Impaired transient vasodilation and increased vasoconstriction to digital local cooling in primary Raynaud's phenomenon

Abstract

Raynaud's phenomenon (RP) is defined as episodic ischemia of the extremities in response to cold. Although the structure of skin capillaries is normal in primary RP, some data suggest impairment of microvascular function. We aimed at testing whether digital skin blood flow was lower in RP than in controls while cooling locally. We further evaluated the contribution of sensory nerves in the response. We recruited 21 patients with primary RP and 20 healthy volunteers matched on age and gender. After a 10-min baseline at 33°C, skin temperature was cooled at 15 or 24°C during 30 min on the forearm and the finger while monitoring perfusion with a custom-design laser Doppler flowmetry probe. Perfusion was also assessed after topical anesthesia. Blood flow was expressed as cutaneous vascular conductance (CVC). Data were subsequently expressed as area above the curve (AAC0 -30) of the percentage decrease from baseline CVC (%BL). CVC on the dorsum of the finger was lower in RP patients compared with controls at 15°C (AAC0 -30 were 106,237.2 and 69,544.3%BL·s, respectively; P ϭ 0.02) and at 24°C (AAC0 -30 were 86,915 and 57,598%BL·s, respectively; P ϭ 0.04) whereas we observed no significant difference on the finger pad and the forearm. Topical anesthesia increased CVC in patients with RP (P ϭ 0.05), whereas it did not affect reactivity in controls (P ϭ 0.86). Our study shows exaggerated skin microvascular vasoconstriction to local cooling on the dorsum of the finger in primary RP compared with controls. Part of this abnormal response in primary RP depends on sensitive nerves. microcirculation; skin blood flow FIRST DESCRIBED BY MAURICE RAYNAUD in 1862 (25), Raynaud's phenomenon (RP) is defined as episodic ischemia of the extremities in response to cold or emotional stimuli, often accompanied by pain. It presents clinically as pallor, cyanosis, and often rubor of the skin. Pallor indicates vasospasm and decreased blood flow, and cyanosis is a sign of deoxygenation of the static venous blood, while rubor implies reactive hyperemia (2). RP can be primary (i.e., idiopathic) or secondary to a connective tissue disease. The pathophysiology of primary RP is multifactorial and complex, with both vascular and neural abnormalities (7,15). Although available evidence suggests that microvascular function is impaired in primary RP, the exact mechanism of such dysfunction remains poorly understood.

Impairment of microcirculation and vascular responsiveness in adolescents with primary Raynaud phenomenon

“…The pathophysiology of primary RP is multifactorial with both vascular and neural abnormalities. The loss of CGRP- and VIP-containing nerves in the cutaneous microvasculature [ 17 , 18 ] and abnormal response of cold-sensitive nerves were described in primary adult RP patients [ 50 ]. A recent study found a strong relationship between microangiopathy and higher serum endothelin-1 and E-selectin levels in children with RP [ 40 ], although previous data had not confirmed the diagnostic value of endothelin concentration [ 51 ].…”

Digital obstructive arterial disease can be detected by laser Doppler measurements with high sensitivity and specificity

“…Several authors have used the cooling test to assess microvascular function because patients with Raynaud symptoms often experience the symptoms in response to cold or emotional stimuli. 14,16,17 However, performing a cooling test in patients with symptoms suggestive of arterial distal upper extremity disease is often painful. It would be useful to define the LDF cutoff value for vasospasm, but no gold standard exists.…”

Sildenafil Increases Digital Skin Blood Flow During All Phases of Local Cooling in Primary Raynaud's Phenomenon

“…Most of its vasoconstrictor effect depends on the inhibition of the NO system and on adrenergic function, 12 particularly through the translocation of α 2c ‐adrenoreceptors mediated by RhoA–Rho kinase 13 . We recently showed that local cooling–induced vasoconstriction on the fingers of patients with primary RP was increased as compared with healthy controls 6 …”

“…Although the morphology of skin capillaries is normal in primary RP, available evidence suggests that skin microvascular function is impaired 3 , 4 , 5 . Using a local cooling test, we recently showed increased digital skin vasoconstriction in participants with primary RP as compared with healthy controls 6 …”