Artery in Patients with Raynaud’s Phenomenon Secondary to Systemic Sclerosis

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831.73.1.3 ◽

2003 ◽

Vol 73 (1) ◽

pp. 3-7 ◽

Cited By ~ 22

Author(s):

M. E. Mavrikakis ◽

J. P. Lekakis ◽

M. Papamichael ◽

K. S. Stamatelopoulos ◽

Ch. C. Kostopoulos ◽

...

Keyword(s):

Ascorbic Acid ◽

Smooth Muscle ◽

Systemic Sclerosis ◽

Endothelial Dysfunction ◽

Brachial Artery ◽

Raynaud’S Phenomenon ◽

Raynaud's Phenomenon ◽

Water Soluble ◽

Placebo Administration ◽

Flow Mediated Dilatation

Previous studies have shown that patients with Raynaud’s phenomenon secondary to systemic sclerosis present abnormal endothelial function; the mechanisms responsible for the endothelial dysfunction are unknown but increased vascular oxidative stress could be a possible cause. The hypothesis that a potent water-soluble antioxidant can reverse endothelial dysfunction in these patients was tested in the present study. We examined 11 female patients with Raynaud’s phenomenon secondary to systemic sclerosis and ten healthy control women by ultrasound imaging of the brachial artery to assess flow-mediated (endothelium-dependent) and nitrate-induced (endothelium-independent) vasodilatation. Flow-mediated dilatation and nitrate-induced dilatation were significantly reduced in patients with Raynaud’s phenomenon, indicating abnormal endothelial and smooth muscle cell function. Patients with Raynaud’s phenomenon entered a double-blind, randomized, crossover placebo-controlled trial and received orally 2 g of ascorbic acid or placebo; vascular studies were repeated two hours after ascorbic acid or placebo administration. Flow-mediated dilatation did not improve after ascorbic acid (1.6 ± 2.2% to 2.2 ± 2.5%, ns) or placebo administration (1.2 ± 1,9% to 1.7 ± 1.4%, ns); also nitrate-induced dilatation was similar after ascorbic acid or placebo (16 ± 7.4% vs 17 ± 8%, ns), suggesting no effect of ascorbic acid on endothelial and vascular smooth muscle function. In conclusion, ascorbic acid does not reverse endothelial vasomotor dysfunction in the brachial circulation of patients with Raynaud’s phenomenon secondary to systemic sclerosis. The use of different antioxidants or different dosing of ascorbic acid may be required to show a beneficial effect on endothelial vasodilator function.

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